FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Suhasini, AN Brosh, RM AF Suhasini, Avvaru N. Brosh, Robert M., Jr. TI Mechanistic and biological aspects of helicase action on damaged DNA SO CELL CYCLE LA English DT Article DE helicase; DNA damage; DNA repair; replication; Werner syndrome; FANCJ; Fanconi anemia; Replication protein A; Xeroderma pigmentosum; nucleotide excision repair ID NUCLEOTIDE EXCISION-REPAIR; REPLICATION PROTEIN-A; WERNER-SYNDROME HELICASE; VINYLPHOSPHONATE INTERNUCLEOTIDE LINKAGES; YEAST RAD3 PROTEIN; ESCHERICHIA-COLI; BINDING PROTEIN; FANCJ HELICASE; SACCHAROMYCES-CEREVISIAE; GENOMIC STABILITY AB Helicases catalytically unwind structured nucleic acids in a nucleoside-triphosphate-dependent and directionally specific manner, and are essential for virtually all aspects of nucleic acid metabolism. ATPase-driven helicases which translocate along nucleic acids play a role in damage recognition or unwinding of a DNA tract containing the lesion. Although classical biochemical experiments provided evidence that bulky covalent adducts inhibit DNA unwinding catalyzed by certain DNA helicases in a strand-specific manner (i.e., block to DNA unwinding restricted to adduct residence in the strand the helicase translocates), recent studies suggest more complex arrangements that may depend on the helicase under study, its assembly in a protein complex, and the type of structural DNA perturbation. Moreover, base and sugar phosphate backbone modifications exert effects on DNA helicases that suggest specialized tracking mechanisms. As a component of the replication stress response, the single-stranded DNA binding protein Replication Protein A (RPA) may serve to enable eukaryotic DNA helicases to overcome certain base lesions. Helicases play important roles in DNA damage signaling which also involve their partnership with RPA. In this review, we will discuss our current understanding of mechanistic and biological aspects of helicase action on damaged DNA. C1 [Suhasini, Avvaru N.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. EM BroshR@mail.nih.gov FU NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. We wish to thank Drs. Deborah Croteau and Zheng Cao (Laboratory of Molecular Gerontology, NIA-NIH) for comments. NR 112 TC 15 Z9 15 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2010 VL 9 IS 12 BP 2317 EP 2329 PG 13 WC Cell Biology SC Cell Biology GA 615QC UT WOS:000279149000021 PM 20574162 ER PT J AU Cao, CM Zhang, Y Weisleder, N Ferrante, C Wang, XH Lv, FX Zhang, Y Song, RS Hwang, M Jin, L Guo, JJ Peng, W Li, G Nishi, M Takeshima, H Ma, JJ Xiao, RP AF Cao, Chun-Mei Zhang, Yan Weisleder, Noah Ferrante, Christopher Wang, Xianhua Lv, Fengxiang Zhang, Yi Song, Ruisheng Hwang, Moonsun Jin, Li Guo, Jiaojiao Peng, Wei Li, Geng Nishi, Miyuki Takeshima, Hiroshi Ma, Jianjie Xiao, Rui-Ping TI MG53 Constitutes a Primary Determinant of Cardiac Ischemic Preconditioning SO CIRCULATION LA English DT Article DE hypoxia; ischemia; myocardial infarction; myocytes; stress ID MUSCLE CELL APOPTOSIS; REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; HEART; AKT; MYOCARDIUM; SURVIVAL; ACTIVATION; CAVEOLIN-3; PROTECTION AB Background-Ischemic heart disease is the greatest cause of death in Western countries. The deleterious effects of cardiac ischemia are ameliorated by ischemic preconditioning (IPC), in which transient ischemia protects against subsequent severe ischemia/reperfusion injury. IPC activates multiple signaling pathways, including the reperfusion injury salvage kinase pathway (mainly PI3K-Akt-glycogen synthase kinase-3 beta [GSK3 beta] and ERK1/2) and the survivor activating factor enhancement pathway involving activation of the JAK-STAT3 axis. Nevertheless, the fundamental mechanism underlying IPC is poorly understood. Methods and Results-In the present study, we define MG53, a muscle-specific TRIM-family protein, as a crucial component of cardiac IPC machinery. Ischemia/reperfusion or hypoxia/oxidative stress applied to perfused mouse hearts or neonatal rat cardiomyocytes, respectively, causes downregulation of MG53, and IPC can prevent ischemia/reperfusion-induced decrease in MG53 expression. MG53 deficiency increases myocardial vulnerability to ischemia/reperfusion injury and abolishes IPC protection. Overexpression of MG53 attenuates whereas knockdown of MG53 enhances hypoxia-and H(2)O(2)-induced cardiomyocyte death. The cardiac protective effects of MG53 are attributable to MG53-dependent interaction of caveolin-3 with phosphatidylinositol 3 kinase and subsequent activation of the reperfusion injury salvage kinase pathway without altering the survivor activating factor enhancement pathway. Conclusions-These results establish MG53 as a primary component of the cardiac IPC response, thus identifying a potentially important novel therapeutic target for the treatment of ischemic heart disease. (Circulation. 2010; 121: 2565-2574.) C1 [Xiao, Rui-Ping] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Cao, Chun-Mei; Zhang, Yan; Wang, Xianhua; Lv, Fengxiang; Zhang, Yi; Song, Ruisheng; Jin, Li; Guo, Jiaojiao; Peng, Wei; Li, Geng; Xiao, Rui-Ping] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. [Weisleder, Noah; Hwang, Moonsun; Ma, Jianjie] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. [Weisleder, Noah; Ferrante, Christopher; Ma, Jianjie] TRIM Edicine Inc, Prot Therapeut Div, N Brunswick, NJ USA. [Nishi, Miyuki; Takeshima, Hiroshi] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Biol Chem, Kyoto, Japan. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM maj2@umdnj.edu; Xiaor@grc.nia.nih.gov RI Zhang, Yan/B-2831-2012; Weisleder, Noah/A-7098-2013 OI Weisleder, Noah/0000-0002-2619-8022 FU National Basic Research Program of China [2007CB512100]; Peking University; National Institutes of Health, National Institute on Aging; National Institutes of Health FX This work was supported by the National Basic Research Program of China (2007CB512100) and the Peking University 985 Project (Dr Xiao, Dr Cao, Dr Yan Zhang, Dr Wang, Dr Lv, Yi Zhang, R. Song, L. Jin, J. Guo, Dr Peng, and G. Li) and, in part, by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (Dr Xiao) and National Institutes of Health extramural grants to Dr Ma and Dr Weisleder. NR 53 TC 68 Z9 77 U1 2 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 15 PY 2010 VL 121 IS 23 BP 2565 EP U74 DI 10.1161/CIRCULATIONAHA.110.954628 PG 25 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 610SF UT WOS:000278754900004 PM 20516375 ER PT J AU Bates, SE Ivy, SP AF Bates, Susan E. Ivy, S. Percy TI Targeting the Journey: From Embryogenesis to Cancer Stem Cell SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 [Bates, Susan E.; Ivy, S. Percy] Natl Canc Inst, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2010 VL 16 IS 12 BP 3105 EP 3105 DI 10.1158/1078-0432.CCR-10-1127 PG 1 WC Oncology SC Oncology GA 610QN UT WOS:000278749400004 PM 20530703 ER PT J AU Takebe, N Ivy, SP AF Takebe, Naoko Ivy, S. Percy TI Controversies in Cancer Stem Cells: Targeting Embryonic Signaling Pathways SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BETA-CATENIN; COLON-CANCER; TUMOR PROGRESSION; NOTCH PATHWAY; LUNG-CANCER; C-MYC; PROGENITORS; DIFFERENTIATION; BREAST AB Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways. Clin Cancer Res; 16(12); 3106-12. (C)2010 AACR. C1 [Takebe, Naoko; Ivy, S. Percy] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD 20852 USA. RP Ivy, SP (reprint author), NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch, EPN7131,6130 Execut Blvd, Rockville, MD 20852 USA. EM ivyp@ctep.nci.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 57 TC 56 Z9 61 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2010 VL 16 IS 12 BP 3106 EP 3112 DI 10.1158/1078-0432.CCR-09-2934 PG 7 WC Oncology SC Oncology GA 610QN UT WOS:000278749400005 PM 20530695 ER PT J AU Baddley, JW Andes, DR Marr, KA Kontoyiannis, DP Alexander, BD Kauffman, CA Oster, RA Anaissie, EJ Walsh, TJ Schuster, MG Wingard, JR Patterson, TF Ito, JI Williams, OD Chiller, T Pappas, PG AF Baddley, John W. Andes, David R. Marr, Kieren A. Kontoyiannis, Dimitrios P. Alexander, Barbara D. Kauffman, Carol A. Oster, Robert A. Anaissie, Elias J. Walsh, Thomas J. Schuster, Mindy G. Wingard, John R. Patterson, Thomas F. Ito, James I. Williams, O. Dale Chiller, Tom Pappas, Peter G. CA Transplant Associated Infect Surve TI Factors Associated with Mortality in Transplant Patients with Invasive Aspergillosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; LIPOSOMAL AMPHOTERICIN-B; PROGNOSTIC-FACTORS; FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; HEMATOLOGIC MALIGNANCIES; ATTRIBUTABLE MORTALITY; PRIMARY THERAPY; EPIDEMIOLOGY AB Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. Methods. Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. Results. Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227;). Independent poor prognostic factors P < .001 in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. Conclusions. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials. C1 [Baddley, John W.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Andes, David R.] Univ Wisconsin, Madison, WI USA. [Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Res Ctr, Houston, TX USA. [Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Patterson, Thomas F.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Alexander, Barbara D.] Duke Univ, Med Ctr, Durham, NC USA. [Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Kauffman, Carol A.] Vet Affairs Hlth Care Syst, Ann Arbor, MI USA. [Anaissie, Elias J.] Univ Arkansas, Dept Med, Div Infect Dis, Little Rock, AR 72204 USA. [Schuster, Mindy G.] Univ Penn, Philadelphia, PA 19104 USA. [Wingard, John R.] Univ Florida, Gainesville, FL USA. [Ito, James I.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Chiller, Tom] Ctr Dis Control & Prevent, Div Mycot Dis, Atlanta, GA USA. RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU NIAID NIH HHS [K24 AI072522, K23 AI064613, K23 AI064613-05, K23AI064613] NR 28 TC 117 Z9 120 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2010 VL 50 IS 12 BP 1559 EP 1567 DI 10.1086/652768 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598BF UT WOS:000277806200002 PM 20450350 ER PT J AU Bernardo, GM Lozada, KL Miedler, JD Harburg, G Hewitt, SC Mosley, JD Godwin, AK Korach, KS Visvader, JE Kaestner, KH Abdul-Karim, FW Montano, MM Keri, RA AF Bernardo, Gina M. Lozada, Kristen L. Miedler, John D. Harburg, Gwyndolen Hewitt, Sylvia C. Mosley, Jonathan D. Godwin, Andrew K. Korach, Kenneth S. Visvader, Jane E. Kaestner, Klaus H. Abdul-Karim, Fadi W. Montano, Monica M. Keri, Ruth A. TI FOXA1 is an essential determinant of ER alpha expression and mammary ductal morphogenesis SO DEVELOPMENT LA English DT Article DE FOXA1; ER alpha; GATA3; Mammary gland; Breast cancer; Mouse ID ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER; GLAND DEVELOPMENT; PROGESTERONE-RECEPTOR; CELL DIFFERENTIATION; GLUCOSE-HOMEOSTASIS; IN-VIVO; GATA-3; MICE; PROLIFERATION AB FOXA1, estrogen receptor alpha (ER alpha) and GATA3 independently predict favorable outcome in breast cancer patients, and their expression correlates with a differentiated, luminal tumor subtype. As transcription factors, each functions in the morphogenesis of various organs, with ER alpha and GATA3 being established regulators of mammary gland development. Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known. Herein, we report that Foxa1 deficiency causes a defect in hormone-induced mammary ductal invasion associated with a loss of terminal end bud formation and ER alpha expression. By contrast, Foxa1 null glands maintain GATA3 expression. Unlike ER alpha and GATA3 deficiency, Foxa1 null glands form milk-producing alveoli, indicating that the defect is restricted to expansion of the ductal epithelium, further emphasizing the novel role for FOXA1 in mammary morphogenesis. Using breast cancer cell lines, we also demonstrate that FOXA1 regulates ER alpha expression, but not GATA3. These data reveal that FOXA1 is necessary for hormonal responsiveness in the developing mammary gland and ER alpha-positive breast cancers, at least in part, through its control of ER alpha expression. C1 [Bernardo, Gina M.; Lozada, Kristen L.; Montano, Monica M.; Keri, Ruth A.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. [Miedler, John D.; Abdul-Karim, Fadi W.] Univ Hosp Case Med Ctr, Dept Pathol, Cleveland, OH 44106 USA. [Harburg, Gwyndolen; Visvader, Jane E.] Walter & Eliza Hall Inst Med Res, VBCRC Lab, Parkville, Vic 3050, Australia. [Hewitt, Sylvia C.; Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Mosley, Jonathan D.] Vanderbilt Univ, Dept Internal Med, Nashville, TN 37235 USA. [Godwin, Andrew K.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Kaestner, Klaus H.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [Abdul-Karim, Fadi W.] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA. [Keri, Ruth A.] Case Western Reserve Univ, Sch Med, Div Gen Med Sci Oncol, Cleveland, OH 44106 USA. [Keri, Ruth A.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. RP Keri, RA (reprint author), Case Western Reserve Univ, Sch Med, Dept Pharmacol, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM keri@case.edu OI Korach, Kenneth/0000-0002-7765-418X FU NICHD; Department of Defense (DoD) [W81XWH-06-1-0712, W81XWH-08-1-0347]; Case Western Reserve University Comprehensive Cancer Center [P30 CA043703]; University Hospitals of Cleveland Pathology Research Associates; Division of Intramural Research of the National Institute of Environmental Health Sciences/NIH; Ohio Innovation Incentive Fellowship; NIH [T32-GM0720, P01 DK049210, R01 CA090398]; Fox Chase Cancer Center [P30 CA006927]; National Health and Medical Research Council of Australia FX We thank Kay-Uwe Wagner and Jennifer Yori for instruction in performing orthotopic transplants, Marie-Liesse Asselin-Labat for assistance with Gata3 deficient mice and Yanduan Hu for technical support for the ChIP analyses. Paraffin embedding and sectioning was performed by the Case Western Reserve University Tissue Procurement and Histology Core Facility. The CK8 antibody was developed by Philippe Brulet and Rolf Kemler, and obtained from the Developmental Studies Hybridoma Bank formed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, USA. G. M. B. is supported through a predoctoral fellowship from the Department of Defense (DoD) (W81XWH-06-1-0712). This work was also supported by the Case Western Reserve University Comprehensive Cancer Center (P30 CA043703), a University Hospitals of Cleveland Pathology Research Associates Grant (F. W. A. K. and R. A. K.), the Division of Intramural Research of the National Institute of Environmental Health Sciences/NIH (S. C. H. and K. S. K.), an Ohio Innovation Incentive Fellowship (J. D. Mosley.), the NIH (T32-GM0720, J. D. Mosley; P01 DK049210, K. H. K.; R01 CA090398, R. A. K.), a Fox Chase Cancer Center Support Grant (P30 CA006927, A. K. G.), the National Health and Medical Research Council of Australia (J. E. V.) and the DoD (W81XWH-08-1-0347, R. A. K.). Deposited in PMC for release after 12 months. NR 49 TC 89 Z9 93 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 15 PY 2010 VL 137 IS 12 BP 2045 EP 2054 DI 10.1242/dev.043299 PG 10 WC Developmental Biology SC Developmental Biology GA 600QG UT WOS:000278001500013 PM 20501593 ER PT J AU Ivankova, N Tretyakova, I Lyozin, GT Avanesyan, E Zolotukhin, A Zatsepina, OG Evgen'ev, MB Mamon, LA AF Ivankova, Natalia Tretyakova, Irina Lyozin, George T. Avanesyan, Elina Zolotukhin, Andrei Zatsepina, Olga G. Evgen'ev, Michael B. Mamon, Ludmila A. TI Alternative transcripts expressed by small bristles, the Drosophila melanogaster nxf1 gene SO GENE LA English DT Article DE Alternative splicing; NXF; Tissue-specific transcription; Pleiotropy ID MESSENGER-RNA EXPORT; DROSOPHILA-MELANOGASTER FEMALES; NUCLEAR EXPORT; VERMILION REGION; MALE-FERTILITY; FACTOR FAMILY; HEAT-SHOCK; PROTEIN; TAP; L(1)TS403 AB The tissue-specific accumulation of small bristles (Dm nxf1) transcripts at different developmental stages of Drosophila melanogaster was analyzed by Northern blots and RT PCR. We identified four distinct transcripts: ubiquitous (3.5 kb); ovary and early embryo specific (3.3 kb); testis specific (1.9 kb and 2.8 kb) and nervous system specific (5.1 kb). The pattern of Dm nxf1 gene expression in ovaries and early embryos (0-2 h) is similar: the sizes of transcripts range from 3.0 to 3.5 kb. We propose that this size variability may reflect the different extent of cytoplasmic polyadenylation. In testes, the 2.8-kb transcript originates from alternative termination of transcription and the 1.9-kb transcript is supposed to originate from an alternative transcription start. During ontogenesis, the 5.1-kb transcript can be clearly detected in 10- to 18-h-old embryos, most prominently in the nervous ganglia of larvae, and it represents a major species in imago head extracts. We found that the 5.1-kb transcript, similarly to the nxf1 heavy transcripts in Homo sapiens and Mus musculus, results from the retention of intron 5-6 that corresponds to the intron 10-11 in Hs nxf1 and Mm nxf1 genes. (C) 2010 Elsevier B.V. All rights reserved. C1 [Ivankova, Natalia; Tretyakova, Irina; Avanesyan, Elina; Mamon, Ludmila A.] St Petersburg State Univ, Dept Genet & Breeding, St Petersburg, Russia. [Lyozin, George T.; Evgen'ev, Michael B.] Cell Biophys Inst, Pushchino, Russia. [Zolotukhin, Andrei] Natl Canc Inst Frederick, NIH, Frederick, MD USA. [Zatsepina, Olga G.; Evgen'ev, Michael B.] VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RP Mamon, LA (reprint author), St Petersburg State Univ, Dept Genet & Breeding, St Petersburg, Russia. EM mamon@LM2010.spb.edu FU CRDF (USA) [ST-012-0]; SSCH, Russia; RFBR [06-04-49519, 09-04-00697]; Russian Foundation for Basic Research [09-04-00643, 09-04-00660]; "Genofond dynamics" program; Program of Molecular and Cellular Biology RAN FX This work was supported by CRDF, grant number ST-012-0 (USA), SSCH Grant Russia and RFBR, Grant nos. 06-04-49519 and 09-04-00697.; Work in the authors' laboratory is supported by the Russian Foundation for Basic Research, project nos. 09-04-00643 and 09-04-00660, project from "Genofond dynamics" program and Grant of the Program of Molecular and Cellular Biology RAN to M.E. NR 50 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 15 PY 2010 VL 458 IS 1-2 BP 11 EP 19 DI 10.1016/j.gene.2010.02.013 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 604UW UT WOS:000278305000002 PM 20214956 ER PT J AU Strunnikova, NV Maminishkis, A Barb, JJ Wang, F Zhi, C Sergeev, Y Chen, W Edwards, AO Stambolian, D Abecasis, G Swaroop, A Munson, PJ Miller, SS AF Strunnikova, N. V. Maminishkis, A. Barb, J. J. Wang, F. Zhi, C. Sergeev, Y. Chen, W. Edwards, A. O. Stambolian, D. Abecasis, G. Swaroop, A. Munson, P. J. Miller, S. S. TI Transcriptome analysis and molecular signature of human retinal pigment epithelium SO HUMAN MOLECULAR GENETICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; OCULAR ALBINISM TYPE-1; EMBRYONIC STEM-CELLS; MACULAR DEGENERATION; DOPACHROME-TAUTOMERASE; DISEASE MECHANISMS; FLUID TRANSPORT; GENE-EXPRESSION; PROTEIN; MICE AB Retinal pigment epithelium (RPE) is a polarized cell layer critical for photoreceptor function and survival. The unique physiology and relationship to the photoreceptors make the RPE a critical determinant of human vision. Therefore, we performed a global expression profiling of native and cultured human fetal and adult RPE and determined a set of highly expressed 'signature' genes by comparing the observed APE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues. Using stringent selection criteria of at least 10-fold higher expression in three distinct preparations, we identified 154 APE signature genes, which were validated by qRT-PCR analysis in RPE and in an independent set of 11 tissues. Several of the highly expressed signature genes encode proteins involved in visual cycle, melanogenesis and cell adhesion and Gene ontology analysis enabled the assignment of APE signature genes to epithelial channels and transporters (CICN4, BEST1, SLCA20) or matrix remodeling (TIMP3, COL8A2). Fifteen APE signature genes were associated with known ophthalmic diseases, and 25 others were mapped to regions of disease loci. An evaluation of the APE signature genes in a recently completed AMD genomewide association (GWA) data set revealed that TIMP3, GRAMD3, PITPNA and CHRNA3 signature genes may have potential roles in AMD pathogenesis and deserve further examination. We propose that APE signature genes are excellent candidates for retinal diseases and for physiological investigations (e.g. dopachrome tautomerase in melanogenesis). The APE signature gene set should allow the validation of APE-like cells derived from human embryonic or induced pluripotent stem cells for cell-based therapies of degenerative retinal diseases. C1 [Strunnikova, N. V.; Maminishkis, A.; Wang, F.; Zhi, C.; Sergeev, Y.; Swaroop, A.; Miller, S. S.] NEI, NIH, Bethesda, MD 20892 USA. [Strunnikova, N. V.; Sergeev, Y.] NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [Maminishkis, A.; Wang, F.; Zhi, C.; Miller, S. S.] NIH, Sect Epithelial & Retinal Physiol & Dis, Bethesda, MD 20892 USA. [Swaroop, A.] NIH, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. [Barb, J. J.; Munson, P. J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. [Chen, W.; Abecasis, G.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Edwards, A. O.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. [Stambolian, D.] Univ Penn, Philadelphia, PA 19104 USA. RP Miller, SS (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM millers@nei.nih.gov RI Abecasis, Goncalo/B-7840-2010; OI Abecasis, Goncalo/0000-0003-1509-1825; Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute, NIH FX This research was supported by the Intramural and Extramural Research Programs of the National Eye Institute, NIH. Funding to pay the Open Access publication charges for this article was provided by NIH Intramural Program. NR 90 TC 84 Z9 84 U1 1 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2010 VL 19 IS 12 BP 2468 EP 2486 DI 10.1093/hmg/ddq129 PG 19 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 611MJ UT WOS:000278819100012 PM 20360305 ER PT J AU Eastwood, SL Walker, M Hyde, TM Kleinman, JE Harrison, PJ AF Eastwood, Sharon L. Walker, Mary Hyde, Thomas M. Kleinman, Joel E. Harrison, Paul J. TI The DISC1 Ser704Cys substitution affects centrosomal localization of its binding partner PCM1 in glia in human brain SO HUMAN MOLECULAR GENETICS LA English DT Article ID CELL-CYCLE; SCHIZOPHRENIA-1 DISC1; PROTEIN; DISRUPTED-IN-SCHIZOPHRENIA-1; RISK; ASSOCIATION; MODULATION; MORPHOLOGY; EXPRESSION; INTERACTS AB Disrupted-in-schizophrenia 1 (DISCI) has been genetically associated with schizophrenia, and with brain phenotypes including grey matter volume and working memory performance. However, the molecular and cellular basis for these associations remains to be elucidated. One potential mechanism may be via an altered interaction of DISCI with its binding partners. In this context, we previously demonstrated that one DISCI variant, Leu607Phe, influenced the extent of centrosomal localization of pericentriolar material 1 (PCM1) in SH-SY5Y cells. The current study extends this work to human brain, and includes another DISC1 coding variant, Ser704Cys. Using immunohistochemistry, we first characterized the distribution of PCM1 in human superior temporal gyrus (STG). PCM1 immunoreactivity was localized to the centrosome in glia, but not in neurons, which showed widespread immunoreactivity. We quantified centrosomal PCM1 immunoreactivity in STG glia of 81 controls and 67 subjects with schizophrenia, genotyped for the two polymorphisms. Centrosomal PCM1 immunoreactive area was smaller in Cys704 carriers than in Ser704 homozygotes, with a similar trend in Phe607 homozygotes compared with Leu607 carriers, replicating the finding in SH-SY5Y cells. No differences were seen between controls and subjects with schizophrenia. These findings confirm in vivo that DISC1 coding variants modulate centrosomal PCM1 localization, highlight a role for DISCI in glial function and provide a possible cellular mechanism contributing to the association of these DISC1 variants with psychiatric phenotypes. Whether this influence of DISCI genotype extends to other centrosomal proteins and DISC1 binding partners remains to be determined. C1 [Eastwood, Sharon L.; Walker, Mary; Harrison, Paul J.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. [Hyde, Thomas M.; Kleinman, Joel E.] NIMH, Sect Neuropathol, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,IRP,NIH, Bethesda, MD 20892 USA. RP Eastwood, SL (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM sharon.eastwood@psych.ox.ac.uk FU UK Medical Research Council; National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, United States Government FX This work was funded by the UK Medical Research Council. The brain specimens utilized in this study were acquired with funding provided by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, United States Government. NR 52 TC 24 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2010 VL 19 IS 12 BP 2487 EP 2496 DI 10.1093/hmg/ddq130 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 611MJ UT WOS:000278819100013 PM 20360304 ER PT J AU Udler, MS Ahmed, S Healey, CS Meyer, K Struewing, J Maranian, M Kwon, EM Zhang, J Tyrer, J Karlins, E Platte, R Kalmyrzaev, B Dicks, E Field, H Maia, AT Prathalingam, R Teschendorff, A McArthur, S Doody, DR Luben, R Caldas, C Bernstein, L Kolonel, LK Henderson, BE Wu, AH Le Marchand, L Ursin, G Press, MF Lindblom, A Margolin, S Shen, CY Yang, SL Hsiung, CN Kang, D Yoo, KY Noh, DY Ahn, SH Malone, KE Haiman, CA Pharoah, PD Ponder, BAJ Ostrander, EA Easton, DF Dunning, AM AF Udler, Miriam S. Ahmed, Shahana Healey, Catherine S. Meyer, Kerstin Struewing, Jeffrey Maranian, Melanie Kwon, Erika M. Zhang, Jinghui Tyrer, Jonathan Karlins, Eric Platte, Radka Kalmyrzaev, Bolot Dicks, Ed Field, Helen Maia, Ana-Teresa Prathalingam, Radhika Teschendorff, Andrew McArthur, Stewart Doody, David R. Luben, Robert Caldas, Carlos Bernstein, Leslie Kolonel, Laurence K. Henderson, Brian E. Wu, Anna H. Le Marchand, Loic Ursin, Giske Press, Michael F. Lindblom, Annika Margolin, Sara Shen, Chen-Yang Yang, Show-Lin Hsiung, Chia-Ni Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Malone, Kathleen E. Haiman, Christopher A. Pharoah, Paul D. Ponder, Bruce A. J. Ostrander, Elaine A. Easton, Douglas F. Dunning, Alison M. TI Fine scale mapping of the breast cancer 16q12 locus SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; SUSCEPTIBILITY; TRANSCRIPTION; VARIANTS; AMERICAN; SUBTYPE; SITES AB Recent genome-wide association studies have identified a breast cancer susceptibility locus on 16q12 with an unknown biological basis. We used a set of single nucleotide polymorphism (SNP) markers to generate a fine-scale map and narrowed the region of association to a 133 kb DNA segment containing the largely uncharacterized hypothetical gene LOC643714, a short intergenic region and the 5' end of TOX3. Re-sequencing this segment in European subjects identified 293 common polymorphisms, including a set of 26 highly correlated candidate causal variants. By evaluation of these SNPs in five breast cancer case-control studies involving more than 23 000 subjects from populations of European and Southeast Asian ancestry, all but 14 variants could be excluded at odds of <1:100. Most of the remaining variants lie in the intergenic region, which exhibits evolutionary conservation and open chromatin conformation, consistent with a regulatory function. African-American case-control studies exhibit a different pattern of association suggestive of an additional causative variant. C1 [Udler, Miriam S.; Luben, Robert; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Ahmed, Shahana; Struewing, Jeffrey; Zhang, Jinghui; Karlins, Eric; Platte, Radka; Kalmyrzaev, Bolot; Dicks, Ed; Field, Helen; Pharoah, Paul D.; Ponder, Bruce A. J.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Udler, Miriam S.; Maranian, Melanie; Tyrer, Jonathan; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Udler, Miriam S.; Healey, Catherine S.; Maia, Ana-Teresa; Prathalingam, Radhika; Teschendorff, Andrew; McArthur, Stewart; Caldas, Carlos; Ponder, Bruce A. J.] Li Ka Shing Ctr, CRUK Cambridge Res Inst, Cambridge CB2 0RE, England. [Meyer, Kerstin; Kwon, Erika M.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. [Teschendorff, Andrew] UCL, Med Genom Grp, UCL Canc Inst, London, England. [Doody, David R.; Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Kolonel, Laurence K.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. [Henderson, Brian E.; Wu, Anna H.; Ursin, Giske; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Lindblom, Annika; Margolin, Sara] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Shen, Chen-Yang; Yang, Show-Lin; Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Ahn, Sei-Hyun] Univ Ulsan, Seoul, South Korea. RP Dunning, AM (reprint author), Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England. EM alison.dunning@srl.cam.ac.uk RI Caldas, Carlos/A-7543-2008; Noh, Dong-Young/G-5531-2011; Maia, Ana-Teresa/F-4404-2012; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Struewing, Jeffery/I-7502-2013; OI Ostrander, Elaine/0000-0001-6075-9738; Dunning, Alison Margaret/0000-0001-6651-7166; Maia, Ana-Teresa/0000-0002-0454-9207; Struewing, Jeffery/0000-0002-4848-3334; Luben, Robert/0000-0002-5088-6343 FU Cancer Research UK [C201A3084, C1287/A10118, C490/A11021, C8197/A10123, C1287/A7497, C8197/A10865]; COGS EU [Health-F2-2009-223175]; National Cancer Institute; National Human Genome Research Institute, NIH, U.S. Department of Health and Human Services; NIH-Oxford/Cambridge; US National Cancer Institute [CA 54281, CA 63464, CA 132839]; California Breast Cancer Research Program [1RB-0287, 3PB-0102, 5PB-008, 10PB-0098]; National Institute of Child Health and Human Development; National Cancer Institute, through contracts with Emory University [N01 HD 3-3168]; Fred Hutchinson Cancer Research Center [N01 HD 2-3166]; Karmanos Cancer Institute at Wayne State University [N01 HD 3-3174]; University of Pennsylvania [N01 HD 3-3176]; University of Southern California [N01 HD 3-3175]; Centers for Disease Control and Prevention [Y01 HD 7022]; SEER [N0I-PC-67006, N01-CN-65064, N01-CN-67010, N01-CN-0532]; Ministry of Health Welfare, ROK [01-PJ3-PG6-01GN07-0004] FX The genotyping and analysis of this study, and the conduct of the SEARCH study, was funded by Cancer Research UK grants (C201A3084, C1287/A10118, C490/A11021, C8197/A10123, C1287/A7497, C8197/A10865) and COGS EU FP7 Health-F2-2009-223175. A.M.D., P.D.P. and H.F. were supported by Cancer Research UK. This research was supported in part by the Intramural Research Programs of the National Cancer Institute and National Human Genome Research Institute, NIH, U.S. Department of Health and Human Services. M.U. was supported by the NIH-Oxford/Cambridge PhD program. The MEC Study was supported by the US National Cancer Institute (CA 54281, CA 63464, CA 132839). The LAABC study was supported by the California Breast Cancer Research Program (1RB-0287, 3PB-0102, 5PB-008, 10PB-0098). The CARE study was supported by the National Institute of Child Health and Human Development, with additional support from the National Cancer Institute, through contracts with Emory University (N01 HD 3-3168), Fred Hutchinson Cancer Research Center (N01 HD 2-3166), Karmanos Cancer Institute at Wayne State University (N01 HD 3-3174), University of Pennsylvania (N01 HD 3-3176), University of Southern California (N01 HD 3-3175) and through an intra-agency agreement with the Centers for Disease Control and Prevention (Y01 HD 7022). General support through SEER contracts [N0I-PC-67006 (Atlanta), N01-CN-65064 (Detroit), N01-CN-67010 (Los Angeles) and N01-CN-0532 (Seattle)] are also acknowledged. B.A.J.P. is Li Ka Shin Professor of Oncology and we acknowledge Hutchison Whampoa Limited. KARBAC thank the Swedish Cancer Society, The Jubilee Foundation, and Bert von Kantzow foundation. The Seoul Breast Cancer Project is supported by the Ministry of Health & Welfare, ROK (01-PJ3-PG6-01GN07-0004). NR 25 TC 28 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2010 VL 19 IS 12 BP 2507 EP 2515 DI 10.1093/hmg/ddq122 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 611MJ UT WOS:000278819100015 PM 20332101 ER PT J AU Gabriel, KP McClain, JJ Schmid, KK Storti, KL High, RR Underwood, DA Kuller, LH Kriska, AM AF Gabriel, Kelley Pettee McClain, James J. Schmid, Kendra K. Storti, Kristi L. High, Robin R. Underwood, Darcy A. Kuller, Lewis H. Kriska, Andrea M. TI Isssus in accelerometer methodology: the role of epoch length on estimates of physical activity and relationships with health outcomes in overweight, post-menopausal women SO INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY LA English DT Article ID ARTIFICIAL NEURAL-NETWORK; ENERGY-EXPENDITURE; CORRELATION-COEFFICIENTS; COMPUTER-SCIENCE; MENOPAUSE; CALIBRATION; CHILDREN; ADULTS; RISK; INC. AB Background: Current accelerometer technology allows for data collection using brief time sampling intervals (i.e., epochs). The study aims were to examine the role of epoch length on physical activity estimates and subsequent relationships with clinically-meaningful health outcomes in post-menopausal women. Methods: Data was obtained from the Woman On the Move through Activity and Nutrition Study (n=102). Differences in activity estimates presented as 60s and 10s epochs were evaluated using paired t-tests. Relationships with health outcomes were examined using correlational and regression analyses to evaluate differences by epoch length. Results: Inactivity, moderate-and vigorous-intensity activity (MVPA) were significantly higher and light-intensity activity was significantly lower (all P < 0.001) when presented as 10s epochs. The correlation between inactivity and self-reported physical activity was stronger with 10s estimates (P < 0.03); however, the regression slopes were not significantly different. Conversely, relationships between MVPA and body weight, BMI, whole body and trunk lean and fat mass, and femoral neck bone mineral density was stronger with 60s estimates (all P < 0.05); however, regression slopes were similar. Conclusion: These findings suggest that although the use of a shorter time sampling interval may suggestively reduce misclassification error of physical activity estimates, associations with health outcomes did not yield strikingly different results. Additional studies are needed to further our understanding of the ways in which epoch length contributes to the ascertainment of physical activity in research studies. C1 [Gabriel, Kelley Pettee] Univ Texas Hlth Sci Ctr, Div Epidemiol & Dis Control, Austin, TX 78701 USA. [McClain, James J.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA. [Schmid, Kendra K.; High, Robin R.] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE 68198 USA. [Storti, Kristi L.; Underwood, Darcy A.; Kuller, Lewis H.; Kriska, Andrea M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Gabriel, KP (reprint author), Univ Texas Hlth Sci Ctr, Div Epidemiol & Dis Control, Austin, TX 78701 USA. EM Kelley.P.Gabriel@uth.tmc.edu FU National Heart, Lung, and Blood [R01-HL-66468] FX The authors would like to thank the WOMAN Study staff and Mr. Eugene Boilesen, BS, Programmer Analyst at the University of Nebraska Medical Center for his help with refining the publically available NHANES accelerometer SAS syntax. This research was funded by National Heart, Lung, and Blood contract R01-HL-66468. ClinicalTrials. gov Identifier: NCT00023543. NR 32 TC 12 Z9 12 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5868 J9 INT J BEHAV NUTR PHY JI Int. J. Behav. Nutr. Phys. Act. PD JUN 15 PY 2010 VL 7 AR 7 DI 10.1186/1479-5868-7-53 PG 10 WC Nutrition & Dietetics; Physiology SC Nutrition & Dietetics; Physiology GA 625OH UT WOS:000279904200001 PM 20550691 ER PT J AU Leitzmann, MF Brenner, A Moore, SC Koebnick, C Park, Y Hollenbeck, A Schatzkin, A Ron, E AF Leitzmann, Michael F. Brenner, Alina Moore, Steven C. Koebnick, Corinna Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur Ron, Elaine TI Prospective study of body mass index, physical activity and thyroid cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE body mass index; physical activity; thyroid cancer; epidemiology; prospective study ID POOLED ANALYSIS; UNITED-STATES; RISK-FACTORS; COHORT; MEN; OVERWEIGHT; CARCINOMA; PAPILLARY; ESTROGEN; OBESITY AB Increased body size and physical inactivity are positively related to risk of several cancers, but only few epidemiologic studies have investigated body-mass index (BMI) and physical activity in relation to thyroid cancer. We examined the relations of BMI and physical activity to thyroid cancer in a prospective cohort of 484,326 United States men and women, followed from 1995/1996 to 2003. During 3,490,300 person-years of follow-up, we documented 352 newly incident cases of thyroid cancer. The multivariate relative risks (RR) of thyroid cancer for BMI values of 18.5-24.9 (reference), 25.0-29.9 and >= 30 kg m(-2) were 1.0, 1.27 and 1.39 [95% confidence interval (CI) = 1.05-1.85]. Adiposity predicted papillary thyroid cancers (RR comparing extreme BMI categories = 1.47; 95% Cl = 1.03-2.10) and, based on small numbers, suggestively predicted follicular thyroid cancers (RR = 1.49; 95% Cl = 0.79-2.82) and anaplastic thyroid cancers (RR = 5.80; 95% Cl = 0.99-34.19). No relation with BMI was noted for medullary thyroid cancers (RR = 0.97; 95% Cl = 0.27-3.43). The positive relation of BMI to total thyroid cancer was evident for men but not for women. However, the test of interaction (p = 0.463) indicated no statistically significant gender difference. Physical activity was unassociated with thyroid cancer. The RRs of total thyroid cancer for low (reference), intermediate, and high level of physical activity were 1.0, 1.01 and 1.01 (95% Cl = 0.76-1.34, p for trend = 0.931), respectively. Our results support an adverse effect of adiposity on risk for developing total and papillary, and possibly follicular thyroid cancers. Based on only 15 cases, adiposity was unrelated to medullary thyroid cancers. Physical activity was unrelated to total thyroid cancer. C1 [Leitzmann, Michael F.; Moore, Steven C.; Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Regensburg, Germany. [Brenner, Alina; Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Koebnick, Corinna] So Calif Permanente Med Grp, Pasadena, CA USA. [Hollenbeck, Albert] AARP, Org & Tracking Res Dept, Washington, DC USA. RP Leitzmann, MF (reprint author), Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM michael.leitzmann@klinik.uni-regensburg.de RI Koebnick, Corinna/P-4767-2016; Moore, Steven/D-8760-2016; OI Koebnick, Corinna/0000-0001-8274-0309; Moore, Steven/0000-0002-8169-1661; Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS [Z01 CP010131-13, Z01 CP010197-01] NR 41 TC 41 Z9 41 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2010 VL 126 IS 12 BP 2947 EP 2956 DI 10.1002/ijc.24913 PG 10 WC Oncology SC Oncology GA 594QA UT WOS:000277551100020 PM 19795465 ER PT J AU Tvermoes, BE Boyd, WA Freedman, JH AF Tvermoes, Brooke E. Boyd, Windy A. Freedman, Jonathan H. TI Molecular characterization of numr-1 and numr-2: genes that increase both resistance to metal-induced stress and lifespan in Caenorhabditis elegans SO JOURNAL OF CELL SCIENCE LA English DT Article DE C. elegans; Cadmium; Stress response; Lifespan; Longevity ID SHOCK TRANSCRIPTION FACTOR-1; UNFOLDED PROTEIN RESPONSE; CELL-SPECIFIC EXPRESSION; C-ELEGANS; CADMIUM TOXICITY; OXIDATIVE STRESS; HEAVY-METAL; METALLOTHIONEIN GENES; REGULATORY ELEMENTS; SIGNALING PATHWAYS AB To define the mechanisms involved in the molecular response to the carcinogenic metal cadmium, two novel metal-inducible genes from C. elegans were characterized: numr-1 and numr-2 (nuclear localized metal responsive). numr-1 and numr-2 sequences and cellular patterns of expression are identical, indicating that these are functionally equivalent genes. Constitutive transcription of numr-1 and numr-2 is developmentally regulated and occurs in the intestine, in head and tail neurons, and vulva muscles. Exposure to metals induces numr-1 and numr-2 transcription in pharyngeal and intestinal cells. Other environmental stressors do not affect transcription, indicating that these are metal-specific, stress-responsive genes. NUMR-1 and NUMR-2 target to nuclei and colocalize with HSF-1, suggesting that they may be components of nuclear stress granules. Nematodes overexpressing NUMR-1 and NUMR-2 are resistant to stress and live longer than control animals; likewise reducing expression increases sensitivity to metals and decreases neuromuscular functions. Upstream regulatory regions of both genes contain potential binding sites for DAF-16 and SKN-1, which are components of the insulin-IGF-like signaling pathway. This pathway regulates longevity and stress responses in C. elegans. NUMR-1 and NUMR-2 may function to promote resistance to environmental stressors and longevity, which is mediated by the insulin-IGF-like signaling pathway. C1 [Tvermoes, Brooke E.; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27009 USA. [Tvermoes, Brooke E.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA. [Boyd, Windy A.; Freedman, Jonathan H.] NIEHS, Biomol Screening Branch, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27009 USA. RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, MD E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27009 USA. EM freedma1@niehs.nih.gov OI Boyd, Windy/0000-0003-3803-3716 FU NIH; NIEHS [Z01ES102045]; National Toxicology Program [Z01ES102046]; NIH National Center for Research Resources (NCRR) FX This work was supported (in part) by the Intramural Research Program of the NIH, and NIEHS (Z01ES102045) and the National Toxicology Program (Z01ES102046). Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). We thank Daniel Snyder (Biomolecular Screening Branch, NTP) for generating transgenic strains and Leping Li (Biostatistics Branch, NIEHS) for numr-1 and numr-2 promoter analyses. We also thank Roger Tsien (UCSD) for the mCherry construct and Scott Alper for his comments on this manuscript and his helpful discussions. Deposited in PMC for release after 12 months. NR 70 TC 4 Z9 4 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2010 VL 123 IS 12 BP 2123 EP 2133 DI 10.1242/jcs.065433 PG 11 WC Cell Biology SC Cell Biology GA 604KK UT WOS:000278277700016 ER PT J AU Milner, JD Fazilleau, N McHeyzer-Williams, M Paul, W AF Milner, Joshua D. Fazilleau, Nicolas McHeyzer-Williams, Michael Paul, William TI Cutting Edge: Lack of High Affinity Competition for Peptide in Polyclonal CD4(+) Responses Unmasks IL-4 Production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; IN-VIVO; ANTIGEN; DIFFERENTIATION; POLARIZATION; MUTAGENESIS; INFECTION; SELECTION; INFANTS; LIGANDS AB Priming of naive monoclonal CD4 T cells via weak agonsim permits GATA-3 transcription and Th2 differentiation. To test whether this process can occur in polyclonal naive populations, where a range of TCR affinities exists for any given Ag/MHC complex, we primed naive CD4 cells from 5CC7 V beta 3 transgenic mice, which have a fixed beta-chain specific for pigeon cytochrome c peptide I-E-k. Priming populations depleted of higher affinity, moth cytochrome c peptide I-E-k tetramer-binding cells resulted in substantial IL-4 production that did not occur in the presence of higher affinity cells. TCR alpha-chain sequence analysis showed that clones that possessed TCR features associated with high affinity responses to pigeon cytochrome c made less IL-4 than clones that possessed fewer such motifs. These results indicate that cells bearing TCRs that are weakly stimulated by their cognate Ag preferentially adopt a Th2 phenotype when primed in the absence of competition from cells with higher affinity receptors. The Journal of Immunology, 2010, 184: 6569-6573. C1 [Milner, Joshua D.; Paul, William] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Fazilleau, Nicolas; McHeyzer-Williams, Michael] Scripps Res Inst, La Jolla, CA 92037 USA. RP Milner, JD (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike,Bldg 10,12S236A, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov RI Fazilleau, Nicolas/J-9883-2014 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 19 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2010 VL 184 IS 12 BP 6569 EP 6573 DI 10.4049/jimmunol.1000674 PG 5 WC Immunology SC Immunology GA 607PB UT WOS:000278516700002 PM 20495070 ER PT J AU Rohrl, J Yang, D Oppenheim, JJ Hehlgans, T AF Roehrl, Johann Yang, De Oppenheim, Joost J. Hehlgans, Thomas TI Human beta-Defensin 2 and 3 and Their Mouse Orthologs Induce Chemotaxis through Interaction with CCR2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN BETA-DEFENSIN-3; DENDRITIC CELLS; ANTIMICROBIAL PEPTIDES; INNATE IMMUNITY; TNF-ALPHA; RECEPTOR; EXPRESSION; CHEMOATTRACTANT; ANTIGEN; IDENTIFICATION AB beta-defensins play a dual role during immune response. Their direct antimicrobial properties contribute to the local innate immune response by combating microbial invasions. Furthermore, previous studies revealed the capacity of certain beta-defensin family members to chemoattract immature dendritic cells and CD45RO(+) CD4(+) T cells through chemokine receptor CCR6. However, because beta-defensins also chemoattract macrophages and monocytes, which do not express CCR6, efforts have been made to identify other receptors for these polypeptides. In this study, we demonstrate the capacity of human beta-defensin (hBD)2 and 3 and their mouse orthologs, beta-defensin 4 and 14, to interact with CCR2, a chemokine receptor expressed on monocytes, macrophages, and neutrophils. These beta-defensins, fused to the Fc region of human IgG(1), showed binding to CCR2-transfected HEK293 cells, as revealed by flow cytometry. The beta-defensin fusion proteins also induced CCR2-specific chemotaxis of transfected HEK293 cells, human peripheral blood monocytes, and mouse peritoneal exudate cells in a dose-dependent manner. Preincubation of human monocytes with CCL2/MCP-1, the chemokine ligand for CCR2, abolished migration induced by beta-defensins. Conversely, pre-incubation with hBD2:Ig or hBD3:Ig inhibited MCP-1 induced migration. Peritoneal exudate cells from CCR2-deficient mice failed to migrate toward these fusion proteins. In conclusion, the beta-defensins used in this study contribute to the innate and adaptive immune response in their role as chemoattractants. Our data indicate that hBD2 and hBD3, together with their mouse orthologs (beta-defensin 4 and 14), are chemotactic for a broad spectrum of leukocytes in a CCR6-and CCR2-dependent manner. The Journal of Immunology, 2010, 184: 6688-6694. C1 [Hehlgans, Thomas] Univ Regensburg, Inst Immunol, D-93042 Regensburg, Germany. [Roehrl, Johann; Yang, De; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Div Basic Sci,Ctr Canc Res, Frederick, MD 21702 USA. RP Hehlgans, T (reprint author), Univ Regensburg, Inst Immunol, Franz Josef Str Allee 11, D-93042 Regensburg, Germany. EM thomas.hehlgans@klinik.uni-regensburg.de FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Center for Cancer Research, National Cancer Institute, National Institutes of Health; Bayerische Forschungsstiftung [PDOK-62-08] FX This work was supported in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E; in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; and by Grant PDOK-62-08 from the Bayerische Forschungsstiftung. NR 42 TC 119 Z9 125 U1 3 U2 12 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2010 VL 184 IS 12 BP 6688 EP 6694 DI 10.4049/jimmunol.0903984 PG 7 WC Immunology SC Immunology GA 607PB UT WOS:000278516700015 PM 20483750 ER PT J AU Cruse, G Fernandes, VE de Salort, J Pankhania, D Marinas, MS Brewin, H Andrew, PW Bradding, P Kadioglu, A AF Cruse, Glenn Fernandes, Vitor E. de Salort, Jose Pankhania, Depesh Marinas, Marta S. Brewin, Hannah Andrew, Peter W. Bradding, Peter Kadioglu, Aras TI Human Lung Mast Cells Mediate Pneumococcal Cell Death in Response to Activation by Pneumolysin SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; ANTIMICROBIAL ACTIVITY; BACTERIAL CLEARANCE; HUMAN NEUTROPHILS; PROTECTIVE ROLE; INFECTION; MICE; PHAGOCYTOSIS; PERITONITIS; BACTEREMIA AB Mast cells are emerging as contributors to innate immunity. Mouse mast cells have a pivotal role in protection against bacterial infection, and human cord blood-derived mast cells reduce bacterial viability in culture. The objectives of this study were to determine whether human lung mast cells (HLMCs) might be protective against pneumococcal lung infection through direct antimicrobial activity. Tissue-derived HLMCs and the human mast cell lines HMC-1 and LAD2 were cocultured with wildtype and mutant pneumococci, and viability and functional assays were performed. Mast cells were also stimulated with purified pneumolysin. HLMCs killed wild-type serotype-2 (D39) pneumococci in coculture but had no effect on an isogenic pneumolysin-deficient (PLN-A) pneumococcus. D39 wild-type, but not PLN-A pneumococci, induced the release of leukotriene C4 from human mast cells in a dose-dependent manner, which was not accompanied by histamine release. Stimulation of mast cells with sublytic concentrations of purified pneumolysin replicated this effect. Furthermore, pneumolysin induced the release of the cathelicidin LL-37 from HLMCs, purified LL-37 reduced pneumococcal viability, and neutralizing Ab to LL-37 attenuated mast cell-dependent pneumococcal killing. In addition, at high concentrations, all pneumococcal strains tested reduced HLMC viability through a combination of pneumolysin and H(2)O(2)-dependent mechanisms. HLMCs exhibit direct antimicrobial activity to pneumococci through their activation by pneumolysin. This antimicrobial activity is mediated, in part, by the release of LL-37 from HLMCs. This suggests that mast cells provide an early warning system and potentially limit pneumococcal dissemination early in the course of invasive pulmonary pneumococcal disease. The Journal of Immunology, 2010, 184: 7108-7115. C1 [Cruse, Glenn; Fernandes, Vitor E.; de Salort, Jose; Pankhania, Depesh; Marinas, Marta S.; Brewin, Hannah; Andrew, Peter W.; Bradding, Peter; Kadioglu, Aras] Univ Leicester, Sch Med, Inst Lung Hlth, Dept Infect Immun & Inflammat, Leicester, Leics, England. RP Cruse, G (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. EM glenncruse@hotmail.com RI Cruse, Glenn/B-4597-2012; kadioglu, aras/E-1458-2012; OI Bradding, Peter/0000-0001-8403-0319 FU University Hospitals of Leicester National Health Service Trust FX This work was funded in part by a grant from University Hospitals of Leicester National Health Service Trust. NR 38 TC 24 Z9 25 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2010 VL 184 IS 12 BP 7108 EP 7115 DI 10.4049/jimmunol.0900802 PG 8 WC Immunology SC Immunology GA 607PB UT WOS:000278516700060 PM 20483738 ER PT J AU Zhang, JA Mendoza, M Guiraldelli, MF Barbu, EA Siraganian, RP AF Zhang, Juan Mendoza, Mary Guiraldelli, Michel F. Barbu, Emilia Alina Siraganian, Reuben P. TI Small Interfering RNA Screen for Phosphatases Involved in IgE-Mediated Mast Cell Degranulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; PROTEIN-KINASE-C; TYROSINE KINASE; NEGATIVE REGULATION; POSITIVE REGULATION; CYTOKINE PRODUCTION; ALLERGIC RESPONSE; ACTIVATION; RECEPTOR; CALCINEURIN AB Mast cells play pivotal roles in the initiation of the allergic response. To gain an understanding of the functions played by phosphatases in IgE-mediated mast cell activation, a small interfering RNA (siRNA) library that targets all mouse phosphatase genes was screened in a mouse mast cell line, MMC-1. Of 198 targets, 10 enhanced and 7 inhibited Fc epsilon RI-induced degranulation. For seven of the strongest hits, four different siRNAs per target were tested, and at least two out of the four single siRNA per target had similar effects as the pool suggesting that these were true hits. Bone marrow-derived mast cells from normal mice further validated these results for six definite positive targets. The mechanism of the reduced mast cell degranulation due to calcineurin B deficiency was investigated. Calcineurin B deficiency reduced the phosphorylation of MAPKs and the phosphorylation of protein kinase D/protein kinase C mu and protein kinase C delta, which are involved in Fc epsilon RI signaling. The screen, therefore, has identified several new molecules that are critical for Fc epsilon RI-induced degranulation. Regulating the function of these proteins may be potential targets for the treatment of allergic inflammation. The result also indicates that the system used is efficient for searching molecules implicated in complex receptor-induced signaling. The Journal of Immunology, 2010, 184: 7178-7185. C1 [Zhang, Juan; Mendoza, Mary; Guiraldelli, Michel F.; Barbu, Emilia Alina; Siraganian, Reuben P.] Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Siraganian, RP (reprint author), Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, NIH,US Dept HHS, 9000 Rockville Pike,MSC 4410,Bldg 49 Room 1A-16, Bethesda, MD 20892 USA. EM rsiraganian@dir.nidcr.nih.gov RI Guiraldelli, Michel/H-1710-2013 FU National Institutes of Health, National Institute of Dental and Craniofacial Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. NR 46 TC 13 Z9 13 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2010 VL 184 IS 12 BP 7178 EP 7185 DI 10.4049/jimmunol.0904169 PG 8 WC Immunology SC Immunology GA 607PB UT WOS:000278516700068 PM 20483767 ER PT J AU Darville, T Hiltke, TJ AF Darville, Toni Hiltke, Thomas J. TI Pathogenesis of Genital Tract Disease Due to Chlamydia trachomatis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PELVIC-INFLAMMATORY-DISEASE; HEAT-SHOCK-PROTEIN; PIG INCLUSION CONJUNCTIVITIS; FEMALE REPRODUCTIVE-TRACT; TOLL-LIKE RECEPTOR-4; GENE KNOCKOUT MICE; CD4 T-CELLS; FALLOPIAN-TUBE; GUINEA-PIGS; EPITHELIAL-CELLS AB Although the pathologic consequences of C. trachomatis genital infection are well-established, the mechanism(s) that result in chlamydia-induced tissue damage are not fully understood. We reviewed in vitro, animal, and human data related to the pathogenesis of chlamydial disease to better understand how reproductive sequelae result from C. trachomatis infection. Abundant in vitro data suggest that the inflammatory response to chlamydiae is initiated and sustained by actively infected nonimmune host epithelial cells. The mouse model indicates a critical role for chlamydia activation of the innate immune receptor, Toll-like receptor 2, and subsequent inflammatory cell influx and activation, which contributes to the development of chronic genital tract tissue damage. Data from recent vaccine studies in the murine model and from human immunoepidemiologic studies support a role for chlamydia-specific CD4 Th1-interferon-gamma-producing cells in protection from infection and disease. However, limited evidence obtained using animal models of repeated infection indicates that, although the adaptive T cell response is a key mechanism involved in controlling or eliminating infection, it may have a double-edged nature and contribute to tissue damage. Important immunologic questions include whether anamnestic CD4 T cell responses drive disease rather than protect against disease and the role of specific immune cells and inflammatory mediators in the induction of tissue damage with primary and repeated infections. Continued study of the complex molecular and cellular interactions between chlamydiae and their host and large-scale prospective immunoepidemiologic and immunopathologic studies are needed to address gaps in our understanding of pathogenesis that thwart development of optimally effective control programs, including vaccine development. C1 [Darville, Toni] Univ Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15201 USA. [Darville, Toni] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA 15201 USA. [Hiltke, Thomas J.] NIAID, Sexually Transmitted Dis Branch, NIH, Bethesda, MD 20892 USA. RP Darville, T (reprint author), Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Infect Dis,Dept Pediat, 45th & Penn Ave, Pittsburgh, PA 15201 USA. EM toni.darville@chp.edu FU National Institute of Allergy and Infectious Diseases [AI054624, AI084024]; Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center FX Financial support: National Institute of Allergy and Infectious Diseases (AI054624 and AI084024 to T. D.) and the Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (to T. D.). NR 80 TC 39 Z9 39 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2010 VL 202 SU 2 BP S114 EP S125 DI 10.1086/652397 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 608WO UT WOS:000278616900005 ER PT J AU Greenberg, DE Marshall-Batty, KR Brinster, LR Zarember, KA Shaw, PA Mellbye, BL Iversen, PL Holland, SM Geller, BL AF Greenberg, David E. Marshall-Batty, Kimberly R. Brinster, Lauren R. Zarember, Kol A. Shaw, Pamela A. Mellbye, Brett L. Iversen, Patrick L. Holland, Steven M. Geller, Bruce L. TI Antisense Phosphorodiamidate Morpholino Oligomers Targeted to an Essential Gene Inhibit Burkholderia cepacia Complex SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; ENTERICA SEROVAR TYPHIMURIUM; PEPTIDE NUCLEIC-ACIDS; ESCHERICHIA-COLI; CYSTIC-FIBROSIS; TISSUE-CULTURE; PURE CULTURE; IN-VITRO; INFECTION; GROWTH AB Background. Members of the Burkholderia cepacia complex (Bcc) cause considerable morbidity and mortality in patients with chronic granulomatous disease and cystic fibrosis. Many Bcc strains are antibiotic resistant, which requires the exploration of novel antimicrobial approaches, including antisense technologies such as phosphorodiamidate morpholino oligomers (PMOs). Methods. Peptide-conjugated PMOs (PPMOs) were developed to target acpP, which encodes an acyl carrier protein (AcpP) that is thought to be essential for growth. Their antimicrobial activities were tested against different strains of Bcc in vitro and in infection models. Results. PPMOs targeting acpP were bactericidal against clinical isolates of Bcc (>4 log reduction), whereas a PPMO with a scrambled base sequence (scrambled PPMO) had no effect on growth. Human neutrophils were infected with Burkholderia multivorans and treated with AcpP PPMO. AcpP PPMO augmented killing, compared with neutrophils alone and compared with neutrophils alone plus scrambled PPMO. Mice with chronic granulomatous disease that were infected with B. multivorans were treated with AcpP PPMO, scrambled PPMO, or water at 0, 3, and 6 h after infection. Compared with water-treated control mice, the AcpP PPMO-treated mice showed an similar to 80% reduction in the risk of dying by day 30 of the experiment and relatively little pathology. Conclusion. AcpP PPMO is active against Bcc infections in vitro and in vivo. C1 [Greenberg, David E.; Marshall-Batty, Kimberly R.; Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Zarember, Kol A.] NIAID, Host Def Lab, Bethesda, MD 20892 USA. [Shaw, Pamela A.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Brinster, Lauren R.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. [Geller, Bruce L.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA. [Mellbye, Brett L.; Iversen, Patrick L.; Geller, Bruce L.] Oregon State Univ, AVI BioPharma, Corvallis, OR 97331 USA. RP Greenberg, DE (reprint author), 33 N Dr,Room 2W10A3, Bethesda, MD 20892 USA. EM degreenberg@niaid.nih.gov OI Mellbye, Brett/0000-0002-3586-1885 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX Financial support: Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases; AVI BioPharma (provided materials and technical support). NR 34 TC 29 Z9 31 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2010 VL 201 IS 12 BP 1822 EP 1830 DI 10.1086/652807 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 596LZ UT WOS:000277687900008 PM 20438352 ER PT J AU Burbelo, PD Issa, AT Ching, KH Wyvill, KM Little, RF Iadarola, MJ Kovacs, JA Yarchoan, R AF Burbelo, Peter D. Issa, Alexandra T. Ching, Kathryn H. Wyvill, Kathleen M. Little, Richard F. Iadarola, Michael J. Kovacs, Joseph A. Yarchoan, Robert TI Distinct Profiles of Antibodies to Kaposi Sarcoma-Associated Herpesvirus Antigens in Patients with Kaposi Sarcoma, Multicentric Castleman Disease, and Primary Effusion Lymphoma SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DNA-SEQUENCES; EXPRESSION; PROTEIN; KSHV AB Antibody responses against lytic and latent Kaposi sarcoma (KS)-associated herpesvirus antigens were investigated in patients with KS, multicentric Castleman disease (MCD), and primary effusion lymphoma. Antibodies against the lytic antigen K8.1 were 5-fold higher in patients with MCD than those with KS, whereas antibodies to the sum of latent antigens v-cyclin and LANA were 27-fold higher in patients with KS, compared with patients with MCD (P < .001). The sum of anti-v-cyclin and anti-LANA antibody titers discriminated patients with KS from those with MCD and KS with 93% sensitivity and 83% specificity. These results suggest that antibody responses to lytic and latent KS-associated herpesvirus antigens differ in these diseases. C1 [Wyvill, Kathleen M.; Little, Richard F.; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kovacs, Joseph A.] NCI, Crit Care Med Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Burbelo, Peter D.; Issa, Alexandra T.; Ching, Kathryn H.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA. RP Burbelo, PD (reprint author), Bldg 49,Rm 1C20,49 Convent Dr, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU NIH; National Institute of Dental and Craniofacial Research; NIH Clinical Center; National Cancer Institute FX Financial support: This work was supported by in part by the Intramural Research Program of the NIH, the National Institute of Dental and Craniofacial Research, the NIH Clinical Center, and the National Cancer Institute and, in part, by a Bench to Bedside award from the NIH Clinical Center. NR 14 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2010 VL 201 IS 12 BP 1919 EP 1922 DI 10.1086/652869 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 596LZ UT WOS:000277687900018 PM 20443737 ER PT J AU Katragkou, A Kruhlak, MJ Simitsopoulou, M Chatzimoschou, A Taparkou, A Cotten, CJ Paliogianni, F Diza-Mataftsi, E Tsantali, C Walsh, TJ Roilides, E AF Katragkou, Aspasia Kruhlak, Michael J. Simitsopoulou, Maria Chatzimoschou, Athanasios Taparkou, Anna Cotten, Catherine J. Paliogianni, Fotini Diza-Mataftsi, Eudoxia Tsantali, Chaido Walsh, Thomas J. Roilides, Emmanuel TI Interactions between Human Phagocytes and Candida albicans Biofilms Alone and in Combination with Antifungal Agents SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ASPERGILLUS-FUMIGATUS; HUMAN MONOCYTES; AMPHOTERICIN-B; IMMUNE RECOGNITION; LIPID FORMULATIONS; FLUORESCENT-PROBES; BETA-GLUCAN; CELL-WALL; EXPRESSION; INFECTIONS AB Background. Biofilm formation is an important component of vascular catheter infections caused by Candida albicans. Little is known about the interactions between human phagocytes, antifungal agents, and Candida biofilms. Methods. The interactions between C. albicans biofilms and human phagocytes alone and in combination with anidulafungin or voriconazole were investigated and compared with their corresponding planktonic counterparts by means of an in vitro biofilm model with clinical intravascular and green fluorescent protein (GFP)-expressing strains. Phagocyte-mediated and antifungal agent-mediated damages were determined by 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5-carboxanilide assay, and structural effects were visualized by confocal microscopy. Oxidative burst was evaluated by flow cytometric measurement of dihydrorhodamine 123 oxidation, and cytokine release was measured by enzyme-linked immunosorbent assay. Results. Phagocytes alone and in combination with antifungal agents induced less damage against biofilms compared with planktonic cells. However, additive effects occurred between phagocytes and anidulafungin against Candida biofilms. Confocal microscopy demonstrated the absence of phagocytosis within biofilms but marked destruction caused by anidulafungin and phagocytes. Anidulafungin but not voriconazole elicited tumor necrosis factor a release from phagocytes compared with that from untreated biofilms. Conclusions. C. albicans within biofilms are more resistant to phagocytic host defenses but are susceptible to additive effects between phagocytes and an echinocandin. C1 [Katragkou, Aspasia; Simitsopoulou, Maria; Chatzimoschou, Athanasios; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Sch Med, Infect Dis Lab, Hippokrat Hosp,Dept Pediat 3, GR-54642 Thessaloniki, Greece. [Taparkou, Anna; Tsantali, Chaido] Aristotle Univ Thessaloniki, Sch Med, Hippokrat Hosp, Dept Pediat 2, GR-54642 Thessaloniki, Greece. [Diza-Mataftsi, Eudoxia] Aristotle Univ Thessaloniki, Sch Med, Dept Microbiol 2, GR-54642 Thessaloniki, Greece. [Paliogianni, Fotini] Univ Patras, Sch Med, Dept Microbiol, GR-26110 Patras, Greece. [Cotten, Catherine J.; Walsh, Thomas J.; Roilides, Emmanuel] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. [Kruhlak, Michael J.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Sch Med, Infect Dis Lab, Hippokrat Hosp,Dept Pediat 3, Konstantinoupoleos 49, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr FU Intramural NIH HHS [Z01 BC010915-01, Z01 SC006830-38] NR 41 TC 36 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2010 VL 201 IS 12 BP 1941 EP 1949 DI 10.1086/652783 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 596LZ UT WOS:000277687900021 PM 20415537 ER PT J AU Darville, T Hiltke, TJ AF Darville, Toni Hiltke, Thomas J. TI Pathogenesis of Genital Tract Disease Due to Chlamydia trachomatis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PELVIC-INFLAMMATORY-DISEASE; HEAT-SHOCK-PROTEIN; PIG INCLUSION CONJUNCTIVITIS; FEMALE REPRODUCTIVE-TRACT; TOLL-LIKE RECEPTOR-4; GENE KNOCKOUT MICE; CD4 T-CELLS; FALLOPIAN-TUBE; GUINEA-PIGS; EPITHELIAL-CELLS AB Although the pathologic consequences of C. trachomatis genital infection are well-established, the mechanism(s) that result in chlamydia-induced tissue damage are not fully understood. We reviewed in vitro, animal, and human data related to the pathogenesis of chlamydial disease to better understand how reproductive sequelae result from C. trachomatis infection. Abundant in vitro data suggest that the inflammatory response to chlamydiae is initiated and sustained by actively infected nonimmune host epithelial cells. The mouse model indicates a critical role for chlamydia activation of the innate immune receptor, Toll-like receptor 2, and subsequent inflammatory cell influx and activation, which contributes to the development of chronic genital tract tissue damage. Data from recent vaccine studies in the murine model and from human immunoepidemiologic studies support a role for chlamydia-specific CD4 Th1-interferon-gamma-producing cells in protection from infection and disease. However, limited evidence obtained using animal models of repeated infection indicates that, although the adaptive T cell response is a key mechanism involved in controlling or eliminating infection, it may have a double-edged nature and contribute to tissue damage. Important immunologic questions include whether anamnestic CD4 T cell responses drive disease rather than protect against disease and the role of specific immune cells and inflammatory mediators in the induction of tissue damage with primary and repeated infections. Continued study of the complex molecular and cellular interactions between chlamydiae and their host and large-scale prospective immunoepidemiologic and immunopathologic studies are needed to address gaps in our understanding of pathogenesis that thwart development of optimally effective control programs, including vaccine development. C1 [Darville, Toni] Univ Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15201 USA. [Darville, Toni] Univ Pittsburgh, Med Ctr, Dept Immunol, Pittsburgh, PA 15201 USA. [Hiltke, Thomas J.] NIAID, Sexually Transmitted Dis Branch, NIH, Bethesda, MD 20892 USA. RP Darville, T (reprint author), Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Infect Dis,Dept Pediat, 45th & Penn Ave, Pittsburgh, PA 15201 USA. EM toni.darville@chp.edu FU National Institute of Allergy and Infectious Diseases [AI054624, AI084024]; Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center; Centers for Disease Control and Prevention FX National Institute of Allergy and Infectious Diseases (AI054624 and AI084024 to T.D.) and the Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (to T.D.).; Supplement sponsorship: This article is part of a supplement entitled "Chlamydia trachomatis Genital Infection: Natural History, Immunobiology, and Implications for Control Programs," which was sponsored by the Centers for Disease Control and Prevention. NR 80 TC 72 Z9 74 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2010 VL 201 SU 2 BP S114 EP S125 DI 10.1086/652397 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 714XD UT WOS:000286841400005 PM 20524234 ER PT J AU Lu, SY Hong, J Itoh, T Fujita, M Inoue, O Innis, RB Pike, VW AF Lu, Shuiyu Hong, Jinsoo Itoh, Tetsuji Fujita, Masahiro Inoue, Osamu Innis, Robert B. Pike, Victor W. TI [carbonyl-C-11]Benzyl acetate: Automated radiosynthesis via Pd-mediated [C-11]carbon monoxide chemistry and PET measurement of brain uptake in monkey SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE [C-11]benzyl acetate; carbon-11; [C-11]carbon monoxide; carbonylation; PET ID GLIAL METABOLISM; RAT-BRAIN; IN-VIVO; RECEPTORS; FLUOROACETATE; RADIOLIGAND; LIGAND; AGENT AB [carbonyl-C-11]Benzyl acetate ([C-11]1) has been proposed as a potential agent for imaging glial metabolism of acetate to glutamate and glutamine with positron emission tomography. [C-11]1 was synthesized from [C-11]carbon monoxide, iodomethane and benzyl alcohol via palladium-mediated chemistry. The radiosynthesis was automated with a modified Synthia platform controlled with in-house developed Labview software. Under production conditions, [C-11]1 was obtained in 10% (n = 6) decay-corrected radiochemical yield from [C-11]carbon monoxide in >96% radiochemical purity and with an average specific radioactivity of 2415 mCi/mu mol. The total radiosynthesis time was about 45 min. Peak uptake of radioactivity in monkey brain (SW = 3.1) was relatively high and may be amenable to measuring uptake and metabolism of acetate in glial cells of the brain. C1 [Lu, Shuiyu; Hong, Jinsoo; Itoh, Tetsuji; Fujita, Masahiro; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Inoue, Osamu] Osaka Univ, Div Hlth Sci, Grad Sch Med, Suita, Osaka 5650871, Japan. RP Lu, SY (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM Shuiyu.Lu@mait.nih.gov OI Lu, Shuiyu/0000-0003-0310-4318 FU National Institutes of Health (National Institute of Mental Health) [Z01-MH-002793, Z01-MH-002795] FX This work was supported by the Intramural Research Program of the National Institutes of Health (National Institute of Mental Health; project #s, Z01-MH-002793 and Z01-MH-002795). We thank Mr D. Smith of Mink Hollow Systems Inc. (Gaithersburg, MD, USA) for assistance with software code-writing. NR 26 TC 12 Z9 12 U1 1 U2 3 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 JUN 15 PY 2010 VL 53 IS 7-8 BP 548 EP 551 DI 10.1002/jlcr.1779 PG 4 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 638VL UT WOS:000280925500026 PM 20694167 ER PT J AU Cherkasova, V Qiu, HF Hinnebusch, AG AF Cherkasova, Vera Qiu, Hongfang Hinnebusch, Alan G. TI Snf1 Promotes Phosphorylation of the alpha Subunit of Eukaryotic Translation Initiation Factor 2 by Activating Gcn2 and Inhibiting Phosphatases Glc7 and Sit4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-KINASE GCN2; TRANSFER-RNA BINDING; AMINO-ACID CONTROL; SACCHAROMYCES-CEREVISIAE; YEAST SNF1; UPSTREAM KINASES; MAMMALIAN-CELLS; EXPRESSION; STRESS; TOR AB Snf1 is the ortholog of mammalian AMP-activated kinase and is responsible for activation of glucose-repressed genes at low glucose levels in budding yeast. We show that Snf1 promotes the formation of phosphorylated alpha subunit of eukaryotic translation initiation factor 2 (eIF2 alpha-P), a regulator of general and gene-specific translation, by stimulating the function of eIF2 alpha kinase Gcn2 during histidine starvation of glucose-grown cells. Thus, eliminating Snf1 or mutating its activation loop lowers Gcn2 kinase activity, reducing the autophosphorylation of Thr-882 in the Gcn2 activation loop, and decreases eIF2 alpha-P levels in starved cells. Consistently, eliminating Reg1, a negative regulator of Snf1, provokes Snf1-dependent hyperphosphorylation of both Thr-882 and eIF2 alpha. Interestingly, Snf1 also promotes eIF2 alpha phosphorylation in the nonpreferred carbon source galactose, but this occurs by inhibition of protein phosphatase 1 alpha (PP1 alpha; Glc7) and the PP2A-like enzyme Sit4, rather than activation of Gcn2. Both Glc7 and Sit4 physically interact with eIF2 alpha in cell extracts, supporting their direct roles as eIF2 alpha phosphatases. Our results show that Snf1 modulates the level of eIF2 alpha phosphorylation by different mechanisms, depending on the kind of nutrient deprivation existing in cells. C1 [Cherkasova, Vera; Qiu, Hongfang; Hinnebusch, Alan G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bldg 6,Room 230, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov FU National Institutes of Health FX This work was supported in part by the Intramural Program of the National Institutes of Health. NR 35 TC 29 Z9 29 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 JUN 15 PY 2010 VL 30 IS 12 BP 2862 EP 2873 DI 10.1128/MCB.00183-10 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 600OZ UT WOS:000277997900002 PM 20404097 ER PT J AU Sakurai, A Gavard, J Annas-Linhares, Y Basile, JR Amornphimoltham, P Palmby, TR Yagi, H Zhang, F Randazzo, PA Li, XR Weigert, R Gutkind, JS AF Sakurai, Atsuko Gavard, Julie Annas-Linhares, Yuliya Basile, John R. Amornphimoltham, Panomwat Palmby, Todd R. Yagi, Hiroshi Zhang, Fan Randazzo, Paul A. Li, Xuri Weigert, Roberto Gutkind, J. Silvio TI Semaphorin 3E Initiates Antiangiogenic Signaling through Plexin D1 by Regulating Arf6 and R-Ras SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; ANGIOGENESIS; ADHESION; ACTIVATION; INHIBITOR; RECEPTORS; VEGF; 4D AB Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here that Sema3E acts as a potent inhibitor of adult and tumor-induced angiogenesis. Activation of plexin D1 by Sema3E causes the rapid disassembly of integrin-mediated adhesive structures, thereby inhibiting endothelial cell adhesion to the extracellular matrix (ECM) and causing the retraction of filopodia in endothelial tip cells. Sema3E acts on plexin D1 to initiate a two-pronged mechanism involving R-Ras inactivation and Arf6 stimulation, which affect the status of activation of integrins and their intracellular trafficking, respectively. Ultimately, our present study provides a molecular framework for antiangiogenesis signaling, thus impinging on a myriad of pathological conditions that are characterized by aberrant increase in neovessel formation, including cancer. C1 [Amornphimoltham, Panomwat; Weigert, Roberto; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Gavard, Julie] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France. [Gavard, Julie] INSERM, U567, Paris, France. [Zhang, Fan; Li, Xuri] NEI, Unit Retinal Vasc Neurobiol, NIH, Rockville, MD 20852 USA. [Randazzo, Paul A.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211,MSC 4340, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012 OI Gavard, Julie/0000-0002-7985-9007 FU JSPS; Howard Hughes Scholars Program; NIH, National Institute of Dental and Craniofacial Research; National Eye Institute FX A. S. was supported by JSPS postdoctoral fellowships for research abroad and Y.A.-L. by the Howard Hughes Scholars Program. This research was supported by the Intramural Research Program of the NIH, National Institute of Dental and Craniofacial Research, and National Eye Institute. NR 30 TC 76 Z9 80 U1 0 U2 7 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 JUN 15 PY 2010 VL 30 IS 12 BP 3086 EP 3098 DI 10.1128/MCB.01652-09 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 600OZ UT WOS:000277997900021 PM 20385769 ER PT J AU Wen, HH Bennett, EE Kopace, R Stein, AF Pai, V AF Wen, Harold H. Bennett, Eric E. Kopace, Rael Stein, Ashley F. Pai, Vinay TI Single-shot x-ray differential phase-contrast and diffraction imaging using two-dimensional transmission gratings SO OPTICS LETTERS LA English DT Article ID INTERFEROMETER; RADIOGRAPHY AB We describe an x-ray differential phase-contrast imaging method based on two-dimensional transmission gratings that are directly resolved by an x-ray camera. X-ray refraction and diffraction in the sample lead to variations of the positions and amplitudes of the grating fringes on the camera. These effects can be quantified through spatial harmonic analysis. The use of 2D gratings allows differential phase contrast in several directions to be obtained from a single image. When compared to previous grating-based interferometry methods, this approach obviates the need for multiple exposures and separate measurements for different directions and thereby accelerates imaging speed. C1 [Wen, Harold H.; Bennett, Eric E.; Kopace, Rael; Stein, Ashley F.; Pai, Vinay] NHLBI, Imaging Phys Sect, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Wen, HH (reprint author), NHLBI, Imaging Phys Sect, Translat Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Bennett, Eric/A-2551-2013; Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-14] NR 21 TC 57 Z9 57 U1 0 U2 12 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD JUN 15 PY 2010 VL 35 IS 12 BP 1932 EP 1934 PG 3 WC Optics SC Optics GA 619NB UT WOS:000279435800002 PM 20548343 ER PT J AU Matsumoto, K Irie, F Mackem, S Yamaguchi, Y AF Matsumoto, Kazu Irie, Fumitoshi Mackem, Susan Yamaguchi, Yu TI A mouse model of chondrocyte-specific somatic mutation reveals a role for Ext1 loss of heterozygosity in multiple hereditary exostoses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bone development; heparan sulfate; osteochondroma ID HEPARAN-SULFATE BIOSYNTHESIS; TUMOR SUPPRESSORS EXT1; EXPRESSION; MICE; OSTEOCHONDROMAS; CHONDROSARCOMAS; GENE; IDENTIFICATION; CHROMOSOME-11; SKELETON AB Multiple hereditary exostoses (MHE) is one of the most common skeletal dysplasias, exhibiting the formation of multiple cartilage-capped bony protrusions (osteochondroma) and characteristic bone deformities. Individuals with MHE carry heterozygous loss-of-function mutations in Ext1 or Ext2, genes which together encode an enzyme essential for heparan sulfate synthesis. Despite the identification of causative genes, the pathogenesis of MHE remains unclear, especially with regard to whether osteochondroma results from loss of heterozygosity of the Ext genes. Hampering elucidation of the pathogenic mechanism of MHE, both Ext1(+/-) and Ext2(+-)heterozygous mutant mice, which mimic the genetic status of human MHE, are highly resistant to osteochondroma formation, especially in long bones. To address these issues, we created a mouse model in which Ext1 is stochastically inactivated in a chondrocyte-specific manner. We show that these mice develop multiple osteochondromas and characteristic bone deformities in a pattern and a frequency that are almost identical to those of human MHE, suggesting a role for Ext1 LOH in MHE. Surprisingly, however, genotyping and fate mapping analyses reveal that chondrocytes constituting osteochondromas are mixtures of mutant and wildtype cells. Moreover, osteochondromas do not possess many typical neoplastic properties. Together, our results suggest that inactivation of Ext1 in a small fraction of chondrocytes is sufficient for the development of osteochondromas and other skeletal defects associated with MHE. Because the observed osteochondromas in our mouse model do not arise from clonal growth of chondrocytes, they cannot be considered true neoplasms. C1 [Matsumoto, Kazu; Irie, Fumitoshi; Yamaguchi, Yu] Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. [Mackem, Susan] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Yamaguchi, Y (reprint author), Sanford Burnham Med Res Inst, Sanford Childrens Hlth Res Ctr, La Jolla, CA 92037 USA. EM yyamaguchi@burnham.org FU MHE Research Foundation; National Institutes of Health [R01 AR055670, P01 HD025938] FX We thank the MHE Research Foundation for support. This work was supported by National Institutes of Health Grants R01 AR055670 and P01 HD025938 (to Y.Y.). NR 35 TC 37 Z9 37 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 2010 VL 107 IS 24 BP 10932 EP 10937 DI 10.1073/pnas.0914642107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 611IC UT WOS:000278807400030 PM 20534475 ER PT J AU Liu, WL Yan, M Liu, YQ Wang, RH Li, CL Deng, CX Singh, A Coleman, WG Rodgers, GP AF Liu, Wenli Yan, Ming Liu, Yueqin Wang, Ruihong Li, Cuiling Deng, Chuxia Singh, Aparna Coleman, William G., Jr. Rodgers, Griffin P. TI Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NF-kappa B; nucleotide oligomerization domain-1 and-2 ID NF-KAPPA-B; OPEN-ANGLE GLAUCOMA; TRANSCRIPTION FACTOR; EPITHELIAL-CELLS; ACTIVATION; EXPRESSION; HGC-1; IDENTIFICATION; PROTEINS; MUCOSA AB Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1 beta, IL-5, IL-12 p70, and MIP-1 alpha was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF-kappa B pathway and has a negative feedback effect on NF-kappa B activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-kappa B activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization. C1 [Yan, Ming; Singh, Aparna; Coleman, William G., Jr.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Liu, Yueqin] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Wang, Ruihong; Li, Cuiling; Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Liu, Wenli; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, Bethesda, MD 20892 USA. RP Coleman, WG (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wc3z@nih.gov; griffinr@extra.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease; National Center on Minority Health and Health Disparities [Y3-DK-3521-07] FX We thank Drs. A. Lee and J. O'Rourke (University of South Wales, Sydney, Australia) for providing us with H. pylori Sydney strain 1 (SS1) and Dr. A. Dubois (Uniformed Services University of the Health Sciences, Bethesda) for providing us with strain US101. We thank Dr. Yoshiaki Tabuchi (University of Toyama, Toyama, Japan) for providing us with GSM06 cells. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, and an Inter-Agency Agreement (Y3-DK-3521-07) with the National Center on Minority Health and Health Disparities. NR 37 TC 43 Z9 44 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 15 PY 2010 VL 107 IS 24 BP 11056 EP 11061 DI 10.1073/pnas.1001269107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 611IC UT WOS:000278807400051 PM 20534456 ER PT J AU Holt, SK Kwon, EM Lin, DW Ostrander, EA Stanford, JL AF Holt, Sarah K. Kwon, Erika M. Lin, Daniel W. Ostrander, Elaine A. Stanford, Janet L. TI Association of Hepsin Gene Variants with Prostate Cancer Risk and Prognosis SO PROSTATE LA English DT Article DE prostate neoplasm; single nucleotide polymorphism; Hepsin; case-control ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; AGGRESSIVENESS LOCI; LAMININ-332; PROGRESSION; SUBSTRATE; SCAN AB BACKGROUND. Hepsin (HPN) is one of the most consistently overexpressed genes in prostate cancer and there is some evidence supporting an association between HPN gene variants and prostate cancer risk. We report results from a population-based case control genetic association study for six tagging single nucleotide polymorphisms (tagSNPs) in the HPN gene. METHODS. Prostate cancer risk was estimated using adjusted unconditional logistic regression in 1,401 incident prostate cancer cases diagnosed in 1993 through 1996 or 2002 through 2005 and 1,351 age-matched controls. Risks of disease recurrence/progression and prostate cancer-specific mortality were estimated using Cox proportional hazards (PH) regression in 437 cases with long-term follow-up. RESULTS. There were 135 recurrence/progression events and 57 cases who died of prostate cancer. Contrary to some earlier studies, we found no evidence of altered risk of developing prostate cancer overall or when clinical measures of tumor aggressiveness were considered for any of the tagSNPs, assessed either individually or by haplotypes. There was no evidence of altered risks of tumor recurrence/progression or prostate cancer death associated with variants in the HPN gene. CONCLUSIONS. Germline genetic variation of HPN does not seem to contribute to risk of prostate cancer or prognosis. Prostate 70: 1012-1019, 2010. (c) 2010 Wiley-Liss, Inc. C1 [Holt, Sarah K.; Lin, Daniel W.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA. [Lin, Daniel W.] Vet Affairs Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA. [Lin, Daniel W.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Holt, SK (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop M4-A402,POB 19024, Seattle, WA 98109 USA. EM skholt@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1-CA56678, RO1-CA092579, RO1-CA082554, P50-CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Grant sponsor: National Cancer Institute; Grant numbers: RO1-CA56678, RO1-CA092579, RO1-CA082554, P50-CA097186; Grant sponsor: Fred Hutchinson Cancer Research Center; Grant sponsor: Intramural Program of the National Human Genome Research Institute. NR 21 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUN 15 PY 2010 VL 70 IS 9 BP 1012 EP 1019 DI 10.1002/pros.21135 PG 8 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 607IO UT WOS:000278494300009 PM 20166135 ER PT J AU Langeberg, WJ Tahir, SA Feng, ZD Kwon, EM Ostrander, EA Thompson, TC Stanford, JL AF Langeberg, Wendy J. Tahir, Salahaldin A. Feng, Ziding Kwon, Erika M. Ostrander, Elaine A. Thompson, Timothy C. Stanford, Janet L. TI Association of Caveolin-1 and -2 Genetic Variants and Post-Treatment Serum Caveolin-1 With Prostate Cancer Risk and Outcomes SO PROSTATE LA English DT Article DE prostate cancer; cayeolin; case control association study; single nucleotide polymorphism; biomarker; recurrence ID RADICAL PROSTATECTOMY; CELL-LINES; SURVIVAL/CLONAL GROWTH; SECRETED CAVEOLIN-1; PROGNOSTIC MARKER; POOR-PROGNOSIS; BREAST-CANCER; UP-REGULATION; EXPRESSION; PROGRESSION AB BACKGROUND. Caveolin-1 (cav-1) is overexpressed by metastatic prostate cancer (PC) cells. Pre-operative serum cav-1 levels have been shown to be a prognostic marker for PC recurrence. This study evaluated the relationship between post-treatment serum cav-1 levels and single nucleotide polymorphisms (SNPs) in the cav-1 and -2 genes with risk of PC, aggressive PC, PC recurrence or death. METHODS. Two case control studies of PC among men in Washington State were combined for this analysis. Cases (n = 1,458) were diagnosed in 1993-1996 or 2002-2005 and identified via a SEER cancer registry. Age-matched controls (n = 1,351) were identified via random digit dialing. Logistic regression was used to assess the relationship between exposures (19 haplotype-tagging SNPs from all subjects and post-treatment serum cav-1 levels from a sample of 202 cases and 226 controls) and PC risk and aggressive PC. Cox proportional hazards regression was used to assess the relationship between exposures and PC recurrence and death. RESULTS. Rs9920 in cav-1 was associated with an increased relative risk of overall PC (OR(CT + CC) = 1.37,95% CI = 1.12, 1.68) and aggressive PC (OR(CT) (+ CC) = 1.57,95% CI = 1.20, 2.06), but not with PC recurrence or death. High post-treatment serum cav-1 levels were not associated with PC risk, aggressive PC, or PC-specific death, but approached a significant inverse association with PC recurrence (hazard ratio = 0.69, 95% CI = 0.47, 1.00). CONCLUSIONS. We found modest evidence for an association with a variant in the cav-1 gene and risk of overall PC and aggressive PC, which merits further study. We found no evidence that higher post-treatment serum cav-1 is associated with risk of aggressive PC or adverse PC outcomes. Prostate 70: 1020-1035, 2010. (c) 2010 Wiley-Liss. Inc. C1 [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Langeberg, Wendy J.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Tahir, Salahaldin A.; Thompson, Timothy C.] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, M4-B874,POB 19024, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1 CA56678, RO1 CA082664, RO1 CA092579, RO1 CA50588, P50 CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Grant sponsor: National Cancer Institute; Grant numbers: RO1 CA56678, RO1 CA082664, RO1 CA092579, RO1 CA50588, P50 CA097186; Grant sponsor: Fred Hutchinson Cancer Research Center; Grant sponsor: National Human Genome Research Institute. NR 47 TC 12 Z9 13 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD JUN 15 PY 2010 VL 70 IS 9 BP 1020 EP 1035 DI 10.1002/pros.21137 PG 16 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 607IO UT WOS:000278494300010 PM 20209490 ER PT J AU Strauss, WJ Ryan, L Morara, M Iroz-Elardo, N Davis, M Cupp, M Nishioka, MG Quackenboss, J Galke, W Ozkaynak, H Scheidt, P AF Strauss, Warren J. Ryan, Louise Morara, Michele Iroz-Elardo, Nicole Davis, Mark Cupp, Matthew Nishioka, Marcia G. Quackenboss, James Galke, Warren Ozkaynak, Haluk Scheidt, Peter TI Improving cost-effectiveness of epidemiological studies via designed missingness strategies SO STATISTICS IN MEDICINE LA English DT Article DE National Children's Study; sampling design; validation sampling; measurement error adjustment ID EVERYDAY ENVIRONMENTS; NATIONAL CHILDRENS; REGRESSION-MODELS; LIKELIHOOD METHOD; EXPOSURES AB Modern epidemiological studies face opportunities and challenges posed by an ever-expanding capacity to measure a wide range of environmental exposures, along with sophisticated biomarkers of exposure and response at the individual level. The challenge of deciding what to measure is further complicated for longitudinal studies, where logistical and cost constraints preclude the collection of all possible measurements on all participants at every follow-up time. This is true for the National Children's Study (NCS), a large-scale longitudinal study that will enroll women both prior to conception and during pregnancy and collect information on their environment, their pregnancies, and their children's development through early adulthood with a goal of assessing key exposure/outcome relationships among a cohort of approximately 100 000 children. The success of the NCS will significantly depend on the accurate, yet cost-effective, characterization of environmental exposures thought to be related to the health outcomes of interest. The purpose of this paper is to explore the use of cost saving, yet valid and adequately powered statistical approaches for gathering exposure information within epidemiological cohort studies. The proposed approach involves the collection of detailed exposure assessment information on a specially selected subset of the study population, and collection of less-costly, and presumably less-detailed and less-burdensome, surrogate measures across the entire cohort. We show that large-scale efficiency in costs and burden may be achieved without making substantive sacrifices on the ability to draw reliable inferences concerning the relationship between exposure and health outcome. Several detailed scenarios are provided that document how the targeted sub-sampling design strategy can benefit large cohort studies like the NCS, as well as other more focused environmental epidemiologic studies. Published in 2010 by John Wiley & Sons, Ltd. C1 [Strauss, Warren J.; Morara, Michele; Iroz-Elardo, Nicole; Davis, Mark; Cupp, Matthew; Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH USA. [Ryan, Louise] Harvard Univ, Boston, MA 02115 USA. [Quackenboss, James; Galke, Warren; Scheidt, Peter] NICHHD, Natl Childrens Study Program Off, Rockville, MD USA. [Ozkaynak, Haluk] US EPA, Off Res & Dev, Res Triangle Pk, NC 27711 USA. RP Strauss, WJ (reprint author), Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA. EM strauss@battelle.org RI Ryan, Louise/A-4562-2009; Quackenboss, James/I-1960-2013 OI Ryan, Louise/0000-0001-5957-2490; FU NICHD NIH HHS [Y01 HD003311-03]; PHS HHS [282-98-0019] NR 19 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2010 VL 29 IS 13 BP 1377 EP 1387 DI 10.1002/sim.3892 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 614LJ UT WOS:000279060000004 PM 20527011 ER PT J AU Berger, VW AF Berger, Vance W. TI Making statistics boring again SO STATISTICS IN MEDICINE LA English DT Letter C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, 6130 Execut Blvd EPN,MSC 7354,Suite 3131, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2010 VL 29 IS 13 BP 1458 EP 1458 DI 10.1002/sim.3884 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 614LJ UT WOS:000279060000012 PM 20527016 ER PT J AU Bhatia, PA Moaddel, R Wainer, IW AF Bhatia, Prateek A. Moaddel, Ruin Wainer, Irving W. TI The synthesis and characterization of cellular membrane affinity chromatography columns for the study of human multidrug resistant proteins MRP1, MRP2 and human breast cancer resistant protein BCRP using membranes obtained from Spodoptera frugiperda (Sf9) insect cells SO TALANTA LA English DT Article DE Sf9; Affinity chromatography; Drug discovery; Receptor screening; ABC transporters; P-glycoprotein; MRP1; MRP2; BCRP; Membrane receptors ID IMMOBILIZED P-GLYCOPROTEIN; DEPENDENT TRANSPORT; DRUG EFFLUX; IN-VIVO; INHIBITORS; IDENTIFICATION; BINDING; ATP; EXPRESSION; PERMEABILITY AB CMAC (cellular membrane affinity chromatography columns) have been developed for the study of the human multidrug transporters MRP1. MRP2 and the breast cancer resistance protein (BCRP) The columns were constructed using the immobilized artificial membrane (IAM) stationary phase and cellular membrane fragments obtained from Spodoptera frugiperda (Sf9) cells that had been stably transfected with human Mrp1. Mrp2 or Bcrp cDNA. using a baculovirus expression system The resulting CMAC(Sf9(MRP1)), CMAC(Sf9(MRP2)) and CMAC(Sf9(BCRP)) columns and a control column produced using membrane fragments from non-transfected Sf9 cells, CMAC(Sf9), were characterized using frontal affinity chromatography using [(3)H]-etoposide as the marker ligand and etoposide, benzbromarone and MK571 as the displacers on the CMAC(Sf9(MRP1)) column, etoposide and furosemide on the CMAC(Sf9(MRP2)) column and etoposide and fumitremorgin C on the CMAC(Sf9(BCPR)) column. The binding affinities (K(i) values) obtained from the chromatographic studies were consistent with the data obtained using non-chromatographic techniques and the results indicate that the immobilized MRP1, MRP2 and BCRP transporters retained their ability to selectively bind known ligands. (S)-verapamil displaced [(3)H]-etoposide on the CMAC(Sf9(MRP1)) column to a greater extent than (R)-verapamil and the relative IC(50) values of the enantiomers were calculated using the changes in the retention times of the marker. The observed enantioselectivity and calculated IC(50) values were consistent with previously reported data The results indicated that the CMAC(Sf9(MRP1)), CMAC(Sf9(MRP2)) and CMAC(Sf9(BCRP)) columns can be used for the study of binding to the MRP1, MRP2 and BCRP transporters and that membranes from the Sf9 cell line can be used to prepare CMAC columns This is the first example of the use of membranes from a non-mammalian cell line in an affinity chromatographic system Published by Elsevier B V C1 [Bhatia, Prateek A.; Moaddel, Ruin; Wainer, Irving W.] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, NIH, Biomed Res Ctr, 8B133 Biomed Res Ctr,251 Bayview Blvd, Baltimore, MD 21224 USA. FU National Institute on Aging/NIH FX This work was supported by funds from the Intramural Research Program of the National Institute on Aging/NIH NR 46 TC 8 Z9 8 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD JUN 15 PY 2010 VL 81 IS 4-5 BP 1477 EP 1481 DI 10.1016/j.talanta.2010.02.055 PG 5 WC Chemistry, Analytical SC Chemistry GA 610MN UT WOS:000278737100050 PM 20441926 ER PT J AU Hurst, FP Sajjad, I Elster, EA Falta, EM Patel, P Abbott, KC Agodoa, LY Jindal, RM AF Hurst, Frank P. Sajjad, Imran Elster, Eric A. Falta, Edward M. Patel, Prem Abbott, Kevin C. Agodoa, Lawrence Y. Jindal, Rahul M. TI Transplantation of A2 Kidneys into B and O Recipients Leads to Reduction in Waiting Time: USRDS Experience SO TRANSPLANTATION LA English DT Article DE Waiting time; Kidney transplant; A2 blood group kidneys ID A(2) KIDNEYS; ABO; DONORS; SURVIVAL AB Introduction. Strategy of transplanting kidneys from A2 donors into patients with blood group B and O recipients has been used to alleviate the long waiting times. Materials and Methods. We used an inception cohort of US Renal Data System data base with patients older than 18 years who underwent renal transplantation between January 1995 and July 2006. The primary outcome variable was allograft loss (including death). Bivariate analysis of factors associated with receiving A2 or A2B kidneys was performed with chi-square testing for categorical variables (Fisher's exact test used for violations of Cochran's assumptions) and Student's t test for continuous variables (Mann-Whitney U test used for nonnormally distributed variables). Results. There were 150,118 first kidney transplants of whom 113 received kidney transplant from A2 to O, and 125 patients received A2 to B kidney transplant. Compared with other recipients from the same blood group, recipients of A2 kidneys had significantly shorter wait times. O recipients had a median wait time of 1.63 years (range 0.00-17.21 years), whereas O recipients who received A2 kidneys had a median wait time of 0.70 years (range 0.02-1.47 years; P < 0.001). B recipients had a median wait time of 1.90 years (range 0.00-17.52 years), whereas B recipients who received A2 kidneys had a median wait time of 0.74 years (range 0.10-5.21 years; P < 0.001). There was no significant difference in graft loss or death between A2 to O and B versus all other recipients. Conclusions. The results showed that comparatively few patients received A2 to B or O kidney transplant. C1 [Hurst, Frank P.; Elster, Eric A.; Falta, Edward M.; Abbott, Kevin C.; Jindal, Rahul M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Sajjad, Imran] Univ Wisconsin, Dept Med, Madison, WI 53706 USA. [Elster, Eric A.; Falta, Edward M.; Jindal, Rahul M.] Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. [Patel, Prem] Bookdale Univ Hosp & Med Ctr, Brooklyn, NY USA. [Agodoa, Lawrence Y.] NIDDK, Dept Surg, NIH, Bethesda, MD USA. [Jindal, Rahul M.] George Washington Univ, Dept Med, Washington, DC USA. [Hurst, Frank P.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Dept Nephrol, Washington, DC 20307 USA. RP Jindal, RM (reprint author), Walter Reed Army Med Ctr, Dept Organ Transplant, 6630 Georgia Ave, Washington, DC 20307 USA. EM jindalr@msn.com OI Abbott, Kevin/0000-0003-2111-7112 NR 20 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 15 PY 2010 VL 89 IS 11 BP 1396 EP 1402 DI 10.1097/TP.0b013e3181da191a PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 605IE UT WOS:000278340400016 PM 20354481 ER PT J AU Saraiya, M Berkowitz, Z Yabroff, KR Wideroff, L Kobrin, S Benard, V AF Saraiya, Mona Berkowitz, Zahava Yabroff, K. Robin Wideroff, Louise Kobrin, Sarah Benard, Vicki TI Cervical Cancer Screening With Both Human Papillomavirus and Papanicolaou Testing vs Papanicolaou Testing Alone What Screening Intervals Are Physicians Recommending? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; EARLY-DETECTION PROGRAM; CONVENTIONAL CYTOLOGY; NATIONAL BREAST; OPINION LEADERS; WOMEN; RISK; DNA; MANAGEMENT; NEOPLASIA AB Background: Guidelines recommend screening for cervical cancer among women 30 years or older 3 years after a normal Papanicolaou test (hereinafter referred to as Pap test) result or a combined normal screening result (normal Pap/negative human papillomavirus [HPV] test results). We assessed reported recommendations by US primary care physicians (PCPs) on screening intervals that incorporate HPV cotesting compared with Pap testing alone. Methods: From September 1, 2006, through May 31, 2007, we conducted a mailed survey of a representative sample of 1212 PCPs, of whom 950 performed Pap tests and recommended the HPV test for screening or management. The main outcome measure included self-reported data on timing of screening intervals for women with normal results using clinical vignettes. Results: Among Pap test providers who recommend HPV testing, 31.8% reported that they would conduct the next Pap test in 3 years for a 35-year-old woman with 3 normal Pap test results. For a 35-year-old woman with a normal Pap test result and a negative HPV test finding, only 19.0% would conduct the next Pap test in 3 years. Most remaining physicians would conduct the Pap test more frequently. Most PCPs did not recommend a second HPV test or recommended the next HPV test at the same frequency as the Pap test. Physician specialty was strongly associated with guideline-consistent recommendations for the next Pap or HPV test. Conclusions: A lower proportion of PCPs recommend extending screening intervals to 3 years with an HPV cotest than those screening with the Pap test alone. Implementation of effective interventions and strategies that improve physician adherence to recommendations will be important for efficient screening practices. C1 [Saraiya, Mona; Berkowitz, Zahava; Benard, Vicki] Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, Atlanta, GA 30341 USA. [Yabroff, K. Robin; Wideroff, Louise; Kobrin, Sarah] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Saraiya, M (reprint author), Ctr Dis Control & Prevent, Epidemiol & Appl Res Branch, Div Canc Prevent & Control, 4770 Buford Hwy,Mailstop K-55, Atlanta, GA 30341 USA. EM msaraiya@cdc.gov RI Hernandez, Jessica/G-6527-2011; OI Yabroff, K. Robin/0000-0003-0644-5572 FU National Cancer Institute; Centers for Disease Control and Prevention; Agency for Healthcare Research and Quality FX Funding/Support: This study was supported by the National Cancer Institute, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality. NR 46 TC 75 Z9 76 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 14 PY 2010 VL 170 IS 11 BP 977 EP 985 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 610YA UT WOS:000278775100012 PM 20548011 ER PT J AU Berezhkovskii, AM Dagdug, L Makhnovskii, YA Zitserman, VY AF Berezhkovskii, Alexander M. Dagdug, Leonardo Makhnovskii, Yurii A. Zitserman, Vladimir Yu. TI Communications: Drift and diffusion in a tube of periodically varying diameter. Driving force induced intermittency SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID TRANSPORT AB We show that the effect of driving force F on the effective mobility and diffusion coefficient of a particle in a tube formed by identical compartments may be qualitatively different depending on the compartment shape. In tubes formed by cylindrical (spherical) compartments the mobility monotonically decreases (increases) with F and the diffusion coefficient diverges (remains finite) as F tends to infinity. In tubes formed by cylindrical compartments, at large F there is intermittency in the particle transitions between openings connecting neighboring compartments. (C) 2010 American Institute of Physics. [doi:10.1063/1.3451115] C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Fis, Mexico City 09340, DF, Mexico. [Makhnovskii, Yurii A.] Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. [Zitserman, Vladimir Yu.] Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. EM berezh@helix.nih.gov RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X FU NIH; Russian Foundation [10-03-00393] FX A.M.B. was supported by the Intramural Research Program of the NIH, Center for Information Technology. Y.A.M. and V.Yu.Z. thank the Russian Foundation for Basic Research for support (Grant No. 10-03-00393). NR 27 TC 54 Z9 54 U1 1 U2 12 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUN 14 PY 2010 VL 132 IS 22 AR 221104 DI 10.1063/1.3451115 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 611XO UT WOS:000278858400004 PM 20550383 ER PT J AU Eerola, J Luoma, PT Peuralinna, T Scholz, S Paisan-Ruiz, C Suomalainen, A Singleton, AB Tienari, PJ AF Eerola, Johanna Luoma, Petri T. Peuralinna, Terhi Scholz, Sonja Paisan-Ruiz, Coro Suomalainen, Anu Singleton, Andrew B. Tienari, Pentti J. TI POLG1 polyglutamine tract variants associated with Parkinson's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Polymerase gamma; Trinucleotide repeat; Polyglutamine; Parkinson's disease; Genetic susceptibility; POLG1 ID DNA-POLYMERASE-GAMMA; SUBSTANTIA-NIGRA NEURONS; MITOCHONDRIAL COMPLEX-I; CAG REPEAT; GLUCOCEREBROSIDASE MUTATIONS; MALE-INFERTILITY; ALPHA-SYNUCLEIN; LRRK2 G2019S; GENE POLG; PATHOGENESIS AB A possible role of allelic variation of the mitochondrial DNA polymerase gamma (POLG I) gene in Parkinson's disease (PD) has been suggested. First, POLG I missense mutations have been found in patients with familial parkinsonism and mitochondrial myopathy. Second, increased frequency of rare alleles of the POLG1 CAG-repeat (poly-Q) has been found in Finnish idiopathic apparently sporadic PD patients, but conflicting reports exist. The POLG1 poly-Q exhibits one major allele with 10 repeats (10Q, frequency >= 80%) and several less common alleles such as 11Q (frequency 6-9%), 6Q-9Q and 12Q-14Q (frequencies <4%). It is not known, whether the poly-Q variation modulates POLG1 function. Here we sequenced the poly-Q in 641 North American Caucasian PD patients and 292 controls. Caucasian literature controls were also used. Normal allele was defined either as 10/11Q or as 10Q according to the previous literature. The frequency of the non-10/11Q alleles in cases was not significantly different from the controls. Variant alleles defined as non-10Q were significantly increased in the PD patients compared to the North American controls (17.6% vs. 12.3%, p=0.004) as well as compared to the larger set of 897 controls (17.6% vs. 13.2%, p=0.0007). These results suggest that POLG1 poly-Q alleles other than the conserved 10Q allele may increase susceptibility to PD. This finding may be attributable to a beneficial function of the 10Q repeat protein or linkage disequilibrium between the 10Q allele and another variation within or close to POLG1. Other large case-control studies and analyses on functional differences of POLG1 poly-Q variants are warranted. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Eerola, Johanna; Luoma, Petri T.; Suomalainen, Anu; Tienari, Pentti J.] Univ Helsinki, Biomedicum, Res Program Mol Neurol, FIN-00290 Helsinki, Finland. [Eerola, Johanna; Luoma, Petri T.; Peuralinna, Terhi; Suomalainen, Anu; Tienari, Pentti J.] Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00290 Helsinki, Finland. [Scholz, Sonja; Singleton, Andrew B.] NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Paisan-Ruiz, Coro] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Paisan-Ruiz, Coro] Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. RP Tienari, PJ (reprint author), Univ Helsinki, Biomedicum, Res Program Mol Neurol, Haartmaninkatu 8, FIN-00290 Helsinki, Finland. EM pentti.tienari@hus.fi RI Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012; OI Scholz, Sonja/0000-0002-6623-0429 FU Helsinki University Central Hospital; Finnish Cultural Foundation; Oskar Oflund Foundation; Finnish Parkinson Foundation; Sigrid Juselius Foundation; Academy of Finland; National Institute on Aging; National Institutes of Health; Department of Health and Human Services [1 Z01 AG000957-05] FX This study has been financially supported by Helsinki University Central Hospital, Finnish Cultural Foundation, Oskar Oflund Foundation, Finnish Parkinson Foundation, Sigrid Juselius Foundation, the Academy of Finland, the Intramural Research Program of the National Institute on Aging, National Institutes of Health and Department of Health and Human Services; project number 1 Z01 AG000957-05. DNA panels from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds) were used in this study, as well as clinical data. The submitters that contributed samples are acknowledged in detailed descriptions of each panel: NDPT001, NDPT005, NDPT007, NDPT014, NDPT015, NDPT016, NDPT017, NDPT018, NDPT002, NDFT022, NDPT023, and NDPT024. P.T.L. and A.S. have filed a patent application concerning the results presented in a previous article [18]. NR 36 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 14 PY 2010 VL 477 IS 1 BP 1 EP 5 DI 10.1016/j.neulet.2010.04.021 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 614HG UT WOS:000279045600001 PM 20399836 ER PT J AU Biffi, A Anderson, CD Nalls, MA Rahman, R Sonni, A Cortellini, L Rost, NS Matarin, M Hernandez, DG Plourde, A de Bakker, PIW Ross, OA Greenberg, SM Furie, KL Meschia, JF Singleton, AB Saxena, R Rosand, J AF Biffi, Alessandro Anderson, Christopher D. Nalls, Michael A. Rahman, Rosanna Sonni, Akshata Cortellini, Lynelle Rost, Natalia S. Matarin, Mar Hernandez, Dena G. Plourde, Anna de Bakker, Paul I. W. Ross, Owen A. Greenberg, Steven M. Furie, Karen L. Meschia, James F. Singleton, Andrew B. Saxena, Richa Rosand, Jonathan TI Principal-Component Analysis for Assessment of Population Stratification in Mitochondrial Medical Genetics SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; DNA; DISEASE; RISK; METAANALYSIS; DIVERSITY AB Although inherited mitochondrial genetic variation can cause human disease, no validated methods exist for control of confounding due to mitochondrial population stratification (PS). We sought to identify a reliable method for PS assessment in mitochondrial medical genetics. We analyzed mitochondria' SNP data from 1513 European American individuals concomitantly genotyped with the use of a previously validated panel of 144 mitochondrial markers as well as the Affymetrix 6.0 (n = 432), Illumina 610-Quad (n = 458), or Illumina 660 (n = 623) platforms. Additional analyses were performed in 938 participants in the Human Genome Diversity Panel (HGDP) (Illumina 650). We compared the following methods for controlling for PS: haplogroup-stratified analyses, mitochondrial principal-component analysis (PCA), and combined autosomal-mitochondrial PCA. We computed mitochondria' genomic inflation factors (mtGIFs) and test statistics for simulated case-control and continuous phenotypes (10,000 simulations each) with varying degrees of correlation with mitochondria' ancestry. Results were then compared across adjustment methods. We also calculated power for discovery of true associations under each method, using a simulation approach. Mitochondria! PCA recapitulated haplogroup information, but haplogroup-stratified analyses were inferior to mitochondria' PCA in controlling for PS. Correlation between nuclear and mitochondria' principal components (PCs) was very limited. Adjustment for nuclear PCs had no effect on mitochondria' analysis of simulated phenotypes. Mitochondria! PCA performed with the use of data from commercially available genome-wide arrays correlated strongly with PCA performed with the use of an exhaustive mitochondria' marker panel. Finally, we demonstrate, through simulation, no loss in power for detection of true associations with the use of mitochondria' PCA. C1 [Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; Saxena, Richa; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; Greenberg, Steven M.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Biffi, Alessandro; Anderson, Christopher D.; Rahman, Rosanna; Sonni, Akshata; Cortellini, Lynelle; Rost, Natalia S.; Plourde, Anna; de Bakker, Paul I. W.; Saxena, Richa; Rosand, Jonathan] 7 Cambridge Ctr, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Nalls, Michael A.; Matarin, Mar; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Matarin, Mar] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. [Hernandez, Dena G.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1E 6BT, England. [Hernandez, Dena G.] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1E 6BT, England. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA. [Ross, Owen A.; Meschia, James F.] Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jrosand@partners.org RI Singleton, Andrew/C-3010-2009; Ross, Owen/D-7573-2013; de Bakker, Paul/B-8730-2009; Matarin, Mar/F-1771-2016; OI de Bakker, Paul/0000-0001-7735-7858; Matarin, Mar/0000-0002-4717-5735; Anderson, Christopher/0000-0002-0053-2002 FU American Heart Association / Bugher Foundation Centers for Stroke Prevention Research [0775010N]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; Myron and Jane Hanley Award in Stroke Research; Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine; National Institute for Neurologic Disorders and Stroke [R01NS052585, R01NS059727, 5K23NS042720, 5P50NS051343]; Fulbright Foundation; American Association of University Women; National Center for Research Resources [U54 RR020278]; NIH National Institute on Aging [Z01 AG000954-06] FX This study was funded by the American Heart Association / Bugher Foundation Centers for Stroke Prevention Research (0775010N), the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke, the Myron and Jane Hanley Award in Stroke Research, the Marriott Disease Risk and Regenerative Medicine Initiative Award in Individualized Medicine, the National Institute for Neurologic Disorders and Stroke (R01NS052585, R01NS059727, 5K23NS042720, 5P50NS051343), the Fulbright Foundation, the American Association of University Women, and the National Center for Research Resources (U54 RR020278). This research was supported in part by the Intramural Research Program of the NIH National Institute on Aging (Z01 AG000954-06). NR 29 TC 20 Z9 21 U1 3 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN 11 PY 2010 VL 86 IS 6 BP 904 EP 917 DI 10.1016/j.ajhg.2010.05.005 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 613AT UT WOS:000278948900008 PM 20537299 ER PT J AU Wu, MC Kraft, P Epstein, MP Taylor, DM Chanock, SJ Hunter, DJ Lin, XH AF Wu, Michael C. Kraft, Peter Epstein, Michael P. Taylor, Deanne M. Chanock, Stephen J. Hunter, David J. Lin, Xihong TI Powerful SNP-Set Analysis for Case-Control Genome-wide Association Studies SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MULTIPLE-TESTING CORRECTION; PROSTATE-CANCER; LINKAGE DISEQUILIBRIUM; BREAST-CANCER; MIXED MODELS; SCORE TESTS; LOCI; REGRESSION; HAPLOTYPES AB GWAS have emerged as popular tools for identifying genetic variants that are associated with disease risk. Standard analysis of a case-control GWAS involves assessing the association between each individual genotyped SNP and disease risk. However, this approach suffers from limited reproducibility and difficulties in detecting multi-SNP and epistatic effects. As an alternative analytical strategy, we propose grouping SNPs together into SNP sets on the basis of proximity to genomic features such as genes or haplotype blocks, then testing the joint effect of each SNP set. Testing of each SNP set proceeds via the logistic kernel-machine-based test, which is based on a statistical framework that allows for flexible modeling of epistatic and nonlinear SNP effects. This flexibility and the ability to naturally adjust for covariate effects are important features of our test that make it appealing in comparison to individual SNP tests and existing multimarker tests. Using simulated data based on the International HapMap Project, we show that SNP-set testing can have improved power over standard individual-SNP analysis under a wide range of settings. In particular, we find that our approach has higher power than individual-SNP analysis when the median correlation between the disease-susceptibility variant and the genotyped SNPs is moderate to high. When the correlation is low, both individual-SNP analysis and the SNP-set analysis tend to have low power. We apply SNP-set analysis to analyze the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer GWAS discovery-phase data. C1 [Kraft, Peter; Taylor, Deanne M.; Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Wu, Michael C.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Epstein, Michael P.] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lin, XH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM xlin@hsph.harvard.edu OI Wu, Michael C./0000-0002-3357-6570 FU National Institutes of Health [CA76404, CA134294, HG003618] FX This work was sponsored by National Institutes of Health grants CA76404 and CA134294 (to XL.) and HG003618 (to M.P.E.). NR 49 TC 224 Z9 236 U1 4 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN 11 PY 2010 VL 86 IS 6 BP 929 EP 942 DI 10.1016/j.ajhg.2010.05.002 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 613AT UT WOS:000278948900010 PM 20560208 ER PT J AU Zhuang, XL Chowdhury, S Northup, JK Ray, K AF Zhuang, Xiaolei Chowdhury, Shoaib Northup, John K. Ray, Kausik TI Sar1-dependent trafficking of the human calcium receptor to the cell surface SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Calcium receptor; Family-C/3 G-protein-coupled receptors; Sar1; ER exit ID HUMAN CA2+; IDENTIFICATION; TRANSPORT; DOMAIN; EXPORT AB The molecular mechanisms underlying the exit from the endoplasmic reticulum (ER) for cell surface trafficking of the human calcium receptor (hCaR) remain poorly understood. We investigated the role of the Sari small GTP-binding protein in cell surface transport of the hCaR. Disruptions of endogenous Sari function with the constitutively active Sar1H79G mutant or depletion using small interfering RNA, attenuates cell surface expression of the hCaR. Mutation of several putative di-acidic ER export motifs in the carboxyl-tail of the receptor revealed no apparent defect in cell surface expression. Truncated mutants lacking most of the carboxyl-terminal sequences or all intracellular domains also showed no impairment in cell surface expression at steady state. A truncated receptor containing only the large amino-terminal extracellular ligand-binding domain (ECD) is secreted into the culture medium and Sar1H79G inhibits this secretion. ECD receptor variants with the cysteines essential for intermolecular disulfide-linked dimerization mutated to serine or four of the asparagine sites for N-glycosylation mutated to alanine also disrupt secretion, indicating proper ECD conformation is critical for forward transport of this receptor. Published by Elsevier Inc. C1 [Zhuang, Xiaolei; Chowdhury, Shoaib; Northup, John K.; Ray, Kausik] NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Ray, K (reprint author), 5 Res Court,Room 2A11, Rockville, MD 20850 USA. EM rayk@nidcd.nih.gov FU National Institute on Deafness and Other Communication Disorders FX This research work was funded and supported by the Intramural Research Program of the National Institute on Deafness and Other Communication Disorders. NR 14 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 11 PY 2010 VL 396 IS 4 BP 874 EP 880 DI 10.1016/j.bbrc.2010.05.014 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 615HJ UT WOS:000279125100017 PM 20457124 ER PT J AU Chen, M Wang, YR Qu, AJ AF Chen, Min Wang, Yanru Qu, Aijuan TI PGC-1 alpha accelerates cytosolic Ca2+ clearance without disturbing Ca2+ homeostasis in cardiac myocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE PGC-1 alpha; Sarcoplasmic reticulum; Calcium transient; Calcium wave; SERCA2a ID SARCOPLASMIC-RETICULUM CA2+; TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; HEART-FAILURE; MITOCHONDRIAL BIOGENESIS; THERAPEUTIC TARGET; ENERGY-METABOLISM; MUSCLE; ATPASE; PGC-1; GENE AB Energy metabolism and Ca2+ handling serve critical roles in cardiac physiology and pathophysiology. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a multi-functional coactivator that is involved in the regulation of cardiac mitochondrial functional capacity and cellular energy metabolism. However, the regulation of PGC-1 alpha in cardiac Ca2+ signaling has not been fully elucidated. To address this issue, we combined confocal line-scan imaging with off-line imaging processing to characterize calcium signaling in cultured adult rat ventricular myocytes expressing PGC-1 alpha via adenoviral transduction. Our data shows that overexpressing PGC-1 alpha improved myocyte contractility without increasing the amplitude of Ca2+ transients, suggesting that myofilament sensitivity to Ca2+ increased. Interestingly, the decay kinetics of global Ca2+ transients and Ca2+ waves accelerated in PGC-1 alpha-expressing cells, but the decay rate of caffeine-elicited Ca2+ transients showed no significant change. This suggests that sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), but not Na+/Ca2+ exchange (NCX) contribute to PGC-1 alpha-induced cytosolic Ca2+ clearance. Furthermore, PGC-1 alpha induced the expression of SERCA2a in cultured cardiac myocytes. Importantly, overexpressing PGC-1 alpha did not disturb cardiac Ca2+ homeostasis, because SR Ca2+ load and the propensity for Ca2+ waves remained unchanged. These data suggest that PGC-1 alpha can ameliorate cardiac Ca2+ cycling and improve cardiac work output in response to physiological stress. Unraveling the PGC-1 alpha-calcium handing pathway sheds new light on the role of PGC-1 alpha in the therapy of cardiac diseases. (c) 2010 Elsevier Inc. All rights reserved. C1 [Chen, Min; Wang, Yanru] Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. [Chen, Min] Yunnan Ctr Dis Prevent & Control, Kunming 650022, Peoples R China. [Qu, Aijuan] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chen, M (reprint author), Peking Univ, Inst Mol Med, State Key Lab Biomembrane & Membrane Biotechnol, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. EM chenminyx@gmail.com FU National Natural Science Foundation of China [30800371] FX We acknowledge Dr. Heping Cheng for critical comments and the NIH Fellows Editorial Board for editorial assistance. This work was supported by the National Natural Science Foundation of China (30800371). NR 40 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 11 PY 2010 VL 396 IS 4 BP 894 EP 900 DI 10.1016/j.bbrc.2010.05.018 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 615HJ UT WOS:000279125100020 PM 20457122 ER PT J AU del Rey, J Prat, E Ponsa, I Lloreta, J Gelabert, A Algaba, F Camps, J Miro, R AF del Rey, Javier Prat, Esther Ponsa, Immaculada Lloreta, Josep Gelabert, Antoni Algaba, Ferran Camps, Jordi Miro, Rosa TI Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors SO BMC CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; 11Q13 AMPLIFICATION; MYCN AMPLIFICATION; URINARY-BLADDER; BREAST-CANCER; INSTABILITY; ANEUPLOIDY; CELLS; EMS1; NEUROBLASTOMA AB Background: Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Methods: Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of alpha, beta and gamma tubulin was also performed. Results: Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Conclusions: Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001). C1 [del Rey, Javier; Prat, Esther; Ponsa, Immaculada; Camps, Jordi; Miro, Rosa] Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Dept Biol Cellular Fisiol & Immunol, Bellaterra 08193, Spain. [Lloreta, Josep] Univ Pompeu Fabra, IMAS, Hosp Mar, Dept Patol, Barcelona 08003, Spain. [Gelabert, Antoni] IMAS UAB, Hosp Mar, Dept Urol, Barcelona 08003, Spain. [Algaba, Ferran] Univ Autonoma Barcelona, Dept Patol, Barcelona 08025, Spain. [Camps, Jordi] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Miro, R (reprint author), Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Dept Biol Cellular Fisiol & Immunol, Bellaterra 08193, Spain. EM rosa.miro@uab.cat RI Lloreta, J/I-2112-2014 OI Lloreta, J/0000-0003-1644-9470 FU ISCIII [FIS G03/174, SAF2007-64167, RD06/0020/1020]; Generalitat de Catalunya [RD06/0020/1020] FX The work has been supported by ISCIII: EPICUR-Red (FIS G03/174), SAF2007-64167 and RD06/0020/1020. Javier del Rey was a fellow of Generalitat de Catalunya and is supported by RD06/0020/1020. We thank The Language Advisory & Translation Unit at The Universitat Autonoma de Barcelona. NR 43 TC 8 Z9 9 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 11 PY 2010 VL 10 AR 280 DI 10.1186/1471-2407-10-280 PG 11 WC Oncology SC Oncology GA 631NV UT WOS:000280355300001 PM 20540739 ER PT J AU Lagranha, CJ Deschamps, A Aponte, A Steenbergen, C Murphy, E AF Lagranha, Claudia J. Deschamps, Anne Aponte, Angel Steenbergen, Charles Murphy, Elizabeth TI Sex Differences in the Phosphorylation of Mitochondrial Proteins Result in Reduced Production of Reactive Oxygen Species and Cardioprotection in Females SO CIRCULATION RESEARCH LA English DT Article DE gender difference; cardioprotection; mitochondria; proteomics; aldehyde dehydrogenase ID ALPHA-KETOGLUTARATE DEHYDROGENASE; ESTROGEN-RECEPTOR; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; CALORIC RESTRICTION; RAT HEARTS; IN-VIVO; ISCHEMIA; ACTIVATION; REPERFUSION AB Rationale: Although premenopausal females have a lower risk for cardiovascular disease, the mechanism(s) are poorly understood. Objective: We tested the hypothesis that cardioprotection in females is mediated by altered mitochondrial protein levels and/or posttranslational modifications. Methods and Results: Using both an in vivo and an isolated heart model of ischemia and reperfusion (I/R), we found that females had less injury than males. Using proteomic methods we found that female hearts had increased phosphorylation and activity of aldehyde dehydrogenase (ALDH) 2, an enzyme that detoxifies reactive oxygen species (ROS)-generated aldehyde adducts, and that an activator of ALDH2 reduced I/R injury in males but had no significant effect in females. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, blocked the protection and the increased phosphorylation of ALDH2 in females, but had no effect in males. Furthermore, we found an increase in phosphorylation of alpha-ketoglutarate dehydrogenase (alpha KGDH) in female hearts. alpha KGDH is a major source of ROS generation particularly with a high NADH/NAD ratio which occurs during I/R. We found decreased ROS generation in permeabilized female mitochondria given alpha KGDH substrates and NADH, suggesting that increased phosphorylation of alpha KGDH might reduce ROS generation by alpha KGDH. In support of this hypothesis, we found that protein kinase C-dependent phosphorylation of purified alpha KGDH reduced ROS generation. Additionally, myocytes from female hearts had less ROS generation following I/R than males and addition of wortmannin increased ROS generation in females to the same levels as in males. Conclusions: These data suggest that posttranslational modifications can modify ROS handling and play an important role in female cardioprotection. (Circ Res. 2010; 106: 1681-1691.) C1 [Lagranha, Claudia J.; Deschamps, Anne; Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Aponte, Angel] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Steenbergen, Charles] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Murphy, E (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr, Bethesda, MD 20892 USA. EM murphy1@mail.nih.gov OI Deschamps, Anne/0000-0001-7415-1408 FU NIH National Heart, Lung, and Blood Institute; NIH [R01-HL39752] FX Supported by the NIH National Heart, Lung, and Blood Institute intramural program. C. S. was supported by NIH grant R01-HL39752. NR 42 TC 92 Z9 94 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 11 PY 2010 VL 106 IS 11 BP 1681 EP U46 DI 10.1161/CIRCRESAHA.109.213645 PG 25 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 608VT UT WOS:000278614800004 PM 20413785 ER PT J AU Guglielmi, KM McDonald, SM Patton, JT AF Guglielmi, Kristen M. McDonald, Sarah M. Patton, John T. TI Mechanism of Intraparticle Synthesis of the Rotavirus Double-stranded RNA Genome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID BLUETONGUE VIRUS CORE; NONSTRUCTURAL PROTEIN NSP2; IN-VITRO RECONSTITUTION; MESSENGER-RNA; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; IMAGE-RECONSTRUCTION; ANGSTROM RESOLUTION; STRUCTURAL-ANALYSIS; REPLICASE PARTICLE AB Rotaviruses perform the remarkable tasks of transcribing and replicating 11 distinct double-stranded RNA genome segments within the confines of a subviral particle. Multiple viral polymerases are tethered to the interior of a particle, each dedicated to a solitary genome segment but acting in synchrony to synthesize RNA. Although the rotavirus polymerase specifically recognizes RNA templates in the absence of other proteins, its enzymatic activity is contingent upon interaction with the viral capsid. This intraparticle strategy of RNA synthesis helps orchestrate the concerted packaging and replication of the viral genome. Here, we review our current understanding of rotavirus RNA synthetic mechanisms. C1 [Guglielmi, Kristen M.; McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 FU National Institutes of Health Intramural Research Program; NIAID FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program, NIAID. This minireview will be reprinted in the 2010 Minireview Compendium, which will be available in January, 2011. NR 80 TC 21 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 2010 VL 285 IS 24 BP 18123 EP 18128 DI 10.1074/jbc.R110.117671 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 606UN UT WOS:000278453900001 PM 20351108 ER PT J AU Brocker, C Lassen, N Estey, T Pappa, A Cantore, M Orlova, VV Chavakis, T Kavanagh, KL Oppermann, U Vasiliou, V AF Brocker, Chad Lassen, Natalie Estey, Tia Pappa, Aglaia Cantore, Miriam Orlova, Valeria V. Chavakis, Triantafyllos Kavanagh, Kathryn L. Oppermann, Udo Vasiliou, Vasilis TI Aldehyde Dehydrogenase 7A1 (ALDH7A1) Is a Novel Enzyme Involved in Cellular Defense against Hyperosmotic Stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PYRIDOXINE-DEPENDENT EPILEPSY; PIPECOLIC ACID METABOLISM; CORNEAL EPITHELIAL-CELLS; TURGOR-RESPONSIVE GENE; MOLECULAR-CLONING; TISSUE DISTRIBUTION; BACULOVIRUS EXPRESSION; SEABREAM ANTIQUITIN; LIPID-PEROXIDATION; CRYSTAL-STRUCTURE AB Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese hamster ovary cells attenuated osmotic stress-induced apoptosis caused by increased extracellular concentrations of sucrose or sodium chloride. Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate specificities. Tissue distribution studies in mice showed the highest expression of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse cDNA sequences revealed mitochondrial and cytosolic transcripts that are differentially expressed in a tissue-specific manner in mice. In conclusion, ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. C1 [Brocker, Chad; Lassen, Natalie; Estey, Tia; Pappa, Aglaia; Cantore, Miriam; Vasiliou, Vasilis] Univ Colorado Denver, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, Aurora, CO 80045 USA. [Orlova, Valeria V.; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kavanagh, Kathryn L.; Oppermann, Udo] Univ Oxford, Struct Genom Consortium, Headington OX3 7DQ, England. [Oppermann, Udo] Univ Oxford, Nuffield Dept Orthoped Surg Rheumatol & Musculosk, Botnar Res Ctr, Biomed Res Unit, Oxford OX3 7LD, England. RP Vasiliou, V (reprint author), Univ Colorado Denver, Dept Pharmaceut Sci, Mol Toxicol & Environm Hlth Sci Program, C238-P15,12700 E 19th Ave, Aurora, CO 80045 USA. EM vasilis.vasiliou@ucdenver.edu RI Pappa, Aglaia/E-8663-2011; Orlova, Valeria/C-6065-2014 OI Orlova, Valeria/0000-0002-1169-2802 FU National Institutes of Health [EY11490, EY17963]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust; Oxford BIHR Biomedical Research Unit FX This work was supported, in whole or in part, by National Institutes of Health Grants EY11490 and EY17963. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. This work was also supported by the Oxford BIHR Biomedical Research Unit. Portions of this work were presented at the 48th Annual Meeting of the Society of Toxicology, Baltimore, MD, March 2009 (50). NR 65 TC 71 Z9 74 U1 2 U2 15 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 JUN 11 PY 2010 VL 285 IS 24 BP 18452 EP 18463 DI 10.1074/jbc.M109.077925 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 606UN UT WOS:000278453900039 PM 20207735 ER PT J AU Iwamoto, T Nakamura, T Doyle, A Ishikawa, M de Vega, S Fukumoto, S Yamada, Y AF Iwamoto, Tsutomu Nakamura, Takashi Doyle, Andrew Ishikawa, Masaki de Vega, Susana Fukumoto, Satoshi Yamada, Yoshihiko TI Pannexin 3 Regulates Intracellular ATP/cAMP Levels and Promotes Chondrocyte Differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-RELATED PEPTIDE; GAP-JUNCTION PROTEINS; BONE MORPHOGENETIC PROTEIN-2; PARATHYROID-HORMONE; PTH/PTHRP RECEPTOR; GROWTH-PLATE; ATDC5 CELLS; CYCLIN D1; EXPRESSION; FAMILY AB Pannexin 3 (Panx3) is a new member of the gap junction pannexin family, but its expression profiles and physiological function are not yet clear. We demonstrate in this study that Panx3 is expressed in cartilage and regulates chondrocyte proliferation and differentiation. Panx3 mRNA was expressed in the prehypertrophic zone in the developing growth plate and was induced during the differentiation of chondrogenic ATDC5 and N1511 cells. Panx3-transfected ATDC5 and N1511 cells promoted chondrogenic differentiation, but the suppression of endogenous Panx3 inhibited differentiation of ATDC5 cells and primary chondrocytes. Panx3-transfected ATDC5 cells reduced parathyroid hormone-induced cell proliferation and promoted the release of ATP into the extracellular space, possibly by action of Panx3 as a hemichannel. Panx3 expression in ATDC5 cells reduced intracellular cAMP levels and the activation of cAMP-response element-binding, a protein kinase A downstream effector. These Panx3 activities were blocked by anti-Panx3 antibody. Our results suggest that Panx3 functions to switch the chondrocyte cell fate from proliferation to differentiation by regulating the intracellular ATP/cAMP levels. C1 [Iwamoto, Tsutomu; Nakamura, Takashi; Doyle, Andrew; Ishikawa, Masaki; de Vega, Susana; Yamada, Yoshihiko] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Iwamoto, Tsutomu; Nakamura, Takashi; Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Pediat Dent, Sendai, Miyagi 9808576, Japan. RP Yamada, Y (reprint author), NIDCR, Lab Cell & Dev Biol, NIH, Bldg 30,Rm 407,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM yoshi.yamada@nih.gov RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 FU National Institutes of Health, NIDCR; Japan Society for the Promotion of Science [20791583]; Ministry of Education, Science, and Culture of Japan [20679006] FX This work was supported, in whole or in part, by a National Institutes of Health grant from Intramural Research Program of NIDCR (to Y. Y.). This work was also supported by Grant-in-aid for Research Fellows 20791583 from the Japan Society for the Promotion of Science (to T. I.) and Grant-in-aid from the Ministry of Education, Science, and Culture of Japan 20679006 (to S. F.). NR 40 TC 66 Z9 66 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 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 11 PY 2010 VL 285 IS 24 BP 18948 EP 18958 DI 10.1074/jbc.M110.127027 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 606UN UT WOS:000278453900085 PM 20404334 ER PT J AU Kotova, S Li, M Dimitriadis, EK Craigie, R AF Kotova, Svetlana Li, Min Dimitriadis, Emilios K. Craigie, Robert TI Nucleoprotein Intermediates in HIV-1 DNA Integration Visualized by Atomic Force Microscopy SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE integrase; intasome; HIV-1; DNA integration; retrovirus ID IMMUNODEFICIENCY-VIRUS INTEGRATION; RETROVIRAL DNA; IN-VITRO; CONCERTED INTEGRATION; STRAND TRANSFER; PREINTEGRATION COMPLEXES; TYPE-1 INTEGRASE; PROTEIN; ENDS; INHIBITION AB Integration of HIV-1 (human immunodeficiency virus type 1) DNA into the genome of the host cell is an essential step in the viral replication cycle that is mediated by the virally encoded integrase protein. We have used atomic force microscopy to study stable complexes formed between HIV-1 integrase and viral DNA and their interaction with host DNA. A tetramer of integrase stably bridges a pair of viral DNA ends, consistent with previous analysis by gel electrophoresis. The intasome, composed of a tetramer of integrase bridging a pair of viral DNA ends, is highly stable to high ionic strength that would strip more loosely associated integrase from internal regions of the viral DNA. We also observed tetramers of integrase associated with single viral DNA ends; time-course experiments suggest that these may be intermediates in intasome assembly. Strikingly, integrase tetramers are only observed in tight association with viral DNA ends. The self-association properties of intasomes suggest that the integrase tetramer within the intasome is different from the integrase tetramer formed at high concentration in solution in the absence of viral DNA. Finally, the integration product remains tightly bound by the integrase tetramer, but the 3' ends of the target DNA in the complex are not restrained and are free to rotate, resulting in relaxation of initially supercoiled target DNA. Published by Elsevier Ltd. C1 [Li, Min; Craigie, Robert] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Kotova, Svetlana; Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM bobc@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health; National Institutes of Health FX This work was supported by the intramural research programs of the National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health and by the National Institutes of Health AIDS Targeted Antiviral Program. NR 28 TC 32 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 11 PY 2010 VL 399 IS 3 BP 491 EP 500 DI 10.1016/j.jmb.2010.04.026 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 619PL UT WOS:000279442000013 PM 20416324 ER PT J AU French, RH Parsegian, VA Podgornik, R Rajter, RF Jagota, A Luo, J Asthagiri, D Chaudhury, MK Chiang, YM Granick, S Kalinin, S Kardar, M Kjellander, R Langreth, DC Lewis, J Lustig, S Wesolowski, D Wettlaufer, JS Ching, WY Finnis, M Houlihan, F von Lilienfeld, OA van Oss, CJ Zemb, T AF French, Roger H. Parsegian, V. Adrian Podgornik, Rudolf Rajter, Rick F. Jagota, Anand Luo, Jian Asthagiri, Dilip Chaudhury, Manoj K. Chiang, Yet-ming Granick, Steve Kalinin, Sergei Kardar, Mehran Kjellander, Roland Langreth, David C. Lewis, Jennifer Lustig, Steve Wesolowski, David Wettlaufer, John S. Ching, Wai-Yim Finnis, Mike Houlihan, Frank von Lilienfeld, O. Anatole van Oss, Carel Jan Zemb, Thomas TI Long range interactions in nanoscale science SO REVIEWS OF MODERN PHYSICS LA English DT Article ID DENSITY-FUNCTIONAL-THEORY; DER-WAALS INTERACTIONS; ATOMIC-FORCE MICROSCOPY; WALLED CARBON NANOTUBES; ELECTRICAL DOUBLE-LAYER; X-RAY REFLECTIVITY; RUTILE 110 SURFACE; DNA DOUBLE HELICES; MOLECULAR-DYNAMICS SIMULATIONS; PRESSURE NEUTRON-DIFFRACTION AB Our understanding of the "long range" electrodynamic, electrostatic, and polar interactions that dominate the organization of small objects at separations beyond an interatomic bond length is reviewed. From this basic-forces perspective, a large number of systems are described from which one can learn about these organizing forces and how to modulate them. The many practical systems that harness these nanoscale forces are then surveyed. The survey reveals not only the promise of new devices and materials, but also the possibility of designing them more effectively. C1 [French, Roger H.; Lustig, Steve] DuPont Co Inc, Cent Res, Wilmington, DE 19880 USA. [French, Roger H.] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA. [Parsegian, V. Adrian; Podgornik, Rudolf] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Podgornik, Rudolf] Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia. [Podgornik, Rudolf] J Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. [Rajter, Rick F.; Chiang, Yet-ming] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Jagota, Anand; Chaudhury, Manoj K.] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. [Jagota, Anand] Lehigh Univ, Bioengn Program, Bethlehem, PA 18015 USA. [Luo, Jian] Clemson Univ, Sch Mat Sci & Engn, Clemson, SC 29634 USA. [Asthagiri, Dilip] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Granick, Steve] Univ Illinois, Mat Res Lab, Urbana, IL 61801 USA. [Kalinin, Sergei] Oak Ridge Natl Lab, Mat Sci & Technol Div, Oak Ridge, TN 37831 USA. [Kalinin, Sergei] Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Oak Ridge, TN 37831 USA. [Kardar, Mehran] MIT, Dept Phys, Cambridge, MA 02139 USA. [Kjellander, Roland] Univ Gothenburg, Dept Chem, SE-41296 Gothenburg, Sweden. [Langreth, David C.] Rutgers State Univ, Ctr Mat Theory, Dept Phys & Astron, Piscataway, NJ 08854 USA. [Lewis, Jennifer] Univ Illinois, Frederick Seitz Mat Res Lab, Mat Sci & Engn Dept, Urbana, IL 61801 USA. [Wesolowski, David] Oak Ridge Natl Lab, Div Chem Sci, Oak Ridge, TN 37831 USA. [Wettlaufer, John S.] Yale Univ, Dept Geol & Geophys, Dept Phys, Program Appl Math, New Haven, CT 06520 USA. [Ching, Wai-Yim] Univ Missouri, Dept Phys, Kansas City, MO 64110 USA. [Finnis, Mike] Univ London Imperial Coll Sci Technol & Med, Dept Mat, London SW7 2AZ, England. [Finnis, Mike] Univ London Imperial Coll Sci Technol & Med, Dept Phys, London SW7 2AZ, England. [Houlihan, Frank] AZ Elect Mat Corp USA, Somerville, NJ 08876 USA. [von Lilienfeld, O. Anatole] Sandia Natl Labs, Multiscale Dynam Mat Modeling Dept, Albuquerque, NM 87185 USA. [van Oss, Carel Jan] SUNY Buffalo, Dept Microbiol & Immunol, Dept Chem & Biol Engn, Buffalo, NY 14260 USA. [van Oss, Carel Jan] SUNY Buffalo, Dept Geol, Buffalo, NY 14260 USA. [Zemb, Thomas] Inst Chim Separat Marcoule, UMR 5257, F-30207 Bagnols Sur Ceze, France. RP French, RH (reprint author), DuPont Co Inc, Cent Res, E400-5207 Expt Stn, Wilmington, DE 19880 USA. EM rogerhfrench@longrangeinteractions.com RI Asthagiri, Dilipkumar/A-3383-2010; Ching, Wai-Yim/B-4686-2009; Luo, Jian/A-4777-2008; von Lilienfeld, O. Anatole/D-8529-2011; French, Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008; Kjellander, Roland/A-7267-2010; Asthagiri, Dilipkumar/P-9450-2016; OI Ching, Wai-Yim/0000-0001-7738-8822; French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637; Asthagiri, Dilipkumar/0000-0001-5869-0807; Kardar, Mehran/0000-0002-1112-5912 FU NSF CAREER [DMR 0448879]; AFOSR Young Investigator award [FA9550-07-1-0125]; DOE-BES [DE-FG02- 08ER46511]; SNL Truman Program LDRD [120209]; United States Department of Energy's National Nuclear Security Administration [DE-AC04-94AL85000]; European Commission [NMP3-CT-2005-013862] FX We thank Harriet Kung, Director of Science, Office of Basic Energy Sciences (OBES) of the U.S. Department of Energy (DOE), and Frances Hellman, chairperson of the Council on Materials Science and Engineering of the Division of Materials Science and Engineering, in the OBES of the U.S. DOE and Arvind Kini of the U.S. DOE, OBES, Division of Materials Science and Engineering for sponsoring the workshop; Christie Ashton and Sophia Kitts for organizational assistance; and Barbara Brown French and Valerie Parsegian for assistance editing the manuscript. J.L. acknowledges support from an NSF CAREER award (Grant No. DMR 0448879, for studying SAFs), an AFOSR Young Investigator award (Grant No. FA9550-07-1-0125, for studying sintering and IGFs in W), and a DOE-BES grant (Grant No. DE-FG02- 08ER46511, for studying GB transitions in Si). O.A.v.L. acknowledges support from SNL Truman Program LDRD under Project No. 120209. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Co., for the United States Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000. R.P. acknowledges support from the European Commission under Contract No. NMP3-CT-2005-013862 (INCEMS). NR 493 TC 187 Z9 187 U1 22 U2 232 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0034-6861 EI 1539-0756 J9 REV MOD PHYS JI Rev. Mod. Phys. PD JUN 11 PY 2010 VL 82 IS 2 BP 1887 EP 1944 DI 10.1103/RevModPhys.82.1887 PG 58 WC Physics, Multidisciplinary SC Physics GA 609MD UT WOS:000278659800001 ER PT J AU Cassetti, MC Durbin, A Harris, E Rico-Hesse, R Roehrig, J Rothman, A Whitehead, S Natarajan, R Laughlin, C AF Cassetti, M. Cristina Durbin, Anna Harris, Eva Rico-Hesse, Rebeca Roehrig, John Rothman, Alan Whitehead, Stephen Natarajan, Ramya Laughlin, Catherine TI Report of an NIAID workshop on dengue animal models SO VACCINE LA English DT Article DE Dengue; Animal; Models ID CLINICAL LABORATORY RESPONSES; TYPE-4 VACCINE CANDIDATE; RHESUS-MONKEYS; INTERFERON RECEPTORS; VIRUS-INFECTIONS; MICE LACKING; MOUSE MODEL; T-CELLS; ANTIBODY; PATHOGENESIS AB Dengue is a mosquito-borne viral disease of humans that has re-emerged in many parts of the world and has become an important international public health threat. Dengue incidence and geographical spread has dramatically increased in the last few decades and is now affecting most tropical and sub-tropical regions of the world. Despite extensive research efforts for several decades, no vaccines or therapeutics are currently available to prevent and treat dengue infections. One of the main obstacles to the development of countermeasures has been the lack of good animal models that recapitulate dengue pathogenesis in humans and reliably predict the safety and efficacy of countermeasures against dengue. In September 2008, the National Institute of Allergy and Infectious Diseases (NIAID) held a workshop to consider the current state-of-the-art developments in animal models for dengue and discuss strategies to accelerate progress in this field. This report summarizes the main discussions and recommendations that resulted from the meeting. C1 [Cassetti, M. Cristina; Whitehead, Stephen; Natarajan, Ramya; Laughlin, Catherine] NIAID, Bethesda, MD 20892 USA. [Durbin, Anna] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Harris, Eva] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Rico-Hesse, Rebeca] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Roehrig, John] Ctr Dis Control, Div Vector Borne Infect Dis, Ft Collins, CO 80522 USA. [Rothman, Alan] Univ Massachusetts, Sch Med, Worcester, MA USA. RP Laughlin, C (reprint author), NIAID, 6610 Rockledge Dr, Bethesda, MD 20892 USA. EM ccassetti@niaid.nih.gov RI Rico-Hesse, Rebeca/C-5294-2011; OI Rico-Hesse, Rebeca/0000-0001-6216-1000; Roehrig, John/0000-0001-7581-0479; Rothman, Alan/0000-0002-4064-6848 FU NIH Office of Rare Diseases FX This workshop was partially supported by the NIH Office of Rare Diseases. We would like to thank Mason Booth, Katrina Gross, Syreeta Tate-Jones and Denise Cinquegrana for their professional support with the workshop logistics. We would also like to thank Drs. Mark Challberg, Patricia Repik and Christopher Beisel for helpful discussions. NR 44 TC 39 Z9 40 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 11 PY 2010 VL 28 IS 26 BP 4229 EP 4234 DI 10.1016/j.vaccine.2010.04.045 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 615IA UT WOS:000279127000001 PM 20434551 ER PT J AU Stender, S Frikke-Schmidt, R Sethi, AA Nordestgaard, BG Tybjaerg-Hansen, A AF Stender, S. Frikke-Schmidt, R. Sethi, A. A. Nordestgaard, B. G. Tybjaerg-Hansen, A. TI GENETIC VARIATION IN LIVER X RECEPTOR ALPHA AND RISK OF ISCHEMIC VASCULAR DISEASE IN THE GENERAL POPULATION SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 78th Congress of the European-Atherosclerosis-Society CY JUN 20-23, 2010 CL Hamburg, GERMANY SP European Atherosclerosis Soc C1 [Stender, S.; Frikke-Schmidt, R.; Tybjaerg-Hansen, A.] Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark. [Sethi, A. A.] Natl Inst Hlth, Natl Heart Lung & Blood Inst, Vasc Med Branch, Lipoprotein Metab Sect, Bethesda, MD USA. [Nordestgaard, B. G.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN 10 PY 2010 VL 11 IS 2 MA W38 BP 8 EP 9 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613IJ UT WOS:000278972300039 ER PT J AU Sviridov, D D'Souza, W Stonik, JA Murphy, A Demosky, SJ Sethi, AA Chin-Dusting, J Remaley, AT AF Sviridov, D. D'Souza, W. Stonik, J. A. Murphy, A. Demosky, S. J. Sethi, A. A. Chin-Dusting, J. Remaley, A. T. TI STRUCTURE-FUNCTION RELATIONSHIPS OF APOLIPOPROTEIN A-I MIMETIC PEPTIDES: IMPLICATIONS FOR ANTI-ATHEROGENIC ACTIVITIES OF HIGH DENSITY LIPOPROTEIN SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 78th Congress of the European-Atherosclerosis-Society CY JUN 20-23, 2010 CL Hamburg, GERMANY SP European Atherosclerosis Soc C1 [Sviridov, D.; D'Souza, W.; Murphy, A.; Chin-Dusting, J.] Baker Heart & Diabet Inst, Melbourne, Vic, Australia. [Stonik, J. A.; Demosky, S. J.; Sethi, A. A.; Remaley, A. T.] NHLBI, NIH, Lipoprotein Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN 10 PY 2010 VL 11 IS 2 MA P288 BP 78 EP 78 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 613IJ UT WOS:000278972300355 ER PT J AU Barrett, J Melenhorst, JJ AF Barrett, John Melenhorst, J. Joseph TI Minor histocompatibility antigen discovery: turning up the HEATR SO BLOOD LA English DT Editorial Material ID IMMUNOTHERAPY; LEUKEMIA; TARGETS; CELLS C1 [Barrett, John; Melenhorst, J. Joseph] NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NIH, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 10 PY 2010 VL 115 IS 23 BP 4630 EP 4631 PG 3 WC Hematology SC Hematology GA 609DS UT WOS:000278635900006 ER PT J AU Wang, SS Abdou, AM Morton, LM Thomas, R Cerhan, JR Gao, XJ Cozen, W Rothman, N Davis, S Severson, RK Bernstein, L Hartge, P Carrington, M AF Wang, Sophia S. Abdou, Amr M. Morton, Lindsay M. Thomas, Rasmi Cerhan, James R. Gao, Xiaojiang Cozen, Wendy Rothman, Nathaniel Davis, Scott Severson, Richard K. Bernstein, Leslie Hartge, Patricia Carrington, Mary TI Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology SO BLOOD LA English DT Article ID CHRONIC HEPATITIS-B; NECROSIS-FACTOR TNF; HETEROZYGOTE ADVANTAGE; INTERLYMPH-CONSORTIUM; GENETIC-VARIANTS; RISK; HLA; ASSOCIATION; SUSCEPTIBILITY; POLYMORPHISMS AB Genome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes. (Blood. 2010;115(23):4820-4823) C1 [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Abdou, Amr M.; Thomas, Rasmi; Gao, Xiaojiang; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD USA. [Morton, Lindsay M.; Rothman, Nathaniel; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA. [Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. [Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Davis, Scott] Univ Washington, Seattle, WA 98195 USA. [Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. [Severson, Richard K.] Karmanos Canc Inst, Detroit, MI USA. [Carrington, Mary] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Carrington, Mary] Harvard Univ, Boston, MA 02115 USA. RP Wang, SS (reprint author), City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. EM sowang@coh.org RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Abdou, Amr/0000-0002-3373-2406; Cerhan, James/0000-0002-7482-178X FU NIH (National Cancer Institute [NCI]) [HHSN261200800001E]; Public Health Service (PHS) [N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105]; NIH, NCI, Center for Cancer Research FX The NCI-SEER study was supported by the Intramural Research Program of the NIH (National Cancer Institute [NCI]), and by Public Health Service (PHS) contracts N01-PC-65064, N01-PC-67008, N01-PC-67009, N01-PC-67010, and N02-PC-71105. HLA typing for the study was funded in part with federal funds from the NCI, NIH, under contract no. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 20 TC 37 Z9 41 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 10 PY 2010 VL 115 IS 23 BP 4820 EP 4823 DI 10.1182/blood-2010-01-266775 PG 4 WC Hematology SC Hematology GA 609DS UT WOS:000278635900029 PM 20385791 ER PT J AU Yao, HH Yang, YJ Kim, KJ Bethel-Brown, C Gong, N Funa, K Gendelman, HE Su, TP Wang, JQ Buch, S AF Yao, Honghong Yang, Yanjing Kim, Kee Jun Bethel-Brown, Crystal Gong, Nan Funa, Keiko Gendelman, Howard E. Su, Tsung-Ping Wang, John Q. Buch, Shilpa TI Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration SO BLOOD LA English DT Article ID BLOOD-BRAIN-BARRIER; HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; PROTEIN-KINASE-C; CHEMOATTRACTANT PROTEIN-1; ENDOTHELIAL-CELLS; CHEMOKINE RECEPTORS; SIGNALING PATHWAYS; HIV-1 INVASION; COCAINE AB Cocaine abuse hastens the neurodegeneration often associated with advanced HIV-1 infection. The mechanisms, in part, revolve around the neuroinflammatory processes mediated by the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2). Understanding factors that modulate MCP-1 and, in turn, facilitate monocyte extravasation in the brain is thus of paramount importance. We now demonstrate that cocaine induces MCP-1 in rodent microglia through translocation of the sigma receptor to the lipid raft microdomains of the plasma membrane. Sequential activation of Src, mitogenactivated protein kinases (MAPKs), and phosphatidylinositol-3' kinase (PI3K)/Akt and nuclear factor kappa B (NF-kappa B) pathways resulted in increased MCP-1 expression. Furthermore, conditioned media from cocaine-exposed microglia increased monocyte transmigration, and thus was blocked by antagonists for CCR2 or sigma receptor. These findings were corroborated by demonstrating increased monocyte transmigration in mice exposed to cocaine, which was attenuated by pretreatment of mice with the sigma receptor antagonist. Interestingly, cocaine-mediated transmigratory effects were not observed in CCR2 knockout mice. We conclude that cocaine-mediated induction of MCP-1 accelerates monocyte extravasation across the endothelium. Understanding the regulation of MCP-1 expression and functional changes by cocaine/sigma receptor system may provide insights into the development of potential therapeutic targets for HIV-1-associated neurocognitive disorders. (Blood. 2010;115(23):4951-4962) C1 [Yao, Honghong; Yang, Yanjing; Bethel-Brown, Crystal; Gong, Nan; Gendelman, Howard E.; Buch, Shilpa] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA. [Kim, Kee Jun] Univ Kansas, Dept Microbiol Mol Genet & Immunol, Kansas City, KS USA. [Funa, Keiko] Univ Gothenburg, Gothenburg, Sweden. [Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, IRP,NIH, Baltimore, MD USA. [Wang, John Q.] Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. RP Buch, S (reprint author), Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, 985880 Nebraska Med Ctr,DRC 8011, Omaha, NE 68198 USA. EM sbuch@unmc.edu OI Buch, Shilpa/0000-0002-3103-6685 FU National Institutes of Health [MH-068212, DA020392, DA023397, DA024442, DA027729] FX This work was supported by grants MH-068212, DA020392, DA023397, DA024442, and DA027729 from the National Institutes of Health (S.B.) in addition to the Nebraska Tobacco Settlement Biomedical Research. NR 49 TC 68 Z9 69 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 10 PY 2010 VL 115 IS 23 BP 4951 EP 4962 DI 10.1182/blood-2010-01-266221 PG 12 WC Hematology SC Hematology GA 609DS UT WOS:000278635900045 PM 20354174 ER PT J AU Moore, AB Yu, L Swartz, CD Zheng, XL Wang, L Castro, L Kissling, GE Walmer, DK Robboy, SJ Dixon, D AF Moore, Alicia B. Yu, Linda Swartz, Carol D. Zheng, Xaiolin Wang, Lu Castro, Lysandra Kissling, Grace E. Walmer, David K. Robboy, Stanley J. Dixon, Darlene TI Human uterine leiomyoma-derived fibroblasts stimulate uterine leiomyoma cell proliferation and collagen type I production, and activate RTKs and TGF beta receptor signaling in coculture SO CELL COMMUNICATION AND SIGNALING LA English DT Article ID SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-BETA; GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; OXYTOCIN RECEPTOR; TUMOR-GROWTH; INSULIN-LIKE; DIFFERENTIAL EXPRESSION; EXTRACELLULAR-MATRIX; FUNCTIONAL-ANALYSIS AB Background: Uterine leiomyomas (fibroids) are benign smooth muscle tumors that often contain an excessive extracellular matrix (ECM). In the present study, we investigated the interactions between human uterine leiomyoma (UtLM) cells and uterine leiomyoma-derived fibroblasts (FB), and their importance in cell growth and ECM protein production using a coculture system. Results: We found enhanced cell proliferation, and elevated levels of ECM collagen type I and insulin-like growth factor-binding protein-3 after coculturing. There was also increased secretion of vascular endothelial growth factor, epidermal growth factor, fibroblast growth factor-2, and platelet derived growth factor A and B in the media of UtLM cells cocultured with FB. Protein arrays revealed increased phosphorylated receptor tyrosine kinases (RTKs) of the above growth factor ligands, and immunoblots showed elevated levels of the RTK downstream effector, phosphomitogen activated protein kinase 44/42 in cocultured UtLM cells. There was also increased secretion of transforming growth factor-beta 1 and 3, and immunoprecipitated transforming growth factor-beta receptor I from cocultured UtLM cells showed elevated phosphoserine expression. The downstream effectors phospho-small mothers against decapentaplegic -2 and -3 protein (SMAD) levels were also increased in cocultured UtLM cells. However, none of the above effects were seen in normal myometrial cells cocultured with FB. The soluble factors released by tumor-derived fibroblasts and/or UtLM cells, and activation of the growth factor receptors and their pathways stimulated the proliferation of UtLM cells and enhanced the production of ECM proteins. Conclusions: These data support the importance of interactions between fibroid tumor cells and ECM fibroblasts in vivo, and the role of growth factors, and ECM proteins in the pathogenesis of uterine fibroids. C1 [Moore, Alicia B.; Yu, Linda; Zheng, Xaiolin; Wang, Lu; Castro, Lysandra; Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,DHHS, Res Triangle Pk, NC 27709 USA. [Swartz, Carol D.] Integrated Syst Lab Inc, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Walmer, David K.; Robboy, Stanley J.] Duke Univ, DUMC, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Robboy, Stanley J.] Duke Univ, DUMC, Dept Pathol, Durham, NC 27710 USA. RP Dixon, D (reprint author), NIEHS, Cellular & Mol Pathol Branch, Natl Toxicol Program, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU NIH, NIEHS FX The authors would like to thank Dr. Gordon Flake and Ms. Retha Newbold for their critical review of this manuscript, and Ms. Eli Ney for her expert assistance with digital imaging. We would also like to thank Dr. Carl Bortner for his expertise with flow cytometry. This research was supported by the Intramural Research Program of the NIH, NIEHS. NR 45 TC 18 Z9 19 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-811X J9 CELL COMMUN SIGNAL JI Cell Commun. Signal. PD JUN 10 PY 2010 VL 8 AR 10 DI 10.1186/1478-811X-8-10 PG 12 WC Cell Biology SC Cell Biology GA 626EK UT WOS:000279948800001 PM 20537183 ER PT J AU Shatz, M Lustig, G Reich, R Liscovitch, M AF Shatz, Maria Lustig, Gila Reich, Reuven Liscovitch, Mordechai TI Caveolin-1 mutants P132L and Y14F are dominant negative regulators of invasion, migration and aggregation in H1299 lung cancer cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Cancer; Caveolin-1; Cell migration; Focal adhesions; Matrix invasiveness; Survival signaling ID FOCAL ADHESION KINASE; HUMAN BREAST-CANCER; TYROSINE PHOSPHORYLATION; PROSTATE-CANCER; MEMBRANE DOMAINS; UP-REGULATION; IN-VIVO; MATRIX METALLOPROTEINASES; ACTIN CYTOSKELETON; CYCLE PROGRESSION AB Caveolin-1 is an essential protein constituent of caveolae. Accumulating evidence indicates that caveolin-1 may act as a positive regulator of cancer progression. In this study, we investigated the function of caveolin-1 in human lung cancer cells. Caveolin-1 knockdown inhibited cell proliferation and reduced focal adhesion kinase (Fak) phosphorylation. Matrix invasion and cell migration as well as expression and activity of matrix metalloproteases were attenuated following caveolin-1 RNAi-mediated knockdown or overexpression of Y14F and P132L mutants, demonstrating dominant-negative activity of these mutants. Time-lapse fluorescence microscopy revealed that caveolin-1 and its mutants P132L and Y14F are localized to the trailing edge of migrating cells during both random and directed cell movement, implying an active role of caveolin-1 in the migration process. Suppression of caveolin-1 function greatly elevated the percentage of H1299 cells exhibiting focal adhesions. In addition, cell aggregation was increased by wild type caveolin-1 and attenuated by both P132L and Y14F mutants. Overexpression of wild type caveolin-1 increased caveolae density, however, P132L and Y14F mutants did not affect caveolae formation, suggesting that in this respect that the mutants do not act in a dominant negative manner, and that effects of caveolin-1 on caveolae and cell invasion, migration, focal adhesion and aggregation, are separable. Our data provide novel mechanistic insights into the role of caveolin-1 in cell motility, invasiveness and aggregation, therefore, expanding our understanding of the tumor-promoting activities of caveolin-1 in advanced-stage cancer. (c) 2010 Elsevier Inc. All rights reserved. C1 [Shatz, Maria; Lustig, Gila; Liscovitch, Mordechai] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. [Reich, Reuven] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Pharmacol & Expt Therapeut, IL-91120 Jerusalem, Israel. RP Shatz, M (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM shatzm@niehs.nih.gov FU Philip Morris USA Inc.; Philip Morris International; Winner Family Center for Vascular Biology FX The authors are grateful to Dr. Ilana Sabanay and Dr. Alex Sigal for assistance in electron and time-lapse microscopy. We thank Prof. Richard Pagano and Dr. Christoph Lorra for providing reagents, Prof. Alexander Bershadsky for stimulating discussions and Dr. Igor Shats for critical reading of the manuscript. Research described in this article was supported by Philip Morris USA Inc. and Philip Morris International, and by the Winner Family Center for Vascular Biology. Professor Mordechai Liscovitch was the incumbent of the Harold L Corda Professorial Chair in Biology. He passed away shortly after this manuscript was ready for submission. NR 70 TC 12 Z9 13 U1 0 U2 10 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2010 VL 316 IS 10 BP 1748 EP 1762 DI 10.1016/j.yexcr.2010.02.006 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 606JY UT WOS:000278422500009 PM 20153318 ER PT J AU Saba, E Grivel, JC Vanpouille, C Lisco, A Margolis, L AF Saba, E. Grivel, J. C. Vanpouille, C. Lisco, A. Margolis, L. TI HIV-1 infection of cervico-vaginal tissue ex vivo SO INFECTION LA English DT Meeting Abstract C1 [Saba, E.; Grivel, J. C.; Vanpouille, C.; Lisco, A.; Margolis, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Program Phys Biol, Bethesda, MD USA. [Saba, E.] IRCCS San Raffaele, Unita Immunopatogenesi AIDS, Milan, Italy. [Saba, E.] Univ Vita Salute San Raffaele, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD JUN 10 PY 2010 VL 38 SU 1 BP 39 EP 39 PG 1 WC Infectious Diseases SC Infectious Diseases GA 613UM UT WOS:000279007400057 ER PT J AU Batchelor, TT Duda, DG di Tomaso, E Ancukiewicz, M Plotkin, SR Gerstner, E Eichler, AF Drappatz, J Hochberg, FH Benner, T Louis, DN Cohen, KS Chea, H Exarhopoulos, A Loeffler, JS Moses, MA Ivy, P Sorensen, AG Wen, PY Jain, RK AF Batchelor, Tracy T. Duda, Dan G. di Tomaso, Emmanuelle Ancukiewicz, Marek Plotkin, Scott R. Gerstner, Elizabeth Eichler, April F. Drappatz, Jan Hochberg, Fred H. Benner, Thomas Louis, David N. Cohen, Kenneth S. Chea, Houng Exarhopoulos, Alexis Loeffler, Jay S. Moses, Marsha A. Ivy, Percy Sorensen, A. Gregory Wen, Patrick Y. Jain, Rakesh K. TI Phase II Study of Cediranib, an Oral Pan-Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent Glioblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTIANGIOGENIC THERAPY; BRAIN-TUMORS; COLORECTAL-CANCER; RESPONSE CRITERIA; MALIGNANT GLIOMA; CLINICAL-TRIALS; ANGIOGENESIS; NORMALIZATION; BEVACIZUMAB; PROGRESSION AB Purpose Glioblastoma is an incurable solid tumor characterized by increased expression of vascular endothelial growth factor (VEGF). We performed a phase II study of cediranib in patients with recurrent glioblastoma. Methods Cediranib, an oral pan-VEGF receptor tyrosine kinase inhibitor, was administered (45 mg/d) until progression or unacceptable toxicity to patients with recurrent glioblastoma. The primary end point was the proportion of patients alive and progression free at 6 months (APF6). We performed magnetic resonance imaging (MRI) and plasma and urinary biomarker evaluations at multiple time points. Results Thirty-one patients with recurrent glioblastoma were accrued. APF6 after cediranib was 25.8%. Radiographic partial responses were observed by MRI in 17 (56.7%) of 30 evaluable patients using three-dimensional measurements and in eight (27%) of 30 evaluable patients using two-dimensional measurements. For the 15 patients who entered the study taking corticosteroids, the dose was reduced (n = 10) or discontinued (n = 5). Toxicities were manageable. Grade 3/4 toxicities included hypertension (four of 31; 12.9%); diarrhea (two of 31; 6.4%); and fatigue (six of 31; 19.4%). Fifteen (48.4%) of 31 patients required at least one dose reduction and 15 patients required temporary drug interruptions due to toxicity. Drug interruptions were not associated with outcome. Changes in plasma placental growth factor, basic fibroblast growth factor, matrix metalloproteinase (MMP) -2, soluble VEGF receptor 1, stromal cell-derived factor-1 alpha, and soluble Tek/Tie2 receptor and in urinary MMP-9/neutrophil gelatinase-associated lipocalin activity after cediranib were associated with radiographic response or survival. Conclusion Cediranib monotherapy for recurrent glioblastoma is associated with encouraging proportions of radiographic response, 6-month progression-free survival, and a steroid-sparing effect with manageable toxicity. We identified early changes in circulating molecules as potential biomarkers of response to cediranib. The efficacy of cediranib and the predictive value of these candidate biomarkers will be explored in prospective trials. J Clin Oncol 28:2817-2823. (C) 2010 by American Society of Clinical Oncology C1 [Batchelor, Tracy T.] Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Vasc Biol Program, Boston, MA 02115 USA. MIT, AA Martinos Ctr Biomed Imaging, Div Hlth Sci & Technol, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Stephen E & Catherine Pappas Ctr Neurooncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM tbatchelor@partners.org FU National Institutes of Health [R21-CA117079, K24-CA125440, R01-CA129371, P01-CA80124, R01-CA115767, M01-RR-01066, P41-RR014075, R01-CA118764, P01-CA455481]; Federal Share/National Cancer Institute Proton Beam Program Income [1UL1RR025758-01]; Harvard Clinical and Translational Science Center, National Center for Research Resources; Montesi Family Research Fund; Simches Fund for Brain Tumor Research FX Supported by Grants No. R21-CA117079, K24-CA125440, R01-CA129371, P01-CA80124, R01-CA115767, M01-RR-01066, P41-RR014075, R01-CA118764, and P01-CA455481 from the National Institutes of Health; by grants from the Federal Share/National Cancer Institute Proton Beam Program Income; by Grant No. 1UL1RR025758-01 from the Harvard Clinical and Translational Science Center, National Center for Research Resources; and by gifts from the Montesi Family Research Fund and the Simches Fund for Brain Tumor Research. NR 43 TC 272 Z9 277 U1 1 U2 20 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 JUN 10 PY 2010 VL 28 IS 17 BP 2817 EP 2823 DI 10.1200/JCO.2009.26.3988 PG 7 WC Oncology SC Oncology GA 608AA UT WOS:000278548000003 PM 20458050 ER PT J AU Rini, BI Garcia, JA Cooney, MM Elson, P Tyler, A Beatty, K Bokar, J Ivy, P Chen, HX Dowlati, A Dreicer, R AF Rini, Brian I. Garcia, Jorge A. Cooney, Matthew M. Elson, Paul Tyler, Allison Beatty, Kristi Bokar, Joseph Ivy, Percy Chen, Helen X. Dowlati, Afshin Dreicer, Robert TI Toxicity of Sunitinib Plus Bevacizumab in Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID THROMBOTIC MICROANGIOPATHY; INTERFERON-ALPHA; CANCER; PACLITAXEL; INHIBITION; TRIAL C1 [Rini, Brian I.; Garcia, Jorge A.; Elson, Paul; Tyler, Allison; Dreicer, Robert] Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. [Cooney, Matthew M.; Beatty, Kristi; Bokar, Joseph; Dowlati, Afshin] Case Western Reserve Univ, Ireland Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Ivy, Percy; Chen, Helen X.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Rini, BI (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Cleveland, OH 44106 USA. NR 12 TC 31 Z9 31 U1 0 U2 0 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 JUN 10 PY 2010 VL 28 IS 17 BP E284 EP E285 DI 10.1200/JCO.2009.27.1759 PG 2 WC Oncology SC Oncology GA 608AA UT WOS:000278548000026 PM 20439632 ER PT J AU Maruoka, H Barrett, MO Ko, HJ Tosh, DK Melman, A Burianek, LE Balasubramanian, R Berk, B Costanzi, S Harden, TK Jacobson, KA AF Maruoka, Hiroshi Barrett, Matthew O. Ko, Hyojin Tosh, Dilip K. Melman, Artem Burianek, Lauren E. Balasubramanian, Ramachandran Berk, Barkin Costanzi, Stefano Harden, T. Kendall Jacobson, Kenneth A. TI Pyrimidine Ribonucleotides with Enhanced Selectivity as P2Y(6) Receptor Agonists: Novel 4-Alkyloxyimino, (S)-Methanocarba, and 5 '-Triphosphate gamma-Ester Modifications SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID STIMULATES INSULIN-SECRETION; NUCLEOTIDE RECEPTORS; DERIVATIVES; ACTIVATION; URACIL; CELLS; UDP; PHARMACOLOGY; APOPTOSIS; POTENCY AB The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC50 = 0.30 mu M). We compared and combined modifications to enhance P2Y(6) receptor agonist selectivity, including ribose ring constraint, 5-iodo and 4-alkyloxyimino modifications, and phosphate modifications such as alpha,beta-methylene and extension of the terminal phosphate group into gamma-esters of UTP analogues. The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC50 = 0.042 mu M). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide. N-4-Benzyloxy-CDP (15, MRS2964) and N-4-methoxy-Cp3U Cp3U (12, MRS2957) were potent, selective P2Y(6) receptor agonists (EC50 of 0.026 and 0.012 mu M, respectively). A hydrophobic binding region near the nucleobase was explored with receptor modeling and docking. UTP-gamma-aryl and cycloalkyl phosphoesters displayed only intermediate P2Y(6) receptor potency but had enhanced stability in acid and cell membranes. UTP-glucose was inactive, but its (S)-methanocarba analogue and N-4-methoxycytidine 5'-triphospho-gamma-[1]glucose were active (EC50 of 2.47 and 0.18 mu M, respectively). Thus, the potency, selectivity, and stability of pyrimidine nucleotides as P2Y(6) receptor agonists may be enhanced by modest structural changes. C1 [Maruoka, Hiroshi; Ko, Hyojin; Tosh, Dilip K.; Melman, Artem; Balasubramanian, Ramachandran; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Barrett, Matthew O.; Burianek, Lauren E.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC USA. [Berk, Barkin; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Berk, Barkin] Yeditepe Univ, Istanbul, Turkey. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; berk, barkin/P-2088-2014; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU NIH; NIDDK; National Institute of General Medical Sciences [GM38213] FX Mass spectral measurements were performed by Dr. Noel Whittaker and NM R measurements by Wesley White and Dr. Hemian Yeh (NI DDK). We thank Dr. Andrei A. Ivanov (NIDDK) for helpful discussions and Rhonda Carter for technical assistance. This research was supported in part by the Intramural Research Program of the NIH, NIDDK, and NIH extramural Grant GM38213 from the National Institute of General Medical Sciences. NR 37 TC 17 Z9 17 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 10 PY 2010 VL 53 IS 11 BP 4488 EP 4501 DI 10.1021/jm100287t PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 604SK UT WOS:000278298600015 PM 20446735 ER PT J AU Leopold, DA AF Leopold, David A. TI NEUROSCIENCE fMRI under the spotlight SO NATURE LA English DT Editorial Material ID SIGNALS C1 NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Leopold, DA (reprint author), NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 FU Intramural NIH HHS [ZIA MH002838-06, ZIC MH002899-04] NR 10 TC 7 Z9 7 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 10 PY 2010 VL 465 IS 7299 BP 700 EP 701 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608AM UT WOS:000278551800028 PM 20535195 ER PT J AU Drayna, D AF Drayna, Dennis TI Genetic Susceptibility to Persistent Stuttering REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Drayna, D (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM drayna@nidcd.nih.gov NR 3 TC 0 Z9 0 U1 2 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 2010 VL 362 IS 23 BP 2227 EP 2227 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 608AL UT WOS:000278551500019 ER PT J AU Malozowski, S AF Malozowski, Saul TI Lasofoxifene for Postmenopausal Women with Osteoporosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Malozowski, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM sm007@nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 10 PY 2010 VL 362 IS 23 BP 2227 EP 2227 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 608AL UT WOS:000278551500020 PM 20558377 ER PT J AU Shumay, E Fowler, JS Volkow, ND AF Shumay, Elena Fowler, Joanna S. Volkow, Nora D. TI Genomic Features of the Human Dopamine Transporter Gene and Its Potential Epigenetic States: Implications for Phenotypic Diversity SO PLOS ONE LA English DT Article ID MESSENGER-RNA EXPRESSION; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TANDEM REPEATS; SEGMENTAL DUPLICATIONS; SYNAPTIC PLASTICITY; ALCOHOL DEPENDENCE; DNA METHYLATION; PROMOTER ARCHITECTURE; TRANSCRIPTION FACTORS AB Human dopamine transporter gene (DAT1 or SLC6A3) has been associated with various brain-related diseases and behavioral traits and, as such, has been investigated intensely in experimental- and clinical-settings. However, the abundance of research data has not clarified the biological mechanism of DAT regulation; similarly, studies of DAT genotype-phenotype associations yielded inconsistent results. Hence, our understanding of the control of the DAT protein product is incomplete; having this knowledge is critical, since DAT plays the major role in the brain's dopaminergic circuitry. Accordingly, we reevaluated the genomic attributes of the SLC6A3 gene that might confer sensitivity to regulation, hypothesizing that its unique genomic characteristics might facilitate highly dynamic, region-specific DAT expression, so enabling multiple regulatory modes. Our comprehensive bioinformatic analyzes revealed very distinctive genomic characteristics of the SLC6A3, including high inter-individual variability of its sequence (897 SNPs, about 90 repeats and several CNVs spell out all abbreviations in abstract) and pronounced sensitivity to regulation by epigenetic mechanisms, as evident from the GC-bias composition (0.55) of the SLC6A3, and numerous intragenic CpG islands (27 CGIs). We propose that this unique combination of the genomic features and the regulatory attributes enables the differential expression of the DAT1 gene and fulfills seemingly contradictory demands to its regulation; that is, robustness of region-specific expression and functional dynamics. C1 [Shumay, Elena; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, NIH, Bethesda, MD USA. RP Shumay, E (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. EM eshumay@bnl.gov; fowler@bnl.gov; nvolkow@nida.nih.gov FU Department of Energy, Office of Biological and Environmental Research; National Institute on Drug Abuse [KO1 DA025280-01A1, K05 DA20001]; NIH FX This work was performed at Brookhaven National Laboratory with infrastructure support from the Department of Energy, Office of Biological and Environmental Research and funded by the National Institute on Drug Abuse, grants KO1 DA025280-01A1 (ES), K05 DA20001 (JSF) and NIH Intramural Research Program, NIDA (NDV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 148 TC 21 Z9 21 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 10 PY 2010 VL 5 IS 6 AR e11067 DI 10.1371/journal.pone.0011067 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608QA UT WOS:000278599600023 PM 20548783 ER PT J AU Torchia, MLG Ciaglia, E Masci, AM Vitiello, L Fogli, M la Sala, A Mavilio, D Racioppi, L AF Torchia, Maria Letizia Giardino Ciaglia, Elena Masci, Anna Maria Vitiello, Laura Fogli, Manuela la Sala, Andrea Mavilio, Domenico Racioppi, Luigi TI Dendritic Cells/Natural Killer Cross-Talk: A Novel Target for Human Immunodeficiency Virus Type-1 Protease Inhibitors SO PLOS ONE LA English DT Article ID ATHEROSCLEROTIC LESION FORMATION; HIV-1 PROTEASE; ANTIRETROVIRAL THERAPY; NK CELLS; T-CELLS; INFECTION; MACROPHAGES; DIFFERENTIATION; DYSLIPIDEMIA; ANTIFUNGAL AB Background: HIV-1 Protease Inhibitors, namely PIs, originally designed to inhibit HIV-1 aspartic protease, can modulate the immune response by mechanisms largely unknown, and independent from their activity on viral replication. Here, we analyzed the ability of PIs to interfere with differentiation program of monocytes toward dendritic cell (DCs) lineage, a key process in the inflammatory response. Methodology/Principal Findings: Monocytes from healthy donors were isolated and induced to differentiate in vitro in the presence or absence of saquinavir, ritonavir, nelfinavir, indinavir or amprenavir (sqv, rtv, nlfv, idv, apv, respectively). These drugs demonstrated a differential ability to sustain the generation of immature DCs (iDCs) with an altered phenotype, including low levels of CD1a, CD86, CD36 and CD209. DCs generated in the presence of rtv also failed to acquire the typical phenotype of mature DCs (mDCs), and secreted lower amounts of IL-12 and IL-15. Accordingly, these aberrant mDCs failed to support activation of autologous Natural Killer (NK) cells, and resulted highly susceptible to NK cell-mediated cytotoxicity. Conclusions/Significance: Our findings uncover novel functional properties of PIs within the DC-NK cell cross-talk, unveiling the heterogeneous ability of members of this class drugs to drive the generation of atypical monocyte-derived DCs (MDDCs) showing an aberrant phenotype, a failure to respond appropriately to bacterial endotoxin, a weak ability to prime autologous NK cells, and a high susceptibility to NK cell killing. These unexpected properties might contribute to limit inflammation and viral spreading in HIV-1 infected patients under PIs treatment, and open novel therapeutical perspectives for this class drugs as immunomodulators in autoimmunity and cancer. C1 [Torchia, Maria Letizia Giardino; Ciaglia, Elena; Masci, Anna Maria; Vitiello, Laura; Racioppi, Luigi] Univ Naples Federico 2, Dept Cellular & Mol Biol & Pathol, Naples, Italy. [Masci, Anna Maria; Vitiello, Laura; la Sala, Andrea] IRCCS San Raffaele Pisana, Dept Med Sci & Rehabil, Lab Mol & Cellular Immunol, Rome, Italy. [Fogli, Manuela] Univ Brescia, Microbiol Sect, Dept Expt & Appl Med, Brescia, Italy. [Mavilio, Domenico] Ist Clin Humanitas, IRCCS, Clin & Expt Immunol Lab, Milan, Italy. [Racioppi, Luigi] Univ Naples Federico 2, CISI, Naples, Italy. RP Torchia, MLG (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM racioppi@unina.it RI la Sala, Andrea/A-3228-2009; vitiello, laura/G-7326-2014; OI la Sala, Andrea/0000-0003-1268-6516; vitiello, laura/0000-0003-0776-3601; racioppi, luigi/0000-0002-9207-6752; Masci, Anna Maria/0000-0003-1940-6740; Mavilio, Domenico/0000-0001-6147-0952 NR 41 TC 7 Z9 7 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 10 PY 2010 VL 5 IS 6 AR e11052 DI 10.1371/journal.pone.0011052 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608QA UT WOS:000278599600013 ER PT J AU Smoak, KA Aloor, JJ Madenspacher, J Merrick, BA Collins, JB Zhu, XW Cavigiolio, G Oda, MN Parks, JS Fessler, MB AF Smoak, Kathleen A. Aloor, Jim J. Madenspacher, Jennifer Merrick, B. Alex Collins, Jennifer B. Zhu, Xuewei Cavigiolio, Giorgio Oda, Michael N. Parks, John S. Fessler, Michael B. TI Myeloid Differentiation Primary Response Protein 88 Couples Reverse Cholesterol Transport to Inflammation SO CELL METABOLISM LA English DT Article ID APOLIPOPROTEIN-A-I; HIGH-DENSITY-LIPOPROTEIN; TOLL-LIKE RECEPTORS; NF-KAPPA-B; LIPID RAFTS; APOA-I; TRANSGENIC MICE; TERMINAL DOMAIN; ATHEROSCLEROSIS; MACROPHAGES AB Crosstalk exists in mammalian cells between cholesterol trafficking and innate immune signaling. Apo lipoprotein A-I (apoA-I), a serum apolipoprotein that induces antiatherogenic efflux of macrophage cholesterol, is widely described as anti-inflammatory because it neutralizes bacterial lipopolysaccharide. Conversely, lipopolysaccharide-induced inflammation is proatherogenic. However, whether innate immunity plays an endogenous, physiological role in host cholesterol homeostasis in the absence of infection is undetermined. We report that apoA-I signals in the macrophage through Toll-like receptor (TLR)2, TLR4, and CD14, utilizing myeloid differentiation primary response protein 88 (MyD88)-dependent and -independent pathways, to activate nuclear factor-kappa B and induce cytokines. MyD88 plays a critical role in reverse cholesterol transport in vitro and in vivo, in part through promoting ATP-binding cassette A1 transporter upregulation. Taken together, this work identifies apoA-I as an endogenous stimulus of innate immunity that couples cholesterol trafficking to inflammation through MyD88 and identifies innate immunity as a physiologic signal in cholesterol homeostasis. C1 [Smoak, Kathleen A.; Aloor, Jim J.; Madenspacher, Jennifer; Merrick, B. Alex; Fessler, Michael B.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer B.] NIEHS, Microarray Core Facil, Res Triangle Pk, NC 27709 USA. [Zhu, Xuewei; Parks, John S.] Wake Forest Univ Hlth Sci, Dept Pathol, Sect Lipid Sci, Winston Salem, NC 27157 USA. [Cavigiolio, Giorgio; Oda, Michael N.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Fessler, MB (reprint author), NIEHS, Lab Resp Biol, POB 12233, Res Triangle Pk, NC 27709 USA. FU National Institutes of Health (NIH), National Institute of Environmental Health Sciences [P01-HL49373, R01 HL94525] FX We thank Zhuowei Li and John Hollingsworth for assistance with PEM harvest, Grace Kissling for statistical consultation, Marcia Moss and Robert Petrovich for protein expression, Donald Cook and Farhad Imam for manuscript review, Ingo Just for providing C toxin B, Shizuo Akira for providing Tlr2-/-, Tlr4-/-, Tnf-/-, and Myd88-/- mice, and Ruslan Medzhitov for providing Tirap-/- mice This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences, and by NIH grants P01-HL49373 and R01 HL94525 (J S P.) NR 49 TC 23 Z9 23 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUN 9 PY 2010 VL 11 IS 6 BP 493 EP 502 DI 10.1016/j.cmet.2010.04.006 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 610PZ UT WOS:000278747800008 PM 20519121 ER PT J AU Good, CH Lupica, CR AF Good, Cameron H. Lupica, Carl R. TI Afferent-Specific AMPA Receptor Subunit Composition and Regulation of Synaptic Plasticity in Midbrain Dopamine Neurons by Abused Drugs SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VENTRAL TEGMENTAL AREA; LONG-TERM POTENTIATION; NUCLEUS LESIONS; PEDUNCULOPONTINE NUCLEUS; GLUTAMATERGIC SYNAPSES; IN-VIVO; RAT; AMPHETAMINE; DEPRESSION; REWARD AB Ventral tegmental area (VTA) dopamine (DA) neurons play a pivotal role in processing reward-related information and are involved in drug addiction and mental illness in humans. Information is conveyed to the VTA in large part by glutamatergic afferents that arise in various brain nuclei, including the pedunculopontine nucleus (PPN). Using a unique rat brain slice preparation, we found that PPN stimulation activates afferents targeting GluR2-containing AMPA receptors (AMPAR) on VTA DA neurons, and these afferents did not exhibit long-term depression (LTD). In contrast, activation of glutamate afferents onto the same DA neurons via stimulation within the VTA evoked EPSCs mediated by GluR2-lacking AMPARs that demonstrated LTD or EPSCs mediated by GluR2-containing AMPA receptors that did not express LTD. Twenty-four hours after single cocaine injections to rats, GluR2-lacking AMPARs were increased at both PPN and local VTA projections, and this permitted LTD expression in both pathways. Single injections with the main psychoactive ingredient of marijuana, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), increased GluR2-lacking AMPA receptors and permitted LTD in only the PPN pathway, and these effects were prevented by in vivo pretreatment with the cannabinoid CB1 receptor antagonist AM251. These results demonstrate that cocaine more globally increases GluR2-lacking AMPA receptors at all glutamate synapses on VTA dopamine neurons, whereas Delta(9)-THC selectively increased GluR2-lacking AMPA receptors at subcortical PPN synapses. This suggests that different abused drugs may exert influence over distinct sets of glutamatergic afferents to VTA DA neurons which may be associated with different reinforcing or addictive properties of these drugs. C1 [Good, Cameron H.; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Lupica, CR (reprint author), NIDA, Electrophysiol Res Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov FU U.S. Department of Health and Human Services; National Institutes of Health; National Institute on Drug Abuse FX This work was supported by The U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute on Drug Abuse Intramural Research Program. We thank Drs. Cristina Backman and YaJun Zhang for performing DAT immunohistochemistry and biocytin reconstructions of VTA neurons, and Drs. Alex Hoffman, Eisuke Koya, and Bruce Hope for helpful comments on the manuscript. NR 47 TC 31 Z9 31 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 9 PY 2010 VL 30 IS 23 BP 7900 EP 7909 DI 10.1523/JNEUROSCI.1507-10.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 608LY UT WOS:000278586900016 PM 20534838 ER PT J AU Batra, VK Pedersen, LC Beard, WA Wilson, SH Kashemirov, BA Upton, TG Goodman, MF McKenna, CE AF Batra, Vinod K. Pedersen, Lars C. Beard, William A. Wilson, Samuel H. Kashemirov, Boris A. Upton, Thomas G. Goodman, Myron F. McKenna, Charles E. TI Halogenated beta,gamma-Methylene- and Ethylidene-dGTP-DNA Ternary Complexes with DNA Polymerase beta: Structural Evidence for Stereospecific Binding of the Fluoromethylene Analogues SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BASE EXCISION-REPAIR; HYDROGEN-BOND; FLUORINATED PHOSPHONATES; CELLULAR-TRANSFORMATION; REVERSE-TRANSCRIPTASE; GASTRIC-CANCER; ACTIVE-SITE; IN-VITRO; MECHANISM; ALPHA AB beta,gamma-Fluoromethylene analogues of nucleotides are considered to be useful mimics of the natural substrates, but direct structural evidence defining their active site interactions has not been available, including the influence of the new chiral center introduced at the CHF carbon, as in beta,gamma-fluoromethylene-dGTP, which forms an active site complex with DNA polymerase beta, a repair enzyme that plays an important role in base excision repair (BER) and oncogenesis. We report X-ray crystallographic results for a series of beta,gamma-CXY dGTP analogues, where X,Y = H, F, Cl, Br, and/or CH(3). For all three R/S monofluorinated analogues examined (CHF, 3/4; CCH(3)F, 13/14; CCIF 15/16), a single CXF-diastereomer (3, 13, 16) is observed in the active site complex, with the CXF fluorine atom at a similar to 3 angstrom (bonding) distance to a guanidinium N of Arg183. In contrast, for the CHCl, CHBr, and CHCH(3) analogues, both diasteromers (617, 8/9, 10/11) populate the dGTP site in the enzyme complex about equally. The structures of the bound dichloro (5) and dimethyl (12) analogue complexes indicate little to no steric effect on the placement of the bound nucleotide backbone. The results suggest that introduction of a single fluorine atom at the beta,gamma-bridging carbon atom of these dNTP analogues enables a new, stereospecific interaction within the preorganized active site complex that is unique to fluorine. The results also provide the first diverse structural data set permitting an assessment of how closely this class of dNTP analogues mimics the conformation of the parent nucleotide within the active site complex. C1 [Kashemirov, Boris A.; Upton, Thomas G.; Goodman, Myron F.; McKenna, Charles E.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Kashemirov, Boris A.; Upton, Thomas G.; Goodman, Myron F.; McKenna, Charles E.] Univ So Calif, Dept Biol, Los Angeles, CA 90089 USA. [Batra, Vinod K.; Pedersen, Lars C.; Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP McKenna, CE (reprint author), Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. EM mckenna@usc.edu RI Upton, Thomas/E-3749-2012 FU NIH [5-U19-CA105010]; NIH, National Institute of Environmental Health Sciences [Z01 ES050158-12, Z01 ES050161-12] FX We thank Dr. Ron New for assistance with HRMS analysis and J.M. Krahn for his help in preparing the analogue parameters and topology files for structure determination. This research was supported by NIH Grant 5-U19-CA105010 and in part by Research Project Numbers Z01 ES050158-12 and Z01 ES050161-12 (S.H.W.) in the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 64 TC 28 Z9 28 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 9 PY 2010 VL 132 IS 22 BP 7617 EP 7625 DI 10.1021/ja909370k PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 611RA UT WOS:000278837100019 PM 20465217 ER PT J AU Portilla, LM Alving, B AF Portilla, Lili M. Alving, Barbara TI Reaping the Benefits of Biomedical Research: Partnerships Required SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article AB Reaping the benefits of investments in biomedical research can be achieved most efficiently through active collaboration among industry, academia, government, and non-profit organizations. The National Institutes of Health (NIH) are exploring multiple ways in which to increase the efficiency of the translational process. Investigators involved in the NIH-funded Clinical and Translational Science Awards are developing public-private partnerships, addressing the barriers to collaboration, training the next generation of interdisciplinary team-oriented researchers, and producing open-source tools for collaboration. NIH is engaging with industry through the Foundation for the NIH and the Small Business Innovation Research Awards. C1 [Portilla, Lili M.; Alving, Barbara] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Portilla, LM (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. EM lilip@nih.gov NR 11 TC 5 Z9 5 U1 2 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 9 PY 2010 VL 2 IS 35 AR 35cm17 DI 10.1126/scitranslmed.3001137 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735OL UT WOS:000288426700001 PM 20538616 ER PT J AU Chen, LW Caballero, B Mitchell, DC Loria, C Lin, PH Champagne, CM Elmer, PJ Ard, JD Batch, BC Anderson, CAM Appel, LJ AF Chen, Liwei Caballero, Benjamin Mitchell, Diane C. Loria, Catherine Lin, Pao-Hwa Champagne, Catherine M. Elmer, Patricia J. Ard, Jamy D. Batch, Bryan C. Anderson, Cheryl A. M. Appel, Lawrence J. TI Reducing Consumption of Sugar-Sweetened Beverages Is Associated With Reduced Blood Pressure A Prospective Study Among United States Adults SO CIRCULATION LA English DT Article DE blood pressure; diet; follow-up studies; hypertension ID LIFE-STYLE MODIFICATION; METABOLIC SYNDROME; CLINICAL-TRIAL; URIC-ACID; HYPERTENSION; FRUCTOSE; WOMEN; RATS; CAFFEINE; OBESITY AB Background-Increased consumption of sugar-sweetened beverages (SSBs) has been associated with an elevated risk of obesity, metabolic syndrome, and type II diabetes mellitus. However, the effects of SSB consumption on blood pressure (BP) are uncertain. The objective of this study was to determine the relationship between changes in SSB consumption and changes in BP among adults. Methods and Results-This was a prospective analysis of 810 adults who participated in the PREMIER Study (an 18-month behavioral intervention trial). BP and dietary intake (by two 24-hour recalls) were measured at baseline and at 6 and 18 months. Mixed-effects models were applied to estimate the changes in BP in responding to changes in SSB consumption. At baseline, mean SSB intake was 0.9 +/- 1.0 servings per day (10.5 +/- 11.9 fl oz/d), and mean systolic BP/diastolic BP was 134.9 +/- 9.6/84.8 +/- 4.2 mm Hg. After potential confounders were controlled for, a reduction in SSB of 1 serving per day was associated with a 1.8-mm Hg (95% confidence interval, 1.2 to 2.4) reduction in systolic BP and 1.1-mm Hg (95% confidence interval, 0.7 to 1.4) reduction in diastolic BP over 18 months. After additional adjustment for weight change over the same period, a reduction in SSB intake was still significantly associated with reductions in systolic and diastolic BPs (P<0.05). Reduced intake of sugars was also significantly associated with reduced BP. No association was found for diet beverage consumption or caffeine intake and BP. These findings suggest that sugars may be the nutrients that contribute to the observed association between SSB and BP. Conclusions-Reduced consumption of SSB and sugars was significantly associated with reduced BP. Reducing SSB and sugar consumption may be an important dietary strategy to lower BP. C1 [Chen, Liwei] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, New Orleans, LA 70112 USA. [Caballero, Benjamin; Anderson, Cheryl A. M.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA. [Mitchell, Diane C.] Penn State Univ, Dept Nutr Sci, Diet Assessment Ctr, University Pk, PA 16802 USA. [Loria, Catherine] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Lin, Pao-Hwa] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Champagne, Catherine M.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Elmer, Patricia J.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Ard, Jamy D.] Univ Alabama, Div Clin Nutr & Dietet, Birmingham, AL USA. [Batch, Bryan C.] Duke Univ, Duke Hypertens Ctr, Durham, NC USA. [Anderson, Cheryl A. M.; Appel, Lawrence J.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. RP Chen, LW (reprint author), Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Program Epidemiol, 1615 Poydras St,Ste 1400, New Orleans, LA 70112 USA. EM lchen@lsuhsc.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health [UO1 HL60570, UO1 HL60571, UO1 HL60573, UO1 HL60574, UO1 HL62828]; School of Public Health, Louisiana State University Health Science Center; Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health FX The PREMIER Trial was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health grants UO1 HL60570, UO1 HL60571, UO1 HL60573, UO1 HL60574, and UO1 HL62828. The present study is supported in part by the School of Public Health, Louisiana State University Health Science Center and by the Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health. NR 29 TC 95 Z9 102 U1 5 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 8 PY 2010 VL 121 IS 22 BP 2398 EP 2406 DI 10.1161/CIRCULATIONAHA.109.911164 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 607KW UT WOS:000278503600004 PM 20497980 ER PT J AU Paoloni, MC Mazcko, C Fox, E Fan, T Lana, S Kisseberth, W Vail, DM Nuckolls, K Osborne, T Yalkowsy, S Gustafson, D Yu, YK Cao, LA Khanna, C AF Paoloni, Melissa C. Mazcko, Christina Fox, Elizabeth Fan, Timothy Lana, Susan Kisseberth, William Vail, David M. Nuckolls, Kaylee Osborne, Tanasa Yalkowsy, Samuel Gustafson, Daniel Yu, Yunkai Cao, Liang Khanna, Chand TI Rapamycin Pharmacokinetic and Pharmacodynamic Relationships in Osteosarcoma: A Comparative Oncology Study in Dogs SO PLOS ONE LA English DT Article ID RENAL-ALLOGRAFT SURVIVAL; TARGETED THERAPY; CELL CANCER; MTOR; SARCOMA; BIOLOGY; MODEL; CYCLOSPORINE; PROGRESSION; ACTIVATION AB Background: Signaling through the mTOR pathway contributes to growth, progression and chemoresistance of several cancers. Accordingly, inhibitors have been developed as potentially valuable therapeutics. Their optimal development requires consideration of dose, regimen, biomarkers and a rationale for their use in combination with other agents. Using the infrastructure of the Comparative Oncology Trials Consortium many of these complex questions were asked within a relevant population of dogs with osteosarcoma to inform the development of mTOR inhibitors for future use in pediatric osteosarcoma patients. Methodology/Principal Findings: This prospective dose escalation study of a parenteral formulation of rapamycin sought to define a safe, pharmacokinetically relevant, and pharmacodynamically active dose of rapamycin in dogs with appendicular osteosarcoma. Dogs entered into dose cohorts consisting of 3 dogs/cohort. Dogs underwent a pre-treatment tumor biopsy and collection of baseline PBMC. Dogs received a single intramuscular dose of rapamycin and underwent 48-hour whole blood pharmacokinetic sampling. Additionally, daily intramuscular doses of rapamycin were administered for 7 days with blood rapamycin trough levels collected on Day 8, 9 and 15. At Day 8 post-treatment collection of tumor and PBMC were obtained. No maximally tolerated dose of rapamycin was attained through escalation to the maximal planned dose of 0.08 mg/kg (2.5 mg/30kg dog). Pharmacokinetic analysis revealed a dose-dependent exposure. In all cohorts modulation of the mTOR pathway in tumor and PBMC (pS6RP/S6RP) was demonstrated. No change in pAKT/AKT was seen in tumor samples following rapamycin therapy. Conclusions/Significance: Rapamycin may be safely administered to dogs and can yield therapeutic exposures. Modulation pS6RP/S6RP in tumor tissue and PBMCs was not dependent on dose. Results from this study confirm that the dog may be included in the translational development of rapamycin and potentially other mTOR inhibitors. Ongoing studies of rapamycin in dogs will define optimal schedules for their use in cancer and evaluate the role of rapamycin use in the setting of minimal residual disease. C1 [Paoloni, Melissa C.; Mazcko, Christina; Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA. [Fox, Elizabeth] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Fan, Timothy] Univ Illinois, Urbana, IL 61801 USA. [Lana, Susan; Gustafson, Daniel] Colorado State Univ, Ft Collins, CO 80523 USA. [Kisseberth, William] Ohio State Univ, Columbus, OH 43210 USA. [Vail, David M.] Univ Wisconsin, Madison, WI USA. [Nuckolls, Kaylee; Osborne, Tanasa; Khanna, Chand] NCI, Tumor Metastasis & Biol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Yalkowsy, Samuel] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. RP Paoloni, MC (reprint author), NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI Kisseberth, William/A-2587-2013 FU Morris Animal Foundation FX The Morris Animal Foundation provided generous support for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 21 Z9 21 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 8 PY 2010 VL 5 IS 6 AR e11013 DI 10.1371/journal.pone.0011013 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 607IR UT WOS:000278494900025 PM 20543980 ER PT J AU Rajagopalan, S Long, EO AF Rajagopalan, Sumati Long, Eric O. TI Antagonizing inhibition gets NK cells going SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID IMMUNOGLOBULIN-LIKE RECEPTOR; CLASS-I; CRYSTAL-STRUCTURE; RECOGNITION; COMPLEX; RESPONSES; ANTIGEN; HLA C1 [Rajagopalan, Sumati; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Rajagopalan, S (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM sumi@nih.gov; elong@nih.gov RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 14 TC 6 Z9 6 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 8 PY 2010 VL 107 IS 23 BP 10333 EP 10334 DI 10.1073/pnas.1005636107 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608AH UT WOS:000278549300003 PM 20534579 ER PT J AU Jang, IK Zhang, JP Chiang, YJ Kole, HK Cronshaw, DG Zou, YR Gu, H AF Jang, Ihn Kyung Zhang, Jinping Chiang, Yungping J. Kole, Hemanta K. Cronshaw, Darran G. Zou, Yongrui Gu, Hua TI Grb2 functions at the top of the T-cell antigen receptor-induced tyrosine kinase cascade to control thymic selection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE signal transduction; T-cell development; Grb2; tyrosine phosphorylation ID STAPHYLOCOCCAL ENTEROTOXIN-B; POSITIVE SELECTION; SIGNAL-TRANSDUCTION; ADAPTER PROTEINS; THYMOCYTES; DELETION; DISRUPTION; ACTIVATION; P56(LCK); PEPTIDE AB Grb2 is an adaptor molecule that mediates Ras-MAPK activation induced by various receptors. Here we show that conditional ablation of Grb2 in thymocytes severely impairs both thymic positive and negative selections. Strikingly, the mutation attenuates T-cell antigen receptor (TCR) proximal signaling, including tyrosine phosphorylation of multiple signaling proteins and Ca(2+) influx. The defective TCR signaling can be attributed to a marked impairment in Lck activation. Ectopic expression of a mutant Grb2 composed of the central SH2 and the C-terminal SH3 domains in Grb2(-/-) thymocytes fully restores thymocyte development. Thus, Grb2 plays a pivotal role in both thymic positive and negative selection. It amplifies TCR signaling at the top end of the tyrosine phosphorylation cascade via a scaffolding function. C1 [Jang, Ihn Kyung; Zhang, Jinping; Gu, Hua] Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. [Chiang, Yungping J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Kole, Hemanta K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Cronshaw, Darran G.; Zou, Yongrui] Feinstein Inst Med Res, Manhasset, NY 11030 USA. RP Gu, H (reprint author), Columbia Univ, Coll Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. EM hg2065@columbia.edu FU National Institutes of Health; Irene Diamond Foundation FX We thank Drs. Larry Samelson for anti-LAT antibody and discussion, A. S. Shaw for anti-phospho-Lck (pY394), J. R. Hayman for Grb2 genomic DNA clone, A. M. Pendergast for Grb2 cDNA, Junji Takeda for Lck-Cre Tg mice, O. Jovanovic for proofreading the manuscript, and other members of our laboratory for discussion. H. G. is an Irene Diamond Associate Professor. This study is supported in part by the National Institutes of Health Intramural Research Programs and by the Irene Diamond Foundation. NR 33 TC 28 Z9 28 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 8 PY 2010 VL 107 IS 23 BP 10620 EP 10625 DI 10.1073/pnas.0905039107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608AH UT WOS:000278549300053 PM 20498059 ER PT J AU Datta, SK Sabet, M Nguyen, KPL Valdez, PA Gonzalez-Navajas, JM Islam, S Mihajlov, I Fierer, J Insel, PA Webster, NJ Guiney, DG Raz, E AF Datta, Sandip K. Sabet, Mojgan Nguyen, Kim Phung L. Valdez, Patricia A. Gonzalez-Navajas, Jose M. Islam, Shamima Mihajlov, Ivan Fierer, Joshua Insel, Paul A. Webster, Nicholas J. Guiney, Donald G. Raz, Eyal TI Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IL-17; dendritic cell; T cell; vaccine; cAMP ID ARYL-HYDROCARBON RECEPTOR; T-HELPER-CELLS; INTERLEUKIN-17 PRODUCTION; BACILLUS-ANTHRACIS; CUTTING EDGE; CYCLIC-AMP; DIFFERENTIATION; MICE; AUTOCRINE; IL-21 AB Cholera toxin (CT) elicits a mucosal immune response in mice when used as a vaccine adjuvant. The mechanisms by which CT exerts its adjuvant effects are incompletely understood. We show that protection against inhalation anthrax by an irradiated spore vaccine depends on CT-mediated induction of IL-17-producing CD4 Th17 cells. Furthermore, IL-17 is involved in the induction of serum and mucosal antibody responses by CT. Th17 cells induced by CT have a unique cytokine profile compared with those induced by IL-6 and TGF-beta, and their induction by CT requiresc AMP-dependent secretion of IL-1 beta and beta-calcitonin gene-related peptide by dendritic cells. These findings demonstrate that Th17 cells mediate mucosal adjuvant effects of CT and identify previously unexplored pathways involved in Th17 induction that could be targeted for development of unique mucosal adjuvants. C1 [Datta, Sandip K.; Valdez, Patricia A.; Islam, Shamima] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Sabet, Mojgan; Nguyen, Kim Phung L.; Gonzalez-Navajas, Jose M.; Mihajlov, Ivan; Fierer, Joshua; Insel, Paul A.; Webster, Nicholas J.; Guiney, Donald G.; Raz, Eyal] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Fierer, Joshua] Vet Affairs Healthcare, Dept Infect Dis, San Diego, CA 92161 USA. RP Datta, SK (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM dattas@niaid.nih.gov OI Gonzalez-Navajas, Jose Manuel/0000-0002-1591-939X; Datta, Sandip/0000-0003-0243-7815 FU National Institutes of Health/National Institute of Allergy and Infectious Diseases; Ellison Medical Foundation; Leukemia and Lymphoma Society; Crohn and Colitis Foundation of America; National Institutes of Health [AI077989, AI083328, AI058743, AI68685, DK35108] FX This research was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Ellison Medical Foundation, the Leukemia and Lymphoma Society, the Crohn and Colitis Foundation of America, and by extramural National Institutes of Health Grants AI077989, AI083328, AI058743, AI68685, and DK35108. NR 46 TC 68 Z9 71 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 8 PY 2010 VL 107 IS 23 BP 10638 EP 10643 DI 10.1073/pnas.1002348107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 608AH UT WOS:000278549300056 PM 20479237 ER PT J AU Patil, J Schwab, A Nussberger, J Schaffner, T Saavedra, JM Imboden, H AF Patil, Jaspal Schwab, Alexander Nussberger, Juerg Schaffner, Thomas Saavedra, Juan M. Imboden, Hans TI Intraneuronal angiotensinergic system in rat and human dorsal root ganglia SO REGULATORY PEPTIDES LA English DT Article DE Renin-angiotensin system; Angiotensin II; Neurotransmitter; Neuronal angiotensin; Sensory system ID SPONTANEOUSLY HYPERTENSIVE-RATS; RECEPTOR MESSENGER-RNA; II AT(1) RECEPTORS; SUBSTANCE-P; SPINAL-CORD; PROPHYLACTIC TREATMENT; TRIGEMINAL GANGLION; SENSORY NEURONS; BRAIN; LOCALIZATION AB To elucidate the local formation of angiotensin II (Ang II) in the neurons of sensory dorsal root ganglia (DRG), we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of protein renin, Ang II, Substance P and calcitonin gene-related peptide (CGRP) in the rat and human thoracic DRG. Quantitative real time PCR (qRT-PCR) studies revealed that rat DRG expressed substantial amounts of Ang-N- and ACE mRNA, while renin mRNA as well as the protein renin were untraceable. Cathepsin D-mRNA and cathepsin D-protein were detected in the rat DRG indicating the possibility of existence of pathways alternative to renin for Ang I formation. Angiotensin peptides were successfully detected with high performance liquid chromatography and radioimmunoassay in human DRG extracts. In situ hybridization in rat DRG confirmed additionally expression of Ang-N mRNA in the cytoplasm of numerous neurons. Intracellular Ang II staining could be shown in number of neurons and their processes in both the rat and human DRG. Interestingly we observed neuronal processes with angiotensinergic synapses en passant, colocalized with synaptophysin, within the DRG. In the DRG, we also identified by qRT-PCR, expression of Ang II receptor AT(1A) and AT(2)-mRNA while AT(1B)-mRNA was not traceable. In some neurons Substance P and CGRP were found colocalized with Ang II. The intracellular localization and colocalization of Ang II with Substance P and CGRP in the DRG neurons may indicate a participation and function of Ang II in the regulation of nociception. In conclusion, these results suggest that Ang II may be produced locally in the neurons of rat and human DRG and act as a neurotransmitter. (C) 2010 Elsevier B.V. All rights reserved. C1 [Patil, Jaspal; Schwab, Alexander; Imboden, Hans] Univ Bern, Inst Cell Biol, CH-3012 Bern, Switzerland. [Nussberger, Juerg] Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland. [Schaffner, Thomas] Univ Bern, Inst Pathol, CH-3012 Bern, Switzerland. [Saavedra, Juan M.] NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Imboden, H (reprint author), Univ Bern, Inst Cell Biol, Baltzerstr 4, CH-3012 Bern, Switzerland. EM hans.imboden@izb.unibe.ch FU Intramural NIH HHS [Z01 MH002762-12, Z99 MH999999] NR 70 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUN 8 PY 2010 VL 162 IS 1-3 BP 90 EP 98 DI 10.1016/j.regpep.2010.03.004 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 609NK UT WOS:000278663300014 PM 20346377 ER PT J AU Maruyama, SR Anatriello, E Anderson, JM Ribeiro, JM Brandao, LG Valenzuela, JG Ferreira, BR Garcia, GR Szabo, MPJ Patel, S Bishop, R de Miranda-Santos, IKF AF Maruyama, Sandra R. Anatriello, Elen Anderson, Jennifer M. Ribeiro, Jose M. Brandao, Lucinda G. Valenzuela, Jesus G. Ferreira, Beatriz R. Garcia, Gustavo R. Szabo, Matias P. J. Patel, Sonal Bishop, Richard de Miranda-Santos, Isabel K. F. TI The expression of genes coding for distinct types of glycine-rich proteins varies according to the biology of three metastriate ticks, Rhipicephalus (Boophilus) microplus, Rhipicephalus sanguineus and Amblyomma cajennense SO BMC GENOMICS LA English DT Article ID SALIVARY-GLANDS; IXODES-SCAPULARIS; CEMENT ANTIGEN; IXODIDAE; ACARI; TRANSCRIPTOME; CATALOG; VACCINE; FEMALE; CATTLE AB Background: Ticks secrete a cement cone composed of many salivary proteins, some of which are rich in the amino acid glycine in order to attach to their hosts' skin. Glycine-rich proteins (GRPs) are a large family of heterogeneous proteins that have different functions and features; noteworthy are their adhesive and tensile characteristics. These properties may be essential for successful attachment of the metastriate ticks to the host and the prolonged feeding necessary for engorgement. In this work, we analyzed Expressed Sequence Tags (ESTs) similar to GRPs from cDNA libraries constructed from salivary glands of adult female ticks representing three hard, metastriate species in order to verify if their expression correlated with biological differences such as the numbers of hosts ticks feed on during their parasitic life cycle, whether one (monoxenous parasite) or two or more (heteroxenous parasite), and the anatomy of their mouthparts, whether short (Brevirostrata) or long (Longirostrata). These ticks were the monoxenous Brevirostrata tick, Rhipicephalus (Boophilus) microplus, a heteroxenous Brevirostrata tick, Rhipicephalus sanguineus, and a heteroxenous Longirostrata tick, Amblyomma cajennense. To further investigate this relationship, we conducted phylogenetic analyses using sequences of GRPs from these ticks as well as from other species of Brevirostrata and Longirostrata ticks. Results: cDNA libraries from salivary glands of the monoxenous tick, R. microplus, contained more contigs of glycine-rich proteins than the two representatives of heteroxenous ticks, R. sanguineus and A. cajennense (33 versus, respectively, 16 and 11). Transcripts of ESTs encoding GRPs were significantly more numerous in the salivary glands of the two Brevirostrata species when compared to the number of transcripts in the Longirostrata tick. The salivary gland libraries from Brevirostrata ticks contained numerous contigs significantly similar to silks of true spiders (17 and 8 in, respectively, R. microplus and R. sanguineus), whereas the Longirostrata tick contained only 4 contigs. The phylogenetic analyses of GRPs from various species of ticks showed that distinct clades encoding proteins with different biochemical properties are represented among species according to their biology. Conclusions: We found that different species of ticks rely on different types and amounts of GRPs in order to attach and feed on their hosts. Metastriate ticks with short mouthparts express more transcripts of GRPs than a tick with long mouthparts and the tick that feeds on a single host during its life cycle contain a greater variety of these proteins than ticks that feed on several hosts. C1 [Maruyama, Sandra R.; Anatriello, Elen; Brandao, Lucinda G.; Garcia, Gustavo R.; de Miranda-Santos, Isabel K. F.] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. [Anderson, Jennifer M.; Ribeiro, Jose M.; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Ferreira, Beatriz R.] Univ Sao Paulo, Ribeirao Preto Sch Nursing, Dept Maternal & Child & Publ Hlth Nursing, BR-14049900 Ribeirao Preto, SP, Brazil. [Szabo, Matias P. J.] Univ Fed Uberlandia, Sch Vet Med, BR-38400902 Uberlandia, MG, Brazil. [Patel, Sonal; Bishop, Richard] Int Livestock Res Inst, Nairobi, Kenya. [de Miranda-Santos, Isabel K. F.] Embrapa Recursos Genet & Biotecnol, BR-70770900 Brasilia, DF, Brazil. [Brandao, Lucinda G.] Univ Paulista, BR-16018280 Aracatuba, SP, Brazil. RP de Miranda-Santos, IKF (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. EM imsantos@fmrp.usp.br RI Ferreira, Beatriz/C-2003-2012; Maruyama, Sandra/G-1171-2012; Szabo, Matias/A-5704-2013; de Miranda Santos, Isabel/B-7597-2012; Garcia, Gustavo/E-5182-2013; Brandao, Lenine/J-5334-2013; Anatriello, Elen/N-1429-2015; de Miranda Santos, Isabel/D-5261-2016; OI Ribeiro, Jose/0000-0002-9107-0818; Ferreira, Beatriz/0000-0002-6781-2236; Szabo, Matias/0000-0001-8642-3968; de Miranda Santos, Isabel/0000-0002-0438-4430; Maruyama, Sandra/0000-0001-6807-1452 FU Conselho Nacional de Desenvolvi-mento Cientifico e Tecnologico - CNPq [420067/2005-1, 505810/2004-2]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [04/09992-7, 06/54041-6, 07/59357-4]; National Institute of Allergy and Infectious Diseases FX This work was supported by grants from the Conselho Nacional de Desenvolvi-mento Cientifico e Tecnologico - CNPq (grant numbers 420067/2005-1 and 505810/2004-2), and the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP (04/09992-7) and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The authors thank Dr. Joao S. Silva for generous and continuing support of this work performed in his laboratory. This work fulfils part of the requirements for a MSc program for S.R.M, supported by scholarships from FAPESP (06/54041-6 and 07/59357-4). NR 43 TC 20 Z9 20 U1 5 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 7 PY 2010 VL 11 AR 363 DI 10.1186/1471-2164-11-363 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 625CA UT WOS:000279868500004 PM 20529354 ER PT J AU Mathias, RA Kim, Y Sung, H Yanek, LR Mantese, VJ Hererra-Galeano, JE Ruczinski, I Wilson, AF Faraday, N Becker, LC Becker, DM AF Mathias, Rasika A. Kim, Yoonhee Sung, Heejong Yanek, Lisa R. Mantese, V. J. Hererra-Galeano, J. Enrique Ruczinski, Ingo Wilson, Alexander F. Faraday, Nauder Becker, Lewis C. Becker, Diane M. TI A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease SO BMC MEDICAL GENOMICS LA English DT Article ID SIB-PAIR LINKAGE; ASPIRIN RESISTANCE; COMPLEX TRAITS; HERITABILITY; POWER AB Background: The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. Methods: Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. Results: Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 x 10(-4)) and significant (p-value < 2 x 10(-5)) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 x 10(4)) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs). Conclusions: Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up. C1 [Mathias, Rasika A.; Kim, Yoonhee; Sung, Heejong; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Mathias, Rasika A.; Yanek, Lisa R.; Mantese, V. J.; Hererra-Galeano, J. Enrique; Faraday, Nauder; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Med Inst, Sch Med, Baltimore, MD 21205 USA. [Ruczinski, Ingo] Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Mathias, RA (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. EM rmathias@jhmi.edu RI Wilson, Alexander/C-2320-2009 FU National Heart, Lung, and Blood Institute [HL72518, HL087698]; National Center for Research Resources [M01-RR000052]; National Human Genome Research Institute, National Institutes of Health FX This work was supported in part by grants from the National Heart, Lung, and Blood Institute, (HL72518 and HL087698), and the National Center for Research Resources (M01-RR000052) and by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. McNeil Consumer and Specialty Pharmaceuticals supplied aspirin to the study. NR 27 TC 17 Z9 18 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD JUN 7 PY 2010 VL 3 AR 22 DI 10.1186/1755-8794-3-22 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 625RT UT WOS:000279913400001 PM 20529293 ER PT J AU Breban, R Drake, JM Rohani, P AF Breban, Romulus Drake, John M. Rohani, Pejman TI A general multi-strain model with environmental transmission: Invasion conditions for the disease-free and endemic states SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE Environmental transmission; Multi-strain model; Endemic state; Epidemic invasion ID INFLUENZA-A VIRUSES; BORNE TRANSMISSION; CHOLERA OUTBREAKS; WILD DUCKS; DYNAMICS; EVOLUTION; PARAMYXOVIRUSES; INFECTIVITY; PERSISTENCE; PARASITES AB Although many infectious diseases of humans and wildlife are transmitted via an environmental reservoir, the theory of environmental transmission remains poorly elaborated. Here we introduce an SIR-type multi-strain disease transmission model with perfect cross immunity where environmental transmission is broadly defined by three axioms. We establish the conditions under which a multi-strain endemic state is invaded by another strain which is both directly and environmentally transmitted. We discuss explicit forms for environmental transmission terms and apply our newly derived invasion conditions to a two-strain system. Then, we consider the case of two strains with matching basic reproduction numbers (i.e., R(0)), one directly transmitted only and the other both directly and environmentally transmitted, invading each other's endemic state. We find that the strain which is only directly transmitted can invade the endemic state of the strain with mixed transmission. However, the endemic state of the first strain is neutrally stable to invasion by the second strain. Thus, our results suggest that environmental transmission makes the endemic state less resistant to invasion. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Rohani, Pejman] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA. [Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Breban, Romulus; Drake, John M.; Rohani, Pejman] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. RP Breban, R (reprint author), Inst Pasteur, Unite Epidemiol Malad Emergentes, F-75724 Paris 15, France. EM romulus.breban@pasteur.fr; jdrake@uga.edu; rohani@uga.edu RI Drake, John/D-6622-2012; OI Drake, John/0000-0003-4646-1235 FU CDC [5U19CI000401]; National Science Foundation [DEB-0917853]; James S. McDonnell Foundation; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This project was supported by Grants from the CDC (5U19CI000401), the National Science Foundation (DEB-0917853) and the James S. McDonnell Foundation. PR was also supported by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 38 TC 19 Z9 20 U1 0 U2 17 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD JUN 7 PY 2010 VL 264 IS 3 BP 729 EP 736 DI 10.1016/j.jtbi.2010.03.005 PG 8 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 645LY UT WOS:000281460900010 PM 20211630 ER PT J AU Leng, Y Marinova, Z Reis-Fernandes, MA Nau, H Chuang, DM AF Leng, Yan Marinova, Zoya Reis-Fernandes, Marcos A. Nau, Heinz Chuang, De-Maw TI Potent neuroprotective effects of novel structural derivatives of valproic acid: Potential roles of HDAC inhibition and HSP70 induction SO NEUROSCIENCE LETTERS LA English DT Article DE HDAC inhibitors; Valproic acid; Neuroprotection; Excitotoxicity; Glutamate; HSP70 ID HISTONE DEACETYLASE INHIBITION; NEURONS; MOUSE AB Emerging evidence suggests that the neuroprotective effects of valproic acid (VPA) occur via inhibition of histone deacetylases (HDACs) and activation of gene expression. This study assessed the ability of four VPA derivatives to cause histone hyperacetylation and protect against glutamate-induced excitotoxicity in cultured neurons. We found that (S)-2-pentyl-4-pentynoic acid (compound III) and (+/-)-2-hexyl-4-pentynoic acid (compound V) were far more potent and robust than VPA in inducing histone hyperacetylation and protecting against glutamate excitotoxicity. Thus, the increase in histone acetylation elicited by compounds III and V was significant at 5 mu M and reached a maximal increase of 600-700% at 50-100 mu M, compared with only a 200% increase by VPA at 100 mu M. The neuroprotective effects of compounds III and V were evident at 10-25 mu M and reached a complete protection at 50-100 mu M, while a significant partial protection by VPA was observed at 100 mu M. These two compounds were also more effective than VPA in increasing HSP70-1a and HSP70-1b mRNA levels. At 50 mu M, compound V was most robust in increasing HSP-1a mRNA levels, followed by compound III, and then by VPA. HSP-1b mRNA was only significantly upregulated by compounds V and III, but not by VPA or other VPA derivatives under these treatment conditions. Our results suggest that these two VPA derivatives may ultimately be developed into potent neuroprotective drugs in preclinical and clinical studies. Published by Elsevier Ireland Ltd. C1 [Leng, Yan; Marinova, Zoya; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Reis-Fernandes, Marcos A.; Nau, Heinz] Univ Vet Med, Inst Food Toxicol & Analyt Chem, Hannover, Germany. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Rm 3D-38,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU National Institute of Mental Health, National Institutes of Health (NIMH-NIH); European Commission [Re ProTecLSHB-CT-2004-503257] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (NIMH-NIH) and a grant from European Commission (Re ProTecLSHB-CT-2004-503257). We greatly thank Peter Leeds and loline Henter for critical reading and editing of the manuscript. NR 18 TC 15 Z9 17 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 7 PY 2010 VL 476 IS 3 BP 127 EP 132 DI 10.1016/j.neulet.2010.04.013 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 608SC UT WOS:000278605300004 PM 20394799 ER PT J AU Liu, JT Wang, YB Qu, XC Li, XS Ma, XP Han, RQ Hu, ZH Chen, XL Sun, DD Zhang, RQ Chen, DF Chen, D Chen, XY Liang, JM Cao, F Tian, J AF Liu, Junting Wang, Yabin Qu, Xiaochao Li, Xiangsi Ma, Xiaopeng Han, Runqiang Hu, Zhenhua Chen, Xueli Sun, Dongdong Zhang, Rongqing Chen, Duofang Chen, Dan Chen, Xiaoyuan Liang, Jimin Cao, Feng Tian, Jie TI In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models SO OPTICS EXPRESS LA English DT Article ID SOURCE RECONSTRUCTION; IMAGE-RECONSTRUCTION; LIGHT; PROPAGATION; ALGORITHM; TISSUE; CELL AB Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor-bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal. (C) 2010 Optical Society of America C1 [Liu, Junting; Qu, Xiaochao; Li, Xiangsi; Ma, Xiaopeng; Han, Runqiang; Hu, Zhenhua; Chen, Xueli; Chen, Duofang; Chen, Dan; Liang, Jimin; Tian, Jie] Xidian Univ, Sch Life Sci & Technol, Life Sci Res Ctr, Xian 710071, Peoples R China. [Wang, Yabin; Sun, Dongdong; Zhang, Rongqing; Cao, Feng] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China. [Tian, Jie] Chinese Acad Sci, Inst Automat, Beijing 100190, Peoples R China. [Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. RP Liu, JT (reprint author), Xidian Univ, Sch Life Sci & Technol, Life Sci Res Ctr, Xian 710071, Peoples R China. EM tian@ieee.org RI Tian, Jie/H-1190-2011; Liu, Junting/D-7175-2012; Tian, Jie/M-5675-2013; Chen, Xueli/M-9152-2013; Life, MC/M-9554-2013; Liu, Junting/F-3550-2010; Liang, Jimin/B-5394-2014; Hu, Zhenhua/E-3375-2016 OI Tian, Jie/0000-0003-0498-0432; Liu, Junting/0000-0002-2099-0190; FU National Basic Research and Development Program of China [2006CB705700]; Chang Jiang Scholars and Innovative Research Team in University (PCSIRT) [IRT0645]; Ministry of Education of China; CAS; National Natural Science Foundation of China [30873462, 30900334, 30970845]; Shaanxi Provincial Natural Science Foundation [2009JQ8018]; Central Universities FX This work is supported by the Program of the National Basic Research and Development Program of China (973) under grant 2006CB705700, the Chang Jiang Scholars and Innovative Research Team in University (PCSIRT) under grant IRT0645, the Chair Professors of Chang Jiang Scholars Program of Ministry of Education of China, CAS Hundred Talents Program, the National Natural Science Foundation of China under grants 30873462, 30900334, 30970845, the Shaanxi Provincial Natural Science Foundation Research Project under grant 2009JQ8018, and the Fundamental Research Funds for the Central Universities. NR 35 TC 38 Z9 42 U1 2 U2 23 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUN 7 PY 2010 VL 18 IS 12 BP 13102 EP 13113 DI 10.1364/OE.18.013102 PG 12 WC Optics SC Optics GA 607SU UT WOS:000278527700115 PM 20588440 ER PT J AU Stein, AF Ilavsky, J Kopace, R Bennett, EE Wen, H AF Stein, Ashley F. Ilavsky, Jan Kopace, Rael Bennett, Eric E. Wen, Han TI Selective imaging of nano-particle contrast agents by a single-shot x-ray diffraction technique SO OPTICS EXPRESS LA English DT Article ID SHEARING INTERFEROMETER; GRATING INTERFEROMETER; SCATTERING AB Iron oxide nano-particles have very different x-ray diffraction properties from tissue. They can be clearly visualized against suppressed tissue background in a single-shot x-ray diffraction imaging technique. This technique is able to acquire both diffraction and absorption images from a single grating-modulated projection image through analysis in the spatial frequency domain. We describe the use of two orthogonal transmission gratings to selectively retain diffraction signal from iron oxide particles that are larger than a threshold size, while eliminating the background signal from soft tissue and bone. This approach should help the tracking of functionalized particles in cell labeling and targeted therapy. (C) 2010 Optical Society of America C1 [Stein, Ashley F.; Kopace, Rael; Bennett, Eric E.; Wen, Han] NHLBI, Imaging Phys Sect, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Ilavsky, Jan] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA. RP Stein, AF (reprint author), NHLBI, Imaging Phys Sect, Translat Med Branch, NIH, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Bennett, Eric/A-2551-2013; Ilavsky, Jan/D-4521-2013; USAXS, APS/D-4198-2013; Wen, Han/G-3081-2010 OI Ilavsky, Jan/0000-0003-1982-8900; Wen, Han/0000-0001-6844-2997 FU U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357] FX Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. NR 12 TC 13 Z9 13 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUN 7 PY 2010 VL 18 IS 12 BP 13271 EP 13278 DI 10.1364/OE.18.013271 PG 8 WC Optics SC Optics GA 607SU UT WOS:000278527700131 PM 20588456 ER PT J AU Zheng, YF Ourmanov, I Goeken, RM Whitted, S Brown, CR Buckler-White, A Iyengar, R Plishka, RJ Hirsch, VM AF Zheng, Yanfang Ourmanov, Ilnour Goeken, Robert M. Whitted, Sonya Brown, Charles R. Buckler-White, Alicia Iyengar, Ranjini Plishka, Ronald J. Hirsch, Vanessa M. TI Correction of a carboxyl terminal simian immunodeficiency virus Nef frameshift mutation restores virus replication in macaques SO VIROLOGY LA English DT Article DE SIV; Macaques; Rhesus; Pathogenesis; Nef ID HIV-1 NEF; DOWN-REGULATION; IN-VIVO; VIRAL REPLICATION; RHESUS-MONKEYS; INFECTION; SIV; ANTIBODY; ANKARA; VACCINE AB Previous studies demonstrated that the nef gene is a critical determinant of the pathogenicity of simian immunodeficiency virus (SIV) in macaques. In the present study, we evaluated the effect of a spontaneous frameshift mutation in the C-terminus of the nef gene of the minimally pathogenic SIVsmH4i clone. This clone exhibited a single nucleotide deletion in the nef gene relative to pathogenic SIV clones that resulted in a frameshift and addition of 46 amino acids to the C-terminus of Net. We generated a corrected version of this clone, SIVsmH4i Nef+ that restored Nef protein expression. Inoculation of macaques with SIVsmH4i resulted in delayed and low levels of peak viremia. This contrasted with improved kinetics and robust peak viremia in macaques inoculated with the corrected version. Despite the restoration of in vivo replication ability, neither clone resulted in memory CD4+ T cell loss or disease in a period of two years. Published by Elsevier Inc. C1 [Zheng, Yanfang; Ourmanov, Ilnour; Goeken, Robert M.; Whitted, Sonya; Brown, Charles R.; Buckler-White, Alicia; Iyengar, Ranjini; Plishka, Ronald J.; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, 4 Ctr Dr,Bldg 4,Room B1-41, Bethesda, MD 20892 USA. EM zyfcn@yahoo.com; iourmanov@niaid.nih.gov; rgoeken@niaid.nih.gov; swhitted@niaid.nih.gov; crbrown@niaid.nih.gov; ABW@niaid.nih.gov; iyengarr@niaid.nih.gov; RPLISHKA@niaid.nih.gov; vhirsch@niaid.nih.gov FU NIAID, NIH FX We thank Simoy Goldstein, Que Dang and Takeo Kuwata for technical assistance, and Bioqual Inc. (Rockville, MD) for conducting the animal studies. This work was supported by the intramural program of NIAID, NIH. NR 43 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2010 VL 401 IS 2 BP 207 EP 214 DI 10.1016/j.virol.2010.02.026 PG 8 WC Virology SC Virology GA 593IL UT WOS:000277447000010 PM 20303562 ER PT J AU Shedlock, DJ Bailey, MA Popernack, PM Cunningham, JM Burton, DR Sullivan, NJ AF Shedlock, Devon J. Bailey, Michael A. Popernack, Paul M. Cunningham, James M. Burton, Dennis R. Sullivan, Nancy J. TI Antibody-mediated neutralization of Ebola virus can occur by two distinct mechanisms SO VIROLOGY LA English DT Article DE Virus; Ebola; Immunity; Neutralization; Antibody; Human; Nonhuman primate; Rodent ID PROTECTS NONHUMAN-PRIMATES; FOLATE RECEPTOR-ALPHA; CATHEPSIN-L; ENDOSOMAL PROTEOLYSIS; HEMORRHAGIC-FEVER; PASSIVE TRANSFER; FILOVIRUS ENTRY; DENDRITIC CELLS; FUSION PROTEIN; DNA VACCINES AB Human Ebola virus causes severe hemorrhagic fever disease with high mortality and there is no vaccine or treatment. Antibodies in survivors occur early, are sustained, and can delay infection when transferred into nonhuman primates. Monoclonal antibodies (mAbs) from survivors exhibit potent neutralizing activity in vitro and are protective in rodents. To better understand targets and mechanisms of neutralization, we investigated a panel of mAbs shown previously to react with the envelope glycoprotein (GP). While one non-neutralizing mAb recognized a GP epitope in the nonessential mucin-like domain, the rest were specific for GP1, were neutralizing, and could be further distinguished by reactivity with secreted GP. We show that survivor antibodies, human KZ52 and monkey JP3K11, were specific for conformation-dependent epitopes comprising residues in GP1 and GP2 and that neutralization occurred by two distinct mechanisms; KZ52 inhibited cathepsin cleavage of GP whereas JP3K11 recognized the cleaved, fusion-active form of GP. Published by Elsevier Inc. C1 [Shedlock, Devon J.; Bailey, Michael A.; Popernack, Paul M.; Sullivan, Nancy J.] NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20814 USA. [Cunningham, James M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cunningham, James M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Sullivan, NJ (reprint author), NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3005, Bethesda, MD 20814 USA. EM shedlock@mail.med.upenn.edu; mike.bailey@taurigroup.com; nsullivan@nih.gov FU NIH, Vaccine Research Center, NIAID; NIH [AI048053] FX This research was supported in part by the Intramural Research Program of the NIH, Vaccine Research Center, NIAID and NIH grant #AI048053. The funding source had no role in study design; collection, analysis, or interpretation of data; writing of the report; or the decision to submit the paper for publication. NR 59 TC 33 Z9 39 U1 0 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2010 VL 401 IS 2 BP 228 EP 235 DI 10.1016/j.virol.2010.02.029 PG 8 WC Virology SC Virology GA 593IL UT WOS:000277447000012 PM 20304456 ER PT J AU Josephson, IR Guia, A Sobie, EA Lederer, WJ Lakatta, EG Stern, MD AF Josephson, Ira R. Guia, Antonio Sobie, Eric A. Lederer, W. Jonathan Lakatta, Edward G. Stern, Michael D. TI Physiologic gating properties of unitary cardiac L-type Ca2+ channels SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Unitary L-type Ca2+ channels; Gating kinetics; Excitation-contraction coupling; Cardiac myocytes; Single Ca2+ currents ID SINGLE CALCIUM CHANNELS; SMOOTH-MUSCLE CELLS; LOCAL-CONTROL; HEART-CELLS; CONCENTRATION-DEPENDENCE; CONDITIONING VOLTAGE; VENTRICULAR MYOCYTES; RYANODINE RECEPTORS; INTEGRATIVE MODEL; ACTION-POTENTIALS AB The contraction of adult mammalian ventricular cardiomyocytes is triggered by the influx of Ca2+ ions through sarcolemmal L-type Ca2+ channels (LCCs). However, the gating properties of unitary LCCs under physiologic conditions have remained elusive. Towards this end, we investigated the voltage-dependence of the gating kinetics of unitary LCCs, with a physiologic concentration of Ca2+ ions permeating the channel. Unitary LCC currents were recorded with 2 mM external Ca2+ ions (in the absence of LCC agonists), using cell-attached patches on K-depolarized adult rat ventricular myocytes. The voltage-dependence of the peak probability of channel opening (Po vs. Vm) displayed a maximum value of 0.3, a midpoint of -12 mV, and a slope factor of 8.5. The maximum value for Po of the unitary LCC was significantly higher than previously assumed, under physiologic conditions. We also found that the mean open dwell time of the unitary LCC increased twofold with depolarization, ranging from 0.53 +/- 0.02 ms at -30 mV to 1.08 +/- 0.03 ms at 0 mV. The increase in mean LCC open time with depolarization counterbalanced the decrease in the single LCC current amplitude; the latter due to the decrease in driving force for Ca2+ ion entry. Thus, the average amount of Ca2+ ions entering through an individual LCC opening (similar to 300-400 ions) remained relatively constant over this range of potentials. These novel results establish the voltage-dependence of unitary LCC gating kinetics using a physiologic Ca2+ ion concentration. Moreover, they provide insight into local Ca2+-induced Ca2+ release and a more accurate basis for mathematical modeling of excitation-contraction coupling in cardiac myocytes. (C) 2010 Elsevier Inc. All rights reserved. C1 [Josephson, Ira R.] CUNY, Sch Med, Dept Physiol & Pharmacol, New York, NY 10031 USA. [Guia, Antonio] AVIVA Biosci Corp, San Diego, CA USA. [Josephson, Ira R.; Sobie, Eric A.; Lederer, W. Jonathan] Univ Maryland, Maryland Biotechnol Inst, Ctr Med Biotechnol, Inst Mol Cardiol, Baltimore, MD 21201 USA. [Lakatta, Edward G.; Stern, Michael D.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Sobie, Eric A.] Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY USA. RP Josephson, IR (reprint author), CUNY, Sch Med, Dept Physiol & Pharmacol, 138th St & Convent Ave, New York, NY 10031 USA. EM josephso@med.cuny.edu FU NIH, National Institute on Aging; National Heart Lung and Blood Institute; National Research Council FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging, and grants from the National Heart Lung and Blood Institute (W.J.L. and E.A.S.). Dr. Josephson was a recipient of a National Research Council Senior Research Associate Award. The author thanks Dr. Christian Soeller for many helpful discussions. NR 36 TC 5 Z9 6 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 4 PY 2010 VL 396 IS 3 BP 763 EP 766 DI 10.1016/j.bbrc.2010.05.016 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 610DG UT WOS:000278710200032 PM 20457123 ER PT J AU Westmoreland, JW Summers, JA Holland, CL Resnick, MA Lewis, LK AF Westmoreland, James W. Summers, Jennifer A. Holland, Cory L. Resnick, Michael A. Lewis, L. Kevin TI Blunt-ended DNA double-strand breaks induced by endonucleases PvuII and EcoRV are poor substrates for repair in Saccharomyces cerevisiae SO DNA REPAIR LA English DT Article DE Endonuclease; DNA repair; End-joining; Homologous recombination; Double-strand break ID HOMOLOGOUS RECOMBINATION; RESTRICTION ENDONUCLEASES; CHROMOSOMAL-ABERRATIONS; CHECKPOINT ACTIVATION; IONIZING-RADIATION; DAMAGE CHECKPOINT; YEAST; PROTEINS; PATHWAYS; MAINTENANCE AB Most mechanistic studies of repair of DNA double-strand breaks (DSBs) produced by in vivo expression of endonucleases have utilized enzymes that produce cohesive-ended DSBs such as HO, I-Scel and EcoRI. We have developed systems for expression of PvuII and EcoRV, nucleases that produce DSBs containing blunt ends, using a modified GAL1 promoter that has reduced basal activity. Expression of PvuII and EcoRV caused growth inhibition and strong cell killing in both haploid and diploid yeast cells. Surprisingly, there was little difference in sensitivities of wildtype cells and mutants defective in homologous recombination, nonhomologous end-joining (NNEJ), or both pathways. Physical analysis using standard and pulsed field gel electrophoresis demonstrated time-dependent breakage of chromosomal DNA within cells. Although ionizing radiation-induced DSBs were largely repaired within 4 h, no repair of PvuII-induced breaks could be detected in diploid cells, even after arrest in G2/M. Rare survivors of PvuII expression had an increased frequency of chromosome XII deletions, an indication that a fraction of the induced DSBs could be repaired by an error-prone process. These results indicate that, unlike DSBs with complementary single-stranded DNA overhangs, blunt-ended DSBs in yeast chromosomes are poor substrates for repair by either NHEJ or recombination. (C) 2010 Elsevier B.V. All rights reserved. C1 [Summers, Jennifer A.; Holland, Cory L.; Lewis, L. Kevin] SW Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. [Westmoreland, James W.; Resnick, Michael A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Lewis, LK (reprint author), SW Texas State Univ, Dept Chem & Biochem, 601 Univ Dr, San Marcos, TX 78666 USA. EM LL18@txstate.edu FU National Institutes of Health [1R15AG028520-01A1]; Welch Foundation; NIEHS (NIH, DHHS) [1Z01ES065073] FX The authors wish to thank Robert Blumenthal and Stephen Halford for gifts of PvuII and EcoRV gene plasmids. LKL was supported in part by National Institutes of Health grant 1R15AG028520-01A1 and a departmental grant from the Welch Foundation. MAR and JWW were supported by the Intramural Research Program of the NIEHS (NIH, DHHS) under project 1Z01ES065073. NR 52 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 4 PY 2010 VL 9 IS 6 BP 617 EP 626 DI 10.1016/j.dnarep.2010.02.008 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 617TM UT WOS:000279304800003 PM 20356803 ER PT J AU Popuri, V Croteau, DL Bohr, VA AF Popuri, Venkateswarlu Croteau, Deborah L. Bohr, Vilhelm A. TI Substrate specific stimulation of NEIL1 by WRN but not the other human RecQ helicases SO DNA REPAIR LA English DT Article DE DNA repair; Base excision repair; NEIL1; NEIL2; RecQ helicase; WRN ID BASE EXCISION-REPAIR; WERNER-SYNDROME PROTEIN; DNA GLYCOSYLASE NEIL1; OXIDIZED BASES; ENDONUCLEASE-VIII; REPLICATION FORK; HUMAN-CELLS; DAMAGE; IDENTIFICATION; PATHWAY AB NEIL1 the mammalian homolog of Escherichia coli endonuclease VIII, is a DNA glycosylase that repairs ring-fragmented purines, saturated pyrimidines and several oxidative lesions like 5-hydroxyuracil, 5-hydroxycytosine, etc. Previous studies from our laboratory have shown that Werner Syndrome protein (WRN), one of the five human RecQ helicases, stimulates NEIL1 DNA glycosylase activity on oxidative DNA lesions. The goal of this study was to extend this observation and analyze the interaction between NEIL1 and all five human RecQ helicases. The DNA substrate specificity of the interaction between WRN and NEIL1 was also analyzed. The results indicate that WRN is the only human RecQ helicase that stimulates NEIL1 DNA glycosylase activity, and that this stimulation requires a double-stranded DNA substrate. (C) 2010 Published by Elsevier B.V. C1 [Popuri, Venkateswarlu; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21229 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21229 USA. EM vbohr@nih.gov FU NIH, National Institute on Aging FX We thank the members of Laboratory of Molecular Gerontology (LMG), Dr. Avik Ghosh and Dr. Dharmendra Kumar Singh for critical reading and constructive comments on the manuscript. We would like to thank Drs. Tomasz Kulikowicz and Takashi Tadokoro for construction of the pCMV24-3xFlag-Myc tagged RecQ4 and RecQ5 vectors [34]. We thank Dr. Robert M. Brosh (Jr) for RECQ1 protein. This work was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 34 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD JUN 4 PY 2010 VL 9 IS 6 BP 636 EP 642 DI 10.1016/j.dnarep.2010.02.012 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 617TM UT WOS:000279304800005 PM 20346739 ER PT J AU Haggstrom, DA Clauser, SB Taplin, SH AF Haggstrom, David A. Clauser, Steven B. Taplin, Stephen H. TI The health disparities cancer collaborative: a case study of practice registry measurement in a quality improvement collaborative SO IMPLEMENTATION SCIENCE LA English DT Article ID CHRONIC DISEASE; CARE; CENTERS; PERFORMANCE; ORGANIZATIONS; BREAST AB Background: Practice registry measurement provides a foundation for quality improvement, but experiences in practice are not widely reported. One setting where practice registry measurement has been implemented is the Health Resources and Services Administration's Health Disparities Cancer Collaborative (HDCC). Methods: Using practice registry data from 16 community health centers participating in the HDCC, we determined the completeness of data for screening, follow-up, and treatment measures. We determined the size of the change in cancer care processes that an aggregation of practices has adequate power to detect. We modeled different ways of presenting before/after changes in cancer screening, including count and proportion data at both the individual health center and aggregate collaborative level. Results: All participating health centers reported data for cancer screening, but less than a third reported data regarding timely follow-up. For individual cancers, the aggregate HDCC had adequate power to detect a 2 to 3% change in cancer screening, but only had the power to detect a change of 40% or more in the initiation of treatment. Almost every health center (98%) improved cancer screening based upon count data, while fewer (77%) improved cancer screening based upon proportion data. The aggregate collaborative appeared to increase breast, cervical, and colorectal cancer screening rates by 12%, 15%, and 4%, respectively (p < 0.001 for all before/after comparisons). In subgroup analyses, significant changes were detectable among individual health centers less than one-half of the time because of small numbers of events. Conclusions: The aggregate HDCC registries had both adequate reporting rates and power to detect significant changes in cancer screening, but not follow-up care. Different measures provided different answers about improvements in cancer screening; more definitive evaluation would require validation of the registries. Limits to the implementation and interpretation of practice registry measurement in the HDCC highlight challenges and opportunities for local and aggregate quality improvement activities. C1 [Haggstrom, David A.] Roudebush VAMC, VA Hlth Serv Res & Dev Ctr Implementing Evidence, Indianapolis, IN USA. [Haggstrom, David A.] IU Sch Med, Div Gen Internal Med & Geriatr, Dept Med, Indianapolis, IN USA. [Haggstrom, David A.] Indiana Univ, Regenstrief Inst Inc, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Clauser, Steven B.; Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Haggstrom, DA (reprint author), Roudebush VAMC, VA Hlth Serv Res & Dev Ctr Implementing Evidence, Indianapolis, IN USA. EM dahaggst@iupui.edu FU VA Award [CD207016-2]; VA/Robert Wood Johnson Foundation FX Dr. Haggstrom is the recipient of VA Award CD207016-2 and a VA/Robert Wood Johnson Foundation Physician Faculty Scholar. Jason Sutherland, Ph.D., Indiana University, Department of Medicine, Division of Biostatistics, contributed to the statistical power analyses. Anne Rodgers, a scientific writer, reviewed and proposed suggestions to a draft of the paper with the support of the Outcomes Research Branch, National Cancer Institute. Ahmed Calvo, MD, MPH, FAAFP, Director & CMO for the HRSA Health Disparities Collaboratives, has contributed his considerable insight and support throughout the evaluation process. NR 37 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JUN 4 PY 2010 VL 5 AR 42 DI 10.1186/1748-5908-5-42 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 627DT UT WOS:000280020100001 PM 20525355 ER PT J AU Li, HX Han, M Bernier, M Zheng, B Sun, SG Su, M Zhang, R Fu, JR Wen, JK AF Li, Hui-xuan Han, Mei Bernier, Michel Zheng, Bin Sun, Shao-guang Su, Ming Zhang, Rui Fu, Jian-ran Wen, Jin-kun TI Kruppel-like Factor 4 Promotes Differentiation by Transforming Growth Factor-beta Receptor-mediated Smad and p38 MAPK Signaling in Vascular Smooth Muscle Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-RETINOIC ACID; TGF-BETA; TRANSCRIPTION FACTORS; NEOINTIMAL FORMATION; GENE-EXPRESSION; DOWN-REGULATION; MARKER GENES; I RECEPTOR; ACTIVATION; INHIBITION AB KLF4 (Kruppel-like factor 4) has been implicated in vascular smooth muscle cell (VSMC) differentiation induced by transforming growth factor beta (TGF-beta). However, the role of KLF4 and mechanism of KLF4 actions in regulating TGF-beta signaling in VSMCs remain unclear. In this study, we showed that TGF-beta 1 inhibited cell cycle progression and induced differentiation in cultured rat VSMCs. This activity of TGF-beta 1 was accompanied by up-regulation of KLF4, with concomitant increase in T beta RI (TGF-beta type I receptor) expression. KLF4 was found to transduce TGF-beta 1 signals via phosphorylation-mediated activation of Smad2, Smad3, and p38 MAPK. The activation of both pathways, in turn, increased the phosphorylation of KLF4, which enabled the formation of KLF4-Smad2 complex in response to TGF-beta 1. Chromatin immunoprecipitation studies and oligonucleotide pull-down assays showed the direct binding of KLF4 to the KLF4-binding sites 2 and 3 of the T beta RI promoter and the recruitment of Smad2 to the Smad-responsive region. Formation of a stable KLF4-Smad2 complex in the promoter's Smad-responsive region mediated cooperative T beta RI promoter transcription in response to TGF-beta 1. These results suggest that KLF4-dependent regulation of Smad and p38 MAPK signaling via T beta RI requires prior phosphorylation of KLF4 through Smad and p38 MAPK pathways. This study demonstrates a novel mechanism by which TGF-beta 1 regulates VSMC differentiation. C1 [Li, Hui-xuan; Han, Mei; Zheng, Bin; Sun, Shao-guang; Su, Ming; Zhang, Rui; Fu, Jian-ran; Wen, Jin-kun] Hebei Med Univ, China Minist Educ, Key Lab Neural & Vasc Biol, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China. [Li, Hui-xuan] Hebei Univ Econ & Business, Coll Biol Sci & Engn, Shijiazhuang 050061, Peoples R China. [Bernier, Michel] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Wen, JK (reprint author), Hebei Med Univ, China Minist Educ, Key Lab Neural & Vasc Biol, Dept Biochem & Mol Biol, 361 Zhongshan E Rd, Shijiazhuang 050017, Peoples R China. EM wjk@hebmu.edu.cn RI Cheng, Yunhui/A-5668-2010; OI Bernier, Michel/0000-0002-5948-368X FU National Institutes of Health, NIA; National Natural Science Foundation of China [30971457, 90919035]; Ministry of Science and Technology of China [2008CB517402]; Natural Science Foundation of Hebei Province [C2008001049] FX This work was supported, in whole or in part, by the National Institutes of Health, NIA, Intramural Research Program. This work is also supported by National Natural Science Foundation of China Grants 30971457 and 90919035, Special Fund for Preliminary Research of Key Basic Research Project of the Ministry of Science and Technology of China Grant 2008CB517402, and Natural Science Foundation of Hebei Province Grant C2008001049. NR 50 TC 38 Z9 45 U1 1 U2 4 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 JUN 4 PY 2010 VL 285 IS 23 BP 17846 EP 17856 DI 10.1074/jbc.M109.076992 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400062 PM 20375011 ER PT J AU Tokesi, N Lehotzky, A Horvath, I Szabo, B Olah, J Lau, P Ovadi, J AF Tokesi, Natalia Lehotzky, Attila Horvath, Istvan Szabo, Balint Olah, Judit Lau, Pierre Ovadi, Judit TI TPPP/p25 Promotes Tubulin Acetylation by Inhibiting Histone Deacetylase 6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-TUBULIN; POSTTRANSLATIONAL MODIFICATIONS; PROTEIN TPPP/P25; OLIGODENDROCYTE DIFFERENTIATION; MICROTUBULE STABILITY; CELL MOTILITY; RAT-BRAIN; HDAC6; TAU; NEURONS AB TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and is aligned along the microtubule network in transfected mammalian cells. In normal human brain, TPPP/p25 is expressed predominantly in oligodendrocytes, where its expression is proved to be crucial for their differentiation process. Here we demonstrated that the expression of TPPP/p25 in HeLa cells, in doxycycline-inducible CHO10 cells, and in the oligodendrocyte CG-4 cells promoted the acetylation of alpha-tubulin at residue Lys-40, whereas its down-regulation by specific small interfering RNA in CG-4 cells or by the withdrawal of doxycycline from CHO10 cells decreased the acetylation level of alpha-tubulin. Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6. The measurement of HDAC6 activity showed that TPPP/p25 is able to induce almost complete (90%) inhibition at 3 mu M concentration. In addition, treatment of the cells with nocodazole, vinblastine, or cold exposure revealed that microtubule acetylation induced by trichostatin A, a well known HDAC6 inhibitor, does not cause microtubule stabilization. In contrast, the microtubule bundling activity of TPPP/p25 was able to protect the microtubules from depolymerization. Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments. Thus, we suggest that TPPP/p25 is a multiple effector of the microtubule organization. C1 Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1113 Budapest, Hungary. [Szabo, Balint] Eotvos Lorand Univ, Dept Biol Phys, H-1117 Budapest, Hungary. [Lau, Pierre] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. EM ovadi@enzim.hu RI Horvath, Istvan/B-1889-2009; OI Horvath, Istvan/0000-0003-4262-1430; Attila, Lehotzky/0000-0001-5235-1812 FU FP6-2003-LIFESCIHEALTH-I: BioSim; Hungarian National Scientific Research Fund [OTKA T-067963, OTKA F-49795]; ELTE CellCom RET FX This work was supported by FP6-2003-LIFESCIHEALTH-I: BioSim and by Hungarian National Scientific Research Fund Grants OTKA T-067963 to (J. Ovadi) and OTKA F-49795 and ELTE CellCom RET (to B. S.). NR 51 TC 45 Z9 48 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 2010 VL 285 IS 23 BP 17896 EP 17906 DI 10.1074/jbc.M109.096578 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400066 PM 20308065 ER PT J AU Gao, YJ Balut, CM Bailey, MA Patino-Lopez, G Shaw, S Devor, DC AF Gao, Yajuan Balut, Corina M. Bailey, Mark A. Patino-Lopez, Genaro Shaw, Stephen Devor, Daniel C. TI Recycling of the Ca2+-activated K+ Channel, KCa2.3, Is Dependent upon RME-1, Rab35/EPI64C, and an N-terminal Domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMALL-CONDUCTANCE; INTERMEDIATE-CONDUCTANCE; HYPERPOLARIZING FACTOR; MESENTERIC-ARTERIES; POTASSIUM CHANNEL; EDHF RESPONSES; BLOOD-PRESSURE; SMOOTH-MUSCLE; CL-SECRETION; CELL LINE AB Regulation of the number of Ca2+-activated K+ channels at the endothelial cell surface contributes to control of the endothelium-derived hyperpolarizing factor response, although this process is poorly understood. To address the fate of plasma membrane-localized KCa2.3, we utilized an extracellular epitope-tagged channel in combination with fluorescence and biotinylation techniques in both human embryonic kidney cells and the human microvascular endothelial cell line, HMEC-1. KCa2.3 was internalized from the plasma membrane and degraded with a time constant of 18 h. Cell surface biotinylation demonstrated that KCa2.3 was rapidly endocytosed and recycled back to the plasma membrane. Consistent with recycling, expression of a dominant negative (DN) RME-1 or Rab35 as well as wild type EPI64C, the Rab35 GTPase-activating protein, resulted in accumulation of KCa2.3 in an intracellular compartment. Expression of DN RME-1, DN Rab35, or wild type EPI64C resulted in a decrease in steady-state plasma membrane expression. Knockdown of EPI64C increased cell surface expression of KCa2.3. Furthermore, the effect of EPI64C was dependent upon its GTPase-activating proteins activity. Co-immunoprecipitation studies confirmed an association between KCa2.3 and both Rab35 and RME-1. In contrast to KCa2.3, KCa3.1 was rapidly endocytosed and degraded in an RME-1 and Rab35-independent manner. A series of N-terminal deletions identified a 12-amino acid region, Gly(206)-Pro(217), as being required for the rapid recycling of KCa2.3. Deletion of Gly(206)-Pro(217) had no effect on the association of KCa2.3 with Rab35 but significantly decreased the association with RME-1. These represent the first studies elucidating the mechanisms by which KCa2.3 is maintained at the plasma membrane. C1 [Devor, Daniel C.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. [Patino-Lopez, Genaro; Shaw, Stephen] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Devor, DC (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, S331 BST,3500 Terrace St, Pittsburgh, PA 15261 USA. EM dd2@pitt.edu OI Patino-Lopez, Genaro/0000-0002-8716-722X FU National Institutes of Health [HL083060, HL092157]; American Heart Fellowship [0825542D] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL083060 and HL092157 (to D. C. D.). This work was also supported by American Heart Fellowship 0825542D (to C. M. B.). NR 47 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 2010 VL 285 IS 23 BP 17938 EP 17953 DI 10.1074/jbc.M109.086553 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400070 PM 20360009 ER PT J AU Hurst, DP Grossfield, A Lynch, DL Feller, S Romo, TD Gawrisch, K Pitman, MC Reggio, PH AF Hurst, Dow P. Grossfield, Alan Lynch, Diane L. Feller, Scott Romo, Tod D. Gawrisch, Klaus Pitman, Michael C. Reggio, Patricia H. TI A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA(2) ADRENERGIC-RECEPTOR; INDUCED CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; MOLECULAR-DYNAMICS; IONIC LOCK; BETA(2)-ADRENERGIC RECEPTOR; FUNCTIONAL MICRODOMAINS; METARHODOPSIN-II; ARGININE-CAGE; PROTON UPTAKE AB Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (-)-7'-isothiocyanato-11-hydroxy-1',1'dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via the lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, A. (2008) Chem. Biol. 15, 1207-1219). However, the sequence of steps involved in such a lipid pathway entry has not yet been elucidated. Here, we test the hypothesis that the endogenous cannabinoid sn-2-arachidonoylglycerol (2-AG) attains access to the CB2 receptor via the lipid bilayer. To this end, we have employed microsecond time scale all-atom molecular dynamics (MD) simulations of the interaction of 2-AG with CB2 via a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. Results suggest the following: 1) 2-AG first partitions out of bulk lipid at the transmembrane alpha-helix (TMH) 6/7 interface; 2) 2-AG then enters the CB2 receptor binding pocket by passing between TMH6 and TMH7; 3) the entrance of the 2-AG headgroup into the CB2 binding pocket is sufficient to trigger breaking of the intracellular TMH3/6 ionic lock and the movement of the TMH6 intracellular end away from TMH3; and 4) subsequent to protonation at D3.49/D6.30, further 2-AG entry into the ligand binding pocket results in both a W6.48 toggle switch change and a large influx of water. To our knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstration via molecular dynamics of G protein-coupled receptor activation triggered by a ligand binding event. C1 [Reggio, Patricia H.] Univ N Carolina, Dept Chem & Biochem, Ctr Drug Discovery, Greensboro, NC 27402 USA. [Grossfield, Alan; Romo, Tod D.] Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. [Feller, Scott] Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. [Gawrisch, Klaus] NIAAA, NIH, Bethesda, MD 20892 USA. [Pitman, Michael C.] IBM Corp, Thomas J Watson Res Ctr, Computat Biol Ctr, Yorktown Hts, NY 10598 USA. RP Reggio, PH (reprint author), Univ N Carolina, Dept Chem & Biochem, POB 26170, Greensboro, NC 27412 USA. EM phreggio@uncg.edu OI Grossfield, Alan/0000-0002-5877-2789 FU National Institutes of Health, NIDA [DA003934, DA021358]; NIAAA; National Science Foundation [MCB-0543124] FX This work was supported, in whole or in part, by National Institutes of Health Grants DA003934 and DA021358 (to P. H. R.) from NIDA and by grants from NIAAA, Intramural Research program (to K. G.). This work was also supported by National Science Foundation Grant MCB-0543124 (to S. F.). NR 74 TC 96 Z9 96 U1 0 U2 24 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 JUN 4 PY 2010 VL 285 IS 23 BP 17954 EP 17964 DI 10.1074/jbc.M109.041590 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400071 PM 20220143 ER PT J AU Fitzkee, NC Masse, JE Shen, Y Davies, DR Bax, A AF Fitzkee, Nicholas C. Masse, James E. Shen, Yang Davies, David R. Bax, Ad TI Solution Conformation and Dynamics of the HIV-1 Integrase Core Domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR-MAGNETIC-RESONANCE; REFINED SOLUTION STRUCTURE; MODEL-FREE APPROACH; DNA-BINDING DOMAIN; PARAMAGNETIC RELAXATION ENHANCEMENT; PROTEIN SECONDARY STRUCTURE; RIBONUCLEASE-H DOMAIN; TERMINAL HHCC DOMAIN; NMR CHEMICAL-SHIFTS AB The human immunodeficiency virus type 1 (HIV-1) integrase (IN) is a critical enzyme involved in infection. It catalyzes two reactions to integrate the viral cDNA into the host genome, 3' processing and strand transfer, but the dynamic behavior of the active site during catalysis of these two processes remains poorly characterized. NMR spectroscopy can reveal important structural details about enzyme mechanisms, but to date the IN catalytic core domain has proven resistant to such an analysis. Here, we present the first NMR studies of a soluble variant of the catalytic core domain. The NMR chemical shifts are found to corroborate structures observed in crystals, and confirm prior studies suggesting that the alpha 4 helix extends toward the active site. We also observe a dramatic improvement in NMR spectra with increasing MgCl(2) concentration. This improvement suggests a structural transition not only near the active site residues but also throughout the entire molecule as IN binds Mg(2+). In particular, the stability of the core domain is linked to the conformation of its C-terminal helix, which has implications for relative domain orientation in the full-length enzyme. (15)N relaxation experiments further show that, although conformationally flexible, the catalytic loop of IN is not fully disordered in the absence of DNA. Indeed, automated chemical shift-based modeling of the active site loop reveals several stable clusters that show striking similarity to a recent crystal structure of prototype foamy virus IN bound to DNA. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Davies, David R.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), 5 Mem Dr, Bethesda, MD 20892 USA. EM bax@nih.gov RI Shen, Yang/C-3064-2008 OI Shen, Yang/0000-0003-1408-8034 FU NIDDK; Office of the Director, NIH FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program of the NIDDK and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. NR 107 TC 17 Z9 18 U1 0 U2 4 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 JUN 4 PY 2010 VL 285 IS 23 BP 18072 EP 18084 DI 10.1074/jbc.M110.113407 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400082 PM 20363759 ER PT J AU Kim, G Cole, NB Lim, JC Zhao, H Levine, RL AF Kim, Geumsoo Cole, Nelson B. Lim, Jung Chae Zhao, Hang Levine, Rodney L. TI Dual Sites of Protein Initiation Control the Localization and Myristoylation of Methionine Sulfoxide Reductase A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; N-MYRISTOYLATION; OXIDATIVE DAMAGE; GENE ENCODES; SUBCELLULAR-LOCALIZATION; CYTOSOLIC ISOFORMS; MESSENGER-RNAS; A MSRA; MITOCHONDRIAL AB Methionine sulfoxide reductase A is an essential enzyme in the antioxidant system, which scavenges reactive oxygen species through cyclic oxidation and reduction of methionine and methionine sulfoxide. In mammals, one gene encodes two forms of the reductase, one targeted to the cytosol and the other to mitochondria. The cytosolic form displays faster mobility than the mitochondrial form, suggesting a lower molecular weight for the former. The apparent size difference and targeting to two cellular compartments had been proposed to result from differential splicing of mRNA. We now show that differential targeting is effected by use of two initiation sites, one of which includes a mitochondrial targeting sequence, whereas the other does not. We also demonstrate that the mass of the cytosolic form is not less than that of the mitochondrial form; the faster mobility of cytosolic form is due to its myristoylation. Lipidation of methionine sulfoxide reductase A occurs in the mouse, in transfected tissue culture cells, and even in a cell-free protein synthesis system. The physiologic role of myristoylation of MsrA remains to be elucidated. C1 [Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Cole, Nelson B.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Zhao, Hang/A-2558-2012; Levine, Rodney/D-9885-2011 FU National Institutes of Health, NHLBI FX This work was supported in whole by the National Institutes of Health, NHLBI, Intramural Research Program. NR 49 TC 35 Z9 39 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 4 PY 2010 VL 285 IS 23 BP 18085 EP 18094 DI 10.1074/jbc.M110.119701 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602IT UT WOS:000278133400083 PM 20368336 ER PT J AU Lee, S Mahler, B Toward, J Jones, B Wyatt, K Dong, LJ Wistow, G Wu, ZR AF Lee, Soojin Mahler, Bryon Toward, Jodie Jones, Blake Wyatt, Keith Dong, Lijin Wistow, Graeme Wu, Zhengrong TI A Single Destabilizing Mutation (F9S) Promotes Concerted Unfolding of an Entire Globular Domain in gamma S-Crystallin SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE H/D exchange; gamma S-crystallin; amyloid; denaturation; cataract ID X-RAY-ANALYSIS; ISOTOPICALLY ENRICHED PROTEINS; TRIPLE-RESONANCE NMR; FIBRILS IN-VITRO; BOVINE EYE LENS; HYDROGEN-EXCHANGE; C-CRYSTALLIN; CONGENITAL CATARACTS; DIPOLAR COUPLINGS; ALPHA-CRYSTALLIN AB Conformational change and aggregation of native proteins are associated with many serious age-related and neurological diseases. gamma S-Crystallin is a highly stable, abundant structural component of vertebrate eye lens. A single F9S mutation in the N-terminal domain of mouse gamma S-crystallin causes the severe Opj cataract, with disruption of cellular organization and appearance of fibrillar structures in the lens. Although the mutant protein has a near-native fold at room temperature, significant increases in hydrogen/deuterium exchange rates were observed by NMR for all the well-protected beta-sheet core residues throughout the entire N-terminal domain of the mutant protein, resulting in up to a 3.5-kcal/mol reduction in the free energy of the folding/unfolding equilibrium. No difference was detected for the C-terminal domain. At a higher temperature, this effect further increases to allow for a much more uniform exchange rate among the N-terminal core residues and those of the least well-structured surface loops. This suggests a concerted unfolding intermediate of the N-terminal domain, while the C-terminal domain stays intact. Increasing concentrations of guanidinium chloride produced two transitions for the Opj mutant, with an unfolding intermediate at similar to 1 M guanidinium chloride. The consequence of this partial unfolding, whether by elevated temperature or by denaturant, is the formation of thioflavin T staining aggregates, which demonstrated fibril-like morphology by atomic force microscopy. Seeding with the already unfolded protein enhanced the formation of fibrils. The Opj mutant protein provides a model for stress-related unfolding of an essentially normally folded protein and production of aggregates with some of the characteristics of amyloid fibrils. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lee, Soojin; Mahler, Bryon; Toward, Jodie; Jones, Blake; Wu, Zhengrong] Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. [Wyatt, Keith; Dong, Lijin; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA. RP Wu, ZR (reprint author), Ohio State Univ, Dept Biochem, 484 W 12Th Ave, Columbus, OH 43210 USA. EM wu.473@osu.edu FU National Institutes of Health [R21EY018423]; NEI; Art and Science Undergraduate Fellowship; National Science Foundation FX We are very grateful for useful discussions with Dr. Ad Bax (National Institutes of Health) and for technical support provided by the AFM facility at The Ohio State University. Z.W. was funded by National Institutes of Health grant R21EY018423. K.W., L.D., and G.W. were funded by the NEI Intramural Program. J.T. was awarded an Art and Science Undergraduate Fellowship, and B.J. was awarded a National Science Foundation/Research Experiences for Undergraduates grant. NR 68 TC 18 Z9 18 U1 0 U2 11 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 4 PY 2010 VL 399 IS 2 BP 320 EP 330 DI 10.1016/j.jmb.2010.04.003 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 612DI UT WOS:000278876600010 PM 20382156 ER PT J AU Boyd, AS Wood, KJ AF Boyd, Ashleigh S. Wood, Kathryn J. TI Characteristics of the Early Immune Response Following Transplantation of Mouse ES Cell Derived Insulin-Producing Cell Clusters SO PLOS ONE LA English DT Article ID EMBRYONIC STEM-CELLS; ALLOGRAFT-REJECTION; ANTIGEN-EXPRESSION; COMPLEMENT-SYSTEM; INNATE IMMUNITY; HUMAN ISLETS; T-CELLS; TOLERANCE; PRIVILEGE; IMMUNOGENICITY C1 [Boyd, Ashleigh S.; Wood, Kathryn J.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Transplantat Res Immunol Grp, Oxford OX3 9DU, England. [Boyd, Ashleigh S.] Boston Univ, Sch Med, Roger Williams Hosp, NIH Ctr Biomed Res Excellence COBRE Tissue Repair, Providence, RI USA. RP Boyd, AS (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Transplantat Res Immunol Grp, Oxford OX3 9DU, England. EM aboyd@rwmc.org; kathryn.wood@nds.ox.ac.uk FU Medical Research Council; BD Preanalytical Systems Europe; NIH [P20RR018757]; NIH COBRE; Wellcome Trust; European Union; Royal Society Wolfson Research FX Funding for this project was provided to ASB by the Medical Research Council and BD Preanalytical Systems Europe through a Collaborative Studentship and by NIH grant P20RR018757. Additional support was provided by the NIH COBRE administrative core at Roger Williams Medical Center, Wellcome Trust and European Union through the Optistem Network. KJW holds a Royal Society Wolfson Research Merit Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 15 Z9 16 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 4 PY 2010 VL 5 IS 6 AR e10965 DI 10.1371/journal.pone.0010965 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 605XA UT WOS:000278380500010 PM 20532031 ER PT J AU Holmes, EC AF Holmes, Edward C. TI Helping the Resistance SO SCIENCE LA English DT Editorial Material ID OSELTAMIVIR; VIRUSES C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 8 TC 11 Z9 12 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 4 PY 2010 VL 328 IS 5983 BP 1243 EP 1244 DI 10.1126/science.1190994 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 605AC UT WOS:000278318600023 PM 20522766 ER PT J AU Royer, RH Koshiol, J Giambarresi, TR Vasquez, LG Pfeiffer, RM McMaster, ML AF Royer, Regan H. Koshiol, Jill Giambarresi, Therese R. Vasquez, Linda G. Pfeiffer, Ruth M. McMaster, Mary L. TI Differential characteristics of Waldenstrom macroglobulinemia according to patterns of familial aggregation SO BLOOD LA English DT Article ID NON-HODGKIN-LYMPHOMA; IGM MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; LONG-TERM; EPIDEMIOLOGY CONSORTIUM; AUTOIMMUNE-DISEASE; MULTIPLE-MYELOMA; POOLED ANALYSIS; UNITED-STATES; HEPATITIS-C AB Familial aggregation of Waldenstrom macroglobulinemia (WM) and related B-cell disorders (BCDs) suggests a role for genetic factors, but few data address environmental influences. We designed a questionnaire-based study to examine clinical and environmental factors in a cohort of WM families with various patterns of case aggregation. We analyzed data on 103 WM patients and 272 unaffected relatives from 35 multiple-case WM and 46 mixed WM/BCD kindred and 28 nonfamilial (sporadic) WM patients, using logistic regression models with generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association. In this study population, the WM disease process appeared similar among patients regardless of family history. Familial WM patients were more likely than unaffected relatives to report a history of autoimmune disease (OR, 2.27; 95% CI = 1.21-4.28) and infections (OR, 2.13; 95% CI = 1.25-3.64). Familial WM patients were also more likely to report exposure to farming (OR, 2.70; 95% CI = 1.34-5.42), pesticides (OR, 2.83; 95% CI = 1.56-5.11), wood dust (OR, 2.86; 95% CI = 1.54-5.33), and organic solvents (multiple-case WM OR, 4.21; 95% CI = 1.69-10.51) compared with unaffected family members. These data provide clues to both genetic and environmental factors that may influence development of WM. Well-designed case-control studies are needed to confirm these findings. (Blood. 2010; 115(22): 4464-4471) C1 [Royer, Regan H.; Koshiol, Jill; Pfeiffer, Ruth M.; McMaster, Mary L.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Giambarresi, Therese R.; Vasquez, Linda G.] Westat Corp, Rockville, MD USA. [McMaster, Mary L.] US PHS, Dept Hlth & Human Serv, Washington, DC USA. RP McMaster, ML (reprint author), 6120 Execut Blvd,Rm 7010, Bethesda, MD 20892 USA. EM mary.mcmaster@nih.hhs.gov RI Pfeiffer, Ruth /F-4748-2011 FU National Institutes of Health, National Cancer Institute FX This research was possible only with the generous support and participation of our patients and their families.; This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 44 TC 15 Z9 16 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 3 PY 2010 VL 115 IS 22 BP 4464 EP 4471 DI 10.1182/blood-2009-10-247973 PG 8 WC Hematology SC Hematology GA 605UN UT WOS:000278372600024 PM 20308603 ER PT J AU Wong, JCY Zhang, Y Lieuw, KH Tran, MT Forgo, E Weinfurtner, K Alzamora, P Kogan, SC Akagi, K Wolff, L Le Beau, MM Killeen, N Shannon, K AF Wong, Jasmine C. Y. Zhang, Yan Lieuw, Kenneth H. Tran, Mary T. Forgo, Erna Weinfurtner, Kelley Alzamora, Pilar Kogan, Scott C. Akagi, Keiko Wolff, Linda Le Beau, Michelle M. Killeen, Nigel Shannon, Kevin TI Use of chromosome engineering to model a segmental deletion of chromosome band 7q22 found in myeloid malignancies SO BLOOD LA English DT Article ID THERAPY-RELATED MYELODYSPLASIA; LONG-ARM DELETIONS; TUMOR-SUPPRESSOR; MYELOPROLIFERATIVE DISORDER; HEMATOPOIETIC-CELLS; CHILDHOOD MONOSOMY-7; CRE RECOMBINASE; CANDIDATE GENE; LEUKEMIA; MUTATIONS AB Monosomy 7 and del(7q) are associated with adverse features in myeloid malignancies. A 2.5-Mb commonly deleted segment (CDS) of chromosome band 7q22 is implicated as harboring a myeloid tumor suppressor gene (TSG); however, molecular analysis of candidate TSGs has not uncovered loss of function. To determine whether haploinsufficiency for the 7q22 CDS contributes to myeloid leukemogenesis, we performed sequential gene targeting to flank a region of orthologous synteny on mouse chromosome band 5A3 with loxP sites. We then generated Mx1-Cre, 5A3(fl) mutant mice and deleted the targeted interval in vivo. Although excision was inefficient, we confirmed somatic deletion of the 5A3 CDS in the hematopoietic stem cell compartment. Mx1-Cre, 5A3(fl) mice show normal hematologic parameters and do not spontaneously develop myeloid malignancies. The 5A3(fl) deletion does not cooperate with oncogenic Kras(G12D) expression, Nf1 inactivation, or retroviral mutagenesis to accelerate leukemia development and did not modulate responsiveness to antileukemia drugs. These studies demonstrate that it is feasible to somatically delete a large chromosomal segment implicated in tumor suppression in hematopoietic cell populations in vivo; however, our data do not support the hypothesis that the 7q22/5A3 CDS interval contains a myeloid TSG. (Blood. 2010; 115(22): 4524-4532) C1 [Zhang, Yan; Killeen, Nigel] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Wong, Jasmine C. Y.; Tran, Mary T.; Forgo, Erna; Weinfurtner, Kelley; Alzamora, Pilar; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Lieuw, Kenneth H.] Uniformed Univ Hlth Sci, Dept Pediat, Bethesda, MD USA. [Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Akagi, Keiko] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Le Beau, Michelle M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Le Beau, Michelle M.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Shannon, K (reprint author), Helen Diller Family Canc Res Bldg,1450 3rd St,Rm, San Francisco, CA 94158 USA. EM nigel.killeen@ucsf.edu; shannonk@peds.ucsf.edu FU National Institutes of Health [P01CA40046, U01CA84221, R37CA72614]; SCOR (Specialized Center of Research); Leukemia & Lymphoma Society of America FX This study was supported by National Institutes of Health grants P01CA40046 (M.M.L.B, K.S.), U01CA84221 (M.M.L.B, S.C.K, N.K., K.S.), and R37CA72614 (K.S.); and by SCOR (Specialized Center of Research; M.M.L.B., S.C.K., K.S.), Scholar (N.K., S.C.K.), and Fellowship awards from the Leukemia & Lymphoma Society of America (J.C.Y.W.). NR 49 TC 14 Z9 16 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 3 PY 2010 VL 115 IS 22 BP 4524 EP 4532 DI 10.1182/blood-2009-07-232504 PG 9 WC Hematology SC Hematology GA 605UN UT WOS:000278372600031 PM 20233966 ER PT J AU Kim, C Basner, J Lee, B AF Kim, Changhoon Basner, Jodi Lee, Byungkook TI Detecting internally symmetric protein structures SO BMC BIOINFORMATICS LA English DT Article ID RELATE 2 SETS; ALTERNATIVE ALIGNMENTS; SEQUENCE ALIGNMENT; CRYSTAL-STRUCTURE; REPEATS; ALPHA; ALGORITHM; EVOLUTION; ROTATION; VECTORS AB Background: Many functional proteins have a symmetric structure. Most of these are multimeric complexes, which are made of non-symmetric monomers arranged in a symmetric manner. However, there are also a large number of proteins that have a symmetric structure in the monomeric state. These internally symmetric proteins are interesting objects from the point of view of their folding, function, and evolution. Most algorithms that detect the internally symmetric proteins depend on finding repeating units of similar structure and do not use the symmetry information. Results: We describe a new method, called SymD, for detecting symmetric protein structures. The SymD procedure works by comparing the structure to its own copy after the copy is circularly permuted by all possible number of residues. The procedure is relatively insensitive to symmetry-breaking insertions and deletions and amplifies positive signals from symmetry. It finds 70% to 80% of the TIM barrel fold domains in the ASTRAL 40 domain database and 100% of the beta-propellers as symmetric. More globally, 10% to 15% of the proteins in the ASTRAL 40 domain database may be considered symmetric according to this procedure depending on the precise cutoff value used to measure the degree of perfection of the symmetry. Symmetrical proteins occur in all structural classes and can have a closed, circular structure, a cylindrical barrel-like structure, or an open, helical structure. Conclusions: SymD is a sensitive procedure for detecting internally symmetric protein structures. Using this procedure, we estimate that 10% to 15% of the known protein domains may be considered symmetric. We also report an initial, overall view of the types of symmetries and symmetric folds that occur in the protein domain structure universe. C1 [Kim, Changhoon; Basner, Jodi; Lee, Byungkook] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kim, Changhoon] Yonsei Univ, Bioinformat & Mol Design Res Ctr, Seoul 120749, South Korea. RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5120,37 Convent Dr MSC 4264, Bethesda, MD 20892 USA. EM bk@nih.gov FU NIH [P41 RR 01081]; NIH, National Cancer Institute, Center for Cancer Research FX We thank the laboratory members Dr Todd Taylor, Dr Dukka KC, Ms. Chin-Hsien Tai, and Dr B. K. Sathyanarayana for their continued interest and support. Molecular graphics images were produced using the UCSF Chimera [27] package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR 01081). This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 31 TC 17 Z9 17 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 3 PY 2010 VL 11 AR 303 DI 10.1186/1471-2105-11-303 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 623JU UT WOS:000279736600004 PM 20525292 ER PT J AU Tong, JH Ng, DC Chau, SL So, KK Leung, PP Lee, TL Lung, RW Chan, MW Chan, AW Lo, KW To, KF AF Tong, Joanna H. Ng, David C. Chau, Shuk L. So, Ken K. Leung, Patrick P. Lee, Tin L. Lung, Raymond W. Chan, Michael W. Chan, Anthony W. Lo, Kwok W. To, Ka F. TI Putative tumour-suppressor gene DAB2 is frequently down regulated by promoter hypermethylation in nasopharyngeal carcinoma SO BMC CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; NORMAL PROSTATIC EPITHELIUM; EPSTEIN-BARR-VIRUS; DISABLED-2 DAB2; EPIGENETIC INACTIVATION; GASTRIC-CANCER; CELL LINES; C-SRC; DOC-2/DAB2; GROWTH AB Background: Human Disabled-2 (DAB2), is a multi-function signalling molecule that it is frequently down-regulated in human cancers. We aimed to investigate the possible tumour suppressor effect of DAB2 in nasopharyngeal carcinoma (NPC). Methods: We studied the expression of DAB2 in NPC cell lines, xenografts and primary tumour samples. The status of promoter methylation was assessed by methylation specific PCR and bisulfite sequencing. The functional role of DAB2 in NPC was investigated by re-introducing DAB2 expression into NPC cell line C666-1. Results: Decrease or absent of DAB2 transcript was observed in NPC cell lines and xenografts. Loss of DAB2 protein expression was seen in 72% (33/46) of primary NPC as demonstrated by immunohistochemistry. Aberrant DAB2 promoter methylation was detected in 65.2% (30/46) of primary NPC samples by methylation specific PCR. Treatment of the DAB2 negative NPC cell line C666-1 with 5-aza-2'-deoxycytidine resulted in restoration of DAB2 expression in a dose-dependent manner. Overexpression of DAB2 in NPC cell line C666-1 resulted in reduced growth rate and 35% reduction in anchorage-dependent colony formation, and inhibition of serum-induced c-Fos expression compared to vector-transfected controls. Over expression of DAB2 resulted in alterations of multiple pathways as demonstrated by expression profiling and functional network analysis, which confirmed the role of DAB2 as an adaptor molecule involved in multiple receptor-mediated signalling pathways. Conclusions: We report the frequent down regulation of DAB2 in NPC and the promoter hypermethylation contributes to the loss of expression of DAB2. This is the first study demonstrating frequent DAB2 promoter hypermethylation in human cancer. Our functional studies support the putative tumour suppressor effect of DAB2 in NPC cells. C1 [Tong, Joanna H.; Ng, David C.; Chau, Shuk L.; So, Ken K.; Leung, Patrick P.; Lung, Raymond W.; Chan, Anthony W.; Lo, Kwok W.; To, Ka F.] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China. [Lo, Kwok W.; To, Ka F.] Chinese Univ Hong Kong, State Key Lab Oncol S China, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China. [To, Ka F.] Chinese Univ Hong Kong, Inst Digest Dis, Hong Kong, Hong Kong, Peoples R China. [Lee, Tin L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Chan, Michael W.] Natl Chung Cheng Univ, Dept Life Sci, Min Hsiung, Chia Yi, Taiwan. RP To, KF (reprint author), Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China. EM kfto@cuhk.edu.hk RI Raymond , Lung/G-3200-2011; Tong, Joanna/J-9327-2013; Lung, Raymond/D-1274-2014; Lee, Tin-Lap/A-7853-2009; OI Raymond , Lung/0000-0002-0813-7429; Lee, Tin-Lap/0000-0002-6654-0988; Chan, Michael/0000-0003-1431-322X FU Hong Kong Research Grant Council [CUHK4417/05M, CUHK4413/05M]; Li Ka Shing Institute of Health Science FX We thank Dr Sai Wah Tsao for providing us immortalized normal nasopharyngeal epithelial cell line NP69. The study is supported by Hong Kong Research Grant Council, Grant number: CUHK4417/05M and CUHK4413/05M, and Li Ka Shing Institute of Health Science. NR 43 TC 32 Z9 36 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 3 PY 2010 VL 10 AR 253 DI 10.1186/1471-2407-10-253 PG 12 WC Oncology SC Oncology GA 624BL UT WOS:000279791000001 PM 20525238 ER PT J AU Lipina, C Kendall, H McPherron, AC Taylor, PM Hundal, HS AF Lipina, Christopher Kendall, Hannah McPherron, Alexandra C. Taylor, Peter M. Hundal, Harinder S. TI Mechanisms involved in the enhancement of mammalian target of rapamycin signalling and hypertrophy in skeletal muscle of myostatin-deficient mice SO FEBS LETTERS LA English DT Article DE Growth differentiation factor-8; mTOR; p70S6K1; PKB/Akt ID PROTEIN-KINASE-B; MYOBLAST DIFFERENTIATION; MYOTUBE HYPERTROPHY; INSULIN SENSITIVITY; WEIGHT-LOSS; IGF-I; EXPRESSION; AKT; PHOSPHORYLATION; RESISTANCE AB Myostatin deficiency leads to both an increased rate of protein synthesis and skeletal muscle hypertrophy. However, the mechanisms involved in mediating these effects are not yet fully understood. Here, we demonstrate that genetic loss of myostatin leads to enhanced muscle expression of both protein kinase B and mammalian target of rapamycin/S6K signalling components, consistent with their elevated activity. This is associated with a reduction in the expression of PGC1 alpha and COX IV, proteins which play important roles in maintaining mitochondrial function. Furthermore, we show that these changes in signalling and protein expression are largely independent of alterations in intramuscular amino acid content. Our findings, therefore, reveal potential new mechanisms and further contribute to our understanding of myostatin-regulated skeletal muscle growth and function. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved. C1 [Lipina, Christopher; Kendall, Hannah; Taylor, Peter M.; Hundal, Harinder S.] Univ Dundee, Div Mol Physiol, Coll Life Sci, Sir James Black Ctr, Dundee DD1 5EH, Scotland. [McPherron, Alexandra C.] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Hundal, HS (reprint author), Univ Dundee, Div Mol Physiol, Coll Life Sci, Sir James Black Ctr, Dundee DD1 5EH, Scotland. EM h.s.hundal@dundee.ac.uk FU NIH, NIDDK; BBSRC; European Commission [LSHM-CT-20004-005272]; Diabetes Research and Wellness Foundation and Diabetes, UK FX This work was supported by the Intramural Research Program of the NIH, NIDDK, the BBSRC, European Commission (Contract LSHM-CT-20004-005272), Diabetes Research and Wellness Foundation and Diabetes, UK. NR 63 TC 36 Z9 38 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 3 PY 2010 VL 584 IS 11 BP 2403 EP 2408 DI 10.1016/j.febslet.2010.04.039 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 597WN UT WOS:000277793200039 PM 20412806 ER PT J AU Revilla-Lopez, G Torras, J Curco, D Casanovas, J Calaza, MI Zanuy, D Jimenez, AI Cativiela, C Nussinov, R Grodzinski, P Aleman, C AF Revilla-Lopez, Guillem Torras, Juan Curco, David Casanovas, Jordi Isabel Calaza, M. Zanuy, David Jimenez, Ana I. Cativiela, Carlos Nussinov, Ruth Grodzinski, Piotr Aleman, Carlos TI NCAD, a Database Integrating the Intrinsic Conformational Preferences of Non-Coded Amino Acids SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SITE-SPECIFIC INCORPORATION; PROTEIN DATA-BANK; MET-ENKEPHALIN; STEREOSELECTIVE-SYNTHESIS; CYCLOPROPANE ANALOG; AQUEOUS-SOLUTION; SIDE-CHAIN; 1-AMINOCYCLOPENTANE-1-CARBOXYLIC ACID; METHIONINE-ENKEPHALIN; BACKBONE INTERACTIONS AB Peptides and proteins find an ever-increasing number of applications in the biomedical and materials engineering fields. The use of non-proteinogenic amino acids endowed with diverse physicochemical and structural features opens the possibility to design proteins and peptides with novel properties and functions. Moreover, non-proteinogenic residues are particularly useful to control the three-dimensional arrangement of peptidic chains, which is a crucial issue for most applications. However. information regarding such amino acids-also called non-coded, nor-canonical. or non-standard-is visually scattered among publications specialized in quite diverse fields as well as in patents. Making all these data useful to the scientific community requires new tools and a framework for their assembly and coherent organization. We have successfully compiled. organized, and built a database (NCAD, Non-Coded Amino acids Database) containing information about the intrinsic conformational preferences of non-proteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, conformational propensities established experimentally, and applications. The architecture of the database is presented in this work together with the first family of non-coded residues included, namely, alpha-tetrasubstituted a-amino acids. Furthermore, the NCAD usefulness is demonstrated through a test-case application example. C1 [Revilla-Lopez, Guillem; Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain. [Torras, Juan] Univ Politecn Cataluna, Dept Engn Quim, EUETII, Igualada 08700, Spain. [Curco, David] Univ Barcelona, Dept Engn Quim, Fac Quim, E-08028 Barcelona, Spain. [Casanovas, Jordi] Univ Lleida, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. [Isabel Calaza, M.; Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, Dept Quim Organ, Inst Ciencia Mat Aragon, CSIC, E-50009 Zaragoza, Spain. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. NCI, Bethesda, MD 20892 USA. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Aleman, C (reprint author), Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain. EM carlos.aleman@upc.edu RI Revilla-Lopez, Guillem/G-8552-2011; Casanovas, Jordi/B-5435-2013; Zanuy, David/G-3930-2014; Torras, Juan/F-5622-2015 OI Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178; Torras, Juan/0000-0001-8737-7609 FU Ministerio de Ciencia e Innovacion - FEDER [CTQ2007-62245, CTQ2008-00423-E/BQU]; Generalitat de Catalunya [SGR 925]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Computer resources were generously provided by the Centre de Supercomputacio de Catalunya (CESCA). Financial support from Ministerio de Ciencia e Innovacion - FEDER (grants CTQ2007-62245 and CTQ2008-00423-E/BQU; Ramon y Cajal contract for D.Z.), Gobierno de Aragon (research group E40), and Generalitat de Catalunya (research group 2009 SGR 925; XRQTC; ICREA Academia prize for excellence in research to C.A.) is gratefully acknowledged. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the view of the policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 118 TC 5 Z9 5 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUN 3 PY 2010 VL 114 IS 21 BP 7413 EP 7422 DI 10.1021/jp102092m PG 10 WC Chemistry, Physical SC Chemistry GA 600RH UT WOS:000278004300031 PM 20455555 ER PT J AU Fiammenghi, L Ancarani, V Rosales, T Knutson, JR Petrini, M Granato, AM Pancisi, E Ridolfi, L Ridolfi, R Riccobon, A Neyroz, P AF Fiammenghi, Laura Ancarani, Valentina Rosales, Tilman Knutson, Jay R. Petrini, Massimiliano Granato, Anna Maria Pancisi, Elena Ridolfi, Laura Ridolfi, Ruggero Riccobon, Angela Neyroz, Paolo TI FRET microscopy autologous tumor lysate processing in mature dendritic cell vaccine therapy SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CLASS-II COMPLEXES; INFLAMMATORY STIMULI; CANCER; MELANOMA; SURFACE; IMMUNE AB Background: Antigen processing by dendritic cells (DC) exposed to specific stimuli has been well characterized in biological studies. Nonetheless, the question of whether autologous whole tumor lysates (as used in clinical trials) are similarly processed by these cells has not yet been resolved. Methods: In this study, we examined the transfer of peptides from whole tumor lysates to major histocompatibility complex class II molecules (MHC II) in mature dendritic cells (mDC) from a patient with advanced melanoma. Tumor antigenic peptides-MHC II proximity was revealed by Forster Resonance Energy Transfer (FRET) measurements, which effectively extends the application of fluorescence microscopy to the molecular level (<100?). Tumor lysates were labelled with Alexa-488, as the donor, and mDC MHC II HLA-DR molecules were labelled with Alexa-546-conjugated IgG, as the acceptor. Results: We detected significant energy transfer between donor and acceptor-labelled antibodies against HLA-DR at the membrane surface of mDC. FRET data indicated that fluorescent peptide-loaded MHC II molecules start to accumulate on mDC membranes at 16 hr from the maturation stimulus, steeply increasing at 22 hr with sustained higher FRET detected up to 46 hr. Conclusions: The results obtained imply that the patient mDC correctly processed the tumor specific antigens and their display on the mDC surface may be effective for several days. These observations support the rationale for immunogenic efficacy of autologous tumor lysates. C1 [Neyroz, Paolo] Univ Bologna, Dept Biochem G Moruzzi, Rimini, Italy. [Fiammenghi, Laura; Ancarani, Valentina; Petrini, Massimiliano; Granato, Anna Maria; Pancisi, Elena; Ridolfi, Laura; Ridolfi, Ruggero; Riccobon, Angela] Ist Sci Romagnolo Studio & Cura Tumori IRST, Immunotherapy & Somat Cell Therapy Lab, Meldola, Italy. [Rosales, Tilman; Knutson, Jay R.] NHLBI, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. RP Neyroz, P (reprint author), Univ Bologna, Dept Biochem G Moruzzi, Rimini, Italy. EM paolo.neyroz@unibo.it OI NEYROZ, PAOLO/0000-0002-9790-4027; , laura/0000-0003-1870-3380 FU University of Bologna; Compagnia di San Paolo, Torino FX The authors wish to thank Dr. Sundararajan Venkatesan and Dr. Ling Yi from the National Institute of Allergy and Infectious Diseases (NIH, Bethesda, USA) for helpful discussion and assistance in running the Leica SP5 TCS confocal apparatus. This project was supported by the Research Program of the Polo Scientifico - Didattico di Rimini, RFO 2007 at the University of Bologna, and was partially funded by Compagnia di San Paolo, Torino. The authors also wish to thank Dr. Ian Seymour for editing the manuscript. NR 18 TC 4 Z9 5 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 3 PY 2010 VL 8 AR 52 DI 10.1186/1479-5876-8-52 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 628ZU UT WOS:000280164600001 PM 20525246 ER PT J AU Richter, HE Albo, ME Zyczynski, HM Kenton, K Norton, PA Sirls, LT Kraus, SR Chai, TC Lemack, GE Dandreo, KJ Varner, RE Menefee, S Ghetti, C Brubaker, L Nygaard, I Khandwala, S Rozanski, TA Johnson, H Schaffer, J Stoddard, AM Holley, RL Nager, CW Moalli, P Mueller, E Arisco, AM Corton, M Tennstedt, S Chang, TD Gormley, EA Litman, HJ AF Richter, Holly E. Albo, Michael E. Zyczynski, Halina M. Kenton, Kimberly Norton, Peggy A. Sirls, Larry T. Kraus, Stephen R. Chai, Toby C. Lemack, Gary E. Dandreo, Kimberly J. Varner, R. Edward Menefee, Shawn Ghetti, Chiara Brubaker, Linda Nygaard, Ingrid Khandwala, Salil Rozanski, Thomas A. Johnson, Harry Schaffer, Joseph Stoddard, Anne M. Holley, Robert L. Nager, Charles W. Moalli, Pamela Mueller, Elizabeth Arisco, Amy M. Corton, Marlene Tennstedt, Sharon Chang, T. Debuene Gormley, E. Ann Litman, Heather J. CA Urinary Incontinence Treatment Net TI Retropubic versus Transobturator Midurethral Slings for Stress Incontinence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; FREE VAGINAL TAPE; URINARY-INCONTINENCE; COMPLICATIONS; WOMEN; METAANALYSIS; COLPOSUSPENSION; DEFINITION; IMPACT; TREAT AB BACKGROUND Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications. METHODS We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/- 12 percentage points. RESULTS A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P = 0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P = 0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life. CONCLUSIONS The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.) C1 [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. [Albo, Michael E.; Nager, Charles W.] Univ Calif San Diego, San Diego, CA 92103 USA. [Menefee, Shawn] Kaiser Permanente Calif, San Diego, CA USA. [Zyczynski, Halina M.; Ghetti, Chiara; Moalli, Pamela] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Norton, Peggy A.; Nygaard, Ingrid] Univ Utah, Salt Lake City, UT USA. [Kenton, Kimberly; Brubaker, Linda; Mueller, Elizabeth] Loyola Univ, Maywood, IL 60153 USA. [Sirls, Larry T.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Kraus, Stephen R.; Rozanski, Thomas A.; Arisco, Amy M.] Univ Texas San Antonio, San Antonio, TX USA. [Chai, Toby C.; Johnson, Harry] Univ Maryland, Baltimore, MD 21201 USA. [Lemack, Gary E.; Schaffer, Joseph; Corton, Marlene] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Dandreo, Kimberly J.; Stoddard, Anne M.; Tennstedt, Sharon; Litman, Heather J.] New England Res Inst, Watertown, MA 02172 USA. [Khandwala, Salil] Oakwood Hosp, Dearborn, MI USA. [Chang, T. Debuene] NIH, Bethesda, MD 20892 USA. [Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Richter, HE (reprint author), Univ Alabama, Dept Obstet & Gynecol, 1700 6th Ave S,Suite 10382, Birmingham, AL 35233 USA. EM hrichter@uabmc.edu OI Wadie, Bassem/0000-0002-6977-6849 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401]; National Institute of Child Health and Human Development FX Supported by cooperative agreements (U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, and U01 DK60401) from the National Institute of Diabetes and Digestive and Kidney Diseases and by the National Institute of Child Health and Human Development. NR 31 TC 245 Z9 252 U1 1 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 2010 VL 362 IS 22 BP 2066 EP 2076 DI 10.1056/NEJMoa0912658 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 603XU UT WOS:000278242200006 PM 20479459 ER PT J AU Follett, KA Weaver, FM Stern, M Hur, K Harris, CL Luo, P Marks, WJ Rothlind, J Sagher, O Moy, C Pahwa, R Burchiel, K Hogarth, P Lai, EC Duda, JE Holloway, K Samii, A Horn, S Bronstein, JM Stoner, G Starr, PA Simpson, R Baltuch, G De Salles, A Huang, GD Reda, DJ AF Follett, Kenneth A. Weaver, Frances M. Stern, Matthew Hur, Kwan Harris, Crystal L. Luo, Ping Marks, William J., Jr. Rothlind, Johannes Sagher, Oren Moy, Claudia Pahwa, Rajesh Burchiel, Kim Hogarth, Penelope Lai, Eugene C. Duda, John E. Holloway, Kathryn Samii, Ali Horn, Stacy Bronstein, Jeff M. Stoner, Gatana Starr, Philip A. Simpson, Richard Baltuch, Gordon De Salles, Antonio Huang, Grant D. Reda, Domenic J. CA CSP 468 Study Grp TI Pallidal versus Subthalamic Deep-Brain Stimulation for Parkinson's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; GLOBUS-PALLIDUS; FOLLOW-UP; MOTOR FLUCTUATIONS; NUCLEUS; TRIAL; VALIDATION; EFFICACY AB BACKGROUND Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.) C1 [Weaver, Frances M.] Hines Vet Affairs Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Follett, Kenneth A.] Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. [Stoner, Gatana] Univ Iowa Hlth Care, Iowa City, IA USA. [Follett, Kenneth A.] Univ Nebraska Med Ctr, Omaha, NE USA. [Hur, Kwan; Luo, Ping; Reda, Domenic J.] Hines Vet Affairs Hosp, Cooperat Studies Coordinating Ctr, Hines, IL 60141 USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Stern, Matthew; Horn, Stacy; Baltuch, Gordon] Univ Penn Hlth Syst, Philadelphia, PA USA. [Stern, Matthew; Duda, John E.; Baltuch, Gordon] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Harris, Crystal L.] VA Cooperat Studies Program, Clin Res Pharm, Albuquerque, NM USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Marks, William J., Jr.; Rothlind, Johannes; Starr, Philip A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sagher, Oren] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Moy, Claudia] NINDS, Rockville, MD USA. [Pahwa, Rajesh] Univ Kansas, Med Ctr, Kansas City, MO USA. [Burchiel, Kim] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA. [Lai, Eugene C.; Simpson, Richard] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Lai, Eugene C.; Simpson, Richard] Baylor Coll Med, Houston, TX 77030 USA. [Hur, Kwan] Richmond VA Med Ctr, Richmond, VA USA. [Samii, Ali] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Bronstein, Jeff M.; De Salles, Antonio] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Huang, Grant D.] US Dept Vet Affairs, Cooperat Studies Program, Cent Off, Washington, DC USA. RP Weaver, FM (reprint author), Hines Vet Affairs Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave,151H, Hines, IL 60141 USA. EM frances.weaver@va.gov FU Department of Veterans Affairs Office of Research and Development; National Institute of Neurological Disorders and Stroke; Medtronic; Novartis; Teva; Schering-Plough; Boehringer Ingelheim; Vernalis; Ipsen; Ceregene; Sofamor Danek; Schering-Plough Research Institute; Samueli Institute; Ipsen Pharmaceuticals; Teva Pharmaceuticals; Boston Scientific; SurgiVision FX Supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, the National Institute of Neurological Disorders and Stroke, and Medtronic.; Dr. Stern reports receiving consulting fees from Novartis, Teva, Schering-Plough, Boehringer Ingelheim, Vernalis, and Ipsen and lecture fees from Novartis and having an equity interest in Adamis; Dr. Harris, having an equity interest in Johnson & Johnson; Dr. Marks, receiving consulting and lecture fees from Medtronic and grant support from Boehringer Ingelheim and Ceregene; Dr. Pahwa, receiving consulting and lecture fees from Medtronic; Dr. Burchiel, having an equity interest in Medtronic and receiving grant support from Medtronic and Sofamor Danek; Dr. Hogarth, receiving grant support from Schering-Plough Research Institute; Dr. Lai, receiving grant support from Medtronic; Dr. Duda, receiving consulting fees from Boehringer Ingelheim and grant support from the Samueli Institute; Dr. Holloway, receiving consulting fees and grant support from Medtronic; Dr. Samii, receiving lecture fees from Ipsen Pharmaceuticals, Boehringer Ingelheim, and Teva Pharmaceuticals; Dr. Starr, receiving consulting fees from Medtronic and Boston Scientific and grant support from SurgiVision; Dr. Simpson, receiving consulting and lecture fees from Medtronic; and Dr. De Salles, receiving fellowship support from Medtronic. No other potential conflict of interest relevant to this article was reported. NR 25 TC 411 Z9 421 U1 6 U2 52 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 3 PY 2010 VL 362 IS 22 BP 2077 EP 2091 DI 10.1056/NEJMoa0907083 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 603XU UT WOS:000278242200007 PM 20519680 ER PT J AU Matrone, MA Whipple, RA Thompson, K Cho, EH Vitolo, MI Balzer, EM Yoon, JR Ioffe, OB Tuttle, KC Tan, M Martin, SS AF Matrone, M. A. Whipple, R. A. Thompson, K. Cho, E. H. Vitolo, M. I. Balzer, E. M. Yoon, J. R. Ioffe, O. B. Tuttle, K. C. Tan, M. Martin, S. S. TI Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells SO ONCOGENE LA English DT Article DE microtentacles; tau; microtubule-associated proteins; microtubules; circulating tumor cells ID MICROTUBULE-ASSOCIATED PROTEINS; PACLITAXEL SENSITIVITY; CANCER; NEURODEGENERATION; 3-REPEAT-TAU; CHEMOTHERAPY; 4-REPEAT-TAU; DYNAMICS; ADHESION; DISEASE AB The cytoskeletal organization of detached and circulating tumor cells (CTCs) is currently not well defined and may provide potential targets for new therapies to limit metastatic tumor spread. In vivo, CTCs reattach in distant tissues by a mechanism that is tubulin-dependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles (McTN), which we have recently identified in detached breast tumor cells. In this study, we aimed to investigate how McTN formation is affected by the microtubule-associated protein, tau, which is expressed in a subset of chemotherapy-resistant breast cancers. We demonstrate that endogenous tau protein localizes to McTNs and is both necessary and sufficient to promote McTN extension in detached breast tumor cells. Tau-induced McTNs increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of patient-matched primary and metastatic tumors reveals that 52% possess tau expression in metastases and 26% display significantly increased tau expression over disease progression. Tau enrichment in metastatic tumors and the ability of tau to promote tumor cell reattachment through McTN formation support a model in which tau-induced microtubule stabilization provides a selective advantage during tumor metastasis. Oncogene (2010) 29, 3217-3227; doi: 10.1038/onc.2010.68; published online 15 March 2010 C1 [Martin, S. S.] Univ Maryland, Greenebaum Canc Ctr, Sch Med, Program Mol Med, Baltimore, MD 21201 USA. [Whipple, R. A.; Thompson, K.; Vitolo, M. I.; Tuttle, K. C.; Tan, M.; Martin, S. S.] Univ Maryland, Marlene & Stewart Greenebaum NCI Canc Ctr, Sch Med, Baltimore, MD 21201 USA. [Yoon, J. R.; Martin, S. S.] Univ Maryland, Dept Physiol, Sch Med, Baltimore, MD 21201 USA. [Ioffe, O. B.] Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. [Tan, M.] Univ Maryland, Dept Epidemiol & Prevent Med, Sch Med, Baltimore, MD 21201 USA. RP Martin, SS (reprint author), Univ Maryland, Greenebaum Canc Ctr, Sch Med, Program Mol Med, 655 W Baltimore St,Rm 10-029, Baltimore, MD 21201 USA. EM ssmartin@som.umaryland.edu FU National Cancer Institute [R01-CA124704]; USA Medical Research and Materiel Command [BC061047]; Flight Attendants Medical Research Institute [CIA-062497] FX This study was supported by Grant R01-CA124704 from National Cancer Institute, Breast Cancer Idea Award from USA Medical Research and Materiel Command (BC061047) and a Clinical Innovator Award from Flight Attendants Medical Research Institute (CIA-062497). We thank Dr I-Chu Tseng and the Dr Chen-Yong Lin laboratory for immunohistochemistry assistance, Dr Larry Changwan Lu for his assistance with the statistical analyses, Aric Colunga and the Dr Laure Aurelian laboratory for imaging assistance, Dr William Twaddell for assistance with pathological scoring of vimentin staining, and Dr Michele Weiss for Figure 6 assistance. NR 41 TC 30 Z9 30 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 3 PY 2010 VL 29 IS 22 BP 3217 EP 3227 DI 10.1038/onc.2010.68 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 605BA UT WOS:000278321100005 PM 20228842 ER PT J AU Collings, CK Fernandez, AG Pitschka, CG Hawkins, TB Anderson, JN AF Collings, Clayton K. Fernandez, Alfonso G. Pitschka, Chad G. Hawkins, Troy B. Anderson, John N. TI Oligonucleotide Sequence Motifs as Nucleosome Positioning Signals SO PLOS ONE LA English DT Article ID DEPENDENT DNA-STRUCTURE; T-G-G; HIGH-RESOLUTION; IN-VIVO; SACCHAROMYCES-CEREVISIAE; CONFORMATIONAL MAPS; DINUCLEOTIDE STEPS; HUMAN GENOME; CORE DNA; B-DNA AB To gain a better understanding of the sequence patterns that characterize positioned nucleosomes, we first performed an analysis of the periodicities of the 256 tetranucleotides in a yeast genome-wide library of nucleosomal DNA sequences that was prepared by in vitro reconstitution. The approach entailed the identification and analysis of 24 unique tetranucleotides that were defined by 8 consensus sequences. These consensus sequences were shown to be responsible for most if not all of the tetranucleotide and dinucleotide periodicities displayed by the entire library, demonstrating that the periodicities of dinucleotides that characterize the yeast genome are, in actuality, due primarily to the 8 consensus sequences. A novel combination of experimental and bioinformatic approaches was then used to show that these tetranucleotides are important for preferred formation of nucleosomes at specific sites along DNA in vitro. These results were then compared to tetranucleotide patterns in genome-wide in vivo libraries from yeast and C. elegans in order to assess the contributions of DNA sequence in the control of nucleosome residency in the cell. These comparisons revealed striking similarities in the tetranucleotide occurrence profiles that are likely to be involved in nucleosome positioning in both in vitro and in vivo libraries, suggesting that DNA sequence is an important factor in the control of nucleosome placement in vivo. However, the strengths of the tetranucleotide periodicities were 3-4 fold higher in the in vitro as compared to the in vivo libraries, which implies that DNA sequence plays less of a role in dictating nucleosome positions in vivo. The results of this study have important implications for models of sequence-dependent positioning since they suggest that a defined subset of tetranucleotides is involved in preferred nucleosome occupancy and that these tetranucleotides are the major source of the dinucleotide periodicities that are characteristic of positioned nucleosomes. C1 [Collings, Clayton K.; Pitschka, Chad G.; Anderson, John N.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Fernandez, Alfonso G.] NCI, NIH, Bethesda, MD 20892 USA. [Hawkins, Troy B.] Indiana Univ Purdue Univ, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. RP Collings, CK (reprint author), Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. EM andersjn@purdue.edu FU Department of Biological Sciences at Purdue University; [R01LM8626] FX The Department of Biological Sciences at Purdue University provided the sources of funding that have supported the project. http://www.bio.purdue.edu/index.php. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; We would like to thank the two anonymous reviewers for helpful suggestions and Dr. Peter Waddell for the use of computing resources, which were funded by R01LM8626 and used for the analysis of the C. elegans data. NR 72 TC 15 Z9 15 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 3 PY 2010 VL 5 IS 6 AR e10933 DI 10.1371/journal.pone.0010933 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 605AD UT WOS:000278318700007 PM 20532171 ER PT J AU Sisan, DR Yarar, D Waterman, CM Urbach, JS AF Sisan, Daniel R. Yarar, Defne Waterman, Clare M. Urbach, Jeffrey S. TI Event Ordering in Live-Cell Imaging Determined from Temporal Cross-Correlation Asymmetry SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE CORRELATION SPECTROSCOPY; SIGNALING NETWORKS; LIVING CELLS; ENDOCYTOSIS; NOISE AB We use the temporal asymmetry of the cross-correlation function to determine the temporal ordering of spatially localized cellular events in live-cell multichannel fluorescence imaging. The analysis is well suited to noisy, stochastic systems where the temporal order may not be apparent in the raw data. The approach is applicable to any biochemical reaction not in chemical equilibrium, including protein complex assembly, sequential enzymatic processes, gene regulation, and other cellular signaling events. As an automated quantitative measure, this approach allows the data to be readily interpreted statistically with minimal subjective biases. We first test the technique using simulations of simple biophysical models with a definite temporal ordering. We then demonstrate the approach by extracting the temporal ordering of three proteins actin, sorting nexin 9, and clathrin-in the endocytic pathway. C1 [Sisan, Daniel R.; Urbach, Jeffrey S.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA. [Yarar, Defne] Whitehead Inst, Cambridge, MA 02142 USA. [Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Sisan, DR (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. EM dan.sisan@gmail.com OI Urbach, Jeffrey/0000-0002-1593-520X; Waterman, Clare/0000-0001-6142-6775 FU National Science Foundation [DBI-0353030]; Air Force Office of Scientific Research [FA9550-07-1-0130] FX This project was supported by National Science Foundation grant DBI-0353030 and Air Force Office of Scientific Research grant FA9550-07-1-0130. NR 24 TC 9 Z9 9 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD JUN 2 PY 2010 VL 98 IS 11 BP 2432 EP 2441 DI 10.1016/j.bpj.2010.02.041 PG 10 WC Biophysics SC Biophysics GA 606LW UT WOS:000278427500005 PM 20513386 ER PT J AU Capone, R Mustata, M Jang, H Arce, FT Nussinov, R Lal, R AF Capone, Ricardo Mustata, Mirela Jang, Hyunbum Arce, Fernando Teran Nussinov, Ruth Lal, Ratnesh TI Antimicrobial Protegrin-1 Forms Ion Channels: Molecular Dynamic Simulation, Atomic Force Microscopy, and Electrical Conductance Studies SO BIOPHYSICAL JOURNAL LA English DT Article ID SOLID-STATE NMR; LIPID-BILAYERS; PEPTIDE PROTEGRIN-1; PORE FORMATION; GRAMICIDIN-A; ALZHEIMERS-DISEASE; PHOSPHOLIPASE A(2); CALCIUM-CHANNELS; AMINO-ACIDS; MEMBRANES AB Antimicrobial peptides (AMPs) are an emerging class of antibiotics for controlling health effects of antibiotic-resistant microbial strains. Protegrin-1 (PG-1) is a model antibiotic among beta-sheet AMPs. Antibiotic activity of AMPs involves cell membrane damage, yet their membrane interactions, their 3D membrane-associated structures and the mechanism underlying their ability to disrupt cell membrane are poorly understood. Using complementary approaches, including molecular dynamics simulations, atomic force microscopy (AFM) imaging, and planar lipid bilayer reconstitution, we provide computational and experimental evidence that PG-1, a beta-hairpin peptide, forms ion channels. Simulations indicate that PG-1 forms channel-like structures with loosely attached subunits when reconstituted in anionic lipid bilayers. AFM images show the presence of channel-like structures when PG-1 is reconstituted in dioleoylphosphatidylserine/palmitoyloleoyl phosphatidylethanolamine bilayers or added to preformed bilayers. Planar lipid bilayer electrical recordings show multiple single channel conductances that are consistent with the heterogeneous oligomeric channel structures seen in AFM images. PG-1 channel formation seems to be lipid-dependent: PG-1 does not easily show ion channel electrical activity in phosphatidylcholine membranes, but readily shows channel activity in membranes rich in phosphatidylethanolamine or phosphatidylserine. The combined results support a model wherein the beta-hairpin PG-1 peptide acts as an antibiotic by altering cell ionic homeostasis through ion channel formation in cell membranes. C1 [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Capone, Ricardo; Mustata, Mirela; Arce, Fernando Teran; Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Capone, Ricardo; Mustata, Mirela; Arce, Fernando Teran; Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. EM ruthnu@helix.nih.gov; rlal@uchicago.edu RI Capone, Ricardo/D-1943-2010 OI Capone, Ricardo/0000-0002-7327-9837 FU National Institutes of Health (National Institute on Aging); National Cancer Institute, National Institutes of Health [HHSN26120080000]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This work has been supported by National Institutes of Health (National Institute on Aging) extramural program (R.L.). 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. HHSN26120080000 I E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 77 TC 34 Z9 35 U1 3 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN 2 PY 2010 VL 98 IS 11 BP 2644 EP 2652 DI 10.1016/j.bpj.2010.02.024 PG 9 WC Biophysics SC Biophysics GA 606LW UT WOS:000278427500028 PM 20513409 ER PT J AU Schuck, P AF Schuck, Peter TI Diffusion of the Reaction Boundary of Rapidly Interacting Macromolecules in Sedimentation Velocity SO BIOPHYSICAL JOURNAL LA English DT Article ID COEFFICIENT DISTRIBUTIONS C(S); PROTEIN-PROTEIN INTERACTIONS; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; LAMM EQUATION; EQUILIBRIUM; SYSTEMS; ASSOCIATION AB Sedimentation velocity analytical ultracentrifugation combines relatively high hydrodynamic resolution of macromolecular species with the ability to study macromolecular interactions, which has great potential for studying dynamically assembled multiprotein complexes. Complicated sedimentation boundary shapes appear in multicomponent mixtures when the timescale of the chemical reaction is short relative to the timescale of sedimentation. Although the Lamm partial differential equation rigorously predicts the evolution of concentration profiles for given reaction schemes and parameter sets, this approach is often not directly applicable to data analysis due to experimental and sample imperfections, and/or due to unknown reaction pathways. Recently, we have introduced the effective particle theory, which explains quantitatively and in a simple physical picture the sedimentation boundary patterns arising in the sedimentation of rapidly interacting systems. However, it does not address the diffusional spread of the reaction boundary from the cosedimentation of interacting macromolecules, which also has been of long-standing interest in the theory of sedimentation velocity analytical ultracentrifugation. Here, effective particle theory is exploited to approximate the concentration gradients during the sedimentation process, and to predict the overall, gradient-average diffusion coefficient of the reaction boundary. The analysis of the heterogeneity of the sedimentation and diffusion coefficients across the reaction boundary shows that both are relatively uniform. These results support the application of diffusion-deconvoluting sedimentation coefficient distributions c(s) to the analysis of rapidly interacting systems, and provide a framework for the quantitative interpretation of the diffusional broadening and the apparent molar mass values of the effective sedimenting particle in dynamically associating systems. C1 Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. RP Schuck, P (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. EM schuckp@mail.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 26 TC 19 Z9 19 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN 2 PY 2010 VL 98 IS 11 BP 2741 EP 2751 DI 10.1016/j.bpj.2010.03.004 PG 11 WC Biophysics SC Biophysics GA 606LW UT WOS:000278427500038 PM 20513419 ER PT J AU Lauer, MS Collins, FS AF Lauer, Michael S. Collins, Francis S. TI Using Science to Improve the Nation's Health System NIH's Commitment to Comparative Effectiveness Research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID TRIAL C1 [Collins, Francis S.] NIH, Off Director, Bethesda, MD 20892 USA. [Lauer, Michael S.] NHLBI, Off Director, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA. EM collinsf@mail.nih.gov RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 10 TC 62 Z9 64 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 2 PY 2010 VL 303 IS 21 BP 2182 EP 2183 DI 10.1001/jama.2010.726 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 603BE UT WOS:000278182100027 PM 20516419 ER PT J AU Li, ZJ Tan, F Liewehr, DJ Steinberg, SM Thiele, CJ AF Li, Zhijie Tan, Fei Liewehr, David J. Steinberg, Seth M. Thiele, Carol J. TI In Vitro and In Vivo Inhibition of Neuroblastoma Tumor Cell Growth by AKT Inhibitor Perifosine SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SOFT-TISSUE SARCOMA; PHASE-II TRIAL; PROSTATE-CANCER; ALKYLPHOSPHOLIPID PERIFOSINE; ACTIVATING MUTATIONS; MULTIPLE-MYELOMA; ALK KINASE; KAPPA-B; PATHWAY; PHOSPHORYLATION AB Activated AKT is a marker of decreased event-free or overall survival in neuroblastoma (NB) patients. The aim of this study was to investigate the effect of perifosine, a nontoxic AKT inhibitor, as a single agent on NB cell growth in vitro and in vivo. Four human NB cell lines (AS, NGP, BE2, and KCNR) were treated with increasing concentrations of perifosine, and a quantitative analysis of cell death (apoptosis) was performed by using MTS and caspase-3/7 activity assays. Survival of mice carrying xenograft NB tumors that were treated with perifosine (n = 6-7 mice per group) was compared with that of untreated mice (n = 7 mice per group) using Kaplan-Meier analysis. Tumor volumes were calculated to determine the effect of perifosine on NB tumor growth. Phosphorylation of AKT and expression of cleaved caspase-3 were measured in proteins from the tumors. All statistical tests were two-sided. Perifosine, at 30 mu M concentration, decreased AKT phosphorylation and increased apoptosis in all four NB cell lines in vitro. Perifosine-treated mice bearing xenograft NB tumors had longer survival than untreated mice (untreated vs treated, median survival: AS, 13 days, 95% confidence interval [CI] = 11 to 16 days vs not reached, P = .003; NGP, 22 days, 95% CI = 20 to 26 days vs not reached, P = .013; BE2, 24 days, 95% CI = 21 to 27 days vs not reached, P < .001; and KCNR, 18 days, 95% CI = 18 to 21 days vs not reached, P < .001). Perifosine treatment induced regression in AS tumors, growth inhibition in BE2 tumors, and slower growth in NGP and KCNR tumors. Inhibition of AKT phosphorylation and induction of caspase-dependent apoptosis were noted in tumors of perifosine-treated mice in all four in vivo NB tumor models. Perifosine inhibited the activation of AKT and was an effective cytotoxic agent in NB cells in vitro and in vivo. Our study supports the future clinical evaluation of perifosine for the treatment of NB tumors. C1 [Li, Zhijie; Tan, Fei; Thiele, Carol J.] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr MSC 1928,Bldg 10 CRC 1-3940, Bethesda, MD 20892 USA. EM ct47a@nih.gov FU Center for Cancer Research, National Cancer Institute, National Institute of Health FX Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institute of Health. NR 59 TC 35 Z9 38 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUN 2 PY 2010 VL 102 IS 11 BP 758 EP 770 DI 10.1093/jnci/djq125 PG 13 WC Oncology SC Oncology GA 606QA UT WOS:000278440900005 PM 20463309 ER PT J AU Zhang, XH Albanes, D Beeson, WL van den Brandt, PA Buring, JE Flood, A Freudenheim, JL Giovannucci, EL Goldbohm, RA Jaceldo-Siegl, K Jacobs, EJ Krogh, V Larsson, SC Marshall, JR McCullough, ML Miller, AB Robien, K Rohan, TE Schatzkin, A Sieri, S Spiegelman, D Virtamo, J Wolk, A Willett, WC Zhang, SMM Smith-Warner, SA AF Zhang, Xuehong Albanes, Demetrius Beeson, W. Lawrence van den Brandt, Piet A. Buring, Julie E. Flood, Andrew Freudenheim, Jo L. Giovannucci, Edward L. Goldbohm, R. Alexandra Jaceldo-Siegl, Karen Jacobs, Eric J. Krogh, Vittorio Larsson, Susanna C. Marshall, James R. McCullough, Marjorie L. Miller, Anthony B. Robien, Kim Rohan, Thomas E. Schatzkin, Arthur Sieri, Sabina Spiegelman, Donna Virtamo, Jarmo Wolk, Alicja Willett, Walter C. Zhang, Shumin M. Smith-Warner, Stephanie A. TI Risk of Colon Cancer and Coffee, Tea, and Sugar-Sweetened Soft Drink Intake: Pooled Analysis of Prospective Cohort Studies SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID METHYLXANTHINE-CONTAINING BEVERAGES; FOOD FREQUENCY QUESTIONNAIRE; DIGESTIVE-TRACT CANCERS; COLORECTAL-CANCER; RECTAL-CANCER; GREEN TEA; BLACK TEA; DIETARY QUESTIONNAIRE; SINGAPORE CHINESE; BREAST-CANCER AB The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P-trend = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P-trend = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P-trend = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study. C1 [Zhang, Xuehong] Harvard Univ, Dept Nutr, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Beeson, W. Lawrence; Jaceldo-Siegl, Karen] Loma Linda Univ, Sch Publ Hlth, Ctr Hlth Res, Loma Linda, CA 92350 USA. [van den Brandt, Piet A.] Maastricht Univ, Dept Epidemiol, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands. [Buring, Julie E.; Zhang, Shumin M.] Harvard Univ, Brigham & Womens Hosp, Div Prevent Med, Sch Med,Dept Med, Boston, MA 02115 USA. [Giovannucci, Edward L.; Willett, Walter C.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med,Dept Med, Boston, MA 02115 USA. [Freudenheim, Jo L.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Goldbohm, R. Alexandra] TNO Qual Life, Dept Food & Chem Risk Anal, Zeist, Netherlands. [Flood, Andrew; Robien, Kim] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Flood, Andrew; Robien, Kim] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Jacobs, Eric J.; McCullough, Marjorie L.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Krogh, Vittorio; Sieri, Sabina] Natl Canc Inst, Nutr Epidemiol Unit, I-20133 Milan, Italy. [Larsson, Susanna C.; Wolk, Alicja] Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Stockholm, Sweden. [Marshall, James R.] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Zhang, XH (reprint author), Harvard Univ, Dept Nutr, Dept Epidemiol, Sch Publ Hlth, 655 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Zhang, Xuehong/E-6219-2012; Albanes, Demetrius/B-9749-2015; Larsson, Susanna/F-6065-2015; Krogh, Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016; OI Larsson, Susanna/0000-0003-0118-0341; Krogh, Vittorio/0000-0003-0122-8624; Sieri, Sabina/0000-0001-5201-172X; Robien, Kim/0000-0002-2120-2280 FU National Institutes of Health [CA55075]; National Colorectal Cancer Research Alliance of the Entertainment Industry Foundation FX National Institutes of Health (CA55075 to W.C.W.); the National Colorectal Cancer Research Alliance of the Entertainment Industry Foundation (to W.C.W.). NR 80 TC 44 Z9 45 U1 3 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN 2 PY 2010 VL 102 IS 11 BP 771 EP 783 DI 10.1093/jnci/djq107 PG 13 WC Oncology SC Oncology GA 606QA UT WOS:000278440900006 PM 20453203 ER PT J AU Dumitriu, D Hao, JD Hara, Y Kaufmann, J Janssen, WGM Lou, W Rapp, PR Morrison, JH AF Dumitriu, Dani Hao, Jiandong Hara, Yuko Kaufmann, Jeffrey Janssen, William G. M. Lou, Wendy Rapp, Peter R. Morrison, John H. TI Selective Changes in Thin Spine Density and Morphology in Monkey Prefrontal Cortex Correlate with Aging-Related Cognitive Impairment SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DENDRITIC SPINES; RHESUS-MONKEYS; RECOGNITION MEMORY; AGED MONKEYS; MICROSCOPY IMAGES; RAT HIPPOCAMPUS; MACAQUE MONKEYS; PYRAMIDAL CELLS; CEREBRAL-CORTEX; DIFFERENT MODES AB Age-associated memory impairment (AAMI) occurs in many mammalian species, including humans. In contrast to Alzheimer's disease (AD), in which circuit disruption occurs through neuron death, AAMI is due to circuit and synapse disruption in the absence of significant neuron loss and thus may be more amenable to prevention or treatment. We have investigated the effects of aging on pyramidal neurons and synapse density in layer III of area 46 in dorsolateral prefrontal cortex of young and aged, male and female rhesus monkeys (Macaca mulatta) that were tested for cognitive status through the delayed non-matching-to-sample (DNMS) and delayed response tasks. Cognitive tests revealed an age-related decrement in both acquisition and performance on DNMS. Our morphometric analyses revealed both an age-related loss of spines (33%, p < 0.05) on pyramidal cells and decreased density of axospinous synapses (32%, p < 0.01) in layer III of area 46. In addition, there was an age-related shift in the distribution of spine types reflecting a selective vulnerability of small, thin spines, thought to be particularly plastic and linked to learning. While both synapse density and the overall spine size average of an animal were predictive of number of trials required for acquisition of DNMS (i.e., learning the task), the strongest correlate of behavior was found to be the head volume of thin spines, with no correlation between behavior and mushroom spine size or density. No synaptic index correlated with memory performance once the task was learned. C1 [Dumitriu, Dani; Hao, Jiandong; Hara, Yuko; Kaufmann, Jeffrey; Janssen, William G. M.; Morrison, John H.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Morrison, John H.] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Hao, Jiandong] Hebei Med Univ, Hosp 3, Ctr Trauma, Shijiazhuang 050051, Hebei, Peoples R China. [Lou, Wendy] Univ Toronto, Dept Publ Hlth Sci, Toronto, ON M5T 3M7, Canada. [Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Morrison, JH (reprint author), Mt Sinai Sch Med, Dept Neurosci, 1425 Madison Ave,Box 1065, New York, NY 10029 USA. EM john.morrison@mssm.edu RI Hara, Yuko/B-9172-2012; Morrison, John/F-9229-2012 OI Hara, Yuko/0000-0001-5828-442X; FU National Institute on Aging (NIA) [AG 006647, AG 010606, AG 016765]; National Research Service [1F30MH083402] FX This work was supported by National Institute on Aging (NIA) Grants AG 006647 (J.H.M.), AG 010606 (J.H.M., P.R.R.), and AG 016765 (J.H.M., P.R.R.), National Research Service Award Training Grant 1F30MH083402 (D.D.), and the Intramural Research Program of the NIA. We thank Ljiljana Minwalla and Mary Roberts for expert technical assistance. NR 53 TC 151 Z9 155 U1 0 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 2 PY 2010 VL 30 IS 22 BP 7507 EP 7515 DI 10.1523/JNEUROSCI.6410-09.2010 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 604OK UT WOS:000278288200008 PM 20519525 ER PT J AU Milescu, LS Bean, BP Smith, JC AF Milescu, Lorin S. Bean, Bruce P. Smith, Jeffrey C. TI Isolation of Somatic Na+ Currents by Selective Inactivation of Axonal Channels with a Voltage Prepulse SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ACTION-POTENTIAL INITIATION; CEREBELLAR GRANULE CELLS; CA1 PYRAMIDAL NEURONS; SPACE-CLAMP ERRORS; SODIUM-CHANNELS; ACTIVE PROPAGATION; MAMMALIAN NEURONS; DENDRITES; PERSISTENT; BACKPROPAGATION AB We present a simple and effective method for isolating the somatic Na+ current recorded under voltage clamp from neurons in brain slices. The principle is to convert the axon from an active compartment capable of generating uncontrolled axonal spikes into a passive structure by selectively inactivating axonal Na+ channels. Typically, whole-cell currents from intact neurons under somatic voltage clamp contain a mixture of Na+ current and axial current caused by escaped axonal spikes. We found that a brief prepulse to voltages near spike threshold evokes the axonal spike, which inactivates axonal but not somatic channels. A subsequent voltage step then evokes only somatic Na+ current from electrotonically proximal sodium channels under good voltage-clamp control. Simulations using a neuron compartmental model support the idea that the prepulse effectively inactivates currents from the axon and isolates well controlled somatic currents. Na+ currents recorded from cortical pyramidal neurons in slices, using the prepulse, were found to have voltage dependence nearly identical to that of currents recorded from acutely dissociated pyramidal neurons. In addition, studies in dissociated neurons show that the prepulse has no visible effect on the voltage dependence and kinetics of Na+ currents elicited by the subsequent voltage step, only decreasing the amplitude of the currents by 10-20%. The technique was effective in several neuronal types in brain slices from male and female neonatal rats and mice, including raphe neurons, cortical pyramidal neurons, inferior olivary neurons, and hypoglossal motoneurons. C1 [Milescu, Lorin S.; Bean, Bruce P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Milescu, Lorin S.; Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Milescu, LS (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave,Goldenson Bldg,Room 420, Boston, MA 02115 USA. EM Lorin_Milescu@hms.harvard.edu FU National Institutes of Health (NIH) [NS36855]; National Institute of Neurological Disorders and Stroke FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Neurological Disorders and Stroke and by NIH R01 Grant NS36855 to B. P. B. We thank our colleagues for suggestions, particularly Drs. Mirela Milescu (NIH, Bethesda, MD), Reese Scroggs (University of Tennessee, Memphis, TN), and Joel Tabak (Florida State University, Tallahassee, FL). Dr. Ruli Zhang (NIH, Bethesda, MD) assisted with animal procedures. NR 39 TC 12 Z9 12 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 2 PY 2010 VL 30 IS 22 BP 7740 EP 7748 DI 10.1523/JNEUROSCI.6136-09.2010 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 604OK UT WOS:000278288200032 PM 20519549 ER PT J AU Schwartz, LM Woloshin, S Kramer, BS AF Schwartz, Lisa M. Woloshin, Steven Kramer, Barnett S. TI Re: Analysis of Fecal DNA Methylation to Detect Gastrointestinal Neoplasia Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Schwartz, Lisa M.; Woloshin, Steven] VA Med Ctr, VA Outcomes Grp 111B, White River Jct, VT 05055 USA. [Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Inst Hlth Policy & Clin Practice, Dept Med, Hanover, NH USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Schwartz, LM (reprint author), VA Med Ctr, VA Outcomes Grp 111B, 215 N Main St, White River Jct, VT 05055 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 2 PY 2010 VL 102 IS 11 BP 830 EP 830 DI 10.1093/jnci/djq139 PG 1 WC Oncology SC Oncology GA 606QA UT WOS:000278440900015 ER PT J AU Chang, LW Kagaayi, J Nakigozi, G Ssempijja, V Packer, AH Serwadda, D Quinn, TC Gray, RH Bollinger, RC Reynolds, SJ AF Chang, Larry W. Kagaayi, Joseph Nakigozi, Gertrude Ssempijja, Victor Packer, Arnold H. Serwadda, David Quinn, Thomas C. Gray, Ronald H. Bollinger, Robert C. Reynolds, Steven J. TI Effect of Peer Health Workers on AIDS Care in Rakai, Uganda: A Cluster-Randomized Trial SO PLOS ONE LA English DT Article ID IMPLEMENTATION RESEARCH; HIV PREVENTION; AFRICA; INTERVENTIONS; METAANALYSIS; ADHERENCE; COUNTRIES AB Background: Human resource limitations are a challenge to the delivery of antiretroviral therapy (ART) in low-resource settings. We conducted a cluster randomized trial to assess the effect of community-based peer health workers (PHW) on AIDS care of adults in Rakai, Uganda. Methodology/Principal Findings: 15 AIDS clinics were randomized 2: 1 to receive the PHW intervention (n = 10) or control (n = 5). PHW tasks included clinic and home-based provision of counseling, clinical, adherence to ART, and social support. Primary outcomes were adherence and cumulative risk of virologic failure (>400 copies/mL). Secondary outcomes were virologic failure at each 24 week time point up to 192 weeks of ART. Analysis was by intention to treat. From May 2006 to July 2008, 1336 patients were followed. 444 (33%) of these patients were already on ART at the start of the study. No significant differences were found in lack of adherence (<95% pill count adherence risk ratio [RR] 0.55, 95% confidence interval [CI] 0.23-1.35; <100% adherence RR 1.10, 95% CI 0.94-1.30), cumulative risk of virologic failure (RR 0.81, 95% CI 0.61-1.08) or in shorter-term virologic outcomes (24 week virologic failure RR 0.93, 95% CI 0.65-1.32; 48 week, RR 0.83, 95% CI 0.47-1.48; 72 week, RR 0.81, 95% CI 0.44-1.49). However, virologic failure rates >= 96 weeks into ART were significantly decreased in the intervention arm compared to the control arm (96 week failure RR 0.50, 95% CI 0.31-0.81; 120 week, RR 0.59, 95% CI 0.22-1.60; 144 week, RR 0.39, 95% CI 0.16-0.95; 168 week, RR 0.30, 95% CI 0.097-0.92; 192 week, RR 0.067, 95% CI 0.0065-0.71). Conclusions/Significance: A PHW intervention was associated with decreased virologic failure rates occurring 96 weeks and longer into ART, but did not affect cumulative risk of virologic failure, adherence measures, or shorter-term virologic outcomes. PHWs may be an effective intervention to sustain long-term ART in low-resource settings. C1 [Chang, Larry W.; Quinn, Thomas C.; Bollinger, Robert C.; Reynolds, Steven J.] Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. [Kagaayi, Joseph; Nakigozi, Gertrude; Ssempijja, Victor; Serwadda, David] Rakai Hlth Sci Program, Kalisizo, Uganda. [Packer, Arnold H.] Johns Hopkins Univ, Baltimore, MD USA. [Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Chang, LW (reprint author), Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. EM lchang8@jhmi.edu FU Doris Duke Charitable Foundation; Division of Intramural Research, The National Institute for Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health [2 T32-AI07291, 1 K23-MH086338] FX This study was funded by the Doris Duke Charitable Foundation, The Division of Intramural Research, The National Institute for Allergy and Infectious Diseases, National Institutes of Health, and a National Institutes of Health Training Grant (2 T32-AI07291) and Career Development Grant (1 K23-MH086338). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of this manuscript. NR 26 TC 71 Z9 71 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 2 PY 2010 VL 5 IS 6 AR e10923 DI 10.1371/journal.pone.0010923 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604NC UT WOS:000278284700006 PM 20532194 ER PT J AU Ahmadibeni, Y Dash, C Le Grice, SFJ Parang, K AF Ahmadibeni, Yousef Dash, Chandravanu Le Grice, Stuart F. J. Parang, Keykavous TI Solid-phase synthesis of 5 '-O-beta,gamma-methylenetriphosphate derivatives of nucleosides and evaluation of their inhibitory activity against HIV-1 reverse transcriptase SO TETRAHEDRON LETTERS LA English DT Article ID TRIPHOSPHATE ANALOGS; DNA-POLYMERASES; G-PROTEINS; PHOSPHORYLATION; REAGENTS; MIMICS AB Bis(dichlorophosphino)methane was converted to a beta,gamma-methylenetriphosphitylating reagent. The reagent was immobilized on aminomethyl polystyrene resin-bound linker of 4-acetoxy-3-phenylbenzyl alcohol to afford a polymer-bound beta,gamma-methylenetriphosphitylating reagent, which was reacted with unprotected nucleosides followed by oxidation with tert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and acidic cleavage to produce 5'-O-beta,gamma-methylene triphosphate nucleosides in 53- 82% overall yields. Among all the compounds, cytidine 5'-O-beta,gamma-methylenetriphosphate inhibited completely RNase H activity of HIV-1 reverse transcriptase at 700 mu M. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Ahmadibeni, Yousef; Parang, Keykavous] Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. [Ahmadibeni, Yousef] Columbus State Univ, Dept Chem, Columbus, GA 31907 USA. [Dash, Chandravanu] Meharry Med Coll, Ctr AIDS Hlth Dispar Res, Nashville, TN 37208 USA. [Le Grice, Stuart F. J.] NCI, Resistance Mech Lab, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. RP Parang, K (reprint author), Univ Rhode Isl, Coll Pharm, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. EM kparang@gmail.com RI Parang, Keykavous/F-9236-2010 FU National Science Foundation [CHE 0748555]; NIDA [R00DA024558]; NIH, NCI, and Center for Cancer Research; National Center for Research Resources, NIH [1 P20 RR16457] FX We acknowledge the financial support from National Science Foundation, Grant Number CHE 0748555. The work at Meharry Medical College was supported by NIDA Grant Number R00DA024558. The research at NCI was supported in part by the Intramural Research Program of the NIH, NCI, and Center for Cancer Research. We also acknowledge National Center for Research Resources, NIH, Grant Number 1 P20 RR16457 for sponsoring the core facility. NR 28 TC 6 Z9 6 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUN 2 PY 2010 VL 51 IS 22 BP 3010 EP 3013 DI 10.1016/j.tetlet.2010.04.005 PG 4 WC Chemistry, Organic SC Chemistry GA 602HA UT WOS:000278128500018 PM 20454539 ER PT J AU Purohit, V Rapaka, R Shurtleff, D AF Purohit, Vishnudutt Rapaka, Rao Shurtleff, David TI Role of Cannabinoids in the Development of Fatty Liver (Steatosis) SO AAPS JOURNAL LA English DT Review DE cannabinoids; CB1 receptor; CB2 receptor; fatty liver ID HEPATIC CB1 RECEPTORS; ENDOCANNABINOID LEVELS; MOLECULAR-MECHANISMS; C VIRUS; ETHANOL; OBESITY; MICE; ABNORMALITIES; ACTIVATION; RESISTANCE AB Emerging evidence suggests that cannabinoids play an important role in the modulation of fatty liver, which appears to be mediated via activation of cannabinoid receptors. Steatogenic agents such as ethanol and high-fat diet can upregulate the activity of cannabinoid 1 (CB1) receptors via increasing synthesis of endocannabinoids, 2-arachidonoylglycerol, and anandamide. CB1 receptors can also be upregulated by obesity. CB1 receptor activation results in upregulation of lipogenic transcription factor, sterol regulatory element-binding protein 1c and its target enzymes, acetyl-CoA carboxylase-1, and fatty acid synthase and concomitantly, downregulation of carnitine palmitoyltransferase-1. This leads to increased de novo fatty acid synthesis as well as decreased fatty acid oxidation, culminating into the development of fatty liver. High-fat diet, in addition to CB1 receptor activation, appears to activate CB2 receptors that may also contribute to fatty liver. In non-alcoholic fatty liver disease, CB2 receptor activation is associated with the development of fatty liver. Cannabis smoking can increase the severity of fatty liver in hepatitis C patients although the precise mechanism is unknown. As the mechanisms involved in endocannabinoid receptor signaling are being increasingly well understood and the biosynthetic regulatory elements elucidated, these present good opportunity for the pharmaceutical scientists to design drugs to treat liver diseases, including steatosis, based on the cannabinoids, endocannabinoids, and related templates. C1 [Purohit, Vishnudutt; Rapaka, Rao] NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD 20892 USA. RP Purohit, V (reprint author), NIDA, Chem & Physiol Syst Res Branch, Div Basic Neurosci & Behav Res, NIH, 6001 Execut Blvd,Rm 4282,MSC 9555, Bethesda, MD 20892 USA. EM vpurohit@nida.nih.gov NR 24 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD JUN PY 2010 VL 12 IS 2 BP 233 EP 237 DI 10.1208/s12248-010-9178-0 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 574FX UT WOS:000275975700014 PM 20204561 ER PT J AU Yu, QS Luo, WM Deschamps, J Holloway, HW Kopajtic, T Katz, JL Brossi, A Greig, NH AF Yu, Qian-sheng Luo, Weiming Deschamps, Jeffery Holloway, Harold W. Kopajtic, Theresa Katz, Jonathan L. Brossi, Arnold Greig, Nigel H. TI Preparation and Characterization of Tetrabenazine Enantiomers against Vesicular Monoamine Transporter 2 SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Tetrabenazine enantiomers; vesicular monoamine transporter 2 (VMAT2); Huntington's chorea; hyperkinesias ID MOVEMENT-DISORDERS; BINDING; DIHYDROTETRABENAZINE; PHARMACOKINETICS; METABOLITE; EMETINE AB As a clinical medication for the treatment of hyperkinetic movement disorders, in conditions such as Huntington's disease, tetrabenazine (TBZ) has always been used in its racemic form. To establish whether or not its beneficial therapeutic actions are enantiospecific, a practical total synthetic route was developed to yield each enantiomeric form to allow their chemical and pharmacological characterization. We briefly summarize the total synthesis of TBZ and report a detailed procedure for resolution of TBZ into its enantiomers, (+)-TBZ and (-)-TBZ. This allowed determination of the optical rotation and absolute configurations of each TBZ enantiomer, based on X-ray crystallographic analysis, together with characterization of their inhibitory action at the vesicular monoamine transporter 2, where (+)-TBZ proved 3-fold more active than (-)-TBZ. C1 [Yu, Qian-sheng; Luo, Weiming; Holloway, Harold W.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Natl Inst Hlth, Baltimore, MD 21224 USA. [Deschamps, Jeffery] USN, Res Lab, Struct Matter Lab, Dept Navy, Washington, DC 20375 USA. [Kopajtic, Theresa; Katz, Jonathan L.] Natl Inst Drug Abuse, Psychol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,Natl Inst Hlth, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM greign@mail.nih.gov OI Deschamps, Jeffrey/0000-0001-5845-0010; Katz, Jonathan/0000-0002-1068-1159 FU National Institute on Aging and National Institute on Drug Abuse, National Institutes of Health FX This work was supported in part by the Intramural Research Programs of the National Institute on Aging and National Institute on Drug Abuse, National Institutes of Health. NR 22 TC 17 Z9 17 U1 0 U2 6 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 JUN PY 2010 VL 1 IS 3 BP 105 EP 109 DI 10.1021/ml1000189 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 641NN UT WOS:000281134700004 PM 20694189 ER PT J AU Liao, CZ Park, JE Bang, JK Nicklaus, MC Lee, KS AF Liao, Chenzhong Park, Jung-Eun Bang, Jeong K. Nicklaus, Marc C. Lee, Kyung S. TI Probing Binding Modes of Small Molecule Inhibitors to the Polo-Box Domain of Human Polo-like Kinase 1 SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Polo-like kinase 1; polo-box domain; induced fit docking; binding mode; cancer therapeutics ID POLO-LIKE-KINASE-1; CANCER; LOCALIZATION AB Purpurogallin (PPG, 2) and poloxin (3) have been reported as inhibitors of the polo-box domain (PBD) of human polo-like kinase 1. However, our experimental results demonstrated that PPG, but not poloxin, binds to the phospho-binding pocket of the PBD, suggesting that their modes of PBD inhibition are distinct. Induced fit docking analyses led us to propose that PPG fills the SpT pocket via pi-pi stacking and hydrogen-bonding interactions, thus providing a rationale for designing novel PBD inhibitors. In contrast, poloxin may fill a different site present near the SpT pocket by forming a covalent bond with a nucleophilic Cys residue. C1 [Park, Jung-Eun; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liao, Chenzhong; Nicklaus, Marc C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Bang, Jeong K.] Korean Basic Sci Inst, Ochang 363883, Chung Buk, South Korea. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov RI Nicklaus, Marc/N-4183-2014 FU National Cancer Institute; Korea Basic Science Institute [F30601] FX This work was supported in part by the Intramural Research Program of the National Cancer Institute (M.C.N. and K.S.L.) and the Korea Basic Science Institute's International Joint Research Program grant F30601 (J.K.B.). NR 23 TC 30 Z9 31 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 JUN PY 2010 VL 1 IS 3 BP 110 EP 114 DI 10.1021/ml100020e PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 641NN UT WOS:000281134700005 PM 20625469 ER PT J AU Li, JS Chen, Y Mak, AFT Tuan, RS Li, L Li, Y AF Li, Jiashen Chen, Yun Mak, Arthur F. T. Tuan, Rocky S. Li, Lin Li, Yi TI A one-step method to fabricate PLLA scaffolds with deposition of bioactive hydroxyapatite and collagen using ice-based microporogens SO ACTA BIOMATERIALIA LA English DT Article DE Ice-based microporogens; Scaffold; Collagen; Hydroxyapatite; Poly(L-lactic acid) ID POLY(DL-LACTIC-CO-GLYCOLIC ACID) SCAFFOLD; ACCELERATED BIOMIMETIC PROCESS; INDUCED PHASE-SEPARATION; OSTEOBLAST-LIKE CELLS; POLY(L-LACTIC ACID); IN-VITRO; POLY(D,L-LACTIC-CO-GLYCOLIC ACID); APATITE; MICROSPONGES; ADHESION AB Porous poly(L-lactic acid) (PLLA) scaffolds with bioactive coatings were prepared by a novel one-step method. In this process, ice-based microporogens containing bioactive molecules, such as hydroxyapatite (HA) and collagen, served as both porogens to form the porous structure and vehicles to transfer the bioactive molecules to the inside of PLLA scaffolds in a single step. Based on scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy analysis, the bioactive components were found to be transferred successfully from the porogens to PLLA scaffolds evenly. Osteoblast cells were used to evaluate the cellular behaviors of the composite scaffolds. After culturing for 8 days, MIT assay and alkaline phosphatase activity results suggested that HA/collagen could improve the interactions between osteoblast cells and the polymeric scaffold. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Li, Jiashen; Chen, Yun; Mak, Arthur F. T.] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China. [Tuan, Rocky S.] NIAMSD, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. [Li, Lin; Li, Yi] Hong Kong Polytech Univ, Inst Text & Clothing, Hong Kong, Hong Kong, Peoples R China. RP Mak, AFT (reprint author), Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China. EM arthur.mak@polyu.edu.hk RI LI, YI/G-4421-2012; Li, Jiashen/J-6946-2012; Li, Jiashen/E-8571-2015 OI LI, YI/0000-0002-2092-4505; Li, Jiashen/0000-0001-7333-5280; FU PolyU [G-U408]; NIAMS, NIH [Z01 AR41131] FX This study was supported by a PolyU Grant (G-U408). R.S.T. is supported by the Intramural Research Program of NIAMS, NIH (Z01 AR41131). NR 36 TC 33 Z9 34 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD JUN PY 2010 VL 6 IS 6 BP 2013 EP 2019 DI 10.1016/j.actbio.2009.12.008 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 604AQ UT WOS:000278250100014 PM 20004261 ER PT J AU Al-Attas, OS Al-Daghri, N Bamakhramah, A Sabico, SS McTernan, P Huang, TTK AF Al-Attas, O. S. Al-Daghri, N. Bamakhramah, A. Sabico, S. Shaun McTernan, P. Huang, T. T-K TI Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth SO ACTA PAEDIATRICA LA English DT Article DE Body-mass index; Insulin resistance; Obese children ID OVERWEIGHT; CHILDREN; SHORTER AB Aim: The aim of this study was to determine the associations of telomere length to markers of obesity, insulin resistance and inflammation in Saudi children. Methods: A total of 69 boys and 79 girls, aged 5-12 years, participated in this cross-sectional study. Anthropometrics were measured. Serum glucose and lipid profile were measured using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumour necrosis factor-alpha and active plasminogen activator inhibitor 1 were quantified using customized multiplex assay kits. C-reactive protein and angiotensin II were quantified using ELISA. Leucocyte telomere length was examined by quantitative real time PCR utilizing IQ cycler. Results: Mean telomere length was significantly shorter in obese boys compared with their lean counterparts (p = 0.049), not in girls. It was not associated to insulin resistance, adipocytokines and markers of inflammation. In girls, the significant predictor of telomere length was waist circumference, explaining 24% of variance (p = 0.041) while in boys, systolic blood pressure explained 84% of the variance (p = 0.01). Conclusion: Childhood obesity in boys corresponds to shorter leucocyte telomere length which is not evident in girls. The association of leucocyte telomere length to blood pressure and waist circumference in children suggests clinical implications as to the contribution of these parameters in premature ageing. C1 [Al-Attas, O. S.; Al-Daghri, N.; Bamakhramah, A.; Sabico, S. Shaun] King Saud Univ, Coll Sci, Dept Biochem, Riyadh 11451, Saudi Arabia. [McTernan, P.] Univ Warwick, Warwick Med Sch, Diabet & Metab Unit, Coventry CV4 7AL, W Midlands, England. [Huang, T. T-K] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Al-Attas, OS (reprint author), King Saud Univ, Coll Sci, Dept Biochem, POB 2455, Riyadh 11451, Saudi Arabia. EM omrattas@ksu.edu.sa RI Al-Daghri, Nasser/G-7736-2011; Sabico, Shaun Louie/C-9086-2011 FU King Abdulaziz City for Science and Technology (KACST) [ARP-26-046] FX This study was generously funded by King Abdulaziz City for Science and Technology (KACST) (Project No. ARP-26-046). The authors wish to thank Dr Assim Alfadda and Dr Majed Alokail for their advice in the subject and data collection. The authors also extend their sincerest gratitude to Prof. Sudhesh Kumar for his inputs in the final draft of the manuscript. NR 17 TC 25 Z9 27 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD JUN PY 2010 VL 99 IS 6 BP 896 EP 899 DI 10.1111/j.1651-2227.2010.01720.x PG 4 WC Pediatrics SC Pediatrics GA 591RJ UT WOS:000277320300022 PM 20178511 ER PT J AU Swendsen, J Conway, KP Degenhardt, L Glantz, M Jin, R Merikangas, KR Sampson, N Kessler, RC AF Swendsen, Joel Conway, Kevin P. Degenhardt, Louisa Glantz, Meyer Jin, Robert Merikangas, Kathleen R. Sampson, Nancy Kessler, Ronald C. TI Mental disorders as risk factors for substance use, abuse and dependence: results from the 10-year follow-up of the National Comorbidity Survey SO ADDICTION LA English DT Article ID INTERNATIONAL DIAGNOSTIC INTERVIEW; DRUG-USE DISORDERS; PSYCHIATRIC-DISORDERS; UNITED-STATES; EPIDEMIOLOGIC SURVEY; NICOTINE DEPENDENCE; ANXIETY DISORDERS; CIGARETTE-SMOKING; MAJOR DEPRESSION; FAMILIAL FACTORS AB Aims The comorbidity of mental disorders and substance dependence is well documented, but prospective investigations in community samples are rare. This investigation examines the role of primary mental disorders as risk factors for the later onset of nicotine, alcohol and illicit drug use, abuse and dependence with abuse. Design The National Comorbidity Survey (NCS) was a nationally representative survey of mental and substance disorders in the United States carried out in 1990-92. The NCS-2 re-interviewed a probability subsample of NCS respondents in 2001-03, a decade after the baseline survey. Participants A total of 5001 NCS respondents were re-interviewed in the NCS-2 (87.6% of baseline sample). Results Aggregate analyses demonstrated significant prospective risks posed by baseline mental disorders for the onset of nicotine, alcohol and illicit drug dependence with abuse over the follow-up period. Particularly strong and consistent associations were observed for behavioral disorders and previous substance use conditions, as well as for certain mood and anxiety disorders. Conditional analyses demonstrated that many observed associations were limited to specific categories of use, abuse or dependence, including several mental disorders that were non-significant predictors in the aggregate analyses. Conclusions Many mental disorders are associated with an increased risk of later substance use conditions, but important differences in these associations are observed across the categories of use, abuse and dependence with abuse. These prospective findings have implications for the precision of prevention and treatment strategies targeting substance use disorders. C1 [Swendsen, Joel] Natl Ctr Sci Res, Bordeaux, France. [Conway, Kevin P.; Glantz, Meyer] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. [Degenhardt, Louisa] Univ NSW, Natl Drug & Alcohol Res Ctr, Sydney, NSW, Australia. [Jin, Robert; Sampson, Nancy; Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Policy, Boston, MA USA. [Merikangas, Kathleen R.] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Swendsen, J (reprint author), Univ Bordeaux 2, CNRS 5231, 146 Rue Leo Saignat, F-33076 Bordeaux, France. EM joel.swendsen@u-bordeaux2.fr RI Degenhardt, Louisa/D-4515-2012; OI Degenhardt, Louisa/0000-0002-8513-2218; Conway, Kevin/0000-0002-7638-339X FU FIC NIH HHS [R03 TW006481, R03TW006481]; NIAAA NIH HHS [R01 AA007080-05A1]; NIDA NIH HHS [R01 DA012058, R01 DA012058-01, R01 DA016558, R01DA012058, R01DA016558]; NIMH NIH HHS [R01 MH069864, R01 MH046376, R01 MH070884, R01 MH070884-01A2, R01 MH077883, R01MH069864, R01MH070884, R01MH077883, R13 MH066849, R13MH066849, U01 MH060220, U01 MH060220-01, U01MH060220] NR 67 TC 157 Z9 164 U1 8 U2 42 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JUN PY 2010 VL 105 IS 6 BP 1117 EP 1128 DI 10.1111/j.1360-0443.2010.02902.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 592SN UT WOS:000277400400027 PM 20331554 ER PT J AU Singh, DK Karmakar, P Aamann, M Schurman, SH May, A Croteau, DL Burks, L Plon, SE Bohr, VA AF Singh, Dharmendra Kumar Karmakar, Parimal Aamann, Maria Schurman, Shepherd H. May, Alfred Croteau, Deborah L. Burks, Lynnette Plon, Sharon E. Bohr, Vilhelm A. TI The involvement of human RECQL4 in DNA double-strand break repair SO AGING CELL LA English DT Article DE Bloom syndrome; BLM; Double-strand break repair; Premature aging; RecQ helicase; Rothmund-Thomson syndrome; RTS; Werner syndrome; WRN ID ROTHMUND-THOMSON-SYNDROME; GENOTOXIC AGENTS; SYNDROME PROTEIN; MAMMALIAN-CELLS; WERNER-SYNDROME; BLOOM-SYNDROME; GENE-PRODUCT; MUTATIONS; REPLICATION; ASSOCIATION AB P>Rothmund-Thomson syndrome (RTS) is an autosomal recessive hereditary disorder associated with mutation in RECQL4 gene, a member of the human RecQ helicases. The disease is characterized by genomic instability, skeletal abnormalities and predisposition to malignant tumors, especially osteosarcomas. The precise role of RECQL4 in cellular pathways is largely unknown; however, recent evidence suggests its involvement in multiple DNA metabolic pathways. This study investigates the roles of RECQL4 in DNA double-strand break (DSB) repair. The results show that RECQL4-deficient fibroblasts are moderately sensitive to gamma-irradiation and accumulate more gamma H2AX and 53BP1 foci than control fibroblasts. This is suggestive of defects in efficient repair of DSB's in the RECQL4-deficient fibroblasts. Real time imaging of live cells using laser confocal microscopy shows that RECQL4 is recruited early to laser-induced DSBs and remains for a shorter duration than WRN and BLM, indicating its distinct role in repair of DSBs. Endogenous RECQL4 also colocalizes with gamma H2AX at the site of DSBs. The RECQL4 domain responsible for its DNA damage localization has been mapped to the unique N-terminus domain between amino acids 363-492, which shares no homology to recruitment domains of WRN and BLM to the DSBs. Further, the recruitment of RECQL4 to laser-induced DNA damage is independent of functional WRN, BLM or ATM proteins. These results suggest distinct cellular dynamics for RECQL4 protein at the site of laser-induced DSB and that it might play important roles in efficient repair of DSB's. C1 [Singh, Dharmendra Kumar; Aamann, Maria; Schurman, Shepherd H.; May, Alfred; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Karmakar, Parimal] Jadavpur Univ, Dept Life Sci & Biotechnol, Kolkata 700032, India. [Aamann, Maria] Univ Aarhus, Danish Ctr Mol Gerontol, MBI, DK-8000 Aarhus C, Denmark. [Burks, Lynnette; Plon, Sharon E.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Burks, Lynnette; Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Schurman, Shepherd/0000-0002-9133-7906 FU National Institute on Aging, NIH; Danish Aging Research Center; Center for Healthy Aging in Copenhagen; Danish Medical research Council FX We thank Drs Suhasini Avvaru and Venkateswarlu Popuri for critical reading of the manuscript. This work was supported by funds from the Intramural Research Program of the National Institute on Aging, NIH. Support is acknowledged from the Danish Aging Research Center, the Center for Healthy Aging in Copenhagen, and from the Danish Medical research Council. NR 49 TC 43 Z9 43 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 EI 1474-9726 J9 AGING CELL JI Aging Cell PD JUN PY 2010 VL 9 IS 3 BP 358 EP 371 DI 10.1111/j.1474-9726.2010.00562.x PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 597VH UT WOS:000277789800007 PM 20222902 ER PT J AU Mattson, MP AF Mattson, Mark P. TI Genes and behavior interact to determine mortality in mice when food is scarce and competition fierce SO AGING CELL LA English DT Editorial Material ID LIFE-SPAN; DIETARY RESTRICTION; ENERGY RESTRICTION; PATHOLOGY; RESPONSES; DISEASE C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 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 NR 13 TC 6 Z9 6 U1 0 U2 3 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 JUN PY 2010 VL 9 IS 3 BP 448 EP 449 DI 10.1111/j.1474-9726.2010.00561.x PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 597VH UT WOS:000277789800014 PM 20156203 ER PT J AU Nesbitt, MJ Reynolds, MA Shiau, H Choe, K Simonsick, EM Ferrucci, L AF Nesbitt, Mark J. Reynolds, Mark A. Shiau, Harlan Choe, Kyong Simonsick, Eleanor M. Ferrucci, Luigi TI Association of periodontitis and metabolic syndrome in the Baltimore Longitudinal Study of Aging SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Inflammation; metabolic syndrome; obesity; periodontal disease; periodontitis ID BLOOD-CELL COUNT; SYSTEMIC INFLAMMATION; ENDOTHELIAL DYSFUNCTION; DISEASE; POPULATION; MORTALITY; OBESITY; INFECTION; MARKERS; HEALTH AB Background and aims: Metabolic syndrome (MetS) comprises central obesity, insulin resistance, hypertension and dyslipidemia, interrelated metabolic risk factors for diabetes and cardiovascular disease. A state of low-grade systemic inflammation may underlie this constellation of risk factors. Chronic inflammatory conditions, such as periodontal disease, may contribute to systemic inflammation and development of MetS. This study examines the association of periodontitis with MetS with and without consideration of systemic inflammatory status. Methods: The association of alveolar bone loss (none/slight vs moderate/severe) determined from panoramic radiographs and MetS parameters were analyzed using logistic regression, adjusting for age, sex, ethnicity, and smoking in 112 men and 78 women (mean+/-SD age 56.7+/-13.3 and 60.0+/-12.1, respectively) participating in the Baltimore Longitudinal Study of Aging. Results: Participants with radiographic evidence of moderate to advanced alveolar bone loss were significantly more likely to have MetS than those with minimal or no bone loss (OR 2.61, 95% CI 1.1-6.1, p<0.05). No significant differences in systemic inflammation were found between periodontal groups. Conclusions: The association of alveolar bone loss to MetS is consistent with the hypothesis that destructive periodontal disease may contribute to the development of MetS and elevations in systemic inflammation. Longitudinal studies are necessary to clarify the role of periodontal disease in the development of MetS and conditions associated with chronic inflammation. (Aging Clin Exp Res 2010; 22: 238-242) (C) 2010, Editrice Kurtis C1 [Ferrucci, Luigi] Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, NIA, Baltimore, MD 21225 USA. [Reynolds, Mark A.; Shiau, Harlan; Choe, Kyong] Univ Maryland, Sch Dent, Dept Periodont, Baltimore, MD 21201 USA. RP Ferrucci, L (reprint author), Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, NIA, 3001 Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov FU NIH, National Institute on Aging FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 37 TC 20 Z9 23 U1 0 U2 4 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD JUN PY 2010 VL 22 IS 3 BP 238 EP 242 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 629FF UT WOS:000280179700007 PM 20634647 ER PT J AU Schug, TT AF Schug, Thaddeus T. TI mTOR favors senescence over quiescence in p53-arrested cells SO AGING-US LA English DT Article ID P53; CANCER C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Schug, TT (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. EM Schugt@niehs.nih.gov NR 9 TC 11 Z9 11 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JUN PY 2010 VL 2 IS 6 BP 327 EP 328 PG 2 WC Cell Biology SC Cell Biology GA 636ID UT WOS:000280724300006 PM 20603524 ER PT J AU Marasa, BS Srikantan, S Martindale, JL Kim, MM Lee, EK Gorospe, M Abdelmohsen, K AF Marasa, Bernard S. Srikantan, Subramanya Martindale, Jennifer L. Kim, Mihee M. Lee, Eun Kyung Gorospe, Myriam Abdelmohsen, Kotb TI MicroRNA profiling in human diploid fibroblasts uncovers miR-519 role in replicative senescence SO AGING-US LA English DT Article DE HuR; miR-519; tumor suppression ID TUMOR SUPPRESSION; IN-VIVO; ANIMAL DEVELOPMENT; MESSENGER-RNA; C. ELEGANS; LIFE-SPAN; EXPRESSION; CELLS; CANCER; HUR AB MicroRNAs (miRNAs) are short non-coding RNAs that regulate diverse biological processes by controlling the pattern of expressed proteins. In mammalian cells, miRNAs partially complement their target sequences leading to mRNA degradation and/or decreased mRNA translation. Here, we have analyzed transcriptome-wide changes in miRNAs in senescent relative to early-passage WI-38 human diploid fibroblasts (HDFs). Among the miRNAs downregulated with senescence were members of the let-7 family, while upregulated miRNAs included miR-1204, miR-663 and miR-519. miR-519 was recently found to reduce tumor growth at least in part by lowering the abundance of the RNA-binding protein HuR. Overexpression of miR-519a in either WI-38 or human cervical carcinoma HeLa cells triggered senescence, as measured by monitoring beta-galactosidase activity and other senescence markers. These data suggest that miR-519 can suppress tumor growth by triggering senescence and that miR-519 elicits these actions by repressing HuR expression. C1 [Marasa, Bernard S.; Srikantan, Subramanya; Martindale, Jennifer L.; Kim, Mihee M.; Lee, Eun Kyung; Gorospe, Myriam; Abdelmohsen, Kotb] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. [Marasa, Bernard S.] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. RP Abdelmohsen, K (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU National Institute on Aging, National Institutes of Health FX This research was supported in full by the National Institute on Aging-Intramural Research Program, National Institutes of Health. NR 47 TC 73 Z9 76 U1 0 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JUN PY 2010 VL 2 IS 6 BP 333 EP 343 PG 11 WC Cell Biology SC Cell Biology GA 636ID UT WOS:000280724300009 PM 20606251 ER PT J AU Papas, RK Sidle, JE Martino, S Baliddawa, JB Songole, R Omolo, OE Gakinya, BN Mwaniki, MM Adina, JO Nafula, T Owino-Ong'or, WD Bryant, KJ Carroll, KM Goulet, JL Justice, AC Maisto, SA AF Papas, Rebecca K. Sidle, John E. Martino, Steve Baliddawa, Joyce B. Songole, Rogers Omolo, Otieno E. Gakinya, Benson N. Mwaniki, Michael M. Adina, Japheth O. Nafula, Tobista Owino-Ong'or, Willis D. Bryant, Kendall J. Carroll, Kathleen M. Goulet, Joseph L. Justice, Amy C. Maisto, Stephen A. TI Systematic Cultural Adaptation of Cognitive-Behavioral Therapy to Reduce Alcohol Use Among HIV-Infected Outpatients in Western Kenya SO AIDS AND BEHAVIOR LA English DT Article DE Alcohol; Cognitive behavioral therapy; Cultural adaptation; HIV; Kenya ID PSYCHOTHERAPY-RESEARCH; HEALTH; CONSUMPTION; ADHERENCE; VETERANS; PROJECT; ISSUES; CARE AB Two-thirds of those with HIV worldwide live in sub-Saharan Africa. Alcohol use is associated with the HIV epidemic through risky sex and suboptimal ARV adherence. In western Kenya, hazardous drinking was reported by HIV (53%) and general medicine (68%) outpatients. Cognitive behavioral treatment (CBT) has demonstrated strong efficacy to reduce alcohol use. This article reports on a systematic cultural adaptation and pilot feasibility study of group paraprofessional-delivered CBT to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Following adaptation and counselor training, five pilot groups were run (n = 27). Overall attendance was 77%. Percent days abstinent from alcohol (PDA) before session 1 was 52-100% (women) and 21-36% (men), and by session 6 was 96-100% (women) and 89-100% (men). PDA effect sizes (Cohen's d) between first and last CBT session were 2.32 (women) and 2.64 (men). Participants reported treatment satisfaction. Results indicate feasibility, acceptability and preliminary efficacy for CBT in Kenya. C1 [Papas, Rebecca K.; Goulet, Joseph L.; Justice, Amy C.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Martino, Steve; Carroll, Kathleen M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Sidle, John E.; Owino-Ong'or, Willis D.] Moi Univ, Sch Med, Dept Med, Eldoret, Kenya. [Baliddawa, Joyce B.] Moi Univ, Sch Med, Dept Behav Sci, Eldoret, Kenya. [Songole, Rogers; Omolo, Otieno E.; Gakinya, Benson N.] Moi Univ, Sch Med, Dept Mental Hlth Serv, Eldoret, Kenya. [Mwaniki, Michael M.; Adina, Japheth O.; Nafula, Tobista] Kenya Hlth Behav Study, Eldoret, Kenya. [Bryant, Kendall J.] NIAAA, Rockville, MD 20852 USA. [Maisto, Stephen A.] Syracuse Univ, Dept Psychol, Syracuse, NY USA. RP Papas, RK (reprint author), Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. EM Rebecca.papas@yale.edu OI Carroll, Kathleen/0000-0003-3263-3374; Goulet, Joseph/0000-0002-0842-804X FU NIAAA NIH HHS [R21 AA016884, R21 AA016884-03, R21AA016884]; NIDA NIH HHS [P50 DA009241-18, P50 DA009241, P50DA09241, U10 DA013038] NR 42 TC 21 Z9 22 U1 4 U2 7 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 JUN PY 2010 VL 14 IS 3 BP 669 EP 678 DI 10.1007/s10461-009-9647-6 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 592VU UT WOS:000277410500020 PM 19967441 ER PT J AU Lee, HK Chou, SP Cho, MJ Park, JI Dawson, DA Grant, BF AF Lee, Hae Kook Chou, S. Patricia Cho, Maeng Je Park, Jong-Ik Dawson, Deborah A. Grant, Bridget F. TI The prevalence and correlates of alcohol use disorders in the United States and Korea-a cross-national comparative study SO ALCOHOL LA English DT Article DE Alcohol use disorder; Cross-national comparisons; Prevalence; Sociodemographic correlates; United States; South Korea ID SUBSTANCE USE DISORDERS; DSM-IV ALCOHOL; DRUG-USE; PSYCHIATRIC EPIDEMIOLOGY; INTERVIEW SCHEDULE; AUDADIS-ADR; III-R; INTERNATIONAL CONSORTIUM; DIAGNOSTIC CONCORDANCE; 12-MONTH PREVALENCE AB The purpose of this study was to compare the prevalence rates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition 12-month diagnoses of alcohol use disorders between the United States and South Korea using two large nationally representative surveys. Cross-tabulations were used to derive weighted prevalences of alcohol abuse and dependence, and odds ratio derived from linear logistic regression analyses were used to determine the relationships between alcohol abuse and dependence across sociodemographic characteristics of the general population samples. The prevalence of 12-month alcohol abuse was greater in the United States (5.3%) than Korea (2.0%), whereas the rate of alcohol dependence was greater in Korea (5.1%) compared with the United States (4.4%). The odds of abuse were significantly greater among men, and in the youngest age groups in both countries. There was increased odds of 12-month dependence among men, and those who were employed or never married in each country. Further, the rates of abuse and dependence in the United States and of abuse in Korea decreased as a function of age, a result that did not generalize to dependence among Koreans. The implications of the results of this study are discussed in terms of national differences between the United States and Korea as the result of gender roles and drinking patterns, and the need to understand the potential influence of the cultural applicability and specificity of psychiatric assessment interviews across countries. Published by Elsevier Inc. C1 [Lee, Hae Kook; Chou, S. Patricia; Dawson, Deborah A.; Grant, Bridget F.] NIAAA, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Lee, Hae Kook] Catholic Med Univ Korea, Dept Psychiat, Seoul, South Korea. [Cho, Maeng Je] Seoul Natl Univ, Coll Med, Inst Behav Med, Dept Psychiat & Behav Sci, Seoul, South Korea. [Park, Jong-Ik] Kangwon Natl Univ, Coll Med, Dept Psychiat, Chunchon, South Korea. RP Grant, BF (reprint author), NIAAA, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM bgrant@mail.nih.gov RI Cho, Maeng Je/F-8837-2012 FU Intramural NIH HHS [Z99 AA999999] NR 43 TC 15 Z9 15 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2010 VL 44 IS 4 BP 297 EP 306 DI 10.1016/j.alcohol.2010.02.005 PG 10 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 642ML UT WOS:000281218500001 PM 20570084 ER PT J AU Barbier, E Cippitelli, A Christensen, L Salvatore, P Thorsell, A Kornel, S Heilig, M AF Barbier, E. Cippitelli, A. Christensen, L. Salvatore, P. Thorsell, A. Kornel, S. Heilig, M. TI STUDY OF EPIGENETIC MODIFICATIONS-INDUCED BY ETHANOL IN POST-DEPENDENT RAT MODEL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Barbier, E.; Cippitelli, A.; Christensen, L.; Salvatore, P.; Thorsell, A.; Kornel, S.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 13A EP 13A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200010 ER PT J AU Cippitelli, A Karlsson, C Shaw, JL Thorsell, A Gehlert, DR Heilig, M AF Cippitelli, A. Karlsson, C. Shaw, J. L. Thorsell, A. Gehlert, D. R. Heilig, M. TI SUPPRESSION OF ALCOHOL SELF-ADMINISTRATION AND REINSTATEMENT OF ALCOHOL SEEKING BY MELANIN-CONCENTRATING HORMONE RECEPTOR 1 (MCH1-R) ANTAGONISM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Cippitelli, A.; Karlsson, C.; Shaw, J. L.; Thorsell, A.; Gehlert, D. R.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 16A EP 16A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200022 ER PT J AU Kuzmin, A Bazov, I Chefer, V Mels, J Yakovleva, T Sheedy, D Garrick, T Harper, C Shippenberg, T Bakalkin, G AF Kuzmin, A. Bazov, I. Chefer, V. Mels, J. Yakovleva, T. Sheedy, D. Garrick, T. Harper, C. Shippenberg, T. Bakalkin, G. TI ALCOHOL AND COGNITION: UPREGULATION OF OPIOID PEPTIDES DYNORPHINS MEDIATES MEMORY IMPAIRMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. NIDA, Integrat Neurosci Branch, NIH, IRP, Baltimore, MD USA. Univ Sydney, Sydney, NSW 2006, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 16A EP 16A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200023 ER PT J AU Schank, JR Rowe, KE Carroll, FI Thorsell, A Heilig, M AF Schank, J. R. Rowe, K. E. Carroll, F. I. Thorsell, A. Heilig, M. TI THE KAPPA OPIOID RECEPTOR ANTAGONIST JDTIC ATTENUATES ALCOHOL WITHDRAWAL ANXIETY AND REINSTATEMENT OF ALCOHOL SEEKING IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Schank, J. R.; Rowe, K. E.; Carroll, F. I.; Thorsell, A.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 16A EP 16A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200025 ER PT J AU Gilman, JM Smith, AR Crouss, T Ramchandani, VA Momenan, R Hommer, DW AF Gilman, J. M. Smith, A. R. Crouss, T. Ramchandani, V. A. Momenan, R. Hommer, D. W. TI THE NEURAL CORRELATES OF RISKY DECISION-MAKING DURING INTRAVENOUS ALCOHOL ADMINISTRATION IN SOCIAL DRINKERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Gilman, J. M.; Smith, A. R.; Crouss, T.; Ramchandani, V. A.; Momenan, R.; Hommer, D. W.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 27A EP 27A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200067 ER PT J AU Cippitelli, A Schwandt, M Zook, M Bell, L Thorsell, A Heilig, M AF Cippitelli, A. Schwandt, M. Zook, M. Bell, L. Thorsell, A. Heilig, M. TI BINGE-LIKE ALCOHOL EXPOSURE PRODUCES SHORT-TERM OBJECT RECOGNITION IMPAIRMENT AS WELL AS LONG-TERM SPATIAL MEMORY DAMAGE IN RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Cippitelli, A.; Schwandt, M.; Zook, M.; Bell, L.; Thorsell, A.; Heilig, M.] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 30A EP 30A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200079 ER PT J AU DeBrouse, LM Hurd, B Saksida, LM Bussey, TJ Camp, MC Holmes, A AF DeBrouse, L. M. Hurd, B. Saksida, L. M. Bussey, T. J. Camp, M. C. Holmes, A. TI EFFECTS OF CHRONIC INTERMITTENT ETHANOL EXPOSURE ON CORTICOSTRIATAL-MEDIATED DISCRIMINATION AND REVERSAL LEARNING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [DeBrouse, L. M.; Hurd, B.; Camp, M. C.; Holmes, A.] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 30A EP 30A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200081 ER PT J AU Gremel, C Carlson, VC Lovinger, D AF Gremel, Christina Carlson, Verginia Cuzon Lovinger, David TI PRENATAL ETHANOL EXPOSURE DISRUPTS SUBSEQUENT HABIT FORMATION IN ADULT MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Gremel, Christina; Carlson, Verginia Cuzon; Lovinger, David] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 33A EP 33A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200093 ER PT J AU Issa, JE Smith, AR Crouss, T Demarais, M Doty, L Lionetti, T Spero, D Geyer, C Schwandt, ML Hommer, DW Heilig, M George, DT Ramchandani, VA AF Issa, J. E. Smith, A. R. Crouss, T. Demarais, M. Doty, L. Lionetti, T. Spero, D. Geyer, C. Schwandt, M. L. Hommer, D. W. Heilig, M. George, D. T. Ramchandani, V. A. TI RELATIONSHIP BETWEEN ADVERSE CHILDHOOD EXPERIENCES AND ALCOHOL-RELATED OUTCOMES IN RECENTLY DETOXIFIED ALCOHOLICS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Issa, J. E.; Smith, A. R.; Crouss, T.; Demarais, M.; Doty, L.; Lionetti, T.; Spero, D.; Geyer, C.; Schwandt, M. L.; Hommer, D. W.; Heilig, M.; George, D. T.; Ramchandani, V. A.] NIAAA, NIH, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 44A EP 44A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200135 ER PT J AU Ruan, WJ Dawson, DA Chou, P Grant, BF AF Ruan, W. J. Dawson, D. A. Chou, P. Grant, B. F. TI ALCOHOL, GENDER AND VIOLENCE-RELATED INJURY: DATA FROM THE WHO COLLABORATIVE ED STUDY IN CHINA SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Ruan, W. J.; Dawson, D. A.; Chou, P.; Grant, B. F.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 55A EP 55A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200178 ER PT J AU George, D Zhang, L Usala, J Blaine, S Ramchandani, V Rio, D Geyer, C Umhau, J Schwandt, M Heilig, M AF George, D. T. Zhang, L. Usala, J. Blaine, S. Ramchandani, V. A. Rio, D. Geyer, C. Umhau, J. Schwandt, M. Heilig, M. TI ADMINISTRATION OF INTRAVENOUS ALCOHOL TO TREATMENT-SEEKING ALCOHOLICS: PRELIMINARY ANSWERS TO ETHICAL CONCERNS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [George, D. T.; Zhang, L.; Usala, J.; Blaine, S.; Ramchandani, V. A.; Rio, D.; Geyer, C.; Umhau, J.; Schwandt, M.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 57A EP 57A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200189 ER PT J AU Stinson, FS Chou, SP Huang, B Pickering, RP Ruan, WJ Smith, SM AF Stinson, F. S. Chou, S. P. Huang, B. Pickering, R. P. Ruan, W. J. Smith, S. M. TI ALCOHOL AND INJURIES IN THE PEOPLE'S REPUBLIC OF CHINA: 2009 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Stinson, F. S.; Chou, S. P.; Huang, B.; Pickering, R. P.; Ruan, W. J.; Smith, S. M.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 57A EP 57A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200186 ER PT J AU Vatsalya, V Issa, JE Hommer, DW Ramchandani, VA AF Vatsalya, V. Issa, J. E. Hommer, D. W. Ramchandani, V. A. TI PHYSIOPHARMACOLOGICAL EFFECTS OF INTRAVENOUS ETHANOL ON GH-IGF1 AXIS AND GONADAL HORMONE REGULATION: ROLE OF AGE AND GENDER SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Vatsalya, V.; Issa, J. E.; Hommer, D. W.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 57A EP 57A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200187 ER PT J AU Usala, JM Ramchandani, VA Zhang, L Singley, ED Blaine, SK Geyer, C Rio, D Heilig, M George, DT AF Usala, J. M. Ramchandani, V. A. Zhang, L. Singley, E. D. Blaine, S. K. Geyer, C. Rio, D. Heilig, M. George, D. T. TI PHARMACOKINETIC VARIABILITY AND PHARMACODYNAMIC RESPONSE TO INTRAVENOUS ALCOHOL IN RECENTLY DETOXIFIED TREATMENT-SEEKING ALCOHOLICS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Usala, J. M.; Ramchandani, V. A.; Zhang, L.; Singley, E. D.; Blaine, S. K.; Geyer, C.; Rio, D.; Heilig, M.; George, D. T.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 63A EP 63A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200213 ER PT J AU Chou, PS Lee, HK Grant, BF AF Chou, Patricia S. Lee, Hae Kook Grant, Bridget F. TI CORRELATES AND DISPARITIES OF SERVICE UTILIZATION AMONG INDIVIDUALS WITH ALCOHOL USE DISORDERS IN THE UNITED STATES AND KOREA: A COMPARATIVE STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Chou, Patricia S.; Lee, Hae Kook; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200215 ER PT J AU Goldstein, RB Dawson, DA Grant, BF AF Goldstein, R. B. Dawson, D. A. Grant, B. F. TI LONGITUDINAL PREDICTORS OF SUBJECTIVE UNMET NEED FOR ALCOHOL USE DISORDER TREATMENT AMONG US ADULTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Goldstein, R. B.; Dawson, D. A.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200216 ER PT J AU Smith, SM Dawson, DA Grant, BF AF Smith, S. M. Dawson, D. A. Grant, B. F. TI THE ASSOCIATION BETWEEN PERCEIVED DISCRIMINATION AND ALCOHOL TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Smith, S. M.; Dawson, D. A.; Grant, B. F.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 65A EP 65A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200218 ER PT J AU Bevilacqua, L Yuan, Q Tikkanen, R Zhou, Z Kaprio, J Paunio, T Hodgkinson, CA Coccaro, E Virkkunen, M Goldman, D AF Bevilacqua, L. Yuan, Q. Tikkanen, R. Zhou, Z. Kaprio, J. Paunio, T. Hodgkinson, C. A. Coccaro, E. Virkkunen, M. Goldman, D. TI A COMMON, POPULATION-SPECIFIC STOP CODON IN HTR2B CO-SEGREGATES WITH SEVERE IMPULSIVITY AND ALCOHOLISM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Bevilacqua, L.; Yuan, Q.; Tikkanen, R.; Zhou, Z.; Kaprio, J.; Paunio, T.; Hodgkinson, C. A.; Coccaro, E.; Virkkunen, M.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 70A EP 70A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200241 ER PT J AU Blaine, SK Claus, ED Harlaar, N Heilig, M Hutchison, KE AF Blaine, S. K. Claus, E. D. Harlaar, N. Heilig, M. Hutchison, K. E. TI TACR1 (NK1R) SNPS THAT INFLUENCE CUE-ELICITED BRAIN ACTIVATION REPLICATE IN THE SAGE/COGA SAMPLE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 MIND Res Network, Albuquerque, NM USA. NIAAA, NIH, LCTS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 70A EP 70A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200240 ER PT J AU Roy, A Gorodetsky, E Yuan, Q Goldman, D Enoch, MA AF Roy, A. Gorodetsky, E. Yuan, Q. Goldman, D. Enoch, M. -A. TI THE INTERACTION OF FKBP5, A STRESS RELATED GENE, WITH CHILDHOOD TRAUMA INFLUENCES SUICIDE RISK IN ALCOHOL AND DRUG DEPENDENT INDIVIDUALS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Roy, A.; Gorodetsky, E.; Yuan, Q.; Goldman, D.; Enoch, M. -A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 70A EP 70A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200239 ER PT J AU Enoch, MA Hodgkinson, C Yuan, Q Gorodetsky, E Roy, A Goldman, D AF Enoch, M. -A. Hodgkinson, C. Yuan, Q. Gorodetsky, E. Roy, A. Goldman, D. TI THE FUNCTIONAL SEROTONIN TRANSPORTER POLYMORPHISM, 5-HTTLPR, PREDICTS ALCOHOL AND DRUG DEPENDENCE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Enoch, M. -A.; Hodgkinson, C.; Yuan, Q.; Gorodetsky, E.; Roy, A.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 72A EP 72A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200248 ER PT J AU Srivastava, V Zhou, Z Hodgkinson, CA Yuan, Q Shen, PH Roy, A Goldman, D Enoch, MA AF Srivastava, V. Zhou, Z. Hodgkinson, C. A. Yuan, Q. Shen, P. H. Roy, A. Goldman, D. Enoch, M. A. TI ASSOCIATION OF NEUROPEPTIDE Y PATHWAY GENE POLYMORPHISMS WITH ADDICTIONS IN TWO DIVERSE POPULATIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Srivastava, V.; Zhou, Z.; Hodgkinson, C. A.; Yuan, Q.; Shen, P. H.; Goldman, D.; Enoch, M. A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 72A EP 72A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200246 ER PT J AU Carlson, VCC Lovinger, DM AF Carlson, V. C. Cuzon Lovinger, D. M. TI PRENATAL ETHANOL EXPOSURE CAUSES DYNAMIC CHANGES IN THE GABAERGIC SYSTEM THROUGHOUT DEVELOPMENT OF THE MOUSE STRIATUM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Carlson, V. C. Cuzon; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 93A EP 93A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200331 ER PT J AU Huang, B Chou, SP Dawson, DA Grant, BF Pulay, AJ Stinson, FS Smith, S Ruan, WJ Saha, TD Goldstein, RB Pickering, RP AF Huang, B. Chou, S. P. Dawson, D. A. Grant, B. F. Pulay, A. J. Stinson, F. S. Smith, S. Ruan, W. J. Saha, T. D. Goldstein, R. B. Pickering, R. P. TI DRINKING PATTERNS AND THE THREE YEAR INCIDENCE OF SUBSTANCE USE DISORDERS: THE NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Huang, B.; Chou, S. P.; Dawson, D. A.; Grant, B. F.; Pulay, A. J.; Stinson, F. S.; Smith, S.; Ruan, W. J.; Saha, T. D.; Goldstein, R. B.; Pickering, R. P.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 116A EP 116A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200423 ER PT J AU Dawson, DA Goldstein, RB Pulay, AJ Stinson, FS Grant, BF AF Dawson, D. A. Goldstein, R. B. Pulay, A. J. Stinson, F. S. Grant, B. F. TI ALCOHOL STATUS, GENDER AND THE COURSE OF MAJOR DEPRESSION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Dawson, D. A.; Goldstein, R. B.; Pulay, A. J.; Stinson, F. S.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 123A EP 123A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200452 ER PT J AU Pulay, AJ Dawson, DA Grant, BF AF Pulay, A. J. Dawson, D. A. Grant, B. F. TI SEX DIFFERENCES IN SUBSTANCE USE DISORDER COMORBIDITY ACROSS THE DSM-IV PERSONALITY DISORDERS: RESULTS FROM A NATIONAL SURVEY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Pulay, A. J.; Dawson, D. A.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 124A EP 124A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200454 ER PT J AU Thorsell, A Pavon, FJ Ruiz-Velasco, V Sun, H Damadzic, R Eskay, B Sommer, WH Schoor, M Parsons, LH Heilig, M AF Thorsell, A. Pavon, F. J. Ruiz-Velasco, V. Sun, H. Damadzic, R. Eskay, B. Sommer, W. H. Schoor, M. Parsons, L. H. Heilig, M. TI A HUMANIZED MOUSE MODEL OF THE FUNCTIONAL OPRM1 A118G POLYMORPHISM: ROLE FOR ALCOHOL REWARD SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Thorsell, A.; Pavon, F. J.; Ruiz-Velasco, V.; Sun, H.; Damadzic, R.; Eskay, B.; Sommer, W. H.; Schoor, M.; Parsons, L. H.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 129A EP 129A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200474 ER PT J AU Schwandt, ML Lindell, SG Singley, E Suomi, SJ Heilig, M Barr, CS AF Schwandt, M. L. Lindell, S. G. Singley, E. Suomi, S. J. Heilig, M. Barr, C. S. TI INTERMITTENT ACCESS TO ALCOHOL, CORTICOTROPIN RELEASING HORMONE (CRH), AND RESPONSE TO CRH RECEPTOR BLOCKADE IN RHESUS MACAQUES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Schwandt, M. L.; Lindell, S. G.; Singley, E.; Suomi, S. J.; Heilig, M.; Barr, C. S.] NIAAA, NIH, LCTS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 143A EP 143A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200531 ER PT J AU Damadzic, R Cippitelli, A Hamelink, C Brunnquell, M Heilig, M Eskay, RL AF Damadzic, R. Cippitelli, A. Hamelink, C. Brunnquell, M. Heilig, M. Eskay, R. L. TI ELEVATED CORTICOSTERONE LEVELS EXACERBATE ALCOHOL-INDUCED NEURODEGENERATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Damadzic, R.; Cippitelli, A.; Hamelink, C.; Brunnquell, M.; Heilig, M.; Eskay, R. L.] NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 149A EP 149A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200557 ER PT J AU Umhau, J Schwandt, M Bowarshi, M Phillips, W Berman, J Heilig, M AF Umhau, J. Schwandt, M. Bowarshi, M. Phillips, W. Berman, J. Heilig, M. TI VITAMIN D STATUS AND MEASURES OF PERSONALITY, PSYCHOPATHOLOGY, AND ALCOHOLISM SEVERITY IN ALCOHOLICS UNDERGOING INPATIENT DETOXIFICATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Umhau, J.; Schwandt, M.; Bowarshi, M.; Phillips, W.; Berman, J.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Dept Hlth & Human Serv, Bethesda, MD 20893 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 153A EP 153A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200572 ER PT J AU Smith, AR Gilman, JM Momenan, R Ramchandani, VA Crouss, T Hommer, DW AF Smith, A. R. Gilman, J. M. Momenan, R. Ramchandani, V. A. Crouss, T. Hommer, D. W. TI USING FMRI TO EXAMINE THE NEURAL CORRELATES OF RISKY DECISION-MAKING IN ALCOHOL DEPENDENT PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Smith, A. R.; Gilman, J. M.; Momenan, R.; Ramchandani, V. A.; Crouss, T.; Hommer, D. W.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 163A EP 163A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200612 ER PT J AU Zhang, L Kerich, MJ Rawlings, RR Momenan, R Hommer, DW George, DT AF Zhang, L. Kerich, M. J. Rawlings, R. R. Momenan, R. Hommer, D. W. George, D. T. TI AMYGDALA ABNORMALITIES IN ALCOHOL DEPENDENT PATIENTS WITH INTIMATE PARTNER VIOLENCE: A VOXEL-BASED MORPHOMETRY STUDY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Zhang, L.; Kerich, M. J.; Rawlings, R. R.; Momenan, R.; Hommer, D. W.; George, D. T.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 165A EP 165A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200620 ER PT J AU Saha, TD Grant, BF Dawson, D AF Saha, T. D. Grant, B. F. Dawson, D. TI PARENTAL ALCOHOL PROBLEMS, ADVERSE CHILDHOOD AND LIFETIME ALCOHOL USE DISORDER IN THE US SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Saha, T. D.; Grant, B. F.; Dawson, D.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 179A EP 179A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200676 ER PT J AU Pickering, RP Dawson, DA Grant, BF AF Pickering, R. P. Dawson, D. A. Grant, B. F. TI DIFFERENCES BY ALCOHOLIC BEVERAGE PREFERENCE: RESULTS OF THE NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS (NESARC) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Pickering, R. P.; Dawson, D. A.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 180A EP 180A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200677 ER PT J AU Hurd, B DeBrouse, LM Todaro, A Camp, MC Holmes, A AF Hurd, B. DeBrouse, L. M. Todaro, A. Camp, M. C. Holmes, A. TI PROBING INTERACTIONS BETWEEN ETHANOL AND DRUGS ACTING AT THE D-SERINE/GLYCINE CO-AGONIST NMDAR SITE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Hurd, B.; DeBrouse, L. M.; Todaro, A.; Camp, M. C.; Holmes, A.] NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 190A EP 190A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200718 ER PT J AU Jun, S Ikeda, SR Lovinger, DM AF Jun, S. Ikeda, S. R. Lovinger, D. M. TI LONG-LASTING ETHANOL POTENTIATION OF GABAERGIC SYNAPTIC TRANSMISSION MODULATED BY 5-HT3 RECEPTORS IN MECHANICALLY ISOLATED HIPPOCAMPAL CA1 NEURONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Jun, S.; Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. [Ikeda, S. R.] NIAAA, Lab Mol Physiol, Rockville, MD 20852 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 194A EP 194A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200735 ER PT J AU Capik, NA Lovinger, DM Mateo, Y AF Capik, N. A. Lovinger, D. M. Mateo, Y. TI ADOLESCENT EXPOSURE TO RITALIN MODIFIES THE STRIATAL NEURONAL RESPONSE TO ETHANOL IN ADULT RAT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Capik, N. A.] MSC 5625 Fishers Ln, Rockville, MD 20892 USA. [Lovinger, D. M.; Mateo, Y.] NIAAA, NIH, Sect Synapt Pharmacol, Lab Integrat Neurosci, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 197A EP 197A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200747 ER PT J AU Schuebel, K Ryu, J Maixner, D Mordi, I Biesecker, K Yuan, Q Goldman, D AF Schuebel, K. Ryu, J. Maixner, D. Mordi, I. Biesecker, K. Yuan, Q. Goldman, D. TI EPIGENETICS OF FETAL ALCOHOL SYNDROME SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Schuebel, K.; Ryu, J.; Maixner, D.; Mordi, I.; Biesecker, K.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 209A EP 209A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200794 ER PT J AU Cooke, ME Vatsalya, V Issa, JE Gilman, JM Hommer, DW Heilig, M Zimmermann, US O'Connor, S Ramchandan, VA AF Cooke, M. E. Vatsalya, V. Issa, J. E. Gilman, J. M. Hommer, D. W. Heilig, M. Zimmermann, U. S. O'Connor, S. Ramchandan, V. A. TI COMPUTER-ASSISTED SELF-INFUSION OF ETHANOL (CASE) IN HUMANS: TEST-RETEST RELIABILITY AND EFFECT OF RECENT DRINKING HISTORY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Cooke, M. E.] NIAAA, NIH, LCTS, Bethesda, MD 20892 USA. [Ramchandan, V. A.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 BP 222A EP 222A PG 1 WC Substance Abuse SC Substance Abuse GA 601ZJ UT WOS:000278107200847 ER PT J AU Barr, CS Schwandt, ML Lindell, SG Sun, H Higley, JD Goldman, D Heilig, M AF Barr, C. S. Schwandt, M. L. Lindell, S. G. Sun, H. Higley, J. D. Goldman, D. Heilig, M. TI OPRM1 VARIATION PREDICTS RESPONSE TO NOVELTY AND ALCOHOL-INDUCED AGGRESSION IN RHESUS MACAQUES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Barr, C. S.; Schwandt, M. L.; Lindell, S. G.; Sun, H.; Higley, J. D.; Goldman, D.; Heilig, M.] NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 SI SI BP 248A EP 248A PG 1 WC Substance Abuse SC Substance Abuse GA 777RF UT WOS:000291641500015 ER PT J AU Grant, BF Saha, T Smith, S Dawson, DA AF Grant, B. F. Saha, T. Smith, S. Dawson, D. A. TI COMBINING ABUSE AND DEPENDENCE IN THE DSM-V AND SEVERITY CONSIDERATIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Grant, B. F.; Saha, T.; Smith, S.; Dawson, D. A.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Rockville, MD 20852 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 SI SI BP 253A EP 253A PG 1 WC Substance Abuse SC Substance Abuse GA 777RF UT WOS:000291641500035 ER PT J AU Faden, VB AF Faden, V. B. TI BRIEF, EMPIRICALLY BASED SCREENING OF CHILDREN AND ADOLESCENTS FOR RISK FOR DRINKING, DRINKING, AND ALCOHOL USE DISORDERS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Faden, V. B.] NIAAA, Bethesda, 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 SI SI BP 267A EP 267A PG 1 WC Substance Abuse SC Substance Abuse GA 777RF UT WOS:000291641500090 ER PT J AU Gao, B AF Gao, B. TI MOLECULAR MECHANISMS OF ALCOHOLIC LIVER DISEASE: ROLES OF IL-6/STAT3 AND NATURAL KILLER CELLS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 33rd Annual Meeting of the Research-Society-on-Alcoholism CY JUN 26-30, 2010 CL San Antonio, TX SP Res Soc Alcoholism C1 [Gao, B.] NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 SU 2 SI SI BP 291A EP 291A PG 1 WC Substance Abuse SC Substance Abuse GA 777RF UT WOS:000291641500187 ER PT J AU Litten, RZ Bradley, AM Moss, HB AF Litten, Raye Z. Bradley, Ann M. Moss, Howard B. TI Alcohol Biomarkers in Applied Settings: Recent Advances and Future Research Opportunities SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Biomarkers; Alcohol Sensors; Alcohol Use Disorders ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; URINARY ETHYL GLUCURONIDE; DISORDERS IDENTIFICATION TEST; GAMMA-GLUTAMYL-TRANSFERASE; DIRECT ETHANOL METABOLITES; CONSUMPTION EDAC TEST; HEAVY DRINKING; DEPENDENT PATIENTS; UNITED-STATES; MODERATE DRINKERS AB During the past decade, advances have been made in the identification, development, and application of alcohol biomarkers. This is important because of the unique functions that alcohol biomarkers can serve in various applied settings. To carry out these functions, biomarkers must display several features including validity, reliability, adequacy of temporal window of assessment, reasonable cost, and transportability. During the past two decades, several traditional alcohol biomarkers have been studied in multiple human studies. Meanwhile, several new, promising biomarkers, including various alcohol metabolites and alcohol biosensors, are being explored in human studies. In addition, researchers have explored using biomarkers in combination and using biomarkers in combination with self-reports, resulting in increased sensitivity with little sacrifice in specificity. Despite these advances, more research is needed to validate biomarkers, especially the new ones, in humans. Moreover, recent advances in high-throughput technologies for genomics, proteomics, and metabolomics offer unique opportunities to discover novel biomarkers, while additional research is needed to perfect newly developed alcohol sensors. Development of more accurate biomarkers will help practicing clinicians to more effectively screen and monitor individuals who suffer from alcohol use disorders. C1 [Litten, Raye Z.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA. [Bradley, Ann M.] NIAAA, Off Sci Policy & Commun, Bethesda, MD 20892 USA. [Moss, Howard B.] NIAAA, Off Director, Bethesda, MD 20892 USA. RP Litten, RZ (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane,Room 2041, Bethesda, MD 20892 USA. EM rlitten@mail.nih.gov NR 98 TC 53 Z9 54 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 BP 955 EP 967 DI 10.1111/j.1530-0277.2010.01170.x PG 13 WC Substance Abuse SC Substance Abuse GA 601PD UT WOS:000278073600004 PM 20374219 ER PT J AU Moss, HB Chen, CM Yi, HY AF Moss, Howard B. Chen, Chiung M. Yi, Hsiao-Ye TI Prospective Follow-Up of Empirically Derived Alcohol Dependence Subtypes in Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC): Recovery Status, Alcohol Use Disorders and Diagnostic Criteria, Alcohol Consumption Behavior, Health Status, and Treatment Seeking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Alcohol Dependence; Recovery; Subtypes; Health Status; Epidemiology ID GENERAL-POPULATION SAMPLE; QUALITY-OF-LIFE; DRINKING TRAJECTORIES; MENTAL-HEALTH; UNITED-STATES; IV; PATTERNS; RELIABILITY; ABUSE; ADOLESCENCE AB Background: We have previously reported on an empirical classification of Alcohol Dependence (AD) individuals into subtypes using nationally representative general population data from the 2001 to 2002 Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and latent class analysis. Our results suggested a typology of 5 separate clusters based upon age of onset of AD, multigenerational familial AD, rates of antisocial personality disorder (ASPD), endorsement of specific AD and Alcohol Abuse (AA) criteria, and the presence of comorbid mood, anxiety, and substance use disorders (SUD). In this report, we focus on the clinical follow-up of these cluster members in Wave 2 of the NESARC (2004 to 2005). Methods: The mean interval between NESARC Wave 1 and NESARC Wave 2 interviews was 36.6 (SD = 2.6) months. For these analyses, we utilized a Wave 2 NESARC sample that was comprised of a total of 1,172 individuals who were initially ascertained as having past-year AD at NESARC Wave 1 and initially subtyped into one of 5 groupings using latent class analysis. We identified these subtypes as: (i) Young Adult, characterized by very early age of onset, minimal family history, and low rates of psychiatric and SUD comorbidity; (ii) Functional, characterized by older age of onset, higher psychosocial functioning, minimal family history, and low rates of psychiatric and SUD comorbidity; (iii) Intermediate Familial, characterized by older age of onset, significant familial AD, and elevated comorbid rates of mood disorders SUD; (iv) Young Antisocial, characterized by early age of onset and elevated rates of ASPD, significant familial AD, and elevated rates of comorbid mood disorders and SUD; (v) Chronic Severe, characterized by later onset, elevated rates of ASPD, significant familial AD, and elevated rates of comorbid mood disorders and SUD. In this report, we examine Wave 2 recovery status, health status, alcohol consumption behavior, and treatment episodes based upon these subtypes. Results: Significantly fewer of the Young Adult and Functional subtypes continued to meet full DSM-IV AD criteria in Wave 2 than did the Intermediate Familial, the Young Antisocial, and the Chronic Severe subtypes. However, we did not find that treatment seeking for alcohol problems increased over Wave 1 reports. In Wave 2, Young Antisocial and Chronic Severe subtypes had highest rates of past-year treatment seeking. In terms of health status, the Intermediate Familial, the Young Antisocial, and the Chronic Severe subtypes had significantly worse mental health scores than the Young Adult and Functional subtypes. For physical health status, the Functional, Intermediate Familial, Young Antisocial, and the Chronic Severe subtypes had significantly worse scores than the Young Adult subtype. In terms of alcohol consumption behavior, the Young Adult, Functional, and Young Antisocial subtypes significantly reduced their risk drinking days between Wave 1 and Wave 2, whereas the Intermediate Familial and the Chronic Severe subtypes did not. Discussion: The results suggest that the empirical AD typology predicts differential clinical outcomes 3 years later. Persistence of full AD, treatment seeking, and worse mental health status were associated most strongly with those subtypes manifesting the greatest degree of psychiatric comorbidity. Reductions in alcohol consumption behavior and good physical health status were seen among the 2 younger subtypes. Overall, the least prevalent subtype, the Chronic Severe, showed the greatest stability in the manifestations of AD, despite having the highest rate of treatment seeking. C1 [Moss, Howard B.] NIAAA, Bethesda, MD 20892 USA. CSR Inc, Alcohol Epidemiol Data Syst, Arlington, VA 22201 USA. RP Moss, HB (reprint author), NIAAA, Bethesda, MD 20892 USA. EM mossh@mail.nih.gov FU NIAAA FX This research was supported by NIAAA internal funds. NR 41 TC 38 Z9 39 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2010 VL 34 IS 6 BP 1073 EP 1083 DI 10.1111/j.1530-0277.2010.01183.x PG 11 WC Substance Abuse SC Substance Abuse GA 601PD UT WOS:000278073600017 PM 20374206 ER PT J AU Radinger, M Kuhen, H Metcalfe, D Lotvall, J Gilfillan, A AF Radinger, M. Kuhen, H. Metcalfe, D. Lotvall, J. Gilfillan, A. TI Glycogen synthase kinase-3 beta is required for SCF-mediated human mast cell SO ALLERGY LA English DT Meeting Abstract CT 29th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 05-09, 2010 CL London, ENGLAND SP European Acad Allergy and Clin Immunol C1 [Radinger, M.; Lotvall, J.] Univ Gothenburg, Sahlgrenska Acad, Krefting Res Ctr, Gothenburg, Sweden. [Kuhen, H.; Metcalfe, D.; Gilfillan, A.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2010 VL 65 SU 92 SI SI MA 13 BP 7 EP 7 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IR UT WOS:000329462100014 ER PT J AU Pomes, A Glesner, J Li, M Wlodawer, A Wuenschmann, S Chapman, M Gustchina, A AF Pomes, A. Glesner, J. Li, M. Wlodawer, A. Wuenschmann, S. Chapman, M. Gustchina, A. TI Mutagenesis analysis of epitopes defined by X-ray crystallography SO ALLERGY LA English DT Meeting Abstract CT 29th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 05-09, 2010 CL London, ENGLAND SP European Acad Allergy and Clin Immunol C1 [Pomes, A.; Glesner, J.; Wuenschmann, S.; Chapman, M.] Indoor Biotechnol Inc, R&D, Charlottesville, VA USA. [Li, M.] NCI, Basic Res Program, SAIC Frederick & Macromol Crystallog Lab, Frederick, MD 21701 USA. [Wlodawer, A.; Gustchina, A.] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2010 VL 65 SU 92 SI SI MA 381 BP 157 EP 157 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IR UT WOS:000329462100372 ER PT J AU Carter, M Clayton, S Scott, L Wilson, T Metcalfe, D AF Carter, M. Clayton, S. Scott, L. Wilson, T. Metcalfe, D. TI Utility of serum tryptase in the classification of pediatric-onset mastocytosis SO ALLERGY LA English DT Meeting Abstract CT 29th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 05-09, 2010 CL London, ENGLAND SP European Acad Allergy and Clin Immunol C1 [Carter, M.; Clayton, S.; Scott, L.; Wilson, T.; Metcalfe, D.] NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD JUN PY 2010 VL 65 SU 92 SI SI MA 917 BP 347 EP 347 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 286IR UT WOS:000329462101396 ER PT J AU Matthews, LJ Paukner, A Suomi, SJ AF Matthews, Luke J. Paukner, Annika Suomi, Stephen J. TI Can Traditions Emerge from the Interaction of Stimulus Enhancement and Reinforcement Learning? An Experimental Model SO AMERICAN ANTHROPOLOGIST LA English DT Article DE social learning; tradition; reinforcement; object manipulation; Cebus ID MONKEYS CEBUS-APELLA; CHIMPANZEES PAN-TROGLODYTES; BROWN CAPUCHIN MONKEYS; TOOL USE; HAND PREFERENCE; TUFTED CAPUCHIN; BEHAVIOR; PRIMATE; CULTURE; IMITATION AB The study of social learning in captivity and behavioral traditions in the wild are two burgeoning areas of research, but few empirical studies have tested how learning mechanisms produce emergent patterns of tradition. Studies have examined how social learning mechanisms that are cognitively complex and possessed by few species, such as imitation, result in traditional patterns, yet traditional patterns are also exhibited by species that may not possess such mechanisms. We propose an explicit model of how stimulus enhancement and reinforcement learning could interact to produce traditions. We tested the model experimentally with tufted capuchin monkeys (Cebus apella), which exhibit traditions in the wild but have rarely demonstrated imitative abilities in captive experiments. Monkeys showed both stimulus enhancement learning and a habitual bias to perform whichever behavior first obtained them a reward. These results support our model that simple social learning mechanisms combined with reinforcement can result in traditional patterns of behavior. C1 [Matthews, Luke J.] Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. [Paukner, Annika; Suomi, Stephen J.] NIH, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Matthews, LJ (reprint author), Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. FU Intramural NIH HHS [Z99 HD999999] NR 67 TC 16 Z9 16 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-7294 J9 AM ANTHROPOL JI Am. Anthropol. PD JUN PY 2010 VL 112 IS 2 BP 257 EP 269 DI 10.1111/j.1548-1433.2010.01224.x PG 13 WC Anthropology SC Anthropology GA 599KY UT WOS:000277912200009 PM 21135912 ER PT J AU Merz, CNB Olson, MB McClure, C Yang, YC Symons, J Sopko, G Kelsey, SF Handberg, E Johnson, BD Cooper-DeHoff, RM Sharaf, B Rogers, WJ Pepine, CJ AF Merz, C. Noel Bairey Olson, Marian B. McClure, Candace Yang, Yu-Ching Symons, James Sopko, George Kelsey, Sheryl F. Handberg, Eileen Johnson, B. Delia Cooper-DeHoff, Rhonda M. Sharaf, Barry Rogers, William J. Pepine, Carl J. TI A randomized controlled trial of low-dose hormone therapy on myocardial ischemia in postmenopausal women with no obstructive coronary artery disease: Results from the National Institutes of Health/National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) SO AMERICAN HEART JOURNAL LA English DT Article ID ESTROGEN PLUS PROGESTIN; QUALITY-OF-LIFE; CHEST-PAIN; SYNDROME-X; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; TERM; ATHEROSCLEROSIS; ANGIOGRAMS; ANGINA AB Background Compared with men, women have more evidence of myocardial ischemia with no obstructive coronary artery disease. Although low endogenous estrogen levels are associated with endothelial dysfunction, the role of low-dose hormone therapy has not been fully evaluated. We postulate that a 12-week duration of low-dose hormone replacement therapy is associated with myocardial ischemia and endothelial dysfunction. Methods and Results Using a multicenter, randomized, placebo-controlled design, subjects were randomized to receive either 1 mg norethindrone/10 mu g ethinyl estradiol or placebo for 12 weeks. Chest pain and menopausal symptoms, cardiac magnetic resonance spectroscopy, brachial artery reactivity, exercise stress testing, and psychosocial questionnaires were evaluated at baseline and exit. Recruitment was closed prematurely because of failure to recruit after publication of the Women's Health Initiative hormone trial. Of the 35 women who completed the study, there was less frequent chest pain in the treatment group compared with the placebo group (P=.02) at exit. Women taking 1 mg norethindrone/10 mu g ethinyl estradiol also had significantly fewer hot flashes/night sweats (P=.003), less avoidance of intimacy (P=.05), and borderline differences in sexual desire and vaginal dryness (P=.06). There were no differences in magnetic resonance spectroscopy, brachial artery reactivity, compliance, or reported adverse events between the groups. Conclusions These data suggest that low-dose hormone therapy improved chest pain symptoms, menopausal symptoms, and quality of life, but did not improve ischemia or endothelial dysfunction. Given that it was not possible to enroll the prespecified sample size, these results should not be considered definitive. (Am Heart J 2010; 159: 987.e1-987.e7.) C1 [Merz, C. Noel Bairey; Yang, Yu-Ching] Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. [Olson, Marian B.; McClure, Candace; Kelsey, Sheryl F.; Johnson, B. Delia] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Handberg, Eileen; Cooper-DeHoff, Rhonda M.; Pepine, Carl J.] Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. [Sharaf, Barry] Rhode Isl Hosp, Div Cardiol, Providence, RI USA. [Rogers, William J.] Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, WISE Coordinating Ctr, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM merz@cshs.org FU NCRR NIH HHS [M01 RR000425, M01 RR000425-290752, M01 RR000425-300752, M01 RR000425-30S10752, M01 RR000425-310752, M01 RR000425-31S70752, M01 RR000425-31S90752, M01 RR000425-320752, M01 RR000425-330752, M01 RR000425-340752]; NHLBI NIH HHS [N01 HV068161, N01 HV068164, N01HV68162, N01HV68163] NR 44 TC 5 Z9 6 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2010 VL 159 IS 6 BP 987 EP U9 AR 987.e1 DI 10.1016/j.ahj.2010.03.024 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 607UU UT WOS:000278533200009 PM 20569710 ER PT J AU Ebbesson, SOE Devereux, RB Cole, S Ebbesson, LOE Fabsitz, RR Haack, K Harris, WS Howard, WJ Laston, S Lopez-Alvarenga, JC MacCluer, JW Okin, PM Tejero, ME Voruganti, VS Wenger, CR Howard, BV Comuzzie, AG AF Ebbesson, Sven O. E. Devereux, Richard B. Cole, Shelley Ebbesson, Lars O. E. Fabsitz, Richard R. Haack, Karin Harris, William S. Howard, Wm James Laston, Sandra Carlos Lopez-Alvarenga, Juan MacCluer, Jean W. Okin, Peter M. Tejero, M. Elizabeth Voruganti, V. Saroja Wenger, Charlotte R. Howard, Barbara V. Comuzzie, Anthony G. TI Heart rate is associated with red blood cell fatty acid concentration: The Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SUDDEN CARDIAC DEATH; FISH CONSUMPTION; RATE-VARIABILITY; RISK; PREVENTION; OMEGA-3-FATTY-ACIDS; SUPPLEMENTATION; MORTALITY; HUMANS AB Background Consumption of omega-3 fatty acids (FAs) is associated with a reduction in deaths from coronary heart disease, arrhythmia, and sudden death. Although these FAs were originally thought to be antiatherosclerotic, recent evidence suggests that their benefits are related to reducing risk for ventricular arrhythmia and that this may be mediated by a slowed heart rate (HR). Methods The study was conducted in Alaskan Eskimos participating in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study, a population experiencing a dietary shift from unsaturated to saturated fats. We compared HR with red blood cell (RBC) FA content in 316 men and 391 women ages 35 to 74 years. Results Multivariate linear regression analyses of individual FAs with HR as the dependent variable and specific FAs as covariates revealed negative associations between HR and docosahexaenoic acid (22:6n-3; P=.004) and eicosapentaenoic acid (20:5n-3; P=.009) and positive associations between HR and palmitoleic acid (16:1n-7; P=.021), eicosanoic acid (20:1n9; P=.007), and dihomo-y-linolenic acid (DGLA; 20:3n-6; P=.021). Factor analysis revealed that the omega-3 FAs were negatively associated with HR (P=.003), whereas a cluster of other, non-omega-3 unsaturated FAs (16:1, 20:1, and 20:3) was positively associated. Conclusions Marine omega-3 FAs are associated with lower HR, whereas palmitoleic and DGLA, previously identified as associated with saturated FA consumption and directly related to cardiovascular mortality, are associated with higher HR. These relations may at least partially explain the relations between omega-3 FAs, ventricular arrhythmia, and sudden death. (Am Heart J 2010; 159:1020-5.) C1 [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, GOCADAN Dept, Nome, AK 99762 USA. [Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA. [Cole, Shelley; Haack, Karin; Laston, Sandra; Carlos Lopez-Alvarenga, Juan; MacCluer, Jean W.; Tejero, M. Elizabeth; Voruganti, V. Saroja; Wenger, Charlotte R.; Comuzzie, Anthony G.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Ebbesson, Lars O. E.] Uni Res AS, Bergen, Norway. [Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA. [Harris, William S.] Sanford Res Univ S Dakota, Cardiovasc Hlth Res Ctr, Sioux Falls, SD USA. [Howard, Wm James] Washington Hosp Ctr, Washington, DC 20010 USA. [Carlos Lopez-Alvarenga, Juan] Hosp Gen Mexico City, Mexico City, DF, Mexico. [Howard, Barbara V.] MedStar Hlth Res Inst, Hyattsville, MD USA. RP Ebbesson, SOE (reprint author), Norton Sound Hlth Corp, GOCADAN Dept, POB 966, Nome, AK 99762 USA. EM soebbesson@alaska.edu RI Ebbesson, Lars/F-9385-2011 FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD [R01-HL64244, U01 HL082458, U01 HL082490, M10RR0047-34] FX The study was funded by grants R01-HL64244, U01 HL082458, U01 HL082490, and M10RR0047-34 (GCRC) from the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD. NR 35 TC 20 Z9 23 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2010 VL 159 IS 6 BP 1020 EP 1025 DI 10.1016/j.ahj.2010.03.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 607UU UT WOS:000278533200014 PM 20569715 ER PT J AU Mills, JL Troendle, J Conley, MR Carter, T Druschel, CM AF Mills, James L. Troendle, James Conley, Mary R. Carter, Tonia Druschel, Charlotte M. TI Maternal obesity and congenital heart defects: a population-based study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BIRTH-DEFECTS; RISK; ANOMALIES; SURVEILLANCE; WEIGHT; HEIGHT; WOMEN AB Background: Obesity affects almost one-third of pregnant women and causes many complications, including neural tube defects. It is not clear whether the risk of congenital heart defects, the most common malformations, is also increased. Objective: This study was conducted to determine whether obesity is associated with an increased risk of congenital heart defects. Design: A population-based, nested, case-control study was conducted in infants born with congenital heart defects and unaffected controls from the cohort of all births (n = 1,536,828) between 1993 and 2003 in New York State, excluding New York City. The type of congenital heart defect, maternal body mass index (BMI; in kg/m(2)), and other risk factors were obtained from the Congenital Malformations Registry and vital records. Mothers of 7392 congenital heart defect cases and 56,304 unaffected controls were studied. Results: All obese women (BMI >= 30) were significantly more likely than normal-weight women (BMI: 19-24.9) to have children with a congenital heart defect [odds ratio (OR): 1.15; 95% CI: 1.07, 1.23; P < 0.0001] Overweight women were not at increased risk (OR: 1.00; 95% CI: 0.94, 1.06). The risk in morbidly obese women (BMI >= 40) was higher (OR: 1.33; 95% CI: 1.15, 1.54; P = 0.0001) than that in obese women with a BMI of 30-39.9 (OR: 1.11; 95% CI: 1.04, 1.20; P = 0.004). There was a highly significant trend of increasing OR for congenital heart defects with increasing maternal obesity (P < 0.0001). The offspring of obese women had significantly higher ORs for atrial septal defects, hypoplastic left heart syndrome, aortic stenosis, pulmonic stenosis, and tetralogy of Fallot. Conclusions: Obese, but not overweight, women are at significantly increased risk of bearing children with a range of congenital heart defects, and the risk increases with increasing BMI. Weight reduction as a way to reduce risk should be investigated. Am J Clin Nutr 2010;91:1543-9. C1 [Mills, James L.; Troendle, James; Conley, Mary R.; Carter, Tonia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Druschel, Charlotte M.] New York State Dept Hlth, New York State Congenital Malformat Registry, New York, NY USA. RP Mills, JL (reprint author), NICHD, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov RI Max, Mad/E-5238-2010 OI Max, Mad/0000-0001-6966-6829 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda. MD FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda. MD. NR 18 TC 59 Z9 64 U1 0 U2 9 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 JUN PY 2010 VL 91 IS 6 BP 1543 EP 1549 DI 10.3945/ajcn.2009.28865 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 598MP UT WOS:000277841700003 PM 20375192 ER PT J AU Hudson, JI Lalonde, JK Coit, CE Tsuang, MT McElroy, SL Crow, SJ Bulik, CM Hudson, MS Yanovski, JA Rosenthal, NR Pope, HG AF Hudson, James I. Lalonde, Justine K. Coit, Caitlin E. Tsuang, Ming T. McElroy, Susan L. Crow, Scott J. Bulik, Cynthia M. Hudson, Margo S. Yanovski, Jack A. Rosenthal, Norman R. Pope, Harrison G., Jr. TI Longitudinal study of the diagnosis of components of the metabolic syndrome in individuals with binge-eating disorder SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID DIABETES-MELLITUS; ADIPOSE-TISSUE; OBESE-PATIENTS; WOMEN; COOCCURRENCE; POPULATION; DEFINITION; PREVALENCE; MANAGEMENT; MORBIDITY AB Background: Binge-eating disorder may represent a risk factor for the metabolic syndrome. Objective: The objective was to assess longitudinally the relation between binge-eating disorder and components of the metabolic syndrome. Design: At 2.5 and 5 y of follow-up, 134 individuals with binge-eating disorder and 134 individuals with no history of eating disorders, who were frequency-matched for age, sex, and baseline body mass index (BMI), were interviewed during the follow-up interval regarding new diagnoses of 3 metabolic syndrome components: hypertension, dyslipidemia, and type 2 diabetes. Results: A comparison of individuals with and without a binge-eating disorder in analyses adjusted for age, sex, baseline BMI, and interval BMI change had hazard ratios (95% CIs) for reporting new diagnoses of metabolic syndrome components of 2.2 (1.2, 4.2; P = 0.023) for dyslipidemia, 1.5 (0.76, 2.9; P = 0.33) for hypertension, 1.6 (0.77, 3.9; P = 0.29) for type 2 diabetes, 1.7 (1.1, 2.6; P = 0.023) for any component, and 2.4 (1.1, 5.7; P = 0.038) for >= 2 components. Conclusion: Binge-eating disorder may confer a risk of components of the metabolic syndrome over and above the risk attributable to obesity alone. This trial was registered at www.clinicaltrials.gov as NCT00777634. Am J Clin Nutr 2010;91:1568-73. C1 [Hudson, James I.; Lalonde, Justine K.; Coit, Caitlin E.; Pope, Harrison G., Jr.] McLean Hosp, Biol Psychiat Lab, Belmont, MA 02478 USA. [Hudson, James I.; Lalonde, Justine K.; Coit, Caitlin E.; Pope, Harrison G., Jr.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, San Diego, CA 92103 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. [Crow, Scott J.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Bulik, Cynthia M.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Bulik, Cynthia M.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Hudson, Margo S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Hudson, Margo S.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Rosenthal, Norman R.] Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. RP Hudson, JI (reprint author), McLean Hosp, Biol Psychiat Lab, 115 Mill St, Belmont, MA 02478 USA. EM jhudson@mclean.harvard.edu FU Ortho-McNeil Janssen Scientific Affairs; NICHD, NIH [Z01-HD-00641]; Eli Lilly Co; Forest Laboratories; Pfizer; Novartis; Bristol-Myers Squibb; Abbott Laboratories; AstraZeneca; Cephalon; GlaxoSmithKline; Jazz Pharmaceuticals Inc; Orexigen Therapeutics Inc; Shire; Takada Pharmaceutical Co Ltd; Johnson & Johnson Pharmaceutical Research & Development, LLC; Solvay Pharmaceuticals FX Supported in part by an investigator-initiated grant from Ortho-McNeil Janssen Scientific Affairs (principal investigator: JIH) and by Z01-HD-00641 (principal investigator: JAY) from the Intramural Research Program of the NICHD, NIH.; The authors responsibilities were as follows-JIH and HGP: designed and conducted the study and wrote the first draft of the manuscript: CMB, SJC, JKL, SLM, NRR, and MTT: helped design the study; JKL and CEC: helped conduct the study; and JIH: performed the statistical analysis and had full access to all of the data in the study and takes responsibility for the integrity of the data and the data analysis. All authors contributed to the interpretation of the results and the critical review of the manuscript. This manuscript was reviewed by Ortho-McNeil Janssen Scientific Affairs prior to submission, but Ortho-McNeil Janssen Scientific Affairs had no control over the content of the manuscript or the authors' freedom to publish it. JIH has been a consultant for Eli Lilly & Co and Pfizer and has received grant support from Ortho-McNeil Janssen Scientific Affairs, Eli Lilly & Co, and Forest Laboratories. JKL was an employee of McLean Hospital during the time that she worked on the study, was an employee of AstraZeneca front September 2006 to May 2008, and has been an employee of Roche since July 2008. SJC has been on the speaker's bureau of Eli Lilly and has received grant support from Pfizer. Novartis, and Bristol-Myers Squibb. SLM has been a consultant or advisory board member for AstraZeneca, Eli Lilly & Co, Jazz Pharmaceuticals Inc, Pfizer, and Schering-Plough; is a principal investigator or co-principal investigator in studies sponsored by Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly & Co, Forest Laboratories, GlaxoSmithKline, Jazz Pharmaceuticals Inc, Orexigen Therapeutics Inc, Shire, and Takada Pharmaceutical Co Ltd; and is the inventor of US patent no. 6,323,236 B2 (Use of Sulfamate Derivatives for Treating Impulse Control Disorders) and, along with the patent's assignee (University of Cincinnati, Cincinnati, OH), has received payments from Johnson & Johnson Pharmaceutical Research & Development, LLC, which has exclusive rights under the patent. JAY has a cooperative research and development agreement with Obecure Ltd for clinical research using betahistine and material transfer agreements for orlistat and matching placebo from Roche for clinical studies and for ritonavir from Abbott Laboratories for in vitro studies. NRR is an employee of Ortho-McNeil Pharmaceutical. HGP has received grant support from Solvay Pharmaceuticals and Eli Lilly & Co. MTT, CMB, MSH, and CEC reported no financial relations with commercial interests. NR 41 TC 78 Z9 81 U1 0 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2010 VL 91 IS 6 BP 1568 EP 1573 DI 10.3945/ajcn.2010.29203 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 598MP UT WOS:000277841700006 PM 20427731 ER PT J AU Voruganti, VS Cole, SA Ebbesson, SOE Goring, HHH Haack, K Laston, S Wenger, CR Tejero, ME Devereux, RB Fabsitz, RR MacCluer, JW Umans, JG Howard, BV Comuzzie, AG AF Voruganti, V. Saroja Cole, Shelley A. Ebbesson, Sven O. E. Goering, Harald H. H. Haack, Karin Laston, Sandra Wenger, Charlotte R. Tejero, M. Elizabeth Devereux, Richard B. Fabsitz, Richard R. MacCluer, Jean W. Umans, Jason G. Howard, Barbara V. Comuzzie, Anthony G. TI Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; IDENTIFIES VARIANTS; ALZHEIMERS-DISEASE; PEDIGREE ANALYSIS; APOLIPOPROTEIN-J; LINKAGE ANALYSIS; RECEPTOR GENE; TRAIL; RISK AB Background: Alterations in plasma fatty acid distribution are linked to metabolic abnormalities related to type 2 diabetes and cardiovascular disease. Objective: The aim of this study was to investigate genetic factors influencing plasma fatty acid distribution in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Design: Fatty acids in plasma were measured by gas chromatography in 761 related individuals (>35 y of age). Results: Quantitative genetic analyses showed that fatty acid distribution is significantly heritable (P < 0.001), with heritabilities ranging from 0.33 to 0.55. A genome-wide scan for plasma fatty acids identified a 20-cM region on chromosome 8 (p12-p21) with a quantitative trait locus for monounsaturated fatty acids (logarithm of odds score = 3.8). The same region had a quantitative trait locus for polyunsaturated fatty acids (logarithm of odds score = 2.6). We genotyped single nucleotide polymorphisms (SNPs) in candidate genes in 8p12-p21 and found a significant association between fatty acids and SNPs in apolipoprotein J (APOJ), lipoprotein lipase (LPL), macrophage scavenger receptor 1 (MSR1), and tumor necrosis factor receptor superfamily member 10b (TNFRSF10B). A Bayesian quantitative trait nucleotide analysis based on a measured genotype model showed that SNPs in LPL, TNFRSF10B, and APOJ had strong statistical evidence of a functional effect (posterior probability >= 75%) on plasma fatty acid distribution. Conclusions: The results indicate that there is strong genetic influence on plasma fatty acid distribution and that genetic variation in APOJ, LPL, and TNFRSF10B may play a role. The GOCADAN study was registered at www.clinicaltrials.gov as NCT00006192. Am J Clin Nutr 2010;91:1574-83. C1 [Voruganti, V. Saroja; Cole, Shelley A.; Goering, Harald H. H.; Haack, Karin; Laston, Sandra; Wenger, Charlotte R.; Tejero, M. Elizabeth; MacCluer, Jean W.; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, Nome, AK USA. [Devereux, Richard B.] Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY 10021 USA. [Fabsitz, Richard R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Umans, Jason G.; Howard, Barbara V.] Medstar Res Inst, Washington, DC USA. RP Voruganti, VS (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM svorugan@sfbrgenetics.org FU Research Facilities Improvement Program [C06 RR014578, C06 RR013556, C06 RR015456, C06 RR017515]; NIH [U01 HL082490, MH59490] FX This investigation was conducted in part in facilities constructed with support from the Research Facilities Improvement Program under grant nos. C06 RR014578, C06 RR013556, C06 RR015456, and C06 RR017515, and with support from NIH grants U01 HL082490 and MH59490. NR 49 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2010 VL 91 IS 6 BP 1574 EP 1583 DI 10.3945/ajcn.2009.28927 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 598MP UT WOS:000277841700007 PM 20410100 ER PT J AU Meinhold, CL Dodd, KW Jiao, L Flood, A Shikany, JM Genkinger, JM Hayes, RB Stolzenberg-Solomon, RZ AF Meinhold, Cari L. Dodd, Kevin W. Jiao, Li Flood, Andrew Shikany, James M. Genkinger, Jeanine M. Hayes, Richard B. Stolzenberg-Solomon, Rachael Z. TI Available Carbohydrates, Glycemic Load, and Pancreatic Cancer: Is There a Link? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; dietary carbohydrates; dietary fats; glycemic index; pancreatic neoplasms; prospective studies ID FOOD FREQUENCY QUESTIONNAIRES; NUTRITIONAL FACTORS; DIETARY FACTORS; RISK; INDEX; INSULIN; GLUCOSE; CANADA; COHORT; WOMEN AB High-carbohydrate diets have been linked to pancreatic cancer risk in case-control studies, but prospective studies have shown mostly null results. The authors investigated the associations of glycemic load, glycemic index, and carbohydrate intake with pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake was assessed by using a self-administered questionnaire. Between 1998 and 2006 (median follow-up = 6.5 years), 266 incident, confirmed pancreatic cancers were identified among 109,175 participants. Hazards ratios and 95% confidence intervals were adjusted for sex, smoking, body mass index, and total energy. Overall, elevated risks for pancreatic cancer were observed in the 90th versus 10th percentile of glycemic load (hazards ratio (HR) = 1.45, 95% confidence interval (CI): 1.05, 2.00), available carbohydrate (HR = 1.47, 95% CI: 1.05, 2.06), and sucrose (HR = 1.37, 95% CI: 0.99, 1.89) intake. The positive association for available carbohydrate intake was observed during the first 4 years of follow-up (HR(< 2 years) = 2.60, 95% CI: 1.34, 5.06; HR(2-< 4 years) = 1.94, 95% CI: 1.06, 3.55) but not subsequently (HR = 0.86, 95% CI: 0.52, 1.44); the opposite pattern was observed for total fat and saturated fat intake. Rather than being causal, the short-term increase in pancreatic cancer risk associated with high available carbohydrate and low fat intake may be capturing dietary changes associated with subclinical disease. C1 [Meinhold, Cari L.; Jiao, Li; Hayes, Richard B.; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Dodd, Kevin W.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Flood, Andrew] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Shikany, James M.] Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA. [Genkinger, Jeanine M.] Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Executive Blvd,Room 3020, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Kitahara, Cari/R-8267-2016 NR 37 TC 16 Z9 16 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 IS 11 BP 1174 EP 1182 DI 10.1093/aje/kwq061 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QH UT WOS:000278222600003 PM 20452999 ER PT J AU Barry, KH Zhang, Y Lan, Q Hosgood, HD Zahm, SH Holford, TR Leaderer, B Boyle, P Rothman, N Zheng, T AF Barry, K. H. Zhang, Y. Lan, Q. Hosgood, H. D., III Zahm, S. H. Holford, T. R. Leaderer, B. Boyle, P. Rothman, N. Zheng, T. TI VARIATION IN METABOLIC GENES, SOLVENT EXPOSURE AND NHL SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Barry, K. H.; Zhang, Y.; Lan, Q.; Hosgood, H. D., III; Zahm, S. H.; Holford, T. R.; Leaderer, B.; Boyle, P.; Rothman, N.; Zheng, T.] NCI, DCEG, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300267 ER PT J AU Beydoun, MA Beydoun, HA Kuczmarski, MTF Hibbeln, JR Evans, MK Zonderman, AB AF Beydoun, M. A. Beydoun, H. A. Kuczmarski, M. T. F. Hibbeln, J. R. Evans, M. K. Zonderman, A. B. TI FISH CONSUMPTION, N-3 FATTY ACID INTAKES AND THEIR ASSOCIATION WITH DEPRESSIVE SYMPTOMS AMONG US ADULTS: HANDLS STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Beydoun, M. A.; Beydoun, H. A.; Kuczmarski, M. T. F.; Hibbeln, J. R.; Evans, M. K.; Zonderman, A. B.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S72 EP S72 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300288 ER PT J AU Bhatti, P Yong, LC Doody, MM Preston, DL Kampa, DM Ramsey, MJ Ward, EM Edwards, AA Ron, E Tucker, JD Sigurdson, AJ AF Bhatti, P. Yong, L. C. Doody, M. M. Preston, D. L. Kampa, D. M. Ramsey, M. J. Ward, E. M. Edwards, A. A. Ron, E. Tucker, J. D. Sigurdson, A. J. TI DIAGNOSTIC X-RAY EXAMINATIONS AND INCREASED CHROMOSOME TRANSLOCATIONS: EVIDENCE FROM THREE STUDIES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Bhatti, P.; Yong, L. C.; Doody, M. M.; Preston, D. L.; Kampa, D. M.; Ramsey, M. J.; Ward, E. M.; Edwards, A. A.; Ron, E.; Tucker, J. D.; Sigurdson, A. J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S117 EP S117 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300467 ER PT J AU Bowers, K Hu, G Yu, Z Yang, X Klebanoff, M Yeung, E Zhang, C AF Bowers, K. Hu, G. Yu, Z. Yang, X. Klebanoff, M. Yeung, E. Zhang, C. TI POSTNATAL WEIGHT GAIN AND HIGH BLOOD PRESSURE AMONG CHINESE CHILDREN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Bowers, K.; Hu, G.; Yu, Z.; Yang, X.; Klebanoff, M.; Yeung, E.; Zhang, C.] NICHD, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S28 EP S28 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300113 ER PT J AU Brinton, L Gierach, G Andaya, A Hollenbeck, A Park, Y Schatzkin, A Spitz, M AF Brinton, L. Gierach, G. Andaya, A. Hollenbeck, A. Park, Y. Schatzkin, A. Spitz, M. TI HORMONAL RISK FACTORS FOR LUNG CANCER IN WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Brinton, L.; Gierach, G.; Andaya, A.; Hollenbeck, A.; Park, Y.; Schatzkin, A.; Spitz, M.] Natl Canc Inst, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S61 EP S61 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300244 ER PT J AU Cao, Y Chen, A Radcliffe, J Dietrich, K Jones, R Caldwell, K Rogan, W AF Cao, Y. Chen, A. Radcliffe, J. Dietrich, K. Jones, R. Caldwell, K. Rogan, W. TI EFFICACY OF SUCCIMER CHELATION OF CADMIUM AT BACKGROUND EXPOSURES IN TODDLERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Cao, Y.; Chen, A.; Radcliffe, J.; Dietrich, K.; Jones, R.; Caldwell, K.; Rogan, W.] NIEHS, Durham, NC 27709 USA. RI Jones, Robert/E-1170-2011; Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S51 EP S51 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300205 ER PT J AU Carter, T Pangilinan, F Troendle, J Molloy, A Kirke, P Conley, M Scott, J Brody, L Mills, J AF Carter, T. Pangilinan, F. Troendle, J. Molloy, A. Kirke, P. Conley, M. Scott, J. Brody, L. Mills, J. TI CANDIDATE GENETIC VARIANTS AND NEURAL TUBE DEFECTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Carter, T.; Pangilinan, F.; Troendle, J.; Molloy, A.; Kirke, P.; Conley, M.; Scott, J.; Brody, L.; Mills, J.] NICHHD, Bethesda, MD 20892 USA. [Carter, T.; Pangilinan, F.; Troendle, J.; Molloy, A.; Kirke, P.; Conley, M.; Scott, J.; Brody, L.; Mills, J.] Eunice Kennedy Shriver Ctr Mental Retardat Inc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S8 EP S8 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300031 ER PT J AU Chen, L Zhang, C Yeung, E Ye, A Hediger, M Mumford, S Wactawski-Wende, J Schisterman, EF AF Chen, L. Zhang, C. Yeung, E. Ye, A. Hediger, M. Mumford, S. Wactawski-Wende, J. Schisterman, E. F. TI YOUNGER AGE AT MENARCHE IS ASSOCIATED WITH RISK FACTORS OF TYPE 2 DIABETES AMONG PREMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Chen, L.; Zhang, C.; Yeung, E.; Ye, A.; Hediger, M.; Mumford, S.; Wactawski-Wende, J.; Schisterman, E. F.] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S69 EP S69 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300276 ER PT J AU Cook, MB Dawsey, SM Diaw, L Blaser, MJ Perez-Perez, GI Abnet, CC Taylor, PR Albanes, D Virtamo, J Kamangar, F AF Cook, M. B. Dawsey, S. M. Diaw, L. Blaser, M. J. Perez-Perez, G. I. Abnet, C. C. Taylor, P. R. Albanes, D. Virtamo, J. Kamangar, F. TI HELICOBACTER PYLORI AND GASTRIC ATROPHY IN RELATION TO THE RISK OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA IN THE ALPHA-TOCOPHEROL, BETA-CAROTENE CANCER PREVENTION (ATBC) STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Cook, M. B.; Dawsey, S. M.; Diaw, L.; Blaser, M. J.; Perez-Perez, G. I.; Abnet, C. C.; Taylor, P. R.; Albanes, D.; Virtamo, J.; Kamangar, F.] NCI, Bethesda, MD 20852 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300262 ER PT J AU Cupul-Uicab, LA Baird, DD Eggesbo, M Skjaerven, R Haug, K Longnecker, MP AF Cupul-Uicab, L. A. Baird, D. D. Eggesbo, M. Skjaerven, R. Haug, K. Longnecker, M. P. TI IN UTERO EXPOSURE TO CIGARETTE SMOKE AND WOMEN'S RISK OF FETAL LOSS LATER IN LIFE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Cupul-Uicab, L. A.; Baird, D. D.; Eggesbo, M.; Skjaerven, R.; Haug, K.; Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH,DHHS,USA, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S27 EP S27 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300109 ER PT J AU Danaher, M Schisterman, EF Roy, A Albert, P AF Danaher, M. Schisterman, E. F. Roy, A. Albert, P. TI GENE-ENVIRONMENT INTERACTION BY POOLING BIOSPECIMENS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Danaher, M.; Schisterman, E. F.; Roy, A.; Albert, P.] NICHD, Rockville, MD 20854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S144 EP S144 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300574 ER PT J AU Deroo, LA Parks, CG Weinberg, CR Sandler, DP AF Deroo, L. A. Parks, C. G. Weinberg, C. R. Sandler, D. P. TI CHILDHOOD TRAUMA, ABUSE AND OTHER STRESSORS IN RELATION TO TELOMERE LENGTH SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Deroo, L. A.; Parks, C. G.; Weinberg, C. R.; Sandler, D. P.] NIEHS, NIH, Epidemiol & Biostat Branches, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S115 EP S115 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300461 ER PT J AU Freedman, DM Kimlin, MG Hoffbeck, RW Alexander, BH Linet, MS AF Freedman, D. M. Kimlin, M. G. Hoffbeck, R. W. Alexander, B. H. Linet, M. S. TI MULTIPLE INDICATORS OF AMBIENT AND PERSONAL ULTRAVIOLET RADIATION EXPOSURE AND RISK OF NON-HODGKIN LYMPHOMA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Freedman, D. M.; Kimlin, M. G.; Hoffbeck, R. W.; Alexander, B. H.; Linet, M. S.] NCI, NIH, DHHS, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300321 ER PT J AU Gaskins, AJ Rovner, AJ Mumford, SL Yeung, EH Wactawski-Wende, J Trevisan, M Perkins, NJ Schisterman, EF AF Gaskins, A. J. Rovner, A. J. Mumford, S. L. Yeung, E. H. Wactawski-Wende, J. Trevisan, M. Perkins, N. J. Schisterman, E. F. TI THE IMPACT OF A MEDITERRANEAN DIET ON OXIDATIVE STRESS IN YOUNG WOMEN: THE BIOCYCLE STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Gaskins, A. J.; Rovner, A. J.; Mumford, S. L.; Yeung, E. H.; Wactawski-Wende, J.; Trevisan, M.; Perkins, N. J.; Schisterman, E. F.] NICHD, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S6 EP S6 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300022 ER PT J AU Gierach, G Freedman, N Andaya, A Hollenbeck, A Park, Y Schatzkin, A Brinton, L AF Gierach, G. Freedman, N. Andaya, A. Hollenbeck, A. Park, Y. Schatzkin, A. Brinton, L. TI COFFEE CONSUMPTION AND BREAST CANCER RISK IN THE NIH-AARP DIET AND HEALTH STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Gierach, G.; Freedman, N.; Andaya, A.; Hollenbeck, A.; Park, Y.; Schatzkin, A.; Brinton, L.] NCI, Bethesda, MD 20852 USA. RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S24 EP S24 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300097 ER PT J AU Gyi, L McCarty, C Chisholm, R Chute, C Crane, P Jarvik, G Kullo, I Larson, E Masys, D Roden, D Li, R AF Gyi, Lin McCarty, Catherine Chisholm, Rex Chute, Christopher Crane, Paul Jarvik, Gail Kullo, Iftikhar Larson, Eric Masys, Daniel Roden, Dan Li, Rongling TI THE EMERGE NETWORK: CHALLENGES AND LESSONS LEARNED SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Gyi, Lin; McCarty, Catherine; Chisholm, Rex; Chute, Christopher; Crane, Paul; Jarvik, Gail; Kullo, Iftikhar; Larson, Eric; Masys, Daniel; Roden, Dan; Li, Rongling] NHGRI, Rockville, MD 20852 USA. RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S131 EP S131 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300524 ER PT J AU Hofmann, JN Yu, K Horst, RL Hayes, RB Purdue, MP AF Hofmann, J. N. Yu, K. Horst, R. L. Hayes, R. B. Purdue, M. P. TI LONG-TERM VARIATION IN SERUM 25-HYDROXYVITAMIN D CONCENTRATION AMONG PARTICIPANTS IN THE PROSTATE, LUNG, COLORECTAL AND OVARIAN CANCER SCREENING TRIAL SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Hofmann, J. N.; Yu, K.; Horst, R. L.; Hayes, R. B.; Purdue, M. P.] Natl Canc Inst, Bethesda, MD 20892 USA. RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S55 EP S55 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300218 ER PT J AU Hoppin, J Jaramillo, R Salo, P London, S Sandler, D Zeldin, D AF Hoppin, J. Jaramillo, R. Salo, P. London, S. Sandler, D. Zeldin, D. TI ARE QUESTIONNAIRES GOOD PREDICTORS OF ATOPIC STATUS? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Hoppin, J.; Jaramillo, R.; Salo, P.; London, S.; Sandler, D.; Zeldin, D.] NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S143 EP S143 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300573 ER PT J AU Jukic, A Weinberg, CR Baird, D Wilcox, A AF Jukic, A. Weinberg, C. R. Baird, D. Wilcox, A. TI PREGNANCY AND MATERNAL FACTORS ASSOCIATED WITH THE TIMING OF IMPLANTATION AND THE INITIAL RATE OF RISE IN URINARY HUMAN CHORIONIC GONADOTROPIN (HCG) SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, CA SP Soc Epidemiol Res C1 [Jukic, A.; Weinberg, C. R.; Baird, D.; Wilcox, A.] NIEHS, Durham, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S33 EP S33 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300133 ER PT J AU Lam, TK Cross, AJ Freedman, ND Park, Y Hollenbeck, AR Schatzkin, A Abnet, CC AF Lam, T. K. Cross, A. J. Freedman, N. D. Park, Y. Hollenbeck, A. R. Schatzkin, A. Abnet, C. C. TI DIETARY FIBER AND WHOLE GRAIN CONSUMPTION IN RELATION TO HEAD AND NECK CANCERS IN THE NIH-AARP DIET AND HEALTH STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Lam, T. K.; Cross, A. J.; Freedman, N. D.; Park, Y.; Hollenbeck, A. R.; Schatzkin, A.; Abnet, C. C.] NCI, Rockville, MD 20852 USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300265 ER PT J AU Laughlin, SK Hartmann, KE Baird, DD AF Laughlin, S. K. Hartmann, K. E. Baird, D. D. TI POSTPARTUM PROGESTERONE USE MAY PREVENT FIBROID REGRESSION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Laughlin, S. K.; Hartmann, K. E.; Baird, D. D.] NIEHS, NIH, Durham, NC 27707 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S37 EP S37 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300146 ER PT J AU Lin, SW Freedman, ND Hollenbeck, AR Abnet, CC AF Lin, S-W Freedman, N. D. Hollenbeck, A. R. Abnet, C. C. TI PROSPECTIVE STUDY OF DIABETES AND THE RISK OF GASTRIC AND ESOPHAGEAL CANCERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Lin, S-W; Freedman, N. D.; Hollenbeck, A. R.; Abnet, C. C.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S60 EP S60 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300241 ER PT J AU Meinhold, CL de Gonzalez, AB Freedman, ND Huxley, R Mok, Y Jee, SH Samet, JM AF Meinhold, C. L. de Gonzalez, A. Berrington Freedman, N. D. Huxley, R. Mok, Y. Jee, S. H. Samet, J. M. TI TOTAL CHOLESTEROL AND CANCER RISK IN A LARGE PROSPECTIVE STUDY IN KOREA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Meinhold, C. L.; de Gonzalez, A. Berrington; Freedman, N. D.; Huxley, R.; Mok, Y.; Jee, S. H.; Samet, J. M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RI Huxley, Rachel/J-4638-2013; Freedman, Neal/B-9741-2015; Huxley, Rachel/C-7032-2013; Kitahara, Cari/R-8267-2016 OI Huxley, Rachel/0000-0002-2705-6616; Freedman, Neal/0000-0003-0074-1098; Huxley, Rachel/0000-0002-2705-6616; NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S57 EP S57 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300228 ER PT J AU Mumford, SL Schisterman, EF Siega-Riz, AM Gaskins, AJ VanderWeele, TJ AF Mumford, S. L. Schisterman, E. F. Siega-Riz, A. M. Gaskins, A. J. VanderWeele, T. J. TI DIRECT EFFECTS OF DIETARY FIBER INTAKE ON LIPOPROTEIN CHOLESTEROL LEVELS IN PREMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Mumford, S. L.; Schisterman, E. F.; Siega-Riz, A. M.; Gaskins, A. J.; VanderWeele, T. J.] NICHD, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S37 EP S37 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300147 ER PT J AU Murphy, G Fan, JH Mark, SD Dawsey, SM Selhub, J Taylor, PR Qiao, YL Abnet, CC AF Murphy, G. Fan, J-H Mark, S. D. Dawsey, S. M. Selhub, J. Taylor, P. R. Qiao, Y-L Abnet, C. C. TI PROSPECTIVE STUDY OF SERUM CYSTEINE LEVELS AND ESOPHAGEAL AND GASTRIC CANCERS IN CHINA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Murphy, G.; Fan, J-H; Mark, S. D.; Dawsey, S. M.; Selhub, J.; Taylor, P. R.; Qiao, Y-L; Abnet, C. C.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RI Qiao, You-Lin/B-4139-2012; Murphy, Gwen/G-7443-2015 OI Qiao, You-Lin/0000-0001-6380-0871; NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S119 EP S119 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300476 ER PT J AU Myers, SL Baird, DD Olshan, AF Herring, AH Nylander-French, L Hartmann, KE AF Myers, S. L. Baird, D. D. Olshan, A. F. Herring, A. H. Nylander-French, L. Hartmann, K. E. TI ACCURACY OF SELF-REPORTED UTERINE FIBROID DIAGNOSIS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Myers, S. L.; Baird, D. D.; Olshan, A. F.; Herring, A. H.; Nylander-French, L.; Hartmann, K. E.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S36 EP S36 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300143 ER PT J AU Parks, CG Deroo, LA Sandler, DP AF Parks, C. G. Deroo, L. A. Sandler, D. P. TI HIGHER BODY MASS INDEX ASSOCIATED WITH LIFETIME HISTORY OF TRAUMATIC STRESS IN WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, CA SP Soc Epidemiol Res C1 [Parks, C. G.; Deroo, L. A.; Sandler, D. P.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S38 EP S38 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300153 ER PT J AU Parks, CG Deroo, LA Miller, DB Sandler, DP AF Parks, C. G. Deroo, L. A. Miller, D. B. Sandler, D. P. TI SEXUAL AND PHYSICAL ABUSE, URINARY CORTISOL AND OBESITY IN WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, CA SP Soc Epidemiol Res C1 [Parks, C. G.; Deroo, L. A.; Miller, D. B.; Sandler, D. P.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S38 EP S38 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300151 ER PT J AU Perkins, N Whitcomb, B Schisterman, E AF Perkins, N. Whitcomb, B. Schisterman, E. TI FLEXIBLE, EFFICIENT BIOMARKER ASSAY CALIBRATION DESIGNS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Perkins, N.; Whitcomb, B.; Schisterman, E.] NICHD, NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S142 EP S142 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300566 ER PT J AU Pollack, AZ Schisterman, EF Goldman, LR Navas-Acien, A Witter, F Wactawski-Wende, J AF Pollack, A. Z. Schisterman, E. F. Goldman, L. R. Navas-Acien, A. Witter, F. Wactawski-Wende, J. TI HEAVY METALS AND HORMONES IN PREMENOPAUSA WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Pollack, A. Z.; Schisterman, E. F.; Goldman, L. R.; Navas-Acien, A.; Witter, F.; Wactawski-Wende, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD 20852 USA. RI Pollack, Anna/F-2021-2011; Goldman, Lynn/D-5372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S82 EP S82 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300327 ER PT J AU Reedy, J AF Reedy, J. TI THE NEXT GENERATION: NOVEL TOOLS TO ASSESS DIET AND PHYSICAL ACTIVITY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Reedy, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S50 EP S50 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300198 ER PT J AU Schisterman, EF Cole, SR Platt, RW Hernan, MA Wacholder, S AF Schisterman, E. F. Cole, S. R. Platt, R. W. Hernan, M. A. Wacholder, S. TI UNNATURAL SELECTION: SURVIVAL OF THE FITTEST SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Schisterman, E. F.; Cole, S. R.; Platt, R. W.; Hernan, M. A.; Wacholder, S.] NICHD, Bethesda, MD 20852 USA. RI Platt, Robert/G-5847-2012 NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S50 EP S50 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300200 ER PT J AU Schonfeld, SJ Hartge, P Pfeiffer, RM Freedman, DM Greenlee, RT Linet, MS Park, Y Schairer, C Schatzkin, A Visvanathan, K Lacey, JV AF Schonfeld, S. J. Hartge, P. Pfeiffer, R. M. Freedman, D. M. Greenlee, R. T. Linet, M. S. Park, Y. Schairer, C. Schatzkin, A. Visvanathan, K. Lacey, J. V. TI HORMONAL FACTORS AND ENDOMETRIAL CANCER RISK BY PARITY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Schonfeld, S. J.; Hartge, P.; Pfeiffer, R. M.; Freedman, D. M.; Greenlee, R. T.; Linet, M. S.; Park, Y.; Schairer, C.; Schatzkin, A.; Visvanathan, K.; Lacey, J. V.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S22 EP S22 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300087 ER PT J AU Thoma, M Gray, R Kiwanuka, N Aluma, S Mei-Cheng, W Sewankambo, N Maria, W AF Thoma, M. Gray, R. Kiwanuka, N. Aluma, S. Mei-Cheng, W. Sewankambo, N. Maria, W. TI THE SHORT-TERM VARIABILITY OF BACTERIAL VAGINOSIS (BV) AMONG SEXUALLY ACTIVE WOMEN IN RAKAI, UGANDA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Thoma, M.; Gray, R.; Kiwanuka, N.; Aluma, S.; Mei-Cheng, W.; Sewankambo, N.; Maria, W.] NICHD, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S30 EP S30 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300121 ER PT J AU Trabert, B Graubard, BI Klebanoff, MA Longnecker, MP McGlynn, KA AF Trabert, B. Graubard, B. I. Klebanoff, M. A. Longnecker, M. P. McGlynn, K. A. TI ARE PLACENTAL CHARACTERISTICS AN INDIRECT MARKER OF IN UTERO HORMONE EXPOSURE? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Trabert, B.; Graubard, B. I.; Klebanoff, M. A.; Longnecker, M. P.; McGlynn, K. A.] Natl Canc Inst, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S58 EP S58 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300231 ER PT J AU Wang, Y Rogan, W AF Wang, Y. Rogan, W. TI BREASTFEEDING, EARLY WEIGHT GAIN, AND SECONDARY SEXUAL MATURATION: RESULTS FROM NORTH CAROLINA INFANT FEEDING STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Wang, Y.; Rogan, W.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S153 EP S153 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300611 ER PT J AU Whitworth, KW Baird, DD Stene, LC Skjaerven, R Longnecker, MP AF Whitworth, K. W. Baird, D. D. Stene, L. C. Skjaerven, R. Longnecker, M. P. TI DIABETES AND TIME TO PREGNANCY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Whitworth, K. W.; Baird, D. D.; Stene, L. C.; Skjaerven, R.; Longnecker, M. P.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S28 EP S28 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300110 ER PT J AU Yeung, E Zhang, C Bowers, K Hu, F Qi, L AF Yeung, E. Zhang, C. Bowers, K. Hu, F. Qi, L. TI NEUROPEPTIDE Y GENE VARIANTS AND OBESITY: LONGITUDINAL ANALYSES IN TWO COHORTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 NICHD, Bethesda, MD 20892 USA. HSPH, Boston, MA 02115 USA. RI Bowers, Katherine/N-5226-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S131 EP S131 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300522 ER PT J AU Yeung, E Qi, L Hu, F Zhang, C AF Yeung, E. Qi, L. Hu, F. Zhang, C. TI NOVEL ABDOMINAL ADIPOSITY GENES, PLASMA ADIPOKINES, AND RISK OF TYPE 2 DIABETES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 23-26, 2010 CL Anaheim, SOLOMON ISLANDS SP Soc Epidemiol Res C1 [Yeung, E.; Qi, L.; Hu, F.; Zhang, C.] NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2010 VL 171 SU 11 BP S68 EP S68 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 603QO UT WOS:000278223300273 ER PT J AU Lynch, PM Ayers, GD Hawk, E Richmond, E Eagle, C Woloj, M Church, J Hasson, H Patterson, S Half, E Burke, CA AF Lynch, Patrick M. Ayers, Gregory D. Hawk, Ernie Richmond, Ellen Eagle, Craig Woloj, Mabel Church, James Hasson, Hennie Patterson, Sherri Half, Elizabeth Burke, Carol A. TI The Safety and Efficacy of Celecoxib in Children With Familial Adenomatous Polyposis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLORECTAL ADENOMA; CYCLOOXYGENASE-2 INHIBITOR; RECTAL POLYPS; SULINDAC; PREVENTION; TRIAL; CHEMOPREVENTION; ROFECOXIB AB OBJECTIVES: Celecoxib is approved as an adjunctive chemopreventive agent in adults with familial adenomatous polyposis (FAP). Its safety and efficacy for colorectal polyps in children is unknown. We evaluated the short-term (3 months) safety and preliminary efficacy of celecoxib in children with FAP. METHODS: This was a phase I, dose-escalation trial, with three successive cohorts of six children. Children of ages 10-14 years with APC gene mutations and/or adenomas with a family history of FAP were studied at M. D. Anderson Cancer Center and the Cleveland Clinic. Colonoscopy was performed at baseline and month 3. Random assignment was in a 2: 1 generic: placebo ratio, escalating from cohort 1 (4 mg/kg/day) to cohort 2 (8 mg/kg/day) to cohort 3 (16 mg/kg/day). Adherence and adverse event (AE) monitoring was conducted at 2-week intervals during drug administration. Safety profile, difference in number, and percent change in colorectal polyps were compared among the four treatments (placebo and the three dose-escalation groups). RESULTS: Eighteen subjects completed drug dosing and both colonoscopies. Median age was 12.3 years (56% female). No clinically meaningful differences in AEs were seen between placebo subjects and subjects at any of the three celecoxib doses. Median polyp count at baseline was 31. There was a 39.1% increase in the number of polyps in placebo subjects at month 3, whereas in the highest dose celecoxib group, 16 mg/kg/day, a 44.2% reduction was seen (P = 0.01). CONCLUSIONS: Celecoxib at a dose of 16 mg/kg/day, corresponding to the adult dose of 400 mg BID, is safe, well tolerated, and significantly reduced the number of colorectal polyps in children with FAP. C1 [Lynch, Patrick M.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77230 USA. [Ayers, Gregory D.] Canc Biostat Ctr, Vanderbilt Ingram Canc Ctr, Dept Biostat, Nashville, TN USA. [Hawk, Ernie; Richmond, Ellen] NCI, Gastrointestinal & Other Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Eagle, Craig; Woloj, Mabel] Pfizer Inc, New York, NY USA. [Church, James] Cleveland Clin, Dept Colorectal Surg, Cleveland, OH 44106 USA. [Hasson, Hennie] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44106 USA. [Patterson, Sherri] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX 77230 USA. [Half, Elizabeth; Burke, Carol A.] Meir Med Canc Ctr, Dept Gastroenterol & Hepatol, Prevent & Familial Canc Serv, Kefar Sava, Israel. RP Lynch, PM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr 436, POB 301402, Houston, TX 77230 USA. EM plynch@mdanderson.org FU NCI/NIH [N01-CN-05126-02]; Pfizer Inc; Division of Cancer Prevention, National Cancer Institute, Bethesda, MD FX This study was supported by NCI/NIH contract N01-CN-05126-02 (P.M.L., PI), and by Pfizer Inc. During the 3 years of enrollment, collection, and interpretation of data, support was provided under contractual arrangement by the Division of Cancer Prevention, National Cancer Institute, Bethesda, MD. Drug and look-alike placebo were provided by Pfizer. NR 15 TC 23 Z9 23 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2010 VL 105 IS 6 BP 1437 EP 1443 DI 10.1038/ajg.2009.758 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 607OU UT WOS:000278515700035 PM 20234350 ER PT J AU Steinberg, MH McCarthy, WF Castro, O Ballas, SK Armstrong, FD Smith, W Ataga, K Swerdlow, P Kutlar, A DeCastro, L Waclawiw, MA AF Steinberg, Martin H. McCarthy, William F. Castro, Oswaldo Ballas, Samir K. Armstrong, F. Danny Smith, Wally Ataga, Kenneth Swerdlow, Paul Kutlar, Abdullah DeCastro, Laura Waclawiw, Myron A. CA Investigators Multictr Study Hydro TI The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID INSTITUTES-OF-HEALTH; PULMONARY-HYPERTENSION; FETAL-HEMOGLOBIN; DISEASE; CHILDREN; DEATH; THERAPY; TESTS; HEMOLYSIS; EQUALITY AB A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 85:403-408, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston Med Ctr, Boston, MA 02118 USA. [McCarthy, William F.] Maryland Med Res Inst, Baltimore, MD USA. [Castro, Oswaldo] Howard Univ, Sch Med, Dept Med, Washington, DC 20059 USA. [Ballas, Samir K.] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA. [Armstrong, F. Danny] Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. [Smith, Wally] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. [Ataga, Kenneth] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Swerdlow, Paul] Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. [Kutlar, Abdullah] Med Coll Georgia, Dept Med, Augusta, GA 30912 USA. [DeCastro, Laura] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Waclawiw, Myron A.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Steinberg, MH (reprint author), 72E Concord St, Boston, MA 02118 USA. EM mhsteinb@bu.edu FU NHLBI NIH HHS [N01 HB067129] NR 46 TC 166 Z9 170 U1 4 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2010 VL 85 IS 6 BP 403 EP 408 DI 10.1002/ajh.21699 PG 6 WC Hematology SC Hematology GA 605MT UT WOS:000278352400002 PM 20513116 ER PT J AU Zhao, Q Gu, DF Kelly, TN Hixson, JE Rao, DC Jaquish, CE Chen, J Huang, JF Chen, CS Gu, CC Whelton, PK He, J AF Zhao, Qi Gu, Dongfeng Kelly, Tanika N. Hixson, James E. Rao, Dabeeru C. Jaquish, Cashell E. Chen, Jing Huang, Jianfeng Chen, Chung-Shivan Gu, C. Charles Whelton, Paul K. He, Jiang TI Association of Genetic Variants in the Apelin-APJ System and ACE2 With Blood Pressure Responses to Potassium Supplementation: The GenSalt Study SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE ACE2; apelin; apelin receptor; blood pressure; hypertension; polymorphism; potassium supplement ID RENIN-ANGIOTENSIN SYSTEM; IN-VIVO; AGTRL1 GENE; HYPERTENSION; POLYMORPHISMS; POPULATION; RECEPTOR; DISEASE; CHINESE; INFARCTION AB BACKGROUND Genetic factors may influence blood pressure (BP) responses to dietary potassium intake. We examined the association of genetic variants in the apelin-APJ system and angiotensin-converting enzyme 2 (ACE2) with BP responses to potassium supplementation. METHODS We conducted a 7-day potassium supplementation (60 mmol/day) intervention among 1,906 Chinese adults who participated in the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Tag single-nucleotide polymorphisms (SNPs) based on HapMap data and potential functional SNPs were selected in the APLN, APLNR, and ACE2 genes. Because the ACE2 and APLN genes are located on the X chromosome, men and women were analyzed separately. RESULTS In women, SNP rs2235306 in the APLN gene was significantly associated with diastolic BP (DBP) response to potassium supplementation (P=0.0009).The DBP responses (95% confidence interval (Cl)) among those with genotypes T/T,T/C, and C/C were -2.22 (-2.74, -1.70), -1.69 (-2.20, -1.19), and -0.81 (-1.54, -0.09) mm Hg, respectively. In men, SNP rs4646174 of the ACE2 gene was significantly associated with systolic BP (SBP), DBP, and mean arterial pressure (MAP) responses to potassium supplementation (P=0.0001, P=0.001, and P=3.0 x 10(-6), respectively). The SBP, DBP, and MAP responses (95% Cl) were -0.79 (-2.27,0.69) vs.-3.53 (-3.94, -3.12), 1.07 (-0.34, 2.49) vs.-1.06 (-1.43, -0.69), and 0.44 (-0.60, 1.48) vs.-1.89 (-2.22,-1.55) mm Hg among men with minor G allele compared to those with major C allele of rs4646174, respectively. CONCLUSION Our study indicates that genetic variation of APLN and ACE2 may influence BP response to potassium intake. C1 [Zhao, Qi; Kelly, Tanika N.; Chen, Chung-Shivan; He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA. [Gu, Dongfeng; Huang, Jianfeng] Chinese Acad Med Sci, Cardiovasc Inst, Fuwai Hosp, Beijing 100037, Peoples R China. [Gu, Dongfeng; Huang, Jianfeng] Peking Union Med Coll, Beijing 100021, Peoples R China. [Gu, Dongfeng; Huang, Jianfeng] Chinese Natl Ctr Cardiovasc Dis Control & Res, Beijing, Peoples R China. [Hixson, James E.] Univ Texas Sch Publ Hlth, Dept Epidemiol, Houston, TX USA. [Rao, Dabeeru C.; Gu, C. Charles] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Jaquish, Cashell E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Chen, Jing; He, Jiang] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. [Whelton, Paul K.] Loyola Univ, Med Ctr, Off President, Maywood, IL 60153 USA. RP Zhao, Q (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70118 USA. EM qizhao@tulane.edu RI Gu, Charles/A-7934-2010 OI Gu, Charles/0000-0002-8527-8145 FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD [U01HL072507, R01HL087263, R01HL090682] FX The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by research grants (U01HL072507, R01HL087263, and R01HL090682) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD. Upsher-Smith Laboratories, Maple Grove, MN has provided Klor-Con M20 potassium tablets for the GenSalt study. NR 38 TC 21 Z9 22 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUN PY 2010 VL 23 IS 6 BP 606 EP 613 DI 10.1038/ajh.2010.36 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 601ES UT WOS:000278041700006 PM 20224560 ER PT J AU Memarzadeh, F Olmsted, RN Bartley, JM AF Memarzadeh, Farhad Olmsted, Russell N. Bartley, Judene M. TI Applications of ultraviolet germicidal irradiation disinfection in health care facilities: Effective adjunct, but not stand-alone technology SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE UVGI; ultraviolet germicidal irradiation; environment; HVAC; airborne infectious agents; air disinfection ID AIRBORNE BACTERIA; SERRATIA-MARCESCENS; RELATIVE-HUMIDITY; MYCOBACTERIUM-TUBERCULOSIS; ACINETOBACTER-BAUMANNII; AIR; ROOM; INFECTION; TRANSMISSION; RADIATION AB This review evaluates the applicability and relative contribution of ultraviolet germicidal irradiation (UVGI) to disinfection of air in health care facilities. A section addressing the use of UVGI for environmental surfaces is also included. The germicidal susceptibility of biologic agents is addressed, but with emphasis on application in health care facilities. The balance of scientific evidence indicates that UVGI should be considered as a disinfection application in a health care setting only in conjunction with other well-established elements, such as appropriate heating, ventilating, and air-conditioning (HVAC) systems; dynamic removal of contaminants from the air; and preventive maintenance in combination with through cleaning of the care environment. We conclude that although UVGI is microbiocidal, it is not "ready for prime time'' as a primary intervention to kill or inactivate infectious microorganisms; rather, it should be considered an adjunct. Other factors, such as careful design of the built environment, installation and effective operation of the HVAC system, and a high level of attention to traditional cleaning and disinfection, must be assessed before a health care facility can decide to rely solely on UVGI to meet indoor air quality requirements for health care facilities. More targeted and multiparameter studies are needed to evaluate the efficacy, safety, and incremental benefit of UVGI for mitigating reservoirs of microorganisms and ultimately preventing cross-transmission of pathogens that lead to health care-associated infections. C1 [Bartley, Judene M.] Epidemiol Consulting Serv Inc, Beverly Hills, MI 48025 USA. [Memarzadeh, Farhad] NIH, Bethesda, MD 20892 USA. [Olmsted, Russell N.] St Joseph Mercy Hlth Syst, Infect Prevent Serv, Ann Arbor, MI USA. [Olmsted, Russell N.] St Joseph Mercy Hlth Syst, Control Serv, Ann Arbor, MI USA. RP Bartley, JM (reprint author), Epidemiol Consulting Serv Inc, 17094 Dunblaine, Beverly Hills, MI 48025 USA. EM jbartley@ameritech.net FU Clorox Company; American Society for Healthcare Engineering; Facility Guidelines Institute FX Publication of this article was made possible by unrestricted educational grants from The Clorox Company, the American Society for Healthcare Engineering, and the Facility Guidelines Institute. NR 61 TC 21 Z9 23 U1 0 U2 22 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD JUN PY 2010 VL 38 IS 5 SU 1 BP S13 EP S24 DI 10.1016/j.ajic.2010.04.208 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 607TV UT WOS:000278530400002 PM 20569852 ER PT J AU Crews, DC Charles, RF Evans, MK Zonderman, AB Powe, NR AF Crews, Deidra C. Charles, Raquel F. Evans, Michele K. Zonderman, Alan B. Powe, Neil R. TI Poverty, Race, and CKD in a Racially and Socioeconomically Diverse Urban Population SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Socioeconomic status; health disparities; epidemiology; renal disease ID STAGE RENAL-DISEASE; NUTRITION EXAMINATION SURVEY; CHRONIC KIDNEY-DISEASE; 3RD NATIONAL-HEALTH; POTENTIAL EXPLANATORY FACTORS; HIGH BLOOD-PRESSURE; UNITED-STATES; ATHEROSCLEROSIS RISK; AFRICAN-AMERICAN; ETHNIC DISPARITIES AB Background: Low socioeconomic status (SES) and African American race are both independently associated with end-stage renal disease and progressive chronic kidney disease (CKD). However, despite their frequent co-occurrence, the effect of low SES independent of race has not been well studied in CKD. Study Design: Cross-sectional study. Setting & Participants: 2,375 community-dwelling adults aged 30-64 years residing within 12 neighborhoods selected for both socioeconomic and racial diversity in Baltimore City, MD. Predictors: Low SES (self-reported household income <125% of 2004 Department of Health and Human Services guideline), higher SES (>= 125% of guideline); white and African American race. Outcomes & Measurements: CKD defined as estimated glomerular filtration rate <60 mL/min/1.73m(2). Logistic regression used to calculate ORs for relationship between poverty and CKD, stratified by race. Results: Of 2,375 participants, 955 were white (347 low SES and 608 higher SES) and 1,420 were African American (713 low SES and 707 higher SES). 146 (6.2%) participants had CKD. Overall, race was not associated with CKD (OR, 1.05; 95% CI, 0.57-1.96); however, African Americans had a much greater odds of advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73m(2)). Low SES was independently associated with 59% greater odds of CKD after adjustment for demographics, insurance status, and comorbid disease (OR, 1.59; 95% CI, 1.27-1.99). However, stratified by race, low SES was associated with CKD in African Americans (OR, 1.91; 95% CI, 1.54-2.38), but not whites (OR, 0.95; 95% CI, 0.58-1.55; P for interaction = 0.003). Limitations: Cross-sectional design; findings may not be generalizable to non-urban populations. Conclusions: Low SES has a profound relationship with CKD in African Americans, but not whites, in an urban population of adults, and its role in the racial disparities seen in CKD is worthy of further investigation. Am J Kidney Dis 55: 992-1000. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Crews, Deidra C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21224 USA. [Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Bethesda, MD 20892 USA. [Powe, Neil R.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Powe, Neil R.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Crews, DC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, 4940 Eastern Ave,B Bldg,Rm 208, Baltimore, MD 21224 USA. EM dcrews1@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging, National Institutes of Health (NIH); National Center for Research Resources, NIH [1KL2RR025006-01]; National Heart, Lung, and Blood Institute [5 T32 HL007180]; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK 02643]; NIH Roadmap for Medical Research FX Support: This work is supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH). Dr Crews is supported by grant 1KL2RR025006-01 from the National Center for Research Resources, a component of the NIH and NIH Roadmap for Medical Research. Dr Charles is supported by grant 5 T32 HL007180 from the National Heart, Lung, and Blood Institute. Dr Powe is supported in part by grant K24 DK 02643 from National Institute of Diabetes and Digestive and Kidney Diseases. NR 36 TC 69 Z9 76 U1 2 U2 7 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 JUN PY 2010 VL 55 IS 6 BP 992 EP 1000 DI 10.1053/j.ajkd.2009.12.032 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 601CU UT WOS:000278036400007 PM 20207457 ER PT J AU Manoli, I Golas, G Westbroek, W Vilboux, T Markello, TC Introne, W Maynard, D Pederson, B Tsilou, E Jordan, MB Hart, PS White, JG Gahl, WA Huizing, M AF Manoli, Irini Golas, Gretchen Westbroek, Wendy Vilboux, Thierry Markello, Thomas C. Introne, Wendy Maynard, Dawn Pederson, Ben Tsilou, Ekaterini Jordan, Michael B. Hart, P. Suzanne White, James G. Gahl, William A. Huizing, Marjan TI Chediak-Higashi Syndrome With Early Developmental Delay Resulting From Paternal Heterodisomy of Chromosome 1 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Chediak-Higashi syndrome; LYST/CHS1; uniparental heterodisomy; SNP genotyping; lysosome-related organelle ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; MATERNAL UNIPARENTAL ISODISOMY; MOLECULAR ANALYSIS; GENOTYPING ARRAYS; MAPPING ARRAYS; GENE DELETION; CANCER-CELLS; DISOMY; PATIENT; IDENTIFICATION AB Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable oculocutaneous albinism, immunodeficiency, mild bleeding diathesis, and an accelerated lymphoproliferative state. Abnormal lysosome-related organelle membrane function leads to the accumulation of large intracellular vesicles in several cell types, including granulocytes, melanocytes, and platelets. This report describes a severe case of CHS resulting from paternal heterodisomy of chromosome 1, causing homozygosity for the most distal nonsense mutation (p.E3668X, exon 50) reported to date in the LYST/CHS1 gene. The mutation is located in the WD40 region of the CHS1 protein. The patient's fibroblasts expressed no detectable CHS1. Besides manifesting the classical CHS findings, the patient exhibited hypotonia and global developmental delays, raising concerns about other effects of heterodisomy. An interstitial 747 kb duplication on 6q14.2-6q14.3 was identified in the propositus and paternal samples by comparative genomic hybridization. SNP genotyping revealed no additional whole chromosome or segmental isodisomic regions or other dosage variations near the crossover breakpoints on chromosome 1. Unmasking of a separate autosomal recessive cause of developmental delay, or an additive effect of the paternal heterodisomy, could underlie the severity of the phenotype in this patient. Published (C) 2010 Wiley-Liss, Inc.(dagger) C1 [Manoli, Irini; Westbroek, Wendy; Vilboux, Thierry; Markello, Thomas C.; Maynard, Dawn; Pederson, Ben; Gahl, William A.; Huizing, Marjan] NHGRI, Human Biochem Genet Sect, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Manoli, Irini; Gahl, William A.] NIH, Intramural Program, Off Rare Dis, Bethesda, MD 20892 USA. [Golas, Gretchen; Introne, Wendy; Hart, P. Suzanne; Gahl, William A.] NIH, Off Clin Director, Med Genet Branch, Bethesda, MD 20892 USA. [Tsilou, Ekaterini] NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [Jordan, Michael B.] Cincinnati Childrens Hosp Med Ctr, Div Hematol & Oncol, Cincinnati, OH USA. [Jordan, Michael B.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Manoli, I (reprint author), NHGRI, Human Biochem Genet Sect, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C107, Bethesda, MD 20892 USA. EM manolii@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 FU National Human Genome Research Institute; National Eye Institute, National Institutes of Health, Bethesda, MD, USA FX Grant sponsor: Intramural Research programs of the National Human Genome Research Institute; Grant sponsor: National Eye Institute, National Institutes of Health, Bethesda, MD, USA. NR 61 TC 11 Z9 13 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2010 VL 152A IS 6 BP 1474 EP 1483 DI 10.1002/ajmg.a.33389 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 610RJ UT WOS:000278752000019 PM 20503323 ER PT J AU Solomon, BD Lange, E Shubrook, J Service, FJ Herman, G Karne, RJ Gorden, P Muenke, M Stratakis, CA AF Solomon, Benjamin D. Lange, Eileen Shubrook, Jay Service, F. John Herman, Gail Karne, Rajaram J. Gorden, Phillip Muenke, Maximilian Stratakis, Constantine A. TI Deletion of 8q24 in an Adult With Mild Dysmorphic Features, Developmental Delay, and Ketotic Hypoglycemia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE 8q; 8q24; microdeletion ID TISSUE TRANSGLUTAMINASE; MULTIPLE EXOSTOSES; LANGER-GIEDION; GENE; IDENTIFICATION; MICRODELETION; ABNORMALITIES; AUTOANTIGEN; PHENOTYPE; PROTEIN AB We present a 56-year-old female with a history of carbohydrate intolerance and ketotic hypoglycemia, dysmorphic features, mild developmental delay, lymphedema, altered pain sensation, and frequent fractures, who was found to have a heterozygous 8.09 Mb deletion of chromosome 8q24.11q24.13 containing more than 39 genes, as well as a duplication of 20q11.23 containing one gene. The deleted region overlaps that of two previously reported patients, who share a subset of clinical characteristics with the patient described here. Some of this patient's clinical features are consistent with the loss of genes in the deleted region. The diagnostic work-up of this patient clearly demonstrates the evolution of genetic testing techniques. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Lange, Eileen; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Shubrook, Jay] Ohio Univ, Coll Osteopath Med, Dept Family Med, Athens, OH 45701 USA. [Service, F. John] Mayo Clin, Dept Endocrinol, Rochester, MN USA. [Herman, Gail] Ohio State Univ, Nationwide Childrens Hosp, Res Inst, Ctr Mol & Human Genet,Dept Pediat, Columbus, OH 43210 USA. [Karne, Rajaram J.] Ohio State Univ, Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Gorden, Phillip] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, SEGEN, PDEGEN, NIH,CRC E Labs, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU National Human Genome Research Institute; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, United States of America FX Grant sponsor: National Human Genome Research Institute; Grant sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, United States of America. NR 18 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2010 VL 152A IS 6 BP 1545 EP 1549 DI 10.1002/ajmg.a.33395 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 610RJ UT WOS:000278752000029 PM 20503333 ER PT J AU Patel, SD Le-Niculescu, H Koller, DL Green, SD Lahiri, DK McMahon, FJ Nurnberger, JI Niculescu, AB AF Patel, S. D. Le-Niculescu, H. Koller, D. L. Green, S. D. Lahiri, D. K. McMahon, F. J. Nurnberger, J. I., Jr. Niculescu, A. B., III TI Coming to Grips With Complex Disorders: Genetic Risk Prediction in Bipolar Disorder Using Panels of Genes Identified Through Convergent Functional Genomics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE convergent functional genomics; pathways; epistasis; genetic risk; prediction; bipolar disorder ID FAMILY-BASED ASSOCIATION; NEUROTROPHIC FACTOR GENE; ANTIDEPRESSANT TREATMENT RESPONSE; SINGLE NUCLEOTIDE POLYMORPHISM; POSSIBLE SUSCEPTIBILITY LOCUS; SEASONAL AFFECTIVE-DISORDER; MAJOR DEPRESSIVE DISORDER; CANDIDATE GENES; WIDE ASSOCIATION; PREFRONTAL CORTEX AB We previously proposed and provided proof of principle for the use of a complementary approach, convergent functional genomics (CFG), combining gene expression and genetic data, from human and animal model studies, as a way of mining the existing GWAS datasets for signals that are there already, but did not reach significance using a genetics-only approach [Le-Niculescu et al., 2009b]. CFG provides a fit-to-disease prioritization of genes that leads to generalizability in independent cohorts, and counterbalances the fit-to-cohort prioritization inherent in classic genetic-only approaches, which have been plagued by poor reproducibility across cohorts. We have now extended our previous work to include more datasets of GWAS, and more recent evidence from other lines of work. In essence our analysis is the most comprehensive integration of genetics and functional genomics to date in the field of bipolar disorder. Biological pathway analyses identified top canonical pathways, and epistatic interaction testing inside these pathways has identified genes that merit future follow-up as direct interactors (intra-pathway epistasis, INPEP). Moreover, we have put together a panel of best P-value single nucleotide polymorphisms (SNPs), based on the top candidate genes we identified. We have developed a genetic risk prediction score (GRPS) based on our panel, and demonstrate how in two independent test cohorts the GRPS differentiates between subjects with bipolar disorder and normal controls, in both European-American and African-American populations. Lastly, we describe a prototype of how such testing could be used to categorize disease risk in individuals and aid personalized medicine approaches, in psychiatry and beyond. (C) 2010 Wiley-Liss, Inc. C1 [Patel, S. D.; Le-Niculescu, H.; Green, S. D.; Lahiri, D. K.; Nurnberger, J. I., Jr.; Niculescu, A. B., III] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Koller, D. L.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [McMahon, F. J.] NIMH, Mood & Anxiety Disorders Branch, Bethesda, MD 20892 USA. [Niculescu, A. B., III] Indianapolis VA Med Ctr, Indianapolis, IN 46202 USA. RP Niculescu, AB (reprint author), Indiana Univ Sch Med, Dept Psychiat, 791 Union Dr, Indianapolis, IN 46202 USA. EM anicules@iupui.edu RI Niculescu, Alexander/A-3328-2012; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X FU INGEN (Indiana Genomics Initiative of Indiana University); INBRAIN (Indiana Center for Biomarker Research In Neuropsychiatry); NARSAD Young Investigator Award; VA Merit Award; NIMH [R01 MH071912-01] FX This work was supported by funds from INGEN (Indiana Genomics Initiative of Indiana University), INBRAIN (Indiana Center for Biomarker Research In Neuropsychiatry), NARSAD Young Investigator Award and VA Merit Award to ABN, as well as NIMH R01 MH071912-01 to Ming Tsuang and ABN. ABN would like to thank Nicholas Schork for extensive discussions on genetic data analyses, Daniel Salomon, Sunil Kurian and Howard Edenberg for help and advice with microarray data analyses, Ming Tsuang and Steven Faraone for help and advice with translational studies, as well as Mariano Erpe, Joyti Gupta and Jesse Townes for their precise work with database maintenance and data analyses. Most importantly, we would like to thank our coworkers in the field whose painstaking work we have cited and integrated in our analyses, particularly the BiGS consortium (see Supplementary Information), as well as the subjects who participated in these studies, their families and their caregivers. Without their contribution, such work to advance the understanding of mental illness would not be possible. This work is, in essence, a field-wide collaboration. NR 166 TC 43 Z9 44 U1 1 U2 10 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2010 VL 153B IS 4 BP 850 EP 877 DI 10.1002/ajmg.b.31087 PG 28 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 604AT UT WOS:000278250400002 PM 20468069 ER PT J AU Abou Jamra, R Schulze, TG Becker, T Brockschmidt, FF Green, E Alblas, MA Wendland, JR Adli, M Grozeva, D Strohmeier, J Georgi, A Craddock, N Propping, P Rietsche, M Nothen, MM Cichon, S Schumacher, J AF Abou Jamra, Rami Schulze, Thomas G. Becker, Tim Brockschmidt, Felix F. Green, Elaine Alblas, Margrieta A. Wendland, Jens R. Adli, Mazda Grozeva, Detelina Strohmeier, Jana Georgi, Alexander Craddock, Nick Propping, Peter Rietsche, Marcella Noethen, Markus M. Cichon, Sven Schumacher, Johannes TI A Systematic Association Mapping on Chromosome 6q in Bipolar Affective Disorder-Evidence for the Melanin-Concentrating-Hormone-Receptor-2 Gene as a Risk Factor for Bipolar Affective Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE BPAD; GPR145; LD; genotype-phenotype analysis; MCHR2 ID MELANIN-CONCENTRATING HORMONE; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCUS; LINKAGE ANALYSES; SCHIZOPHRENIA; FAMILIES; MICE; HAPLOTYPE; PROVIDES; REVEALS AB Strong evidence of linkage between chromosomal region 6q16-q22 and bipolar affective disorder (BPAD) has previously been reported. We conducted a systematic association mapping of the 6q-linkage interval using 617 SNP markers in a BPAD case control sample of German descent (cases = 330, controls = 325). In this screening step, 46 SNPs showed nominally significant BPAD-association (P-values between 0.0007 and 0.0484). Although none of the 46 SNPs survived correction for multiple testing, they were genotyped in a second and ethnically matched BPAD sample (cases = 328, controls = 397). At the melanin-concentrating-hormone-receptor-2 (MCHR2) gene, we found nominal association in both the initial and second BPAD samples (combined P = 0.008). This finding was followed up by the genotyping of 17 additional MCHR2-SNPs in the combined sample in order to define our findings more precisely. We found that the MCHR2-locus can be divided into three different haplotype-blocks, and observed that the MCHR2-association was most pronounced in BPAD male patients with psychotic symptoms. In two neighboring blocks, putative risk-haplotypes were found to be 7% more frequent in patients (block II: 23.3% vs. 16.2%, P=0.005, block III: 39.2% vs. 32.0%, P=0.024), whereas the putative protective haplotypes were found to be 5-8% less frequent in patients (block II: 11.6% vs. 16.4%, P=0.041, block III: 30.0% vs. 38.8%, P=0.007). The corresponding odds ratios (single-marker analysis) ranged between 1.25 and 1.46. Our findings may indicate that MCHR2 is a putative risk factor for BPAD. These findings should be interpreted with caution and replicated in independent BPAD samples. (C) 2009 Wilcy-Liss, Inc. C1 [Abou Jamra, Rami; Propping, Peter; Noethen, Markus M.; Cichon, Sven; Schumacher, Johannes] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany. [Schulze, Thomas G.; Strohmeier, Jana; Georgi, Alexander; Rietsche, Marcella] Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schulze, Thomas G.; Schumacher, Johannes] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA. [Becker, Tim] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-53111 Bonn, Germany. [Brockschmidt, Felix F.; Alblas, Margrieta A.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-53111 Bonn, Germany. [Green, Elaine; Grozeva, Detelina; Craddock, Nick] Cardiff Univ, Dept Psychol Med, Welsh Coll Med, Cardiff, S Glam, Wales. [Wendland, Jens R.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Adli, Mazda] Charite, Dept Psychiat & Psychotherapy CCM, D-13353 Berlin, Germany. RP Abou Jamra, R (reprint author), Univ Bonn, Inst Human Genet, Wilhelm Str 31, D-53111 Bonn, Germany. EM rami.aboujamra@uni-bonn.de; schumacherj@mail.nih.gov RI Wendland, Jens/A-1809-2012; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; Georgi, Alexander/0000-0002-1499-8524; Nothen, Markus/0000-0002-8770-2464 FU National Genomic Network of the "Bundesministerium fur Bildung und Forschung" (BMBF); NIH/DFG Research Career Transition Awards Program; Alfried Krupp von Bohlen und Halbach-Stiftung FX The authors are grateful to all patients, their families, and controls for their cooperation in this research. This study was supported by the National Genomic Network of the "Bundesministerium fur Bildung und Forschung" (BMBF). J.S. was supported by the NIH/DFG Research Career Transition Awards Program, and M.M.N. was supported by the Alfried Krupp von Bohlen und Halbach-Stiftung. NR 33 TC 2 Z9 2 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN PY 2010 VL 153B IS 4 BP 878 EP 884 DI 10.1002/ajmg.b.31051 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 604AT UT WOS:000278250400003 PM 19927306 ER PT J AU Zhang, J Merialdi, M Platt, LD Kramer, MS AF Zhang, Jun Merialdi, Mario Platt, Lawrence D. Kramer, Michael S. TI Defining normal and abnormal fetal growth: promises and challenges SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE biomarker; definition; Doppler; fetal growth; restriction; standard ID FOR-GESTATIONAL-AGE; BIRTH-WEIGHT STANDARDS; UTERINE ARTERY DOPPLER; SUBCUTANEOUS TISSUE THICKNESS; HIGH-RISK PREGNANCIES; INTRAUTERINE GROWTH; 3-DIMENSIONAL ULTRASONOGRAPHY; UNITED-STATES; PRETERM DELIVERY; MATERNAL CHARACTERISTICS AB Normal fetal growth is a critical component of a healthy pregnancy and influences the long-term health of the offspring. However, defining normal and abnormal fetal growth has been a long-standing challenge in clinical practice and research. We review various references and standards that are used widely to evaluate fetal growth and discuss common pitfalls of current definitions of abnormal fetal growth. Pros and cons of different approaches to customize fetal growth standards are described. We further discuss recent advances toward an integrated definition for fetal growth restriction. Such a definition may incorporate fetal size with the status of placental health that is measured by maternal and fetal Doppler velocimetry and biomarkers, biophysical findings, and genetics. Although the concept of an integrated definition appears promising, further development and testing are required. An improved definition of abnormal fetal growth should benefit both research and clinical practice. C1 [Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. [Merialdi, Mario] WHO, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland. [Platt, Lawrence D.] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Fetal Med & Womens Ultrasound, Los Angeles, CA 90095 USA. [Kramer, Michael S.] McGill Univ, Fac Med, Dept Pediat, Montreal, PQ, Canada. [Kramer, Michael S.] McGill Univ, Dept Epidemiol & Biostat, Fac Med, Montreal, PQ, Canada. RP Zhang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. FU Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health FX This study was supported in part by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (J.Z.). NR 121 TC 92 Z9 94 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 JUN PY 2010 VL 202 IS 6 BP 522 EP 528 DI 10.1016/j.ajog.2009.10.889 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 607VD UT WOS:000278534200003 PM 20074690 ER PT J AU Cahill, AG Odibo, AO Caughey, AB Stamilio, DM Hassan, SS Macones, GA Romero, R AF Cahill, Alison G. Odibo, Anthony O. Caughey, Aaron B. Stamilio, David M. Hassan, Sonia S. Macones, George A. Romero, Roberto TI Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical length screening; preterm birth; prevention; progesterone ID PLACEBO-CONTROLLED TRIAL; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; FETAL FIBRONECTIN; BACTERIAL VAGINOSIS; GESTATIONAL-AGE; RISK-ASSESSMENT; PREGNANT-WOMEN; DOUBLE-BLIND; DELIVERY; PREDICTION AB OBJECTIVE: The purpose of this study was to estimate which strategy is the most cost-effective for the prevention of preterm birth and associated morbidity. STUDY DESIGN: We used decision-analytic and cost-effectiveness analyses to estimate which of 4 strategies was superior based on quality-adjusted life-years, cost in US dollars, and number of preterm births prevented. RESULTS: Universal sonographic screening for cervical length and treatment with vaginal progesterone was the most cost-effective strategy and was the dominant choice over the 3 alternatives: cervical length screening for women at increased risk for preterm birth and treatment with vaginal progesterone; risk-based treatment with 17 alpha-hydroxyprogesterone caproate (17-OHP-C) without screening; no screening or treatment. Universal screening represented savings of $1339 ($8325 vs $9664), when compared with treatment with 17-OHP-C, and led to a reduction of 95,920 preterm births annually in the United States. CONCLUSION: Universal sonographic screening for short cervical length and treatment with vaginal progesterone appears to be cost-effective and yields the greatest reduction in preterm birth at <34 weeks' gestation. C1 [Cahill, Alison G.; Odibo, Anthony O.; Stamilio, David M.; Macones, George A.] Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63130 USA. [Caughey, Aaron B.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Res, Perinatol Res Branch, NIH DHHS, Bethesda, MD USA. [Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto] Michigan State Univ, Dept Epidemiol, Detroit, MI USA. RP Cahill, AG (reprint author), Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63130 USA. FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS FX Funded in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS. NR 36 TC 1 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2010 VL 202 IS 6 AR 548.e1 DI 10.1016/j.ajog.2009.12.005 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 607VD UT WOS:000278534200012 PM 20079888 ER PT J AU Chaiworapongsa, T Romero, R Tarca, AL Kusanovic, JP Gotsch, F Mittal, P Kim, SK Vaisbuch, E Mazaki-Tovi, S Erez, O Dong, Z Kim, CJ Yeo, L Hassan, SS AF Chaiworapongsa, Tinnakorn Romero, Roberto Tarca, Adi L. Kusanovic, Juan Pedro Gotsch, Francesca Mittal, Pooja Kim, Sun Kwon Vaisbuch, Edi Mazaki-Tovi, Shali Erez, Offer Dong, Zhong Kim, Chong Jai Yeo, Lami Hassan, Sonia S. TI A decrease in maternal plasma concentrations of sVEGFR-2 precedes the clinical diagnosis of preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 17-21, 2009 CL Glasgow, SCOTLAND SP Soc Gynecol Invest DE angiogenesis; biomarker; longitudinal study; mechanisms of disease; pregnancy-induced hypertension ID VASCULAR-ENDOTHELIAL-GROWTH; FOR-GESTATIONAL-AGE; CIRCULATING ANGIOGENIC FACTORS; LATE-ONSET PREECLAMPSIA; FACTOR RECEPTOR-1; TYROSINE KINASE-1; SOLUBLE ENDOGLIN; TUMOR-GROWTH; VEGF; PREGNANCIES AB OBJECTIVE: The aim of this study was to examine if maternal plasma concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-2 change prior to the diagnosis of preeclampsia. STUDY DESIGN: A longitudinal study was conducted in normal pregnant women (n = 160) and patients with preeclampsia (n = 40). Blood samples were collected at 7 gestational age intervals from 6 weeks to term. Plasma concentrations of sVEGFR-2 were determined by enzyme-linked immunosorbent assay. Analysis was performed with cross-sectional and longitudinal (mixed effects model) approaches. RESULTS: Mothers destined to develop preeclampsia have lower plasma sVEGFR-2 concentrations than those who will have a normal pregnancy (longitudinal approach; P < .05). Cross-sectional analysis suggested that the median plasma sVEGFR-2 concentration in women destined to develop preeclampsia was significantly lower than that in normal pregnant women from 28-31 weeks of gestation (P = .001) or 6-10 weeks prior to the diagnosis (P < .001). CONCLUSION: A lower maternal plasma sVEGFR-2 concentration precedes the development of preeclampsia, both term and preterm. C1 [Chaiworapongsa, Tinnakorn] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHHD,NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Tarca, Adi L.; Kusanovic, Juan Pedro; Gotsch, Francesca; Mittal, Pooja; Kim, Sun Kwon; Vaisbuch, Edi; Mazaki-Tovi, Shali; Erez, Offer; Dong, Zhong; Kim, Chong Jai; Yeo, Lami; Hassan, Sonia S.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chaiworapongsa, Tinnakorn; Romero, Roberto; Kusanovic, Juan Pedro; Mittal, Pooja; Vaisbuch, Edi; Mazaki-Tovi, Shali; Erez, Offer; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Chaiworapongsa, T (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHHD,NIH,Dept Hlth & Human Serv, 3990 John R,Box 4, Detroit, MI 48201 USA. EM tchaiwor@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural NIH HHS [ZIA HD002400-19] NR 60 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2010 VL 202 IS 6 AR 550.e1 DI 10.1016/j.ajog.2010.04.002 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 607VD UT WOS:000278534200013 PM 20510958 ER PT J AU Joe, MK Tomarev, SI AF Joe, Myung Kuk Tomarev, Stanislav I. TI Expression of Myocilin Mutants Sensitizes Cells to Oxidative Stress-Induced Apoptosis Implication for Glaucoma Pathogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; TRABECULAR MESHWORK CELLS; ENDOPLASMIC-RETICULUM STRESS; EXTRACELLULAR-MATRIX; OLFACTOMEDIN DOMAIN; CIGARETTE-SMOKING; TRANSGENIC MICE; AQUEOUS-HUMOR; MUTATED MOUSE; NON-SECRETION AB Mutations in the myocilin gene are associated with juvenile and adult-onset primary open-angle glaucoma. However, the pathogenic mechanisms of myocilin-induced glaucoma are still largely unknown. To investigate these mechanisms, we developed stably transfected HEK293 cell lines expressing wild-type or mutant (Y437H and I477N) myocilins under an inducible promoter. Expression of two mutant myocilins led to different levels of endoplasmic reticulum stress and increased apoptosis after treatment of cells with hydrogen peroxide. The Y437H mutant myocilin cell line showed the highest sensitivity to the oxidant treatment. Several antioxidant genes were down-regulated in the Y437H mutant myocilin cell line, but not in other cell lines. The Y437H mutant myocilin cell line also produced more reactive oxygen species than other cell lines examined. Consistent with the data obtained in cultured cells, the endoplasmic reticulum stress marker, 78 kDa glucose-regulated protein, was up-regulated, whereas antioxidant proteins, paraoxonase 2 and glutathione peroxidase 3, were down-regulated in the eye angle tissue of 18-month-old transgenic mice expressing Y437H myocilin mutant. In addition, a pro-apoptotic factor, CCAAT/enhancer-binding protein-homologous protein, was up-regulated in the aged transgenic mouse angle tissue. Our results suggest that expression of mutated myocilins may have a sensitization effect, which can lead to a severe phenotype in combination with oxidative stress. Mutant myocilins may confer different sensitivity to oxidative stress depending on the mutation. (Ant J Pathol 2010, 176:2880-2890. DOI: 10.2353/ajpath.2010.090853) C1 [Joe, Myung Kuk; Tomarev, Stanislav I.] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tomarev, SI (reprint author), NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, 5635 Fishers Lane,Room 1124, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov FU National Institutes of Health, National Eye Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Eye Institute. NR 59 TC 25 Z9 29 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2010 VL 176 IS 6 BP 2880 EP 2890 DI 10.2353/ajpath.2010.090853 PG 11 WC Pathology SC Pathology GA 609WU UT WOS:000278689700030 PM 20382707 ER PT J AU Contag, SA Clifton, RG Bloom, SL Spong, CY Varner, MW Rouse, DJ Ramin, SM Caritis, SN Peaceman, AM Sorokin, Y Sciscione, A Carpenter, MW Mercer, BM Thorp, JM Malone, FD Iams, JD AF Contag, Stephen A. Clifton, Rebecca G. Bloom, Steven L. Spong, Catherine Y. Varner, Michael W. Rouse, Dwight J. Ramin, Susan M. Caritis, Steve N. Peaceman, Alan M. Sorokin, Yoram Sciscione, Anthony Carpenter, Marshall W. Mercer, Brian M. Thorp, John M., Jr. Malone, Fergal D. Iams, Jay D. TI Neonatal Outcomes and Operative Vaginal Delivery Versus Cesarean Delivery SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Cesarean; forceps; umbilical cord blood gases; vacuum ID INFANT OUTCOMES; BIRTH ASPHYXIA; POPULATION; 2ND-STAGE; FORCEPS; INJURY; LABOR; MODE; TERM AB We compared outcomes for neonates with forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. This is a secondary analysis of a randomized trial in laboring, low-risk, nulliparous women at >= 36 weeks' gestation. Neonatal outcomes after use of forceps, vacuum, and cesarean were compared among women in the second stage of labor at station +1 or below (thirds scale) for failure of descent or nonreassuring fetal status. Nine hundred ninety women were included in this analysis: 549 (55%) with an indication for delivery of failure of descent and 441 (45%) for a nonreassuring fetal status. Umbilical cord gases were available for 87% of neonates. We found no differences in the base excess (p = 0.35 and 0.78 for failure of descent and nonreassuring fetal status) or frequencies of pH below 7.0 (p = 0.73 and 0.34 for failure of descent and nonreassuring fetal status) among the three delivery methods. Birth outcomes and umbilical cord blood gas values were similar for those neonates with a forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. The occurrence of significant fetal acidemia was not different among the three delivery methods regardless of the indication. C1 [Contag, Stephen A.] Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. [Clifton, Rebecca G.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Bloom, Steven L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA. [Ramin, Susan M.] Univ Texas Houston, Houston, TX USA. [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA. [Carpenter, Marshall W.] Brown Univ, Providence, RI 02912 USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Malone, Fergal D.] Columbia Univ, New York, NY USA. [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA. RP Contag, SA (reprint author), Sinai Hosp, Inst Maternal Fetal Med, Dept Obstet & Gynecol, 2401 W Belvedere Ave, Baltimore, MD 21215 USA. EM scontag@lifebridgehealth.org RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973; Contag, Stephen/0000-0002-1745-8144 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, and HD36801). NR 28 TC 7 Z9 8 U1 0 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JUN PY 2010 VL 27 IS 6 BP 493 EP 499 DI 10.1055/s-0030-1247605 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 600UC UT WOS:000278013400010 PM 20099218 ER PT J AU Da Silva, N Pisitkun, T Belleannee, C Miller, LR Nelson, R Knepper, MA Brown, D Breton, S AF Da Silva, Nicolas Pisitkun, Trairak Belleannee, Clemence Miller, Lance R. Nelson, Raoul Knepper, Mark A. Brown, Dennis Breton, Sylvie TI Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence-activated cell sorting SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE intercalated cells; mass spectrometry; proteome; proton secretion; clear cells ID MALE REPRODUCTIVE-TRACT; VACUOLAR H+-ATPASE; POLARIZED EPITHELIAL-CELLS; B2 SUBUNIT ISOFORM; PROTON PUMP ATPASE; RAT EPIDIDYMIS; INTERCALATED CELLS; CLEAR CELLS; LUMINAL ACIDIFICATION; CONNECTING TUBULE AB Da Silva N, Pisitkun T, Belleannee C, Miller LR, Nelson R, Knepper MA, Brown D, Breton S. Proteomic analysis of V-ATPase-rich cells harvested from the kidney and epididymis by fluorescence activated cell sorting. Am J Physiol Cell Physiol 298: C1326-C1342, 2010. First published February 24, 2010; doi:10.1152/ajpcell.00552.2009.-Proton-transporting cells are located in several tissues where they acidify the extracellular environment. These cells express the vacuolar H(+)-ATPase (V-ATPase) B1 subunit (ATP6V1B1) in their plasma membrane. We provide here a comprehensive catalog of the proteins that are expressed in these cells, after their isolation by enzymatic digestion and fluorescence-activated cell sorting (FACS) from transgenic B1-enhanced green fluorescent protein (EGFP) mice. In these mice, type A and B intercalated cells and connecting segment cells of the kidney, and narrow and clear cells of the epididymis, which all express ATP6V1B1, also express EGFP, while all other cell types are negative. The proteome of renal and epididymal EGFP-positive (EGFP(+)) cells was identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared with their respective EGFP-negative (EGFP(-)) cell populations. A total of 2,297 and 1,564 proteins were detected in EGFP(+) cells from the kidney and epididymis, respectively. Out of these proteins, 202 and 178 were enriched by a factor greater than 1.5 in EGFP(+) cells compared with EGFP(-) cells, in the kidney and epididymis respectively, and included subunits of the V-ATPase (B1, a4, and A). In addition, several proteins involved in intracellular trafficking, signaling, and cytoskeletal dynamics were identified. A novel common protein that was enriched in renal and epididymal EGFP(+) cells is the progesterone receptor, which might be a potential candidate for the regulation of V-ATPase-dependent proton transport. These proteomic databases provide a framework for comprehensive future analysis of the common and distinct functions of V-ATPase-B1-expressing cells in the kidney and epididymis. C1 [Da Silva, Nicolas; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Da Silva, Nicolas; Belleannee, Clemence; Brown, Dennis; Breton, Sylvie] Harvard Univ, Sch Med, Boston, MA USA. [Pisitkun, Trairak; Miller, Lance R.; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Miller, Lance R.; Nelson, Raoul] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. RP Breton, S (reprint author), MGH Program Membrane Biol, 185 Cambridge St,CPZN 8-204, Boston, MA 02114 USA. EM Breton.Sylvie@mgh.harvard.edu OI Pisitkun, Trairak/0000-0001-6677-2271 FU National Institutes of Health [HD-40793, DK-38452, DK-42956]; NHLBI Project [HL-001285]; American Physiological Society; Boston Area Diabetes and Endocrinology Research Center [DK-57521]; Center for the Study of Inflammatory Bowel Disease [DK-43341] FX This work was supported by National Institutes of Health Grants HD-40793 (to S. Breton), DK-38452 (to S. Breton and D. Brown), and DK-42956 (to D. Brown) as well as the intramural research budget of NHLBI Project HL-001285 (to M. A. Knepper). N. Da Silva was supported by a research career enhancement award from the American Physiological Society. The Microscopy Core facility of the MGH Program in Membrane Biology receives support from the Boston Area Diabetes and Endocrinology Research Center (DK-57521) and the Center for the Study of Inflammatory Bowel Disease (DK-43341). NR 61 TC 24 Z9 24 U1 0 U2 2 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 JUN PY 2010 VL 298 IS 6 BP C1326 EP C1342 DI 10.1152/ajpcell.00552.2009 PG 17 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 599YD UT WOS:000277949300010 PM 20181927 ER PT J AU Xue, L Zhang, F Chen, XH Lin, JJ Shi, J AF Xue, Lei Zhang, Fan Chen, Xianhua Lin, Junji Shi, Jian TI PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor; N-methyl-D-aspartate receptor; long-term potentiation; long-term depression; glutamate receptor-interacting protein; protein interacting with C kinase 1 ID LONG-TERM DEPRESSION; AMPA-RECEPTOR TRAFFICKING; NR2B-CONTAINING NMDA RECEPTORS; JUVENILE SUPERIOR COLLICULUS; DOMAIN-CONTAINING PROTEINS; SYNAPTIC PLASTICITY; VISUAL-CORTEX; IN-VIVO; THALAMOCORTICAL SYNAPSES; HIPPOCAMPAL-NEURONS AB Xue L, Zhang F, Chen X, Lin J, Shi J. PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses. Am J Physiol Cell Physiol 298: C1572-C1582, 2010. First published March 24, 2010; doi:10.1152/ajpcell.00012.2010.-The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects. C1 [Xue, Lei; Shi, Jian] Fudan Univ, Sch Life Sci, Ctr Brain Sci Res, Shanghai 200433, Peoples R China. [Chen, Xianhua; Lin, Junji] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Zhang, Fan] NEI, Rockville, MD USA. RP Xue, L (reprint author), NINDS, Synapt Transmiss Sect, NIH, Porter Neurosci Res Ctr, Bldg 35,Rm 2B-713,35 Convent Dr, Bethesda, MD 20892 USA. EM xuel@ninds.nih.gov RI yu, yan/C-2322-2012 FU National Natural Science Foundation of China [30170314, 30570588, 90208013]; Shanghai Leading Academic Discipline Project [B111] FX This work was supported by the National Natural Science Foundation of China (grant numbers: 30170314, 30570588, and 90208013) and Shanghai Leading Academic Discipline Project (project number: B111) to J. Shi. NR 71 TC 2 Z9 2 U1 3 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 JUN PY 2010 VL 298 IS 6 BP C1572 EP C1582 DI 10.1152/ajpcell.00012.2010 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 599YD UT WOS:000277949300033 PM 20457829 ER PT J AU Jeong, MY Walker, JS Brown, RD Moore, RL Vinson, CS Colucci, WS Long, CS AF Jeong, Mark Y. Walker, John S. Brown, R. Dale Moore, Russell L. Vinson, Charles S. Colucci, Wilson S. Long, Carlin S. TI AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE alpha-adrenergic; activator protein 1; hypertrophy; myocyte ID BETA-ADRENERGIC STIMULATION; MYOSIN HEAVY-CHAIN; LACKING C-FOS; ACTIVATOR PROTEIN-1; CARDIOMYOCYTE HYPERTROPHY; DILATED CARDIOMYOPATHY; CARDIAC MYOCYTES; HEART-FAILURE; KAPPA-B; MYOCARDIUM AB Jeong MY, Walker JS, Moore RD, Vinson CS, Colucci WS, Long CS. AFos inhibits phenylephrine-mediated contractile dysfunction by altering phospholamban phosphorylation. Am J Physiol Heart Circ Physiol 298: H1719-H1726, 2010. First published April 2, 2010; doi:10.1152/ajpheart.00937.2009.-Using neonatal rat ventricular myocytes, we previously reported that the expression of a dominant negative form of the c-Fos proto-oncogene (AFos) inhibited activator protein 1 activity and blocked the induction of the pathological gene profile stimulated by phenylephrine (PE) while leaving growth unaffected. We now extend these observations to the adult rat ventricular myocyte (ARVM) to understand the relationship between gene expression, growth, and function. Ventricular myocytes were isolated from adult rats and infected with adenovirus expressing beta-galactosidase (control) or AFos. The cells were subsequently treated with PE, and protein synthesis, gene program, calcium transients, and contractility were evaluated. As seen with the neonatal rat ventricular myocytes, in control cells PE stimulated an increase in protein synthesis, induced the pathological gene profile, and exhibited both depressed contractility and calcium transients. Although ARVMs expressing AFos still had PE-induced growth, pathological gene expression as well as contractility and calcium handling abnormalities were inhibited. To determine a possible mechanism of the preserved myocyte function in AFos-expressing cells, we examined phospholamban (PLB) and sarco(endo)plasmic reticulum calcium-ATPase proteins. Although there was no change in total PLB or sarco(endo) plasmic reticulum calcium-ATPase expression in response to PE treatment, PE decreased the phosphorylation of PLB at serine-16, an observation that was prevented in AFos-expressing cells. In conclusion, although PE-induced growth was unaffected in AFos-expressing ARVMs, the expression of the pathological gene profile was inhibited and both contractile function and calcium cycling were preserved. The inhibition of functional deterioration was, in part, due to the preservation of PLB phosphorylation. C1 [Jeong, Mark Y.; Walker, John S.; Brown, R. Dale; Long, Carlin S.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. [Colucci, Wilson S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Moore, Russell L.] Univ Colorado, Boulder, CO 80309 USA. [Vinson, Charles S.] NCI, Bethesda, MD 20892 USA. RP Long, CS (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiol Sect, Denver Hlth Med Ctr, 777 Bannock St, Denver, CO 80204 USA. EM carlin.long@dhha.org RI Moore, Russell/D-1040-2013 OI Moore, Russell/0000-0002-6727-8985 FU National Heart, Lung, and Blood Institute [HL-059428, F32-HL-087479] FX This study was supported by National Heart, Lung, and Blood Institute Grants HL-059428 (to C. S. Long) and F32-HL-087479 (to M. Y. Jeong). NR 35 TC 7 Z9 7 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2010 VL 298 IS 6 BP H1719 EP H1726 DI 10.1152/ajpheart.00937.2009 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 598UB UT WOS:000277863100012 PM 20363890 ER PT J AU Maltsev, VA Lakatta, EG AF Maltsev, Victor A. Lakatta, Edward G. TI A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE calcium; sarcoplasmic reticulum; ion channels; numerical modeling; sinoatrial node cell ID RABBIT SINOATRIAL NODE; L-TYPE CA2+; RECTIFIER POTASSIUM CURRENT; PIG VENTRICULAR MYOCYTES; MATHEMATICAL-MODEL; RYANODINE RECEPTOR; DIASTOLIC DEPOLARIZATION; SARCOPLASMIC-RETICULUM; ELECTRICAL-ACTIVITY; CALCIUM CURRENT AB Maltsev VA, Lakatta EG. A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins. Am J Physiol Heart Circ Physiol 298: H2010-H2023, 2010. First published March 12, 2010; doi:10.1152/ajpheart.00783.2009.-Classical numerical models have attributed the regulation of normal cardiac automaticity in sinoatrial node cells (SANCs) largely to G protein-coupled receptor (GPCR) modulation of sarcolemmal ion currents. More recent experimental evidence, however, has indicated that GPCR modulation of SANCs automaticity involves spontaneous, rhythmic, local Ca(2+) releases (LCRs) from the sarcoplasmic reticulum (SR). We explored the GPCR rate modulation of SANCs using a unique and novel numerical model of SANCs in which Ca(2+)-release characteristics are graded by variations in the SR Ca(2+) pumping capability, mimicking the modulation by phospholamban regulated by cAMP-mediated, PKA-activated signaling. The model faithfully predicted the entire range of physiological chronotropic modulation of SANCs by the activation of beta-adrenergic receptors or cholinergic receptors only when experimentally documented changes of sarcolemmal ion channels are combined with a simultaneous increase/decrease in SR Ca(2+) pumping capability. The novel numerical mechanism of GPCR rate modulation is based on numerous complex synergistic interactions between sarcolemmal and intracellular processes via membrane voltage and Ca(2+). Major interactions include changes of diastolic Na(+)/Ca(2+) exchanger current that couple earlier/later diastolic Ca(2+) releases (predicting the experimentally defined LCR period shift) of increased/decreased amplitude (predicting changes in LCR signal mass, i.e., the product of LCR spatial size, amplitude, and number per cycle) to the diastolic depolarization and ultimately to the spontaneous action potential firing rate. Concomitantly, larger/smaller and more/less frequent activation of L-type Ca(2+) current shifts the cellular Ca(2+) balance to support the respective Ca(2+) cycling changes. In conclusion, our model simulations corroborate recent experimental results in rabbit SANCs pointing to a new paradigm for GPCR heart rate modulation by a complex system of dynamically coupled sarcolemmal and intracellular proteins. C1 [Maltsev, Victor A.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU National Institute on Aging (National Institutes of Health) FX This work was supported by the Intramural Research Program of the National Institute on Aging (National Institutes of Health). NR 58 TC 25 Z9 25 U1 1 U2 7 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 JUN PY 2010 VL 298 IS 6 BP H2010 EP H2023 DI 10.1152/ajpheart.00783.2009 PG 14 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 598UB UT WOS:000277863100042 PM 20228256 ER PT J AU Peters, TM Moore, SC Xiang, YB Yang, G Shu, XO Ekelund, U Ji, BT Tan, YT Liu, DK Schatzkin, A Zheng, W Chow, WH Matthews, CE Leitzmann, MF AF Peters, Tricia M. Moore, Steven C. Xiang, Yong Bing Yang, Gong Shu, Xiao Ou Ekelund, Ulf Ji, Bu-Tian Tan, Yu Ting Liu, Da Ke Schatzkin, Arthur Zheng, Wei Chow, Wong Ho Matthews, Charles E. Leitzmann, Michael F. TI Accelerometer-Measured Physical Activity in Chinese Adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SHANGHAI WOMENS HEALTH; DOUBLY LABELED WATER; BODY-MASS INDEX; LEISURE-TIME; ACTIVITY QUESTIONNAIRE; ACTIVITY PATTERNS; UNITED-STATES; POPULATION; INACTIVITY; VALIDITY AB Background: Following adoption of a Western lifestyle, China is experiencing a decline in physical activity levels, which is projected to contribute to future increases in the burden of chronic diseases. Purpose: This study aims to target public health interventions and identify personal characteristics associated with physical activity and sedentary behavior in urban Chinese adults. Methods: In a sample of 576 men and women aged 40-74 years from Shanghai, multiple logistic regression was used to examine demographic, anthropometric, and lifestyle factors in relation to levels of physical activity and sedentary behavior assessed by Actigraph accelerometers. Results: Participants spent 317 minutes/day in physical activity and 509 minutes/day sedentary. In multivariate models, people aged 60 years were significantly less likely than those aged <50 years to engage in physical activity (OR=0.29, 95% CI=0.17, 0.49) and more likely to spend time sedentary (OR=2.77, 95% CI=1.53, 5.05). Similarly, obese individuals were less likely to be physically active (OR=0.34, 95% CI=0.17, 0.66) and they were suggestively more likely to be sedentary (OR=1.87, 95% CI=0.94, 3.71) than normal-weight individuals. Furthermore, current cigarette smokers were less physically active than those who formerly or never smoked (OR=0.47, 95% CI=0.28, 0.78). Conclusions: Physical activity promotion programs in urban China should target older people, obese individuals, and cigarette smokers, as these population subgroups exhibited low levels of physical activity. (Am J Prey Med 2010;38(6):583-591) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, D-93042 Regensburg, Germany. [Peters, Tricia M.; Moore, Steven C.; Ji, Bu-Tian; Schatzkin, Arthur; Chow, Wong Ho; Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Peters, Tricia M.; Ekelund, Ulf] Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Xiang, Yong Bing; Tan, Yu Ting; Liu, Da Ke] Shanghai Canc Inst, Shanghai, Peoples R China. [Yang, Gong; Shu, Xiao Ou; Zheng, Wei] Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr,Sch Med, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA. RP Leitzmann, MF (reprint author), Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, D-93042 Regensburg, Germany. EM Michael.Leitzmann@klinik.uni-regensburg.de RI matthews, Charles/E-8073-2015; Moore, Steven/D-8760-2016 OI matthews, Charles/0000-0001-8037-3103; Moore, Steven/0000-0002-8169-1661 FU Intramural NIH HHS [Z01 CP010197-01]; Medical Research Council [MC_U106179473]; NCI NIH HHS [R37 CA070867, R01 CA082729]; NIGMS NIH HHS [T32 GM008444] NR 51 TC 38 Z9 40 U1 4 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2010 VL 38 IS 6 BP 583 EP 591 DI 10.1016/j.amepre.2010.02.012 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 606AM UT WOS:000278392400002 PM 20494234 ER PT J AU Forman, MR Greene, SM Avis, NE Taplin, SH Courtney, P Schad, PA Hesse, BW Winn, DM AF Forman, Michele R. Greene, Sarah M. Avis, Nancy E. Taplin, Stephen H. Courtney, Paul Schad, Peter A. Hesse, Bradford W. Winn, Deborah M. TI Tools to Accelerate Population Science and Disease Control Research SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ELECTRONIC MEDICAL-RECORD; GENOME-WIDE ASSOCIATION; TEAM SCIENCE; CANCER-RESEARCH; DBGAP DATABASE; UNITED-STATES; BIG DATA; HEALTH; COLLABORATION; CARE AB Population science and disease control researchers can benefit from a more proactive approach to applying bioinformatics tools for clinical and public health research. Bioinformatics utilizes principles of information sciences and technologies to transform vast, diverse, and complex life sciences data into a more coherent format for wider application. Bioinformatics provides the means to collect and process data, enhance data standardization and harmonization for scientific discovery, and merge disparate data sources. Achieving interoperability (i.e. the development of an informatics system that provides access to and use of data from different systems) will facilitate scientific explorations and careers and opportunities for interventions in population health. The National Cancer Institute's (NCI's) interoperable Cancer Biomedical Informatics Grid (caBIG') is one of a number of illustrative tools in this report that are being mined by population scientists. Tools are not all that is needed for progress. Challenges persist, including a lack of common data standards, proprietary barriers to data access, and difficulties pooling data from studies. Population scientists and informaticists are developing promising and innovative solutions to these barriers. The purpose of this paper is to describe how the application of bioinformatics systems can accelerate population health research across the continuum from prevention to detection, diagnosis, treatment, and outcome. (Am J Prey Med 2010;38(6):646-651) (C) 2010 American Journal of Preventive Medicine C1 [Forman, Michele R.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77230 USA. [Greene, Sarah M.] Grp Hlth Inst, Seattle, WA USA. [Avis, Nancy E.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Taplin, Stephen H.; Hesse, Bradford W.; Winn, Deborah M.] NCI, Bethesda, MD 20892 USA. [Courtney, Paul] Booz Allen Hamilton, Rockville, MD USA. [Courtney, Paul] Dartmouth Med Sch, Lebanon, NH USA. [Schad, Peter A.] RTI Int, Res Triangle Pk, NC USA. RP Forman, MR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, POB 301439, Houston, TX 77230 USA. EM mforman@mdanderson.org RI Courtney, Paul/C-9906-2009 FU National Cancer Institute [1435-04-04-CT73980, 79848CBS10, 941634NBS23, 94315DBS47, 94278NBS23] FX This paper was funded by National Cancer Institute: Contracts: Booz Allen Hamilton (1435-04-04-CT73980); Dartmouth College (79848CBS10); M.D. Anderson Cancer Center: (941634NBS23); Wake Forest (94315DBS47); Group Health Center for Health Studies (94278NBS23). NR 54 TC 9 Z9 9 U1 8 U2 34 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2010 VL 38 IS 6 BP 646 EP 651 DI 10.1016/j.amepre.2010.03.002 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 606AM UT WOS:000278392400009 PM 20494241 ER PT J AU Troiano, RP Freedson, PS AF Troiano, Richard P. Freedson, Patty S. TI Promises and Pitfalls of Emerging Measures of Physical Activity and the Environment SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 [Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA. RP Troiano, RP (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM troianor@mail.nih.gov OI Troiano, Richard/0000-0002-6807-989X FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUN PY 2010 VL 38 IS 6 BP 682 EP 683 DI 10.1016/j.amepre.2010.03.005 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 606AM UT WOS:000278392400016 PM 20494248 ER PT J AU Bar-Haim, Y Holoshitz, Y Eldar, S Frenkel, TI Muller, D Charney, DS Pine, DS Fox, NA Wald, I AF Bar-Haim, Yair Holoshitz, Yael Eldar, Sharon Frenkel, Tahl I. Muller, David Charney, Dennis S. Pine, Daniel S. Fox, Nathan A. Wald, Ilan TI Life-Threatening Danger and Suppression of Attention Bias to Threat SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY; TRAUMATIC EVENTS; SOCIAL ANXIETY; DEPRESSION; PHQ-9; VULNERABILITY; INDIVIDUALS; ADOLESCENTS; COGNITION AB Objective: Life-threatening danger is assumed to produce, in tandem, increases in both vigilance toward threat and stress-related symptoms, but no data test the validity of this assumption. The authors examined associations, in real time, among imminent life-threatening danger, stress-related symptoms, and vigilance. Method: Symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety were measured in a civilian population (N=131) as a function of war-related stress, operationalized as the time available for seeking cover from rocket attack. A computerized measure of threatrelated vigilance using a classic dot-probe attention task was also collected. Results: PTSD symptoms, depression, and anxiety increased as a function of war-related threat. Acute proximal threat was associated with avoidance of, rather than vigilance toward, negative valence information. For participants within rocket range, the magnitude of threat bias varied with the magnitude of distress symptoms, such that as bias away from threat increased, distress symptoms increased. Conclusions: These data challenge current thinking about the role of attention in stress responding. Attentional threat avoidance may reduce the acute impact of imminent threat, but this may come at a price in terms of an elevated risk for psychopathology. (Am J Psychiatry 2010; 167:694-698) C1 [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. Mt Sinai Sch Med, New York, NY USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Bar-Haim, Y (reprint author), Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. EM yair1@post.tau.ac.il FU Israeli Science Foundation [964/08] FX Supported by the Israeli Science Foundation (grant no. 964/08 [Dr. Bar-Haim]). NR 37 TC 71 Z9 72 U1 8 U2 29 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2010 VL 167 IS 6 BP 694 EP 698 PG 5 WC Psychiatry SC Psychiatry GA 604HG UT WOS:000278269500014 PM 20395400 ER PT J AU Shah, S Grady, C AF Shah, Seema Grady, Christine TI ETHICAL IMPERATIVE OF POSTTRIAL ACCESS TO ANTIRETROVIRAL TREATMENT RESPONSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 [Shah, Seema; Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Shah, Seema] NIH, Div Aids, Bethesda, MD 20892 USA. RP Shah, S (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM shahse@mail.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2010 VL 100 IS 6 BP 967 EP 967 DI 10.2105/AJPH.2009.188383 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 596YT UT WOS:000277722500002 ER PT J AU Fee, E Bird, ME AF Fee, Elizabeth Bird, Michael E. TI Chief In-mut-too-yah-lat-lat (Thunder-Traveling-Over-the-Mountains): A Reluctant Warrior SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Fee, Elizabeth] Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. [Bird, Michael E.] Amer Publ Hlth Assoc, Washington, DC USA. RP Fee, E (reprint author), Care of Chang BB, Natl Lib Med, Hist Med Div, NIH, 8600 Rockville Pike,MSC-3819,Bldg 38,Room 1-E-21, Bethesda, MD 20894 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2010 VL 100 IS 6 BP 1007 EP 1007 DI 10.2105/AJPH.2009.184697 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 596YT UT WOS:000277722500017 PM 20395570 ER PT J AU Lane, HJ Blum, N Fee, E AF Lane, Hilary J. Blum, Nava Fee, Elizabeth TI Oliver Wendell Holmes (1809-1894) and Ignaz Philipp Semmelweis (1818-1865): Preventing the Transmission of Puerperal Fever SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Lane, Hilary J.] Mayo Fdn Hist Med Lib, Rochester, MN USA. [Blum, Nava] Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci, IL-31999 Haifa, Israel. [Fee, Elizabeth] Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. RP Lane, HJ (reprint author), Care of Chang BB, Natl Lib Med, Hist Med Div, NIH, 8600 Rockville Pike,Bldg 38, Bethesda, MD 20894 USA. NR 7 TC 5 Z9 5 U1 0 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2010 VL 100 IS 6 BP 1008 EP 1009 DI 10.2105/AJPH.2009.185363 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 596YT UT WOS:000277722500018 PM 20395569 ER PT J AU Yoshinaga, K AF Yoshinaga, Koji TI Research on Blastocyst Implantation Essential Factors (BIEFs) SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Blastocyst implantation essential factors; implantation; immune cells ID NATURAL-KILLER-CELLS; LEUKEMIA INHIBITORY FACTOR; FEMALE REPRODUCTIVE-TRACT; MATERNAL-FETAL INTERFACE; MURINE DENDRITIC CELLS; METRIAL GLAND-CELLS; REGULATORY T-CELLS; DECIDUAL NK CELLS; EMBRYO IMPLANTATION; HUMAN ENDOMETRIUM AB Blastocyst implantation is a process of interaction between embryo and the uterus. To understand this process, this review tries to summarize what blastocyst implantation essential factors (BIEFs) play what roles, as well as where in the uterus and at what stage of implantation process. Addition of more new data to this kind of compilation of information will help the development of diagnosis and treatment of infertility caused by implantation failure. The major, important cells of the endometrial cells that interact with invading blastocyst (trophoblast) are luminal epithelial cells, stromal cells (decidual cells) and resident immune cells. BIEFs regulate these cells to successfully maintain pregnancy. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Sci Branch, Populat Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Yoshinaga, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Sci Branch, Populat Res Ctr, NIH,DHHS, Bldg 6100,Room 8B01, Bethesda, MD 20892 USA. EM ky6a@nih.gov NR 83 TC 27 Z9 30 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JUN PY 2010 VL 63 IS 6 BP 413 EP 424 DI 10.1111/j.1600-0897.2010.00853.x PG 12 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 594FR UT WOS:000277521800002 PM 20455874 ER PT J AU Verma, S Rajesh, A Futterer, JJ Turkbey, B Scheenen, TWJ Pang, YX Choyke, PL Kurhanewicz, J AF Verma, Sadhna Rajesh, Arumugam Futterer, Jurgen J. Turkbey, Baris Scheenen, Tom W. J. Pang, Yuxi Choyke, Peter L. Kurhanewicz, John TI Prostate MRI and 3D MR Spectroscopy: How We Do It SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE choline; citrate; metabolites; MRI; MR spectroscopy; oncologic imaging; polyamines; prostate cancer; prostate ID SPATIAL RF PULSES; ENDORECTAL COIL; CANCER; SUPPRESSION; WATER; 3T; LOCALIZATION; SEQUENCE; DESIGN; ZONE AB OBJECTIVE. This review is a primer on the technical aspects of performing a high-quality MRI and MR spectroscopic imaging examination of the prostate. CONCLUSION. MRI and MR spectroscopic imaging are useful tools in the localization, staging, and functional assessment of prostate cancer. Performing a high-quality MR spectroscopic examination requires understanding of the technical aspects and limitations of spectral acquisition, postprocessing techniques, and spectral evaluation. C1 [Verma, Sadhna] Univ Cincinnati, Med Ctr, Dept Radiol, Cincinnati, OH 45267 USA. [Rajesh, Arumugam] NHS Trust Leicester Gen Hosp, Univ Hosp Leicester, Dept Radiol, Leicester, Leics, England. [Futterer, Jurgen J.; Scheenen, Tom W. J.] Radboud Univ Nijmegen, Dept Radiol, Nijmegen Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Turkbey, Baris; Pang, Yuxi; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Kurhanewicz, John] Univ Calif San Francisco, Dept Radiol, Prostate Imaging Grp, San Francisco, CA 94143 USA. [Kurhanewicz, John] Univ Calif San Francisco, Dept Urol, Prostate Imaging Grp, San Francisco, CA 94143 USA. [Kurhanewicz, John] Univ Calif San Francisco, Dept Pharmaceut Chem, Prostate Imaging Grp, San Francisco, CA 94143 USA. [Kurhanewicz, John] Univ Calif San Francisco, Biomed NMR Lab, San Francisco, CA 94143 USA. RP Verma, S (reprint author), Univ Cincinnati, Med Ctr, Dept Radiol, 234 Goodman St,POB 670761, Cincinnati, OH 45267 USA. RI Scheenen, Tom/I-5921-2013; futterer, jurgen/A-1455-2014 FU NCI NIH HHS [R01 CA059897, R01 CA111291, R01 CA111291-04] NR 35 TC 55 Z9 55 U1 0 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 JUN PY 2010 VL 194 IS 6 BP 1414 EP 1426 DI 10.2214/AJR.10.4312 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 599XU UT WOS:000277948400002 PM 20489079 ER PT J AU Courcoutsakis, N Prassopoulos, P Stratakis, CA AF Courcoutsakis, Nikos Prassopoulos, Panos Stratakis, Constantine A. TI CT Findings of Primary Pigmented Nodular Adrenocortical Disease: Rare Cause of ACTH-Independent Cushing Syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID COMPLEX C1 [Courcoutsakis, Nikos; Stratakis, Constantine A.] NICHHD, NIH, Bethesda, MD 20892 USA. [Courcoutsakis, Nikos; Prassopoulos, Panos] Democritus Univ Thrace, Alexandroupolis, Greece. RP Courcoutsakis, N (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 5 U1 0 U2 1 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 JUN PY 2010 VL 194 IS 6 BP W541 EP W541 DI 10.2214/AJR.09.4056 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 599XU UT WOS:000277948400052 PM 20489078 ER PT J AU Zhong, MH De Angelo, P Osborne, L Keane-Tarchichi, M Goldfischer, M Edelmann, L Yang, YF Linehan, M Merino, MJ Aisner, S Hameed, M AF Zhong, Minghao De Angelo, Patricia Osborne, Lisa Keane-Tarchichi, Megan Goldfischer, Michael Edelmann, Lisa Yang, Youfeng Linehan, Marston Merino, Maria J. Aisner, Seena Hameed, Meera TI Dual-color, Break-apart FISH Assay on Paraffin-embedded Tissues as an Adjunct to Diagnosis of Xp11 Translocation Renal Cell Carcinoma and Alveolar Soft Part Sarcoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE FISH; Xp11 translocation renal cell carcinoma; alveolar soft part sarcoma ID OF-THE-LITERATURE; GENE FUSION; TFE3 GENE; KIDNEY CANCER; TUMORS; IMMUNOREACTIVITY; NEOPLASMS; FEATURES; THERAPY AB Both Xp11.2 translocation renal cell carcinoma (RCC) and alveolar soft part sarcoma (ASPS) are characterized by various translocations disrupting chromosome Xp11.2, which result in gene fusions involving the TFE3 transcription factor gene. Diagnostic tools to detect translocations involving the TFE3 gene on chromosome X would be valuable in the evaluation of these tumors. We developed a dual-color, break-apart fluorescence in situ hybridization (FISH) assay to identify the chromosomal break point in paraffin-embedded tissue. This assay was validated using 4 cases of Xp11.2 RCC [ proven by karyotype and/or reverse-transcriptase polymerase chain reaction (RT-PCR)], 2 cases of ASPS (proven by karyotype or RT-PCR), the UOK109 cell line carrying the inv(X) (p11; q12), and several negative controls (both neoplastic and non-neoplastic). This break-apart FISH assay is a relatively quick procedure for detecting Xp11.2 RCC and ASPS translocations and can be applied to archival paraffin-embedded tissue. C1 [Zhong, Minghao] Univ Med & Dent New Jersey, Dept Pathol & Lab Med, Sch Med, Newark, NJ 07103 USA. [De Angelo, Patricia; Osborne, Lisa] Univ Med & Dent New Jersey, Inst Genom Med, Sch Med, Newark, NJ 07103 USA. [Goldfischer, Michael] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Edelmann, Lisa] Mt Sinai Sch Med, New York, NY USA. [Yang, Youfeng; Linehan, Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zhong, MH (reprint author), Univ Med & Dent New Jersey, Dept Pathol & Lab Med, Sch Med, Newark, NJ 07103 USA. EM minghaozhong@gmail.com; Hameedm@mskcc.org FU NJMS pathology department FX Supported by NJMS pathology department resident research fund. NR 28 TC 52 Z9 55 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUN PY 2010 VL 34 IS 6 BP 757 EP 766 DI 10.1097/PAS.0b013e3181dd577e PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 601YK UT WOS:000278104000001 PM 20421778 ER PT J AU Ribeiro, JMC Valenzuela, JG Pham, VM Kleeman, L Barbian, KD Favreau, AJ Eaton, DP Aoki, V Hans, G Rivitti, EA Diaz, LA AF Ribeiro, Jose M. C. Valenzuela, Jesus G. Pham, Van M. Kleeman, Lindsay Barbian, Kent D. Favreau, Amanda J. Eaton, Donald P. Aoki, Valeria Hans-Filho, Gunter Rivitti, Evandro A. Diaz, Luis A. TI An Insight into the Sialotranscriptome of Simulium nigrimanum, a Black Fly Associated with Fogo Selvagem in South America SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ADULT FEMALE MOSQUITO; ENDEMIC PEMPHIGUS FOLIACEUS; PANCREATIC TRYPSIN-INHIBITOR; SALIVARY-GLAND TRANSCRIPTOME; RICH SECRETORY PROTEINS; ANOPHELES-GAMBIAE; BINDING-PROTEIN; 5'-NUCLEOTIDASE FAMILY; ANTIMICROBIAL ACTIVITY; LUTZOMYIA-LONGIPALPIS AB Pemphigus foliaceus is a life threatening skin disease that is associated with autoimmunity to desmoglein, a skin protein involved in the adhesion of keratinocytes. This disease is endemic in certain areas of South America, suggesting the mediation of environmental factors triggering autoimmunity. Among the possible environmental factors, exposure to bites of black flies, in particular Simulittm nigrimanum has been suggested. In this work, we describe the sialotranscriptome of adult female S. nigrimanum flies. It reveals the complexity of the salivary potion of this insect, comprised by over 70 distinct genes within over 30 protein families, including several novel families, even when compared with the previously described sialotranscriptome of the autogenous black fly, S. vitiation. The uncovering of this sialotranscriptome provides a platform for testing pemphigus patient sera against recombinant salivary proteins from S. nigrimanum and for the discovery of novel pharmacologically active compounds. C1 [Ribeiro, Jose M. C.; Valenzuela, Jesus G.; Pham, Van M.; Kleeman, Lindsay] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. [Barbian, Kent D.; Favreau, Amanda J.] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect, Hamilton, MT 59840 USA. [Diaz, Luis A.] Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. [Aoki, Valeria; Rivitti, Evandro A.] Univ Sao Paulo, Dept Dermatol, BR-05508 Sao Paulo, Brazil. [Hans-Filho, Gunter] Univ Fed Mato Grosso do Sul, Dept Dermatol, Campo Grande, MS, Brazil. [Eaton, Donald P.] Wildlife Conservat Soc Brazil, Campo Grande, MS, Brazil. RP Ribeiro, JMC (reprint author), 12735 Twinbrook Pkwy,Room 2E32D, Rockville, MD 20852 USA. EM jribeiro@niaid.nih.gov; jvalenzuela@niaid.nih.gov; vpham@niaid.nih.gov; kleemanli@niaid.nih.gov; KBarbian@niaid.nih.gov; favreaua@niaid.nih.gov; ksadeaton@yahoo.com; valaoki@hotmail.com; ghansfilho@hotmail.com; elimaria@hcnet.usp.br; ldiaz@med.unc.edu RI Aoki, Valeria/H-1415-2012; OI Ribeiro, Jose/0000-0002-9107-0818 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIH [ROI AR32599] FX This work was supported in part by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, and NIH grant ROI AR32599 to LAD. NR 104 TC 21 Z9 21 U1 0 U2 4 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 JUN PY 2010 VL 82 IS 6 BP 1060 EP 1075 DI 10.4269/ajtmh.2010.09-0769 PG 16 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 606XP UT WOS:000278462600016 PM 20519601 ER PT J AU Barker, CM Johnson, WO Eldridge, BF Park, BK Melton, F Reisen, WK AF Barker, Christopher M. Johnson, Wesley O. Eldridge, Bruce F. Park, Bborie K. Melton, Forrest Reisen, William K. TI Temporal Connections between Culex tarsalis Abundance and Transmission of Western Equine Encephalomyelitis Virus in California SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ST-LOUIS ENCEPHALITIS; VECTOR COMPETENCE; TEMPERATURE; CULICIDAE; DIPTERA; MOSQUITOS; VALLEY; ARBOVIRUSES; COACHELLA; INFECTION AB Definition of targets for vector control requires an understanding of the relationship between vector abundance and the intensity of arbovirus transmission. Using an extensive surveillance dataset with observations from sentinel chicken flocks and mosquito traps paired in time and space, hierarchical autoregressive logistic regression models were developed to predict the probability of seroconversion in chickens for western equine encephalomyelitis virus (WEEV) based on the relative abundance of the principal vector, Culex tarsalis. After adjustments for confounders, the abundance of Cx. tarsalis 29-42 d before the date of chicken sampling was credibly associated with the risk of WEEV transmission in both the Central and Coachella Valleys, and a doubling of relative Cx. tarsalis abundance was associated with a 58% increase in the odds of seroconversion. The critical time windows identified in our study highlight the need for surveillance of vector populations and forecasting models to guide proactive vector control measures before the detection of transmission to sentinel chickens. C1 [Barker, Christopher M.; Eldridge, Bruce F.; Park, Bborie K.; Reisen, William K.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA. [Johnson, Wesley O.] Univ Calif Irvine, Dept Stat, Donald Bren Sch Informat & Comp Sci, Irvine, CA USA. Calif State Univ, Seaside, CA USA. [Melton, Forrest] NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Barker, CM (reprint author), Univ Calif Davis, Ctr Vectorborne Dis, Old Davis Rd, Davis, CA 95616 USA. EM cmbarker@ucdavis.edu FU NASA [RM08-6044, NNA06CN02A]; NOAA Office of Global Programs, Climate Variability and Human Health [00-543] FX This work was funded by NASA Earth-Sun Science Applied Sciences Program Research Opportunities in Space and Earth Science, Decision Support through Earth-Sun Science Research Results grant RM08-6044 for NNA06CN02A and NOAA Office of Global Programs, Climate Variability and Human Health grant 00-543. NR 53 TC 2 Z9 2 U1 0 U2 4 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 JUN PY 2010 VL 82 IS 6 BP 1185 EP 1193 DI 10.4269/ajtmh.2010.09-0324 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 606XP UT WOS:000278462600036 PM 20519621 ER PT J AU Moaddel, R Bighi, F Yamaguchi, R Patel, S Ravichandran, S Wainer, IW AF Moaddel, R. Bighi, F. Yamaguchi, R. Patel, S. Ravichandran, S. Wainer, I. W. TI Stereoselective binding of chiral ligands to single nucleotide polymorphisms of the human organic cation transporter-1 determined using cellular membrane affinity chromatography SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE SNPs; Frontal affinity chromatography; Molecular modeling; Pharmacophore; Chirality ID FUNCTIONAL-CHARACTERIZATION; STATIONARY-PHASE; POPULATION; VARIANTS; HOCT1; GENE AB Membranes from stably transfected cell lines that express two point mutations of the human organic cation transporter-1 (hOCT1), R488 M and G465R, have been immobilized on the immobilized artificial membrane (IAM) liquid chromatographic stationary phase to form two cellular membrane affinity chromatography (CMAC) columns, CMAC(hOCT1(G465R)) and CMAC(hOCT1(R488m)). Columns were created using both stationary phases, and frontal displacement chromatography experiments were conducted using [(3)H] MMP(+) (1-methyl-4-phenylpyridinium) as the marker ligand and various displacers, including the single enantiomers of verapamil, fenoterol, and isoproterenol. The chromatographic data obtained were used to refine a previously developed pharmacophore for hOCT1. Published by Elsevier Inc. C1 [Moaddel, R.; Bighi, F.; Yamaguchi, R.; Patel, S.; Wainer, I. W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Ravichandran, S.] NCI, Informat Syst Program, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. RP Moaddel, R (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov FU National Institute on Aging, National Institutes of Health (NIH); National Cancer Institute, NIH [HHSN261200800001E] FX This work was supported in part by funds from the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH), and from the National Cancer Institute, NIH, under contract HHSN261200800001E. S.R. acknowledges the help of Sumeet Salaniwal (lead scientist, Client Services, Accelrys) regarding file format conversions in DS and helpful discussion regarding the analysis of HypoGen results. NR 13 TC 3 Z9 3 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 1 PY 2010 VL 401 IS 1 BP 148 EP 153 DI 10.1016/j.ab.2010.02.034 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 587GR UT WOS:000276978700020 PM 20206116 ER PT J AU Win, MK Chow, A Chen, M Lau, YF Ooi, EE Leo, YS AF Win, Mar Kyaw Chow, Angela Chen, Mark Lau, Yuk Fai Ooi, Eng Eong Leo, Yee Sin TI Influenza B Outbreak among Influenza-vaccinated Welfare Home Residents in Singapore SO ANNALS ACADEMY OF MEDICINE SINGAPORE LA English DT Article DE Antigenic drift; Influenza; Long-term care facilities ID TERM-CARE FACILITIES; NURSING-HOME; A H3N2; POPULATION; AMANTADINE; PREVENTION; EFFICACY; STAFF AB Introduction: Outbreaks of acute respiratory illness occur commonly in long-term care facilities (LTCF), due to the close proximity of residents. Most influenza outbreak reports have been from temperate countries. This study reports an outbreak of influenza B among a highly immunised resident population in a welfare home in tropical Singapore, and discusses vaccine efficacy and the role of acute respiratory illness surveillance for outbreak prevention and control. Materials and Methods: During the period from 16 to 21 March 2007, outbreak investigations and active case finding were carried out among residents and nursing staff at the welfare home. Interviews and medical notes review were conducted to obtain epidemiological and clinical data. Hospitalised patients were tested for respiratory pathogens. Further genetic studies were also carried out on positive respiratory samples. Results: The overall clinical attack rate was 9.4% (17/180) in residents and 6.7% (2/30) in staff. All infected residents and staff had received influenza immunisation. Fifteen residents were hospitalised, with 2 developing severe complications. Genetic sequencing revealed that the outbreak strain had an 8.2% amino acid difference from B/Malaysia/2506/2004, the 2006 southern hemisphere influenza vaccine strain, which the residents and staff had earlier received. Conclusions: A mismatch between the vaccine and circulating influenza virus strains can result in an outbreak in a highly immunised LTCF resident population. Active surveillance for acute respiratory illness in LTCFs could be implemented for rapid detection of antigenic drift. Enhanced infection control and other preventive measures can then be deployed in a timely manner to mitigate the effect of any outbreaks. Ann Acad Med Singapore 2010;39:448-52 C1 [Win, Mar Kyaw; Leo, Yee Sin] Tan Tock Seng Hosp, Dept Infect Dis, Singapore 308433, Singapore. [Chow, Angela; Chen, Mark; Leo, Yee Sin] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Chen, Mark; Ooi, Eng Eong] Duke NUS Grad Med Sch, Singapore, Singapore. [Lau, Yuk Fai; Ooi, Eng Eong] DSO Natl Labs, Def Med & Environm Res Inst, Singapore, Singapore. [Lau, Yuk Fai] NIAID, NIH, Bethesda, MD 20892 USA. RP Win, MK (reprint author), Tan Tock Seng Hosp, Dept Infect Dis, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. EM mar_kyaw_win@ttsh.com.sg OI Ooi, Eng Eong/0000-0002-0520-1544 NR 23 TC 3 Z9 3 U1 0 U2 3 PU ACAD MEDICINE SINGAPORE PI REPUBLIC SINGAPORE PA 142 NEIL RD, REPUBLIC SINGAPORE 088871, SINGAPORE SN 0304-4602 J9 ANN ACAD MED SINGAP JI Ann. Acad. Med. Singap. PD JUN PY 2010 VL 39 IS 6 BP 448 EP 452 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 627IN UT WOS:000280032800007 PM 20625620 ER PT J AU Brownson, RC Hartge, P Samet, JM Ness, RB AF Brownson, Ross C. Hartge, Patricia Samet, Jonathan M. Ness, Roberta B. TI From Epidemiology to Policy: Toward More Effective Practice SO ANNALS OF EPIDEMIOLOGY LA English DT Editorial Material ID PUBLIC-HEALTH POLICY; SCIENCE C1 [Brownson, Ross C.] Washington Univ, Prevent Res Ctr St Louis, George Warren Brown Sch Social Work, St Louis, MO 63110 USA. [Brownson, Ross C.] Washington Univ, Dept Surg, Washington Univ Sch Med, St Louis, MO 63110 USA. [Brownson, Ross C.] Washington Univ, Alvin J Siteman Canc Ctr, Washington Univ Sch Med, St Louis, MO 63110 USA. [Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Samet, Jonathan M.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. RP Brownson, RC (reprint author), Washington Univ, Prevent Res Ctr St Louis, George Warren Brown Sch Social Work, 660 S Euclid, St Louis, MO 63110 USA. EM rbrownson@wustl.edu NR 13 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUN PY 2010 VL 20 IS 6 BP 409 EP 411 DI 10.1016/j.annepidem.2010.03.003 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 601BL UT WOS:000278032900001 PM 20470966 ER PT J AU McArthur, JC Steiner, J Sacktor, N Nath, A AF McArthur, Justin C. Steiner, Joseph Sacktor, Ned Nath, Avi TI Human Immunodeficiency Virus-Associated Neurocognitive Disorders Mind the Gap SO ANNALS OF NEUROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-ASSOCIATED DEMENTIA; CENTRAL-NERVOUS-SYSTEM; HEPATITIS-C VIRUS; RECONSTITUTION INFLAMMATORY SYNDROME; MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN FETAL ASTROCYTES; IN-SITU HYBRIDIZATION; TUMOR-NECROSIS-FACTOR; SUB-SAHARAN AFRICA AB Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) remain among the most common disorders in people infected with HIV, even in an era when potent antiretroviral therapy is widely deployed. This review discusses the clinical features of HANDs and the implications for more effective treatment. With the improved survival of individuals treated with antiretrovirals, comorbid conditions are increasingly salient, including particularly coinfection with hepatitis C and the effects of aging. This review attempts to answer why there appears to be a therapeutic gap between the salutary effects of antiretroviral regimens and normalization of neurological function. A second gap is found in the understanding of the pathophysiology of HANDs. This review addresses this and discusses the animal models that have helped to elucidate these mechanisms. Although triggered by productive HIV infection of brain macrophages, aberrant and sustained immune activation appears to play a major role in inducing HANDs, and may explain the often incomplete neurological response to highly active antiretroviral therapy. Novel therapies aimed at persistent central nervous system inflammation will be needed to close this gap. ANN NEUROL 2010;67:699-714 C1 [McArthur, Justin C.; Steiner, Joseph; Sacktor, Ned; Nath, Avi] Johns Hopkins Univ, NIMH Ctr Novel Therapeut HIV Associated Cognit Di, Baltimore, MD USA. [Steiner, Joseph; Nath, Avi] Johns Hopkins Univ, Dept Neurol, HIV Neurosci Program, Baltimore, MD 21218 USA. RP McArthur, JC (reprint author), 600 N Wolfe St,Meyer 6113, Baltimore, MD 21287 USA. EM jm@jhmi.edu FU NIND [NS44807, NS35609, NS49465]; NIMH [1P30MH075673, UL1RR025005] FX J.C.M. has been supported by NIND grants NS44807, NS35609, and NS49465, and is currently supported by NIMH 1P30MH075673 and UL1RR025005. NR 186 TC 180 Z9 183 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 2010 VL 67 IS 6 BP 699 EP 714 DI 10.1002/ana.22053 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 603KV UT WOS:000278208400005 PM 20517932 ER PT J AU Hein, MJ Waters, MA Ruder, AM Stenzel, MR Blair, A Stewart, PA AF Hein, Misty J. Waters, Martha A. Ruder, Avima M. Stenzel, Mark R. Blair, Aaron Stewart, Patricia A. TI Statistical modeling of occupational chlorinated solvent exposures for case-control studies using a literature-based database SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE case-control study; exposure assessment; exposure determinants; occupational exposure ID POLYCYCLIC AROMATIC-HYDROCARBONS; WOOD DUST; FORMALDEHYDE EXPOSURE; DETECTION LIMITS; US INDUSTRIES; DETERMINANTS; WORKER; RISK AB Methods: A measurement database was developed after an extensive review of the published industrial hygiene literature. The database of nearly 3000 measurements or summary measurements included sample size, measurement characteristics (year, duration, and type), and several potential exposure determinants associated with the measurements: mechanism of release (e.g. evaporation), process condition, temperature, usage rate, type of ventilation, location, presence of a confined space, and proximity to the source. The natural log-transformed measurement levels in the exposure database were modeled as a function of the measurement characteristics and exposure determinants using maximum likelihood methods. Assuming a single lognormal distribution of the measurements, an arithmetic mean exposure intensity level was estimated for each unique combination of exposure determinants and decade. Results: The proportions of variability in the measurement data explained by the modeled measurement characteristics and exposure determinants were 36, 38, and 54% for methylene chloride, 1,1,1-trichloroethane, and trichloroethylene, respectively. Model parameter estimates for the exposure determinants were in the anticipated direction. Exposure intensity estimates were plausible and exhibited internal consistency, but the ability to evaluate validity was limited. Conclusions: These prediction models can be used to estimate chlorinated solvent exposure intensity for jobs reported by population-based case-control study participants that have sufficiently detailed information regarding the exposure determinants. C1 [Hein, Misty J.; Ruder, Avima M.] NIOSH, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. [Waters, Martha A.] NIOSH, Div Appl Res & Technol, Cincinnati, OH 45226 USA. [Stenzel, Mark R.] Exposure Assessment Applicat LLC, Arlington, VA 22207 USA. [Blair, Aaron] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA. RP Hein, MJ (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studi, 4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM mhein@cdc.gov RI Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 FU National Institutes of Health; CDC/NIOSH Initiative for Cancer Control Projects for Farmers; CDC/NIOSH National Occupational Research Agenda; National Cancer Institute; CDC FX Intramural Federal research funding from National Institutes of Health and CDC, including CDC/NIOSH Initiative for Cancer Control Projects for Farmers; CDC/NIOSH National Occupational Research Agenda; Intramural Research Program of the National Institutes of Health (National Cancer Institute). NR 33 TC 13 Z9 13 U1 1 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 JUN PY 2010 VL 54 IS 4 BP 459 EP 472 DI 10.1093/annhyg/meq027 PG 14 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 603OP UT WOS:000278218200011 PM 20418277 ER PT J AU Edge, SB Compton, CC AF Edge, Stephen B. Compton, Carolyn C. TI The American Joint Committee on Cancer: the 7th Edition of the AJCC Cancer Staging Manual and the Future of TNM SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material AB The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor-node-metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms. C1 [Edge, Stephen B.; Compton, Carolyn C.] Amer Joint Comm Canc, Chicago, IL USA. [Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA. [Compton, Carolyn C.] NCI, Bethesda, MD 20892 USA. RP Edge, SB (reprint author), Amer Joint Comm Canc, Chicago, IL USA. EM stephen.edge@roswellpark.org NR 1 TC 1672 Z9 1801 U1 20 U2 107 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2010 VL 17 IS 6 BP 1471 EP 1474 DI 10.1245/s10434-010-0985-4 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA 595EU UT WOS:000277594300001 PM 20180029 ER PT J AU Rogers, SO Gray, SW Landrum, MB Klabunde, CN Kahn, KL Fletcher, RH Clauser, S Tisnado, D Doucette, W Keating, NL AF Rogers, Selwyn O., Jr. Gray, Stacy W. Landrum, Mary Beth Klabunde, Carrie N. Kahn, Katherine L. Fletcher, Robert H. Clauser, Steven Tisnado, Diana Doucette, William Keating, Nancy L. TI Variations in Surgeon Treatment Recommendations for Lobectomy in Early-Stage Non-Small-Cell Lung Cancer by Patient Age and Comorbidity SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID MINIMALLY INVASIVE LOBECTOMY; PULMONARY RESECTION; SURGICAL RESECTION; ELDERLY-PATIENTS; COMPLICATIONS; SURVEILLANCE; MANAGEMENT; MORTALITY; SURVIVAL; DATABASE AB Prior research suggests that older patients are less likely to undergo resection of early-stage non-small-cell lung carcinomas (NSCLCs). We surveyed surgeons to understand how their recommendations for lobectomy were influenced by age, the presence and severity of smoking-related lung disease, or by characteristics of the surgeons and their practices. We surveyed surgeons caring for NSCLC patients regarding whether they would recommend lobectomy for hypothetical patients with early-stage NSCLC who varied by age (55 vs. 80 years) and comorbid illness (none, moderate, severe chronic obstructive pulmonary disease [COPD]). Ordinal logistic regression was used to identify the importance of patient, surgeon, and practice characteristics on surgery recommendations. Surgeons recommended lobectomy for nearly all patients who were 55 years old with no comorbidity (adjusted proportion 98.6%), 55 years old with moderate COPD (adjusted proportion 97.8%), or 80 years old with no comorbidity (adjusted proportion 98.1%). Fewer recommended lobectomy for 80-year-old patients with moderate COPD (adjusted proportion 82.3%), and far fewer recommended lobectomy for severe COPD, irrespective of age (adjusted rate 18.7% for the 55-year-old patient and 6.1% for the 80-year-old patient) (P < 0.002). Surgeons who enroll patients onto clinical trials (P = 0.03) were more likely than others to recommend lobectomy, but no other surgeon characteristic predicted recommendations. Lower rates of lobectomy among older patients do not seem to be explained by age-related biases among surgeons for otherwise healthy patients. C1 [Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Rogers, Selwyn O., Jr.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Landrum, Mary Beth; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Klabunde, Carrie N.; Clauser, Steven] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Kahn, Katherine L.; Tisnado, Diana] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Fletcher, Robert H.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Doucette, William] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Rogers, SO (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM srogers@partners.org FU National Cancer Institute (NCI) [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA01013, U01 CA093326]; Department of Veteran's Affairs [CRS 02-164] FX This work of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by grants from the National Cancer Institute (NCI) to the Statistical Coordinating Center (U01 CA093344) and the NCI-supported Primary Data Collection and Research Centers (Dana Farber Cancer Institute/Cancer Research Network U01 CA093332, Harvard Medical School/Northern California Cancer Center U01 CA093324, RAND/UCLA U01 CA093348, University of Alabama at Birmingham U01 CA093329, University of Iowa U01 CA01013, University of North Carolina U01 CA093326) and by a Department of Veteran's Affairs grant to the Durham VA Medical Center CRS 02-164. NR 31 TC 10 Z9 10 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2010 VL 17 IS 6 BP 1581 EP 1588 DI 10.1245/s10434-010-0946-y PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 595EU UT WOS:000277594300017 PM 20162461 ER PT J AU Roescher, N Tak, PP Illei, GG AF Roescher, Nienke Tak, Paul P. Illei, Gabor G. TI Cytokines in Sjogren's syndrome: potential therapeutic targets SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; CLINICAL-TRIAL; GENE-TRANSFER; MURINE MODEL; DOUBLE-BLIND; ALPHA; INTERFERON; ETANERCEPT; ACTIVATION AB The dysregulated cytokine network in Sjogren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low dose interferon (IFN) alpha showed inconsistent efficacy in various studies and failed to achieve the primary endpoint in a pivotal randomised controlled trial. Similarly, neither of the two tumour necrosis factor (TNF)-alpha blockers tested (etanercept and infliximab) showed efficacy in placebo controlled trials. Although the rationale for low dose oral IFN treatment has not been firmly established, TNF blockade was based on solid preclinical data. Therefore, the reason for the lack of efficacy is unclear, but recent data suggest that unexpected biological effects of TNF antagonists may have contributed to this. Cytokines, given their central role in the pathogenesis of SS, remain attractive targets for future treatments, despite the disappointing early results. Inflammatory cytokines are obvious candidates, and agents against several of them are available or under development for other autoimmune diseases similar to SS. New candidate cytokines such as IL-17 and IL-12 and/or IL-23 may provide promising targets for SS. Additionally, as an alternative to systemic treatment, which has the risk of potentially severe side effects, the use of local cytokine directed therapy should be explored. C1 [Roescher, Nienke; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Roescher, Nienke; Tak, Paul P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. RP Roescher, N (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, 10 Ctr Dr, Bethesda, MD 20892 USA. EM roeschern@mail.nih.gov FU NIH NIDCR FX NR and GGI are funded by an NIH NIDCR intramural research grant. NR 30 TC 40 Z9 45 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2010 VL 69 IS 6 BP 945 EP 948 DI 10.1136/ard.2009.115378 PG 4 WC Rheumatology SC Rheumatology GA 600VT UT WOS:000278017700003 PM 20410069 ER PT J AU Pointon, JJ Harvey, D Karaderi, T Appleton, LH Farrar, C Stone, MA Sturrock, RD Reveille, JD Weisman, MH Ward, MM Brown, MA Wordsworth, BP AF Pointon, Jennifer J. Harvey, David Karaderi, Tugce Appleton, Louise H. Farrar, Claire Stone, Millicent A. Sturrock, Roger D. Reveille, John D. Weisman, Michael H. Ward, Michael M. Brown, Matthew A. Wordsworth, B. Paul TI The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD) SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID SUSCEPTIBILITY; POLYMORPHISM; EXPRESSION; VARIANTS AB Objective To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS. C1 [Pointon, Jennifer J.; Harvey, David; Karaderi, Tugce; Appleton, Louise H.; Farrar, Claire; Brown, Matthew A.; Wordsworth, B. Paul] Univ Oxford, Inst Musculoskeletal Sci, Botnar Res Ctr, Oxford OX3 7LD, England. [Stone, Millicent A.] Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England. [Sturrock, Roger D.] Univ Glasgow, Ctr Rheumat Dis, Div Immunol Inflammat & Infect, Glasgow, Lanark, Scotland. [Reveille, John D.] Univ Texas Houston Hlth Sci Ctr, Houston, TX USA. [Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ward, Michael M.] NIAMS, Intramural Res Program, Bethesda, MD USA. [Brown, Matthew A.] Univ Queensland, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia. RP Pointon, JJ (reprint author), Univ Oxford, Inst Musculoskeletal Sci, Botnar Res Ctr, Oxford OX3 7LD, England. EM jenny.pointon@ndorms.ox.ac.uk OI Brown, Matthew A/0000-0003-0538-8211 FU Arthritis Research Campaign; Oxford Radcliffe Hospitals Biomedical Research Centre; National Ankylosing Spondylitis Society FX Funding Arthritis Research Campaign, Oxford Radcliffe Hospitals Biomedical Research Centre and National Ankylosing Spondylitis Society. NR 18 TC 15 Z9 17 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUN PY 2010 VL 69 IS 6 BP 1243 EP 1246 DI 10.1136/ard.2009.115147 PG 4 WC Rheumatology SC Rheumatology GA 600VT UT WOS:000278017700056 PM 19854717 ER PT J AU Khan, OA Davenhall, W Ali, M Castillo-Salgado, C Vazquez-Prokopec, G Kitron, U Magalhaes, RJS Clements, ACA AF Khan, O. A. Davenhall, W. Ali, M. Castillo-Salgado, C. Vazquez-Prokopec, G. Kitron, U. Magalhaes, R. J. Soares Clements, A. C. A. TI Geographical information systems and tropical medicine SO ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY LA English DT Review ID TRANSMITTED HELMINTH INFECTIONS; SPATIAL RISK PREDICTION; VECTOR-BORNE DISEASES; WESTERN COTE-DIVOIRE; LYMPHATIC FILARIASIS; GEOSTATISTICAL PREDICTION; SCHISTOSOMIASIS CONTROL; HERD-IMMUNITY; EPIDEMIOLOGY; VACCINE AB In terms of their applicability to the field of tropical medicine, geographical information systems (GIS) have developed enormously in the last two decades. This article reviews some of the pertinent and representative applications of GIS, including the use of such systems and remote sensing for the mapping of Chagas disease and human helminthiases, the use of GIS in vaccine trials, and the global applications of GIS for health-information management, disease epidemiology, and pandemic planning. The future use of GIS as a decision-making tool and some barriers to the widespread implementation of such systems in developing settings are also discussed. C1 [Khan, O. A.] Christiana Care Hlth Syst, Wilmington, DE 19810 USA. [Khan, O. A.] Univ Vermont, Dept Family Med, Burlington, VT 05405 USA. [Khan, O. A.] Univ Penn, Dept Family Med, Philadelphia, PA 19104 USA. [Davenhall, W.] ESRI Inc, Redlands, CA 92373 USA. [Ali, M.] Seoul Natl Univ Res Pk, Int Vaccine Inst, Seoul 151191, South Korea. [Castillo-Salgado, C.] Pan Amer Hlth Org, Washington, DC 20037 USA. [Castillo-Salgado, C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Vazquez-Prokopec, G.; Kitron, U.] Emory Univ, Dept Environm Studies, Atlanta, GA 30322 USA. [Kitron, U.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Magalhaes, R. J. Soares; Clements, A. C. A.] Univ Queensland, Sch Populat Hlth, Herston, Qld 4006, Australia. [Clements, A. C. A.] Queensland Inst Med Res, Australian Ctr Int & Trop Hlth, Herston, Qld 4006, Australia. RP Khan, OA (reprint author), Christiana Care Hlth Syst, 1309 Veale Rd, Wilmington, DE 19810 USA. EM omar.khan@vtmednet.org RI Soares Magalhaes, Ricardo/A-5316-2010; Clements, Archie/D-9619-2013 OI Soares Magalhaes, Ricardo/0000-0001-9157-8470; FU Fogarty International Center [R01 TW05836]; U.S. National Institute of Environmental Health Sciences; U.S. Science and Technology Directorate; U.S. Department of Homeland Security; Fogarty International Center, National Institutes of Health; University of Queensland [41795457]; Australian National Health and Medical Research Council [631619] FX During the research described here, two of the authors (G. V.-P. and U. K.) were supported by awards from the U.S. National Institutes of Health/National Science Foundation Ecology of Infectious Disease programme (award R01 TW05836; funded by the Fogarty International Center), the U. S. National Institute of Environmental Health Sciences, the Research and Policy for Infectious Disease Dynamics programme of the U. S. Science and Technology Directorate, the U. S. Department of Homeland Security, and the Fogarty International Center, National Institutes of Health.; A University of Queensland Research Scholarship and an International Postgraduate Research Award (#41795457) supported R.J.S.M., while A. C. A. C. was supported by an Australian National Health and Medical Research Council Career Development Award (#631619). NR 71 TC 8 Z9 9 U1 1 U2 14 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 0003-4983 J9 ANN TROP MED PARASIT JI Ann. Trop. Med. Parasitol. PD JUN PY 2010 VL 104 IS 4 BP 303 EP 318 DI 10.1179/136485910X12743554759867 PG 16 WC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine SC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine GA 628HW UT WOS:000280107700002 PM 20659391 ER PT J AU Varma, A Kwon-Chung, KJ AF Varma, A. Kwon-Chung, K. J. TI Heteroresistance of Cryptococcus gattii to Fluconazole SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NEOFORMANS VAR GATTII; CANDIDA-ALBICANS; ANTIFUNGAL SUSCEPTIBILITY; 2 VARIETIES; SEROTYPE-A; RESISTANCE; INFECTION; AIDS; MENINGITIS; EPIDEMIOLOGY AB We analyzed 71 clinical and environmental Cryptococcus gattii strains that had been isolated before or after the advent of azole antifungals to determine their level of heteroresistance to fluconazole (LHF). All strains of C. gattii manifested heteroresistance, with LHFs that ranged between 4 mu g/ml and 32 mu g/ml. A considerably higher proportion of the C. gattii strains (86%) than Cryptococcus neoformans strains (46%) exhibited LHFs that were >= 16 mu g/ml. No significant correlation was observed between the molecular type or serotypes of strains and their respective LHF. The strains which expressed a higher LHF were also more resistant to xenobiotics than the strains with a low LHF, and the level of resistance to xenobiotics was significantly higher than that reported for C. neoformans. The heteroresistant subpopulation, whose level of drug resistance had been raised in a stepwise manner to 64 mu g/ml, reverted to the original LHF upon daily transfers in drug-free medium. Importantly, the strains with high LHFs were significantly more virulent than those with low LHFs. Since all the clinical isolates that had not been exposed to azole drugs as well as the environmental strains manifested heteroresistance to fluconazole, heteroresistance of C. gattii to azoles is an intrinsic mechanism as in C. neoformans and is associated with the strain's virulence. C1 [Varma, A.; Kwon-Chung, K. J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N234, Bethesda, MD 20892 USA. EM June_kwon-chung@nih.gov FU National Institute of Allergy and Infectious Diseases FX We thank John E. Bennett for kindly providing C. gattii cultures in his collection that were deposited before 1980. We also thank Elizabeth Castaneda for her contribution of the Colombian strains of C. gattii.; This work was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases. NR 37 TC 45 Z9 45 U1 1 U2 3 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 JUN PY 2010 VL 54 IS 6 BP 2303 EP 2311 DI 10.1128/AAC.00153-10 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 597KO UT WOS:000277756000003 PM 20385871 ER PT J AU Beigel, JH Nordstrom, JL Pillemer, SR Roncal, C Goldwater, DR Li, H Holland, PC Johnson, S Stein, K Koenig, S AF Beigel, John H. Nordstrom, Jeffrey L. Pillemer, Stanley R. Roncal, Cory Goldwater, D. Ronald Li, Hua Holland, P. Chris Johnson, Syd Stein, Kathryn Koenig, Scott TI Safety and Pharmacokinetics of Single Intravenous Dose of MGAWN1, a Novel Monoclonal Antibody to West Nile Virus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NEUROINVASIVE DISEASE; INFECTION; RITUXIMAB; ENCEPHALITIS; PALIVIZUMAB; EPIDEMIC; LYMPHOMA; CHILDREN; THERAPY AB West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 mu g/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 mu g/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted. C1 [Beigel, John H.; Nordstrom, Jeffrey L.; Pillemer, Stanley R.; Roncal, Cory; Li, Hua; Holland, P. Chris; Johnson, Syd; Stein, Kathryn; Koenig, Scott] MacroGenics Inc, Rockville, MD 20850 USA. [Goldwater, D. Ronald] Parexel Int, Baltimore, MD USA. RP Beigel, JH (reprint author), NIAID, Clin Res Sect, Immunoregulat Lab, NIH, Bldg 10,8N246,10 Ctr Dr,MSC 1763, Bethesda, MD 20892 USA. EM jbeigel@niaid.nih.gov; NordstromJ@Macrogenics.com FU Microbiology and Infectious Diseases, NIAID, NIH [HHSN 266200600013C] FX This research was supported by the Division of Microbiology and Infectious Diseases, NIAID, NIH (DPHS contract HHSN 266200600013C). NR 22 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2010 VL 54 IS 6 BP 2431 EP 2436 DI 10.1128/AAC.01178-09 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 597KO UT WOS:000277756000020 PM 20350945 ER PT J AU Hope, WW Smith, PB Arrieta, A Buell, DN Roy, M Kaibara, A Walsh, TJ Cohen-Wolkowiez, M Benjamin, DK AF Hope, William W. Smith, P. Brian Arrieta, Antonio Buell, Donald N. Roy, Michael Kaibara, Atsunori Walsh, Thomas J. Cohen-Wolkowiez, Michael Benjamin, Daniel K., Jr. TI Population Pharmacokinetics of Micafungin in Neonates and Young Infants SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PEDIATRIC-PATIENTS; ECHINOCANDIN; CANDIDIASIS; CANDIDEMIA; DESIGN; SAFETY AB Micafungin is an echinocandin with potent activity against Candida spp. Hematogenous Candida meningoencephalitis (HCME) is a frequent complication of disseminated Candida infection in premature infants. A preclinical model of HCME suggests that micafungin may be an effective agent for this syndrome, but relatively high weight-based dosages are required. This prompted the further study of the safety and pharmacokinetics (PK) of micafungin in infants. Here, we describe the population pharmacokinetics of micafungin in 47 infants with a proven or presumptive diagnosis of disseminated candidiasis, who received 0.75, 1.5, 3, 7, 10, and 15 mg/kg of micafungin. The drug was infused daily, and samples were taken in the first dosing interval and at steady state. Serum concentrations were measured using high-performance liquid chromatography (HPLC). Data were modeled using an allometric pharmacokinetic model using a three-fourths scaling exponent for clearance and parameters normalized to a 70-kg adult. Drug exposures were estimated using Monte Carlo simulation. Optimal sampling times were determined using D-optimal design theory. The fit of the allometric model to the data was highly acceptable. The pharmacokinetics of micafungin were linear. The weight-normalized estimates of clearance and volume of distribution approximated those previously described for adults. The original population parameter values could be recapitulated in the Monte Carlo simulations. A dosage of 10 mg/kg/day resulted in 82.6% of patients with areas under the concentration-time curve (AUCs) that are associated with near-maximal decline in fungal burden within the central nervous system (CNS). C1 [Hope, William W.] Univ Manchester, Manchester Acad Hlth Sci Ctr, NIHR Translat Res Facil Resp Med, Univ Hosp S Manchester NHS Fdn Trust, Manchester, Lancs, England. [Smith, P. Brian; Cohen-Wolkowiez, Michael; Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Smith, P. Brian; Cohen-Wolkowiez, Michael; Benjamin, Daniel K., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. [Buell, Donald N.; Roy, Michael; Kaibara, Atsunori] Astellas Pharma Global Dev Inc, Deerfield, IL USA. [Arrieta, Antonio] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Walsh, Thomas J.] NCI, NIH, Bethesda, MD 20892 USA. RP Hope, WW (reprint author), 1-800 Stopford Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England. EM william.hope@manchester.ac.uk RI Smith, Phillip/I-5565-2014; OI Hope, William/0000-0001-6187-878X FU National Institute of Health Research (NIHR); National Institute of Child Health and Human Development Pediatric Pharmacology Research Unit [1U10-HD45962-06, NIH-1K23HD060040-01]; United States government [1R01HD057956-02, 1R01FD003519-01, 1U10HD45962- 06, 1K24HD058735-01, HHSN 267200700051C]; Astellas Pharma Global Development, Inc; National Cancer Institute; Astellas US FX William W. Hope is supported by a National Institute of Health Research (NIHR) Clinician Scientist Award. This study was supported, in part, by the National Institute of Child Health and Human Development Pediatric Pharmacology Research Unit (grant 1U10-HD45962-06 to Daniel K. Benjamin, Jr., and grant NIH-1K23HD060040-01 to P. Brian Smith) and by the intramural research program of the National Cancer Institute. Laura Kovanda (Astellas Pharma Global Development Inc.) helped with the design, conduct, and analysis of the clinical trials. We declare the following potential conflicts of interest. William W. Hope has received grant support for preclinical pharmacology and consultancy fees from Astellas Pharma Europe and has previously received grant support from Astellas US. Daniel K. Benjamin, Jr., receives support from the United States government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-02, 1R01FD003519-01, 1U10HD45962- 06, 1K24HD058735-01, and government contract HHSN 267200700051C), the nonprofit organization Thrasher Research Foundation for his work in neonatal candidiasis (http://www. thrasherresearch.org/), and from the industry for neonatal and pediatric drug development (http: //www. dcri.duke.edu/research/coi.jsp). P. Brian Smith has received grant support from Astellas Pharma Global Development, Inc. Antonio Arrieta has received grant support and consultancy fees from Astellas Pharma Global Development, Inc. Donald N. Buell, Michael Roy, and Atsunori Kaibara are employees of Astellas Pharma Global Development, Inc. NR 21 TC 55 Z9 57 U1 0 U2 5 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 JUN PY 2010 VL 54 IS 6 BP 2633 EP 2637 DI 10.1128/AAC.01679-09 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 597KO UT WOS:000277756000045 PM 20308367 ER PT J AU Mohan, KVK Rao, SS Atreya, CD AF Mohan, Ketha V. K. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Antiviral activity of selected antimicrobial peptides against vaccinia virus SO ANTIVIRAL RESEARCH LA English DT Article DE AMPs; RW peptides; Platelet-derived peptides; Microbicidal; pfu ID WEST-NILE-VIRUS; SARS-COV; INACTIVATION; PROTEIN; ENTRY; IDENTIFICATION; INFECTIONS; INHIBITION; MECHANISMS; PRODUCTS AB Antimicrobial peptides (AMPS) are gaining importance as effective therapeutic alternatives to conventional antibiotics. Recently we have shown that a set of nine synthetic antimicrobial peptides, four originating from thrombin-induced human platelet-derived antimicrobial proteins named PD1-PD4 and five synthetic repeats of arginine-tryptophan (RW) repeats (RW1-5) demonstrate antibacterial activity in plasma and platelets. Using WR strain of vaccinia virus (VV) as a model virus for enveloped virus in the present study, we tested the same nine synthetic peptides for their antiviral activity. A cell culture-based standard plaque reduction assay was utilized to estimate antiviral effectiveness of the peptides. Our analysis revealed that peptides PD3, PD4, and RW3 were virucidal against W with PD3 demonstrating the highest antiviral activity of 100-fold reduction in viral titers, whereas, PD4 and RW3 peptide treatments resulted in 10-30-fold reduction. The EC(50) values of PD3, PD4 and RW3 were found to be 40 mu g/ml, 50 mu g/ml and 6.5 mu M, respectively. In VV-spiked plasma samples, the virucidal activity of PD3, PD4 and RW3 was close to 100% (90-100-fold reduction). Overall, the present study constitutes a new proof-of-concept in developing peptide therapeutics for vaccinia virus infections in biothreat scenarios and as in vitro viral reduction agents. Published by Elsevier B.V. C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mohan, KVK (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX The authors wish to acknowledge Dr. Bernard Moss, NIH, Bethesda, for providing the WR virus strain. SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra-agency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. Review of the manuscript by Drs. Tahir Malik and Zhiping Ye, CBER is gratefully acknowledged. NR 35 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUN PY 2010 VL 86 IS 3 BP 306 EP 311 DI 10.1016/j.antiviral.2010.03.012 PG 6 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 604VL UT WOS:000278306500010 PM 20347875 ER PT J AU Blake, PW Bradford, PT Devesa, SS Toro, JR AF Blake, Patrick W. Bradford, Porcia T. Devesa, Susan S. Toro, Jorge R. TI Cutaneous Appendageal Carcinoma Incidence and Survival Patterns in the United States A Population-Based Study SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 10th International Congress of Dermatology CY MAY 20-24, 2009 CL Prague, CZECH REPUBLIC SP Washington DC Dermatol Soc ID OF-THE-LITERATURE; MICROCYSTIC ADNEXAL CARCINOMA; ADENOID CYSTIC CARCINOMA; MUIR-TORRE-SYNDROME; SEBACEOUS CARCINOMA; APOCRINE CARCINOMA; RISK; SKIN; ADENOCARCINOMA; CANCER AB Objective: To examine incidence patterns of patients diagnosed as having cutaneous appendageal carcinoma (CAC). Design: Population-based study using the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute data from 1978 through 2005. Participants: A total of 1801 subjects from SEER 16 registries (2001-2005) for incidence analyses, 2228 from SEER 9 registries (1987-2005) for trend analysis, and 1984 subjects (1992-2004) for survival analysis. Main Outcome Measure: Incidence rates (IRs) per 1 million person-years according to anatomic site, race, sex, age, and histologic type. Results: Cutaneous appendageal carcinomas are uncommon (age-adjusted ER, 5.1 per 1 million person-years), with the IR among men statistically significantly higher than women (6.3 vs 4.2, respectively; male to female IR ratio 1.51; P<.001). Hispanic whites (IR, 3.7), blacks (IR, 3.5), and Asian/Pacific Islanders (IR, 2.5) all had significantly lower IRs than non-Hispanic whites (IR, 5.7) (P<.001). Apocrine-eccrine carcinoma overall was the most common category (IR, 2.6), and the IR was highest among non-Hispanic white (IR, 2.8) compared with other ethnic/racial groups (P<.001). Cutaneous appendageal carcinomas IRs rose 100-fold with age, from 0.37 among those aged 20 to 29 years to 37.3 among those 80 years or older. From 1978-1982 to 2002-2005, the CAC IRs increased 150%, from 2.0 to 5.0; the apocrine-eccrine carcinoma and the sebaceous carcinoma IRs rose 170%, from 1.0 to 2.7, and 21.7%, from 0.6 to 1.9, respectively. Five-year relative survival rates overall were 99% for localized and 43% for distant disease. Conclusions: Cutaneous appendageal carcinomas are rare tumors with IRs that vary by sex and racial/ethnic group. Cutaneous appendageal carcinoma IRs are increasing in the United States, especially for sebaceous carcinoma, perhaps related to improved recognition and classification, but factors such as UV exposure and immunosuppression may also play a role. C1 [Toro, Jorge R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Blake, Patrick W.] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. [Toro, Jorge R.] Dept Vet Affairs Med Ctr, Washington, DC USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,,Execut Plaza S,Room 7012, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov FU Howard Hughes Medical Institute; Intramural NIH HHS NR 40 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUN PY 2010 VL 146 IS 6 BP 625 EP 632 PG 8 WC Dermatology SC Dermatology GA 611ZM UT WOS:000278864200006 PM 20566926 ER PT J AU Seidman, LJ Giuliano, AJ Meyer, EC Addington, J Cadenhead, KS Cannon, TD McGlashan, TH Perkins, DO Tsuang, MT Walker, EF Woods, SW Bearden, CE Christensen, BK Hawkins, K Heaton, R Keefe, RSE Heinssen, R Cornblatt, BA AF Seidman, Larry J. Giuliano, Anthony J. Meyer, Eric C. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Bearden, Carrie E. Christensen, Bruce K. Hawkins, Keith Heaton, Robert Keefe, Richard S. E. Heinssen, Robert Cornblatt, Barbara A. CA N Amer Prodrome Longitudinal Study TI Neuropsychology of the Prodrome to Psychosis in the NAPLS Consortium Relationship to Family History and Conversion to Psychosis SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ULTRA-HIGH-RISK; CLINICAL HIGH-RISK; NEUROCOGNITIVE DEFICITS; WORKING-MEMORY; 1ST EPISODE; 1ST-DEGREE RELATIVES; PREDICTIVE-VALIDITY; INTERRATER RELIABILITY; SCHIZOPHRENIA-PATIENTS; COGNITIVE PERFORMANCE AB Context: Early detection and prospective evaluation of clinical high-risk (CHR) individuals who may develop schizophrenia or other psychotic disorders is critical for predicting psychosis onset and for testing preventive interventions. Objectives: To elucidate the neuropsychology of the CHR syndrome, to determine the association of neuropsychological function with conversion to psychosis and family history of psychosis, and to examine whether baseline neuropsychological functioning predicts subsequent psychosis. Design: Longitudinal study with 2 1/2 years of follow-up. Setting: Eight centers participating in the North American Prodrome Longitudinal Study. Participants: Three hundred four prospectively identified CHR individuals meeting Structured Interview for Prodromal Syndromes criteria, 52 non-CHR persons with a family history of psychosis in first- or second-degree relatives (family high-risk group), and 193 normal controls with neither a family history of psychosis nor a CHR syndrome, all of whom underwent baseline neuropsychological evaluations. Main Outcome Measures: A neurocognitive composite score, 8 individual neuropsychological measures, an IQ estimate, and high-risk status. Results: Global ("composite") neuropsychological functioning was comparably impaired in the CHR and family high-risk groups compared with controls, but profiles differed significantly between groups. Neuropsychological functioning in the CHR group was significantly lower in persons who progressed to psychosis than in those who did not and was worst in the subgroup with a family history of psychosis. Tests of processing speed and verbal learning and memory were most sensitive in discriminating CHR individuals from controls, although reductions were less severe than in established schizophrenia. Neuropsychological functioning did not contribute uniquely to the prediction of psychosis beyond clinical criteria, but worse verbal memory predicted more rapid conversion. Conclusions: These findings document that CHR individuals have significant neuropsychological difficulties, particularly those who later develop psychosis. This dysfunction is generally of moderate severity but less than in first-episode schizophrenia, suggesting that further decline may occur after baseline CHR assessment. C1 [Seidman, Larry J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Massachusetts Mental Hlth Ctr,Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meyer, Eric C.] Texas A&M Hlth Sci Ctr, Coll Med, Dept Psychiat & Behav Sci, Waco, TX USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.; Heaton, Robert] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cannon, Tyrone D.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.; Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [McGlashan, Thomas H.; Woods, Scott W.; Hawkins, Keith] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Christensen, Bruce K.] McMaster Univ, Dept Psychiat & Behav Neurosci, Hamilton, ON, Canada. [Keefe, Richard S. E.] Duke Univ, Dept Psychiat & Behav Sci & Psychol, Chapel Hill, NC USA. [Heinssen, Robert] NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. RP Seidman, LJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Publ Psychiat Div, Massachusetts Mental Hlth Ctr,Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA. EM lseidman@bidmc.harvard.edu FU National Institute of Mental Health [R18 MH 43518, U01 MH081928, P50 M11080272]; [U01 MH066134]; [RO1 MH60720]; [K24 MH76191]; [R01 MH65079]; [K05MH01654]; [U01 MH066069]; [P50 MH064065]; [RO1MH062066]; [5 U01 MH081988]; [U01 MH74356]; [U01 MH082022]; [R41 MH083436]; [RO1 MH061523] FX This study was supported by the National Institute of Mental Health (grants R18 MH 43518, U01 MH081928, and P50 M11080272 to Dr Seidman; grant U01 MH066134 to Dr Addington; grants RO1 MH60720 and K24 MH76191 to Dr Cadenhead; grant R01 MH65079 to Dr Cannon; grant K05MH01654 to Dr McGlashan; grants U01 MH066069 and P50 MH064065 to Dr Perkins; grant R18 MH 43518 to Dr Tsuang; grants RO1MH062066 and 5 U01 MH081988 to Dr Walker; grants U01 MH74356, U01 MH082022, and R41 MH083436 to Dr Woods; and grant RO1 MH061523 to Dr Cornblatt). NR 88 TC 195 Z9 202 U1 7 U2 27 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2010 VL 67 IS 6 BP 578 EP 588 PG 11 WC Psychiatry SC Psychiatry GA 605CD UT WOS:000278324000006 PM 20530007 ER PT J AU Good, WV Hardy, RJ Dobson, V Palmer, EA Phelps, DL Tung, B Redford, M AF Good, William V. Hardy, Robert J. Dobson, Velma Palmer, Earl A. Phelps, Dale L. Tung, Betty Redford, Maryann TI Final Visual Acuity Results in the Early Treatment for Retinopathy of Prematurity Study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID THRESHOLD RETINOPATHY; MULTICENTER TRIAL; CRYOTHERAPY; CHILDREN; OUTCOMES AB Objective: To compare visual acuity at 6 years of age in eyes that received early treatment for high-risk pre-threshold retinopathy of prematurity (ROP) with conventionally managed eyes. Methods: Infants with symmetrical, high-risk prethreshold ROP (n= 317) had one eye randomized to earlier treatment at high-risk prethreshold disease and the other eye managed conventionally, treated if ROP progressed to threshold severity. For asymmetric cases (n= 84), the high-risk prethreshold eye was randomized to either early treatment or conventional management. The main outcome measure was ETDRS visual acuity measured at 6 years of age by masked testers. Retinal structure was assessed as a secondary outcome. Results: Analysis of all subjects with high-risk prethreshold ROP showed no statistically significant benefit for early treatment (24.6% vs 29.0% unfavorable outcome; P=.15). Analysis of 6-year visual acuity results according to the Type 1 and 2 clinical algorithm showed a benefit for Type 1 eyes (25.1% vs 32.8%; P=.02) treated early but not Type 2 eyes (23.6% vs 19.4%; P=.37). Early-treated eyes showed a significantly better structural outcome compared with conventionally managed eyes (8.9% vs 15.2% unfavorable outcome; P<.001), with no greater risk of ocular complications. Conclusions: Early treatment for Type 1 high-risk prethreshold eyes improved visual acuity outcomes at 6 years of age. Early treatment for Type 2 high-risk prethreshold eyes did not. Application to Clinical Practice: Type 1 eyes, not Type 2 eyes, should be treated early. These results are particularly important considering that 52% of Type 2 high-risk prethreshold eyes underwent regression of ROP without requiring treatment. C1 [Good, William V.] San Francisco Ctr, San Francisco, CA USA. [Good, William V.] Univ Calif San Francisco, San Francisco Med Ctr, Childrens Hosp Oakland, Calif Pacific Med Ctr, San Francisco, CA USA. [Redford, Maryann] NEI, Bethesda, MD 20892 USA. [Good, William V.] Smith Kettlewell Eye Res Inst, San Francisco, CA 94115 USA. [Hardy, Robert J.; Tung, Betty] Univ Texas Hlth Sci Ctr, Coordinating Ctr Clin Trials, Sch Publ Hlth, Houston, TX USA. [Dobson, Velma] Univ Arizona, Coll Med, Tucson, AZ USA. [Phelps, Dale L.] Univ Rochester, Med Ctr, Crouse Irving Mem Hosp, Rochester, NY 14627 USA. RP Good, WV (reprint author), Smith Kettlewell Eye Res Inst, 2318 Fillmore St, San Francisco, CA 94115 USA. EM good@ski.org FU National Institutes of Health [5U10 EY12471, 5U10 EY12472]; US Department of Health and Human Services, Bethesda, Maryland FX This work was supported by cooperative agreements 5U10 EY12471 and 5U10 EY12472 with the National Eye Institute of the National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland. NR 20 TC 60 Z9 64 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2010 VL 128 IS 6 BP 663 EP 671 PG 9 WC Ophthalmology SC Ophthalmology GA 610QA UT WOS:000278747900001 ER PT J AU Hugosson, T Friedman, JS Ponjavic, V Abrahamson, M Swaroop, A Andreasson, S AF Hugosson, Therese Friedman, James S. Ponjavic, Vesna Abrahamson, Magnus Swaroop, Anand Andreasson, Sten TI Phenotype Associated With Mutation in the Recently Identified Autosomal Dominant Retinitis Pigmentosa KLHL7 Gene SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LIGHT AB Objective: To characterize the clinical phenotype, with an emphasis on electrophysiologic findings, in a family with autosomal dominant retinitis pigmentosa caused by mutation in the recently identified KLHL7 gene. Methods: Eleven patients from a single family were selected from the Swedish retinitis pigmentosa register. Four patients had been examined 13 to 17 years earlier and underwent further ophthalmologic examination, including visual acuity, fundus inspection, Goldmann perimetry, full-field electroretinography (ERG), multifocal ERG, and optical coherence tomography. KLHL7 mutation was identified by sequence analysis. Results: In most examined family members, the fundus showed minor abnormalities. Full-field ERG demonstrated reduced cone and rod function, but rod responses were preserved in some patients late in life. Follow-up (<= 17 years) demonstrated slowly progressive retinal degeneration. In an adolescent family member, cone and rod function was initially normal, but retinitis pigmentosa was confirmed by electrophysiology 17 years later. Optical coherence tomography and multifocal ERG demonstrated macular abnormalities of varying degree among family members. Genetic analysis revealed a heterozygous exon 6 change (c.458C>T) in 7 family members. Conclusions: Observed in 2 Scandinavian families to date, KLHL7 mutation has recently been associated with autosomal dominant retinitis pigmentosa. Clinical examination with long-term follow-up verified a phenotype with a varying degree of retinal photoreceptor dysfunction and, in some family members, with late onset and preserved rod function until late in life. Clinical Relevance: Patients with minor retinal abnormalities and normal ERG findings early in life can harbor an autosomal dominant form of retinitis pigmentosa with a varying degree of visual impediment. Some patients with late onset may retain night vision for many years. C1 [Hugosson, Therese; Ponjavic, Vesna; Andreasson, Sten] Lund Univ, Dept Clin Sci, S-22185 Lund, Sweden. [Abrahamson, Magnus] Univ Lund Hosp, Dept Clin Chem, S-22185 Lund, Sweden. [Hugosson, Therese] Cent Hosp Kristianstad, Dept Ophthalmol, Kristianstad, Sweden. [Friedman, James S.; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Hugosson, T (reprint author), Lund Univ, Dept Clin Sci, S-22185 Lund, Sweden. EM Therese.Hugosson@med.lu.se OI Swaroop, Anand/0000-0002-1975-1141 FU Faculty of Medicine, Lund University; Swedish Medical Research Council; Foundation Fighting Blindness; Swedish Association of the Visually Impaired; National Eye Institute, National Institutes of Health FX This study was supported by the Faculty of Medicine, Lund University; by grants from the Swedish Medical Research Council, Foundation Fighting Blindness, and Swedish Association of the Visually Impaired; and by intramural support from the National Eye Institute, National Institutes of Health. NR 14 TC 7 Z9 8 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUN PY 2010 VL 128 IS 6 BP 772 EP 778 PG 7 WC Ophthalmology SC Ophthalmology GA 610QA UT WOS:000278747900017 PM 20547956 ER PT J AU Hammond, MEH Hayes, DF Dowsett, M Allred, DC Hagerty, KL Badve, S Fitzgibbons, PL Francis, G Goldstein, NS Hayes, M Hicks, DG Lester, S Love, R Mangu, PB McShane, L Miller, K Osborne, CK Paik, S Perlmutter, J Rhodes, A Sasano, H Schwartz, JN Sweep, FCG Taube, S Torlakovic, EE Valenstein, P Viale, G Visscher, D Wheeler, T Williams, RB Wittliff, JL Wolff, AC AF Hammond, M. Elizabeth H. Hayes, Daniel F. Dowsett, Mitch Allred, D. Craig Hagerty, Karen L. Badve, Sunil Fitzgibbons, Patrick L. Francis, Glenn Goldstein, Neil S. Hayes, Malcolm Hicks, David G. Lester, Susan Love, Richard Mangu, Pamela B. McShane, Lisa Miller, Keith Osborne, C. Kent Paik, Soonmyung Perlmutter, Jane Rhodes, Anthony Sasano, Hironobu Schwartz, Jared N. Sweep, Fred C. G. Taube, Sheila Torlakovic, Emina Emilia Valenstein, Paul Viale, Giuseppe Visscher, Daniel Wheeler, Thomas Williams, R. Bruce Wittliff, James L. Wolff, Antonio C. TI American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CENTRALLY REVIEWED EXPRESSION; LIGAND-BINDING ASSAY; PREDICTING RESPONSE; FORMALIN FIXATION; TAMOXIFEN; THERAPY; ISSUES; TRIAL; RECURRENCE; SUPERIOR AB Purpose.-To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers. Methods.-The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance. Results.-Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in preanalytic variables, thresholds for positivity, and interpretation criteria. Recommendations.-The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials. (Arch Pathol Lab Med. 2010;134:907-922) C1 Univ Utah, Sch Med, Intermt Healthcare, Salt Lake City, UT USA. Washington Univ, Sch Med, St Louis, MO USA. ASCO, Alexandria, VA 22314 USA. Univ Michigan Hlth Syst, Univ Michigan Comprehens Canc Ctr, Ann Arbor, MI USA. St Joseph Mercy Hosp, Ann Arbor, MI 48104 USA. Gemini Grp, Ann Arbor, MI USA. Adv Diagnost Lab, Redford, MI USA. Presbyterian Hosp, Charlotte, NC USA. Indiana Univ, Bloomington, IN USA. St Jude Med Ctr, Fullerton, CA USA. Univ Rochester, Rochester, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Baylor Coll Med, Houston, TX 77030 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Delta Pathol Grp, Shreveport, LA USA. Univ Louisville, Louisville, KY 40292 USA. Royal Marsden Hosp, London SW3 6JJ, England. Natl External Qual Assessment Serv, Sheffield, S Yorkshire, England. Univ W England, Bristol BS16 1QY, Avon, England. Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Royal Univ Hosp, Saskatoon, SK S7N 0W8, Canada. Tohoku Univ, Sch Med, Sendai, Miyagi 980, Japan. Radboud Univ Nijmegen, NL-6525 ED Nijmegen, Netherlands. European Inst Oncol, Milan, Italy. Univ Milan, Milan, Italy. RP Hammond, MEH (reprint author), ASCO, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org OI Fitzgibbons, Patrick/0000-0002-2998-6913; Wolff, Antonio/0000-0003-3734-1063 FU NCI NIH HHS [R01 CA097375, R01 CA097375-08] NR 34 TC 167 Z9 189 U1 1 U2 5 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 JUN PY 2010 VL 134 IS 6 BP 907 EP 922 PG 16 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 609FT UT WOS:000278642000014 PM 20524868 ER PT J AU Hussong, JW Arber, DA Bradley, KT Brown, MS Chang, CC de Baca, ME Ellis, DW Foucar, K Hsi, ED Jaffe, ES Lill, M McClure, SP Medeiros, LJ Perkins, SL AF Hussong, Jerry W. Arber, Daniel A. Bradley, Kyle T. Brown, Michael S. Chang, Chung-Che (Jeff) de Baca, Monica E. Ellis, David W. Foucar, Kathryn Hsi, Eric D. Jaffe, Elaine S. Lill, Michael McClure, Stephen P. Medeiros, L. Jeffrey Perkins, Sherrie L. TI Protocol for the Examination of Specimens From Patients With Non-Hodgkin Lymphoma/Lymphoid Neoplasms SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID EUROPEAN-AMERICAN CLASSIFICATION; INTERNATIONAL PROGNOSTIC INDEX; LYMPHOMA STUDY-GROUP; HEMATOLOGIC NEOPLASMS; DISEASE; DIAGNOSIS; COMMITTEE; SURVIVAL C1 [Hussong, Jerry W.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Lill, Michael] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. [Arber, Daniel A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Bradley, Kyle T.] Emory Univ Hosp, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Brown, Michael S.] Yellowstone Pathol Inst Inc, Dept Pathol, Billings, MT USA. [Chang, Chung-Che (Jeff)] Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. [de Baca, Monica E.] Phys Lab Ltd, Dept Pathol & Lab Med, Sioux Falls, SD USA. [Ellis, David W.] Flinders Med Ctr, Dept Anat Pathol, Bedford Pk, SA, Australia. [Foucar, Kathryn] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Hsi, Eric D.] Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [McClure, Stephen P.] Presbyterian Pathol Grp, Dept Pathol & Lab Med, Charlotte, NC USA. [Medeiros, L. Jeffrey] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Perkins, Sherrie L.] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. RP Hussong, JW (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, 8700 Beverly Blvd,Room 4708, Los Angeles, CA 90048 USA. EM hussongj@cshs.org NR 36 TC 3 Z9 3 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 JUN PY 2010 VL 134 IS 6 BP E40 EP E47 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 609FT UT WOS:000278642000001 PM 20524855 ER PT J AU Kiringoda, R Thurm, AE Hirschtritt, ME Koziol, D Wesley, R Swedo, SE O'Grady, NP Quezado, ZMN AF Kiringoda, Ruwan Thurm, Audrey E. Hirschtritt, Matthew E. Koziol, Debris Wesley, Robert Swedo, Susan E. O'Grady, Naomi P. Quezado, Zenaide M. N. TI Risks of Propofol Sedation/Anesthesia for Imaging Studies in Pediatric Research Eight Years of Experience in a Clinical Research Center SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID SEDATION RESEARCH CONSORTIUM; PERIOPERATIVE CARDIAC-ARREST; ADVERSE EVENTS; OPERATING-ROOM; CHILDREN; ANESTHESIA; MANAGEMENT; BENEFIT; SAFETY; UPDATE AB Objectives: To quantify the incidence of adverse events associated with anesthesia given for research-driven imaging studies and to identify risk factors for those events in pediatric research subjects. Design: Retrospective cohort study. Setting: National Institutes of Health Clinical Center. Participants: Children and adolescents enrolled in clinical research protocols who required anesthesia for research-related imaging studies from January 2000 to September 2008. Intervention: Propofol sedation/anesthesia. Main Outcome Measure: The occurrence of respiratory, cardiovascular, and all anesthesia-related adverse events that required intervention while receiving anesthetics for research-driven imaging studies and other noninvasive procedures. Results: We identified 607 children who received 1480 propofol anesthetic procedures for imaging studies. Seventy percent of anesthetics were given to subjects with severe diseases and significant disabilities (American Society of Anesthesiologists Physical Status [ASA] III). Anesthesia had a mean (SD) duration of 115 (55) minutes, and in 12.5% of procedures, an airway device was necessary. There were 98 notable respiratory, cardiovascular, and other events in 79 anesthetic procedures, a rate of 534 per 10 000 anesthetic procedures with 1 or more adverse events. There was no long-lasting morbidity or mortality. The ASA classification (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.24-6.88), anesthetic effect duration (OR, 1.46;.95% CI, 1.25-1.70), and presence of airway abnormalities (OR, 4.41; 95% CI, 1.60-12.12) were independently associated with adverse events during anesthetic use. Conclusion: In our clinical research sample of high-risk children who received sedation/anesthesia by an anesthesiologist, we observed a low incidence of adverse events and no long-term complications. Risk factors for adverse events included higher ASA classification, increasing anesthetic duration, and presence of airway abnormalities. C1 [Kiringoda, Ruwan; Thurm, Audrey E.; Hirschtritt, Matthew E.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. [Koziol, Debris; Wesley, Robert] NIH, Biostat & Clin Epidemiol Serv, Off Director, Ctr Clin, Bethesda, MD 20892 USA. [O'Grady, Naomi P.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Quezado, Zenaide M. N.] NIH, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA. EM zquezado@cnmc.org RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU National Institutes of Mental Health; National Institutes of Health Clinical Center FX This study was supported by the Intramural Research Program of the National Institutes of Mental Health and the National Institutes of Health Clinical Center. NR 28 TC 18 Z9 19 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2010 VL 164 IS 6 BP 554 EP 560 PG 7 WC Pediatrics SC Pediatrics GA 605CG UT WOS:000278324300009 PM 20530306 ER PT J AU Lopez, CA Vazquez, M Hill, MD Colon, MD Porrata-Doria, T Johnston, ICD Lorenzo, E AF Lopez, Carlos A. Vazquez, Manuel Hill, Martin D. Colon, Maria Del C. Porrata-Doria, Tirtsa Johnston, Ian C. D. Lorenzo, Eric TI Characterization of HIV-1 RNA forms in the plasma of patients undergoing successful HAART SO ARCHIVES OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; REPLICATION IN-VIVO; CD4(+) T-CELLS; DRUG-RESISTANCE; OPPORTUNISTIC INFECTION; HIV-1-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; LATENT RESERVOIR AB An assay to characterize plasma human immunodeficiency virus 1 (HIV-1) sequences for patients with low viral loads was developed by combining the selective binding of anti-CD44 MicroBeads with a nested RT-PCR targeting the env C2V4 region. Sequences were obtained from 10 of 20 HIV+ patients who had viral loads below 48 copies/ml. Sequences derived from plasma were compared to those from CD14+ CD16 +monocytes and CD4+ T cells. The plasma sequences were most closely related to those amplified from monocytes, suggesting that during successful antiretroviral therapy, the predominant plasma virus originates from myeloid cells. By characterizing HIV-1 RNA sequences from 8 ml of plasma while avoiding multiple steps, which can lead to contamination and deterioration, this method can help elucidate the viral forms in patients with therapeutically suppressed HIV-1. Understanding the source of residual viremia is crucial in developing approaches for viral eradication. C1 [Lopez, Carlos A.; Vazquez, Manuel; Hill, Martin D.; Colon, Maria Del C.; Porrata-Doria, Tirtsa; Lorenzo, Eric] Ponce Sch Med, Dept Physiol & Pharmacol, Mol Virol Lab, Ponce, PR 00732 USA. [Johnston, Ian C. D.] Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany. RP Lorenzo, E (reprint author), NIAID, Sci Review Program, AIDS Res Review Branch, DEA, 6700B Rockledge Dr,Room 3134, Bethesda, MD 20892 USA. EM mhill@psm.edu; lorenzoe@niaid.nih.gov FU National Institutes of Health, National Institute of General Medical Sciences-Minority Biomedical Research Support (NIGMS-MBRS) [S06-GM008239]; Research Centers in Minority Institutions (RCMI) [2G12RR003050-20] FX This work would not have been possible without the HIV+ individuals who voluntarily and kindly donated their time and samples for the benefit of society in general. Thanks to Dr. Grisell Tirado for contributions in the discussion of the study. Also, thanks to Mr. Pablo Lopez and the AIDS Research Program at Ponce School of Medicine (PSM) for flow cytometry cell sorting and determination of the plasma viral loads. The work was financially supported by the National Institutes of Health grants National Institute of General Medical Sciences-Minority Biomedical Research Support (NIGMS-MBRS) (S06-GM008239) (to E. Lorenzo) and Research Centers in Minority Institutions (RCMI) (2G12RR003050-20) (PSM Molecular Biology Core). NR 58 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD JUN PY 2010 VL 155 IS 6 BP 895 EP 903 DI 10.1007/s00705-010-0659-3 PG 9 WC Virology SC Virology GA 605KV UT WOS:000278347400010 PM 20414690 ER PT J AU Suyarnsestakorn, C Thanasupawat, T Leelahavanichkul, K Gutkind, JS Mutirangura, A AF Suyarnsestakorn, Chotika Thanasupawat, Thatchawan Leelahavanichkul, Kantima Gutkind, J. Silvio Mutirangura, Apiwat TI Ataxia telangiectasia mutated nuclear localization in head and neck cancer cells is PPP2R2B-dependent SO ASIAN BIOMEDICINE LA English DT Article DE ATM; head; neck; nuclear localization; PPP2R2B; PP2A; SCA12; squamous cell carcinoma ID PROTEIN PHOSPHATASE 2A; DOUBLE-STRAND BREAKS; DNA-DAMAGE; IONIZING-RADIATION; ATM GENE; REGULATORY SUBUNIT; HISTONE H2AX; CARCINOMA; PROMOTER; AUTOPHOSPHORYLATION AB Background: Protein phosphatase 2A (PP2A) has been implicated in radiation-induced activation of cellular responses, likely by its ability to regulate the autophosphorylation of the ataxia telangiectasia mutated (ATM) protein, a key molecule involved in the DNA damage response initiated by double-stranded DNA breaks. Interestingly, a hereditary defect in the PPP2R2B gene, which encodes the beta isoform of PP2A regulatory subunit B, causes autosomal dominant spinocerebellar ataxia 12, a clinical condition resembling that of ataxia telangiectasia patients. Moreover, PPP2R2B is significantly downregulated in many human cancers, including head and neck squamous cell carcinomas (HNSCCs). Objective: Examine whether PPP2R2B regulates ATM function, thereby contributing to tumor progression due to the resulting defective DNA repair. Methods: The roles of PPP2R2B were evaluated in irradiated HNSCC cell lines, siRNA(ppp2R2B) cells and okadaic acid treated cells. Expression of PPP2R2B was measured by microarray, Western blot analysis and real time quantitative rtPCR. ATM quantity and localization, ATM phosphorylation and gamma-H2AX were determined by Western blot analysis and/or immunofluorescence assay. Clonogenic cell survival assay was performed to determine ionizing radiation sensitivity. Results: PPP2R2B expression is reduced in multiple tumor types, including HNSCCs. Indeed, HNSCC cell lines that have lower PPP2R2B mRNA expression and siRNA(PPP2R2B) cells lower basal and radiation-induced levels of phosphorylated ATM and the consequent reduction in the levels of phosphorylation of the downstream ATM target, gamma-H2AX. Depletion of PPP2R2B and inhibition of PP2A with okadaic acid resulted in limited ATM nuclear localization. Finally, siRNA(PPP2R2B) cells displayed enhanced sensitivity to death after radiation. Conclusion: In HNSCCs, ATM nuclear localization is PPP2R2B dependent, and decreased PPP2R2B expression may result in limited ATM activation by preventing its nuclear accumulation and ATM-chromatin interaction. Therefore, decreased PPP2R2B expression in HNSCCs may contribute to genomic instability, cancer development and radiation sensitivity by limiting ATM functions. C1 [Thanasupawat, Thatchawan; Mutirangura, Apiwat] Chulalongkorn Univ, Dept Anat, Ctr Excellence Mol Genet Canc & Human Dis, Fac Med, Bangkok 10330, Thailand. [Leelahavanichkul, Kantima; Gutkind, J. Silvio] NIDCR, NIH, Bethesda, MD 20892 USA. [Suyarnsestakorn, Chotika] Chulalongkorn Univ, Fac Grad Sch, Inter Dept Program BioMed Sci, Bangkok 10330, Thailand. [Suyarnsestakorn, Chotika] Natl Sci & Technol Dev Agcy, Natl Ctr Genet Engn & Biotechnol, Pathum Thani 12120, Thailand. RP Mutirangura, A (reprint author), Chulalongkorn Univ, Dept Anat, Ctr Excellence Mol Genet Canc & Human Dis, Fac Med, Bangkok 10330, Thailand. EM mapiwat@chula.ac.th RI Mutirangura, Apiwat /C-8197-2009; Gutkind, J. Silvio/A-1053-2009 FU Thailand Research Funds; 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund); Royal Golden Jubilee; National Institute of Dental and Craniofacial Research, National Institutes of Health FX This study was supported by the Thailand Research Funds and the 90th Anniversary of Chulalongkorn University Fund (Ratchadaphiseksomphot Endowment Fund). C Suyarnsestakorn was supported by the Royal Golden Jubilee Ph.D. grant. KL and JSG were supported by the Intramural Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. NR 41 TC 1 Z9 1 U1 0 U2 1 PU CHULALONGKORN UNIV, FAC MED PI BANGKOK PA CHULALONGKORN UNIV, FAC MED, 1873, RAMA 4, BANGKOK, 10330, THAILAND SN 1905-7415 J9 ASIAN BIOMED JI Asian Biomed. PD JUN PY 2010 VL 4 IS 3 BP 373 EP 383 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 625QH UT WOS:000279909600002 ER PT J AU Glaser, V Ferrer, M AF Glaser, Vicki Ferrer, Marc TI Interview with Marc Ferrer, Ph.D. SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Editorial Material RP Ferrer, M (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,Bidg B, Rockville, MD 20850 USA. EM marc.ferrer@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD JUN PY 2010 VL 8 IS 3 BP 263 EP 267 DI 10.1089/adt.2010.0803.pr PG 5 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 615VD UT WOS:000279165100001 ER PT J AU Liu, K Southall, N Titus, SA Inglese, J Eskay, RL Shinn, P Austin, CP Heilig, MA Zheng, W AF Liu, Ke Southall, Noel Titus, Steve A. Inglese, James Eskay, Robert L. Shinn, Paul Austin, Christopher P. Heilig, Markus A. Zheng, Wei TI A Multiplex Calcium Assay for Identification of GPCR Agonists and Antagonists SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID IMAGING PLATE READER; NEUROPEPTIDE-S; INDICATORS; RECEPTORS; DISCOVERY; AROUSAL; TOOLS; CA-2 AB Activation of G(q) protein-coupled receptors can be monitored by measuring the increase in intracellular calcium with fluorescent dyes. Recent advances in fluorescent kinetic plate readers and liquid-handling technology have made it possible to follow these transient changes in intracellular calcium in a 1,536-well plate format for high-throughput screening (HTS). Here, we have applied the latest generation of fluorescence kinetic plate readers to multiplex the agonist and antagonist screens of a G protein-coupled receptor (GPCR). This multiplexed assay format provides an efficient and cost-effective method for HTS of G(q)-coupled GPCR targets. C1 [Liu, Ke; Southall, Noel; Titus, Steve A.; Inglese, James; Shinn, Paul; Austin, Christopher P.; Zheng, Wei] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Eskay, Robert L.; Heilig, Markus A.] NIAAA, NIH, Bethesda, MD USA. RP Zheng, W (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov RI Southall, Noel/H-8991-2012; OI Southall, Noel/0000-0003-4500-880X; Heilig, Markus/0000-0003-2706-2482; Zheng, Wei/0000-0003-1034-0757 FU Molecular Libraries Initiative, NIH; National Human Genome Research Institute; National Institute on Alcohol Abuse and Alcoholism (NIAAA) FX This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Programs of the National Human Genome Research Institute. This work was also supported by the intramural research programs of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The authors thank Hui Sun and Anton Terasmaa for their technical assistance on the NPS cell line. NR 24 TC 13 Z9 14 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD JUN PY 2010 VL 8 IS 3 BP 367 EP 379 DI 10.1089/adt.2009.0245 PG 13 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 615VD UT WOS:000279165100007 PM 20230302 ER PT J AU Lehman, SJ Massaro, JM Schlett, CL O'Donnell, CJ Hoffmann, U Fox, CS AF Lehman, Sam J. Massaro, Joseph M. Schlett, Christopher L. O'Donnell, Christopher J. Hoffmann, Udo Fox, Caroline S. TI Peri-aortic fat, cardiovascular disease risk factors, and aortic calcification: The Framingham Heart Study SO ATHEROSCLEROSIS LA English DT Article DE Obesity; Atherosclerosis; Calcium; Risk factors ID VISCERAL ADIPOSE-TISSUE; COMPUTED-TOMOGRAPHY; VASCULAR-DISEASE; PERICARDIAL FAT; ASSOCIATION; MEN; ATHEROSCLEROSIS; ADIPOCYTES; COMMUNITY; OBESITY AB Objective: Perivascular fat through the secretion of paracrine and pro-inflammatory mediators may play a role in obesity-mediated vascular disease. We sought to examine associations between adipose tissue depots immediately surrounding the thoracic aorta, metabolic risk factors, and vascular calcification. Methods: In participants free of cardiovascular disease (CVD) from the Framingham Heart Study Offspring cohort who underwent computed tomography (n = 1067, mean age 59 years, 56.1% women), thoracic periaortic fat depots were quantified. Visceral abdominal tissue (VAT) and calcification of the thoracic and abdominal aorta were also measured. Results: Peri-aortic fat depots were correlated with body mass index, waist circumference (WC), VAT (all p < 0.0001), hypertension (p = 0.007), low HDL (p < 0.0001), serum triglycerides (p < 0.0001), impaired fasting glucose (p = 0.005), and diabetes (p = 0.02). These associations generally remained significant after adjustment for BMI and WC (all p-values < 0.05), but not after VAT adjustment. Thoracic aortic fat was associated with thoracic calcification in models containing VAT (OR 1.31, 95% CI 1.01-1.71, p = 0.04), but was not significant after adjustment for CVD risk factors (OR 1.16, 95% CI 0.88-1.51, p = 0.30). Thoracic aortic fat, however, was associated with abdominal aortic calcification (OR 1.48, 95% CI 1.11-1.98, p = 0.008) and coronary artery calcification (OR 1.47, 95% CI 1.09-1.98, p = 0.001) even in models including CVD risk factors and VAT. Conclusions: Thoracic peri-aortic fat is associated with measures of adiposity, metabolic risk factors, and coronary and abdominal aortic calcification. Published by Elsevier Ireland Ltd. C1 [Lehman, Sam J.; Schlett, Christopher L.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA. [Lehman, Sam J.] Flinders Univ S Australia, Dept Cardiol, Adelaide, SA 5001, Australia. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Bloods Framingham Heart Study, Bethesda, MD USA. [O'Donnell, Christopher J.; Fox, Caroline S.] Natl Heart Lung & Bloods Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Heart Foundation of Australia; Royal Australian College of Physicians Research and Education Committee FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195). Dr. Lehman is supported by grants from the National Heart Foundation of Australia and Royal Australian College of Physicians Research and Education Committee. NR 26 TC 75 Z9 79 U1 0 U2 1 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 JUN PY 2010 VL 210 IS 2 BP 656 EP 661 DI 10.1016/j.atherosclerosis.2010.01.007 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 601CY UT WOS:000278036800056 PM 20152980 ER PT J AU Burstein, M Ginsburg, GS AF Burstein, Marcy Ginsburg, Golda S. TI The effect of parental modeling of anxious behaviors and cognitions in school-aged children: An experimental pilot study SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Parental modeling of anxiety; Child anxiety; Parent gender; Etiology ID ANXIETY DISORDERS; CHILDHOOD ANXIETY; HIGH-RISK; FAMILY; MOTHERS; PSYCHOPATHOLOGY; METAANALYSIS; THREAT; EXPECTATIONS; PERFORMANCE AB The current study tested: (1) the impact of parental modeling of anxious behaviors and cognitions on child anxiety level, anxious cognitions, desired avoidance, and objective performance using an experimental paradigm; and (2) whether the impact of parental modeling of anxious behaviors and cognitions differed by parent gender. Twenty-five parents (a random selection of 12 male and 13 female parents) participated with one of their children (ages 8-12 years: 56.0% male; 76.0% Caucasian). All children experienced two test conditions: an anxious condition in which their parent was trained to act anxiously before a planned spelling test and a non-anxious condition in which their parent was trained to act in a relaxed and confident manner before a planned spelling test. Results showed that, regardless of parent gender, children endorsed higher anxiety levels, anxious cognitions, and desired avoidance of the spelling test in the anxious relative to the non-anxious condition. Parental modeling of anxiety did not affect child spelling performance. Significant interaction effects indicated that fathers had a stronger impact on child anxiety level and cognitions than did mothers. Results highlight the importance of parental modeling and the potential role of both mothers and fathers in prevention and treatment for child anxiety. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Burstein, Marcy; Ginsburg, Golda S.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA. RP Burstein, M (reprint author), NIMH, Sect Dev Genet Epidemiol, 35 Convent Dr,Room 1A104,MSC 3720, Bethesda, MD 20814 USA. EM bursteinme@mail.nih.gov FU NIMH NIH HHS [T32 MH020033, T32 MH020033-10, T32MH020033] NR 63 TC 21 Z9 22 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JUN PY 2010 VL 48 IS 6 BP 506 EP 515 DI 10.1016/j.brat.2010.02.006 PG 10 WC Psychology, Clinical SC Psychology GA 607ED UT WOS:000278480800007 PM 20299004 ER PT J AU Stratakis, CA AF Stratakis, Constantine A. TI Prologue to the volume: Endocrine tumors and their genetics, a perspective Preface SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE endocrine tumors; genetics; multiple endocrine neoplasias ID HYPERPARATHYROIDISM; NEOPLASIAS C1 NICHD, Sect Endocrinol & Genet, PDEGEN, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, PDEGEN, NIH, Bldg 10,CRC,Room 1-1330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU Intramural NIH HHS [ZIA HD000642-12] NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP VII EP VIII DI 10.1016/j.beem.2010.07.004 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000001 PM 20833328 ER PT J AU Rothenbuhler, A Stratakis, CA AF Rothenbuhler, Anya Stratakis, Constantine A. TI Clinical and molecular genetics of Carney complex SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE Carney complex; Cushing's syndrome; PPNAD; Adrenocortical hyperplasia; Multiple endocrine neoplasias; PRKAR1A; Myxoma; Lentiginosis ID PROTEIN-KINASE-A; NODULAR ADRENOCORTICAL DISEASE; SPOTTY SKIN PIGMENTATION; SUBUNIT TYPE 1A; PSAMMOMATOUS MELANOTIC SCHWANNOMA; PEUTZ-JEGHERS-SYNDROME; REGULATORY SUBUNIT; ENDOCRINE OVERACTIVITY; PRKAR1A MUTATIONS; SIGNALING PATHWAYS AB Carney complex (CNC) is a rare multiple familial neoplasia syndrome that is characterized by multiple types of skin tumors and pigmented lesions, endocrine neoplasms, myxomas and schwannomas and is inherited in an autosomal dominant manner. Clinical and pathologic diagnostic criteria are well established. Over 100 pathogenic variants in the regulatory subunit type 1A (RI-A) of the cAMP-dependant proteine kinase (PRKAR1A) have been detected in approximately 60% of CNC patients, most leading to R1A haploinsufficiency. Other CNC-causing genes remain to be identified. Recent studies provided some genotype-phenotype correlations in CNC patients carrying PRKAR 1A-inactivating mutations, which provide useful information for genetic counseling and/or prognosis; however, CNC remains a disease with significant clinical heterogeneity. Recent mouse and in vitro studies have shed light into how R1A haploinsufficiency causes tumors. PRKAR 1A defects appear to be weak tumorigenic signals for most tissues; Wnt signaling activation and cell cycle dysregulation appear to be important mediators of the tumorigenic effect of a defective R1A. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Rothenbuhler, Anya] Paris Descartes Univ, Pediat Endocrinol Unit, Grp Hosp Cochin St Vincent de Paul, F-75014 Paris, France. [Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Rothenbuhler, A (reprint author), Paris Descartes Univ, Pediat Endocrinol Unit, Grp Hosp Cochin St Vincent de Paul, 82 Ave Denfert Rochereau, F-75014 Paris, France. EM anya.rothenbuhler@svp.aphp.fr; stratakc@mail.nih.gov NR 53 TC 37 Z9 41 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP 389 EP 399 DI 10.1016/j.beem.2010.03.003 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000004 PM 20833331 ER PT J AU Kantorovich, V King, KS Pacak, K AF Kantorovich, Vitaly King, Kathryn S. Pacak, Karel TI SDH-related pheochromocytoma and paraganglioma SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE Pheochromocytoma; Paraganglioma; Succinate dehydrogenase; Adrenal; Paragangia; Succinate dehydrogenase subunit A; Succinate dehydrogenase subunit B; Succinate dehydrogenase subunit C; Succinate dehydrogenase subunit D; Succinate dehydrogenase subunit 5; Malignant pheochromocytoma and paragangioma; Familial pheochromocytoma and paragangioma ID SUCCINATE-DEHYDROGENASE; GENE-MUTATIONS; HEREDITARY PARAGANGLIOMA; MALIGNANT PHEOCHROMOCYTOMA; RESPIRATORY-CHAIN; COMPLEX II; PHASE-II; B GENE; TUMORS; SUSCEPTIBILITY AB Pheochromocytoma and paraganglioma are rare tumors of adrenals as well as the sympathetic and parasympathetic paraganglia. Clinical presentation of these tumors depends on localization, secretory profile and malignant potential. Four distinct syndromes - PGL1-4 - are related to mutations in the succinate dehydrogenase gene - mitochondrial complex involved in electron transfer and Krebs cycle. Here we describe etiology, genetics, as well as clinical aspects of SDH-related tumors. We also describe recent discoveries in HIF-related pathway of tumorigenesis and mutations in new SDH-related genes that have improved our understanding of this disease. Published by Elsevier Ltd. C1 [Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Kantorovich, Vitaly] Univ Arkansas Med Sci, Div Endocrinol & Metab, ACRC, Little Rock, AR 72205 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM vkantorovich@uams.edu; kingkath@mail.nih.gov; karel@mail.nih.gov FU Intramural NIH HHS [Z01 HD008735-08, Z01 HD008735-07] NR 63 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP 415 EP 424 DI 10.1016/j.beem.2010.04.001 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000006 PM 20833333 ER PT J AU Lodish, MB Stratakis, CA AF Lodish, Maya B. Stratakis, Constantine A. TI Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE phakomatoses; neuroendocrine tumours; tumour suppressor; mammalian target of rapamycin; Cowden; Peutz-Jegher ID MTOR INHIBITOR EVEROLIMUS; PEUTZ-JEGHERS-SYNDROME; NEUROENDOCRINE TUMORS; MAMMALIAN TARGET; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; RECKLINGHAUSEN DISEASE; DIAGNOSTIC EVALUATION; CONSENSUS CONFERENCE; PARATHYROID ADENOMA; ELLISON-SYNDROME AB Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours. These hereditary cutaneous conditions affect the central nervous system and are characterised by the development of hamartomas. Over the past 20 years, there have been major advances in our understanding of the molecular basis of these diseases. Both NF-1 and TSC are disorders of unregulated progression through the cell cycle, in which causative genes behave as tumour suppressor genes. The pathogenesis of these familial syndromes is linked by the shared regulation of a common pathway, the protein kinase mammalian target of rapamycin (mTOR). Additional related disorders that also converge on the mTOR pathway include Peutz-Jeghers syndrome and Cowden syndrome. All of these inherited cancer syndromes are associated with characteristic skin findings that offer a clue to their recognition and treatment. The discovery of mTOR inhibitors has led to a possible new therapeutic modality for patients with endocrine tumours as part of these familial syndromes. Published by Elsevier Ltd. C1 [Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Pae, Sect Endocrinol Genet, Program Dev Endocrinol Genet, Interinst Training Program,NIH, Bethesda, MD 20892 USA. RP Lodish, MB (reprint author), 10 Ctr Dr,CRC Room 1-3330, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX This work was supported by intramural research funding of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. NR 87 TC 15 Z9 16 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X EI 1532-1908 J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP 439 EP 449 DI 10.1016/j.beem.2010.02.002 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000008 PM 20833335 ER PT J AU Sharretts, JM Simonds, WF AF Sharretts, John M. Simonds, William F. TI Clinical and molecular genetics of parathyroid neoplasms SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE hyperparathyroidism; parathyroid neoplasms; genes, tumour suppressor; oncogenes; multiple endocrine neoplasia; CDC73; CCND1; RET ID MULTIPLE-ENDOCRINE-NEOPLASIA; FAMILIAL ISOLATED HYPERPARATHYROIDISM; JAW TUMOR SYNDROME; CALCIUM-SENSING RECEPTOR; COMPARATIVE GENOMIC HYBRIDIZATION; SPORADIC PRIMARY HYPERPARATHYROIDISM; NEONATAL SEVERE HYPERPARATHYROIDISM; HISTONE METHYLTRANSFERASE COMPLEX; GERM-LINE MUTATIONS; MEN1 GENE AB Primary hyperparathyroidism (HPT) results from the excessive secretion of parathyroid hormone from parathyroid tumours. While most HPT is sporadic, it is associated with a familial syndrome in a minority of cases. The study of these syndromes has helped define the pathophysiology of both familial and sporadic parathyroid neoplasms. Investigation of kindred with multiple endocrine neoplasia type 1 (MEN1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT) led to the discovery of the tumour suppressor genes MEN land HRPT2. We now recognise that somatic mutations in MEN1 and HRPT2 tumour suppressor genes are frequent events in sporadic parathyroid adenomas and carcinomas, respectively. Parathyroid tumours in the MEN2A syndrome result from mutational activation of the R ET oncogene. The CCND1/PRAD1 oncogene was discovered by analysis of sporadic parathyroid tumours. Studies of familial isolated HPT and analysis of chromosomal loss and gain in parathyroid tumours suggest that other genes relevant to parathyroid neoplasia await identification. Published by Elsevier Ltd. C1 [Sharretts, John M.; Simonds, William F.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C-101,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM sharrettsj@niddk.nih.gov; wfs@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX The authors thank Dr. Stephen. J. Marx for critical reading of the manuscript and our colleagues Drs. Lee S. Weinstein, Monica C. Skarulis and Sunita K. Agarwal of the National Institute of Diabetes and Digestive and Kidney Diseases for their ongoing support and encouragement. The Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases supported this research. NR 100 TC 40 Z9 43 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X EI 1532-1908 J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP 491 EP 502 DI 10.1016/j.beem.2010.01.003 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000012 PM 20833339 ER PT J AU Kratz, CP Mai, PL Greene, MH AF Kratz, Christian P. Mai, Phuong L. Greene, Mark H. TI Familial testicular germ cell tumours SO BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article DE familial testicular cancer germ cell tumours; genetic susceptibility; KITLG-KIT signalling ID OF-THE-LITERATURE; DYSGENESIS SYNDROME; CANCER INCIDENCE; RISK-FACTOR; CARCINOMA-INSITU; UNITED-STATES; C-KIT; MEN; SUSCEPTIBILITY; TESTIS AB This article defines familial testicular germ cell tumours (FTGCTs) as testicular germ cell tumours (TGCTs) diagnosed in at least two blood relatives, a situation which occurs in 1-2% of all cases of TGCT. Brothers and fathers of TGCT patients have an 8-10- and 4-6-fold increased risk of TGCT, respectively, and an even higher elevated risk of TGCT in twin brothers of men with TGCT has been observed, suggesting that genetic elements play an important role in these tumours. Nevertheless, previous linkage studies with multiple FTGCT families did not uncover any high-penetrance genes and it has been concluded that the combined effects of multiple common alleles, each conferring a modest risk, might underlie FTGCT. In agreement with this assumption, recent candidate gene-association analyses have identified the chromosome Y gr/gr deletion and mutations in the PDE11A gene as genetic modifiers of FTGCT risk. Moreover, two genome-wide association studies of predominantly sporadic but also familial cases of TGCT have identified three additional susceptibility loci, KITLG, SPRY4 and BAK1. Notably, all five loci are involved in the biology of primordial germ cells, representing the cell of origin of TGCT, suggesting that the tumours arise as a result of disturbed testicular development. Published by Elsevier Ltd. C1 [Kratz, Christian P.; Mai, Phuong L.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. EM greenem@mail.nih.gov FU US National Cancer Institute, National Institutes of Health; Westat, Inc., Rockville, MD [NO2-CP-11019-50, N02-CP-65504] FX This work was supported by the Intramural Research Program of the US National Cancer Institute, National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD. NR 83 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-690X J9 BEST PRACT RES CL EN JI Best Pract. Res. Clin. Endoc. Metab. PD JUN PY 2010 VL 24 IS 3 BP 503 EP 513 DI 10.1016/j.beem.2010.01.005 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IK UT WOS:000282560000013 PM 20833340 ER PT J AU Husain, M Kumar, V Kumar, R Shakil, NA Sharma, SK Prasad, AK Olsen, CE Gupta, RK Malhotra, SV Van Der Eycken, E Depass, AL Levon, K Parmar, VS AF Husain, Mofazzal Kumar, Vineet Kumar, Rajesh Shakil, Najam A. Sharma, Sunil K. Prasad, Ashok K. Olsen, Carl E. Gupta, Rajendra K. Malhotra, Sanjay V. Van Der Eycken, Erik Depass, Anthony L. Levon, Kalle Parmar, Virinder S. TI Enantioselective biocatalytic reactions on (+/-)-aryl alkyl ketones with native and modified porcine pancreatic lipase SO BIOCATALYSIS AND BIOTRANSFORMATION LA English DT Article DE Lipase; aryl akyl ketones; enzymatic deacylation; Schiff's base complex ID CATALYZED SELECTIVE DEACETYLATION; DIRECTED ENZYME EVOLUTION; ONE-POT SYNTHESIS; MECHANISTIC ASPECTS; ORGANIC-SOLVENTS; EFFICIENT; ACETYLATION; POLYPHENOLS; DEACYLATION; CHEMISTRY AB Porcine pancreatic lipase (PPL), pre-incubated with acetophenone in tetrahydrofuran, fails to recognize ortho- and para acyloxy functions with respect to the nuclear carbonyl group in (+/-)-2,4-diacyloxyphenyl alkyl ketones and produces novel aryl alkyl ketones in moderate-to-highly optically active forms; this result supports the hypothesis on the mechanism of action of PPL in deacylation reactions on peracylated polyphenolics. C1 [Husain, Mofazzal; Kumar, Vineet; Kumar, Rajesh; Shakil, Najam A.; Sharma, Sunil K.; Prasad, Ashok K.; Parmar, Virinder S.] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India. [Husain, Mofazzal; Gupta, Rajendra K.] GGSIP Univ, Sch Biotechnol, Delhi, India. [Husain, Mofazzal; Van Der Eycken, Erik] Katholieke Univ Leuven, Dept Chem, LOMAC, Louvain, Belgium. [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, Dev Therapeut Program Support, Frederick, MD 21701 USA. [Olsen, Carl E.] Univ Copenhagen, Fac Life Sci, Dept Nat Sci, Frederiksberg, Denmark. [Depass, Anthony L.] Long Isl Univ, Dept Biol, Brooklyn, NY USA. [Levon, Kalle] Polytech Univ, Dept Chem, Brooklyn, NY 11201 USA. [Shakil, Najam A.] Indian Agr Res Inst, Div Agr Chem, New Delhi 110012, India. RP Parmar, VS (reprint author), Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India. EM virparmar@gmail.com RI SHAKIL, NAJAM/H-1377-2011; Olsen, Carl/H-3031-2014; Levon, Kalle/H-7990-2016 OI Olsen, Carl/0000-0002-2275-0596; Levon, Kalle/0000-0001-6833-6254 FU University of Delhi (Delhi, India); Polytechnic University (New York, USA); Department of Biotechnology (DBT, Government of India, New Delhi) FX The authors thank the University of Delhi (Delhi, India), Polytechnic University (New York, USA) and the Department of Biotechnology (DBT, Government of India, New Delhi) for financial assistance for this work. We also thank Dr Hemant Sharma (APL Research Center, Aurobindo Pharma Ltd., Hyderabad, India) for his help in recording the Raman spectra of several of our samples. NR 45 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1024-2422 J9 BIOCATAL BIOTRANSFOR JI Biocatal. Biotransform. PD JUN PY 2010 VL 28 IS 3 BP 172 EP 184 DI 10.3109/10242421003734704 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 628EZ UT WOS:000280098700003 ER PT J AU Weiman, S Uchiyama, S Lin, FYC Chaffin, D Varki, A Nizet, V Lewis, AL AF Weiman, Shannon Uchiyama, Satoshi Lin, Feng-Ying C. Chaffin, Donald Varki, Ajit Nizet, Victor Lewis, Amanda L. TI O-Acetylation of sialic acid on Group B Streptococcus inhibits neutrophil suppression and virulence SO BIOCHEMICAL JOURNAL LA English DT Article DE capsular polysaccharide; neutrophil; O-acetylation; sialic acid; Streptococcus agalactiae ID NEISSERIA-MENINGITIDIS; ESCHERICHIA-COLI; CAPSULAR POLYSACCHARIDE; COLONIZING STRAINS; FACTOR-H; SEROTYPE; VACCINES; SIGLECS; HOST; LIPOPOLYSACCHARIDE AB GBS (Group B Streptococus) requires capsular Sia (sialic acid) for virulence and partially modifies this sugar by O-acetylation. In die present paper we describe serotype-specific patterns of GBS Sia O-acetylation that can be manipulated by genetic and biochemical means. In vitro and in vivo assays demonstrate that this subtle modification attenuates GBS Sia-mediated neutrophil suppression and animal virulence. C1 [Weiman, Shannon; Uchiyama, Satoshi; Varki, Ajit; Nizet, Victor; Lewis, Amanda L.] Univ Calif San Diego, Dept Pediat, Glycobiol Res & Training Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Weiman, Shannon; Uchiyama, Satoshi; Varki, Ajit; Nizet, Victor; Lewis, Amanda L.] Univ Calif San Diego, Dept Med, Glycobiol Res & Training Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Weiman, Shannon; Uchiyama, Satoshi; Varki, Ajit; Nizet, Victor; Lewis, Amanda L.] Univ Calif San Diego, Dept Cellular & Mol Med, Glycobiol Res & Training Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Lin, Feng-Ying C.] NICHHD, NIH, Bethesda, MD 20892 USA. [Chaffin, Donald] Univ Washington, Childrens Hosp, Seattle, WA 98195 USA. [Chaffin, Donald] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Lewis, Amanda L.] Washington Univ, Dept Mol Microbiol, Sch Med, St Louis, MO 63110 USA. [Lewis, Amanda L.] Washington Univ, Ctr Womens Infect Dis Res, Sch Med, St Louis, MO 63110 USA. [Chaffin, Donald] Univ Washington, Reg Med Ctr, Seattle, WA 98195 USA. RP Lewis, AL (reprint author), Univ Calif San Diego, Dept Pediat, Glycobiol Res & Training Ctr, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. EM allewis@wustl.edu OI Lewis, Amanda/0000-0001-6195-3030 FU University of California President's; Gianinni Family Foundation; National Institutes of Health [R01-HD051796, P01-HL057345] FX This work was supported by the University of California President's Postdoctoral Fellowship Program (to AL.); the Gianinni Family Foundation (to At); and the National Institutes of Health [grant numbers R01-HD051796 (to V.N.) and P01-HL057345 (to A.V.)[. NR 45 TC 16 Z9 16 U1 2 U2 9 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2010 VL 428 BP 163 EP 168 DI 10.1042/BJ20100232 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607TF UT WOS:000278528800003 PM 20334627 ER PT J AU Jozwiak, K Toll, L Jimenez, L Woo, AYH Xiao, RP Wainer, IW AF Jozwiak, Krzysztof Toll, Lawrence Jimenez, Lucita Woo, Anthony Yiu-Ho Xiao, Rui-Ping Wainer, Irving W. TI The effect of stereochemistry on the thermodynamic characteristics of the binding of fenoterol stereoisomers to the beta(2)-adrenoceptor SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Enantiomers; Enantiospecific binding; Thermodynamic agonist-antagonist discrimination; Binding mechanisms; Binding thermodynamics; Chirality ID BETA-ADRENERGIC RECEPTORS; MOLECULAR-FIELD ANALYSIS; FUNDAMENTAL DIFFERENCE; AGONISTS; CONFORMATIONS; DERIVATIVES; ANTAGONISTS; AFFINITY; STATES AB The binding thermodynamics of the stereoisomers of fenoterol, (R,R')-, (S,S')-, (R,S')-, and (S,R')-fenoterol, to the beta(2)-adrenergic receptor (beta(2)-AR) have been determined. The experiments utilized membranes obtained from HEK cells stably transfected with cDNA encoding human beta(2)-AR. Competitive displacement studies using [H-3]CGP-12177 as the marker ligand were conducted at 4, 15, 25, 30 and 37 degrees C, the binding affinities calculated and the standard enthalpic (Delta H degrees) and standard entropic (Delta S degrees) contribution to the standard free energy change (Delta G degrees) associated with the binding process determined through the construction of van't Hoff plots. The results indicate that the binding of (S,S')- and (S,R')fenoterol were predominately enthalpy-driven processes while the binding of (R,R')- and (R,S')-fenoterol were entropy-driven. All of the fenoterol stereoisomers are full agonists of the beta(2)-AR, and, therefore, the results of this study are inconsistent with the previously described "thermodynamic agonist-antagonist discrimination", in which the binding of an agonist to the beta-AR is entropy-driven and the binding of an antagonist is enthalpy-driven. In addition, the data demonstrate that the chirality of the carbon atom containing the beta-hydroxyl group of the fenoterol molecule (the beta-OH carbon) is a key factor in the determination of whether the binding process will be enthalpy-driven or entropy-driven. When the configuration at the beta-OH carbon is S the binding process is enthalpy-driven while the R configuration produces an entropy-driven process. Published by Elsevier Inc. C1 [Wainer, Irving W.] NIA, Clin Invest Lab, Biomed Res Ctr, NIH,Intramural Res Program, Baltimore, MD 21224 USA. [Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, Lublin, Poland. [Toll, Lawrence; Jimenez, Lucita] SRI Int, Menlo Pk, CA 94025 USA. [Woo, Anthony Yiu-Ho; Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Clin Invest Lab, Biomed Res Ctr, NIH,Intramural Res Program, 8B133,251 Bayview Blvd, Baltimore, MD 21224 USA. EM krzysztof.jozwiak@umlub.pl; lawrence.toll@sri.com; lucita.jimenez@sri.com; wooa@mail.nih.gov; xiaor@grc.nia.nih.gov; wainerir@grc.nia.nih.gov RI Woo, Anthony/D-4305-2014 OI Woo, Anthony/0000-0003-0662-698X FU National Institute; National Institutes on Aging [N01AG-3-1009]; Foundation for Polish Science [4/2006] FX This work was supported in part by funds from the National Institute on Aging Intramural Research Program, by the National Institutes on Aging under contract number N01AG-3-1009 and the Foundation for Polish Science (FOCUS 4/2006 Programme). NR 16 TC 17 Z9 17 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUN 1 PY 2010 VL 79 IS 11 BP 1610 EP 1615 DI 10.1016/j.bcp.2010.01.035 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 581RA UT WOS:000276540800009 PM 20144591 ER PT J AU Raghuram, N Carrero, G Stasevich, TJ McNally, JG Th'ng, J Hendzel, MJ AF Raghuram, Nikhil Carrero, Gustavo Stasevich, Timothy J. McNally, James G. Th'ng, John Hendzel, Michael J. TI Core Histone Hyperacetylation Impacts Cooperative Behavior and High-Affinity Binding of Histone H1 to Chromatin SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTIONALLY ACTIVE CHROMATIN; DNASE-I SENSITIVITY; C-TERMINAL DOMAIN; LINKER HISTONES; GENE-EXPRESSION; FLUORESCENCE RECOVERY; NUCLEAR PROTEINS; TRICHOSTATIN-A; ACETYLATION; NUCLEOSOME AB Linker histones stabilize higher order chromatin structures and limit access to proteins involved in DNA-dependent processes. Core histone acetylation is thought to modulate HI binding. In the current study, we employed kinetic modeling of H1 recovery curves obtained during fluorescence recovery after photo-bleaching (FRAP) experiments to determine the impact of core histone acetylation on the different variants of H Following brief treatments with histone deacetylase inhibitor, most variants showed no change in HI dynamics. A change in mobility was detected only when longer treatments were used to induce high levels of histone acetylation. This hyperacetylation imparted marked changes in the dynamics of low-affinity HI population, while conferring variant-specific changes in the mobility of H I molecules that were strongly bound. Both the C-terminal domain (CTD) and globular domain were responsible for this differential response to TSA. Furthermore, we found that neither the CTD nor the globular domain, by themselves, undergoes a change in kinetics following hyperacetylation. This led us to conclude that hyperacetylation of core histones affects the cooperative nature of low-affinity H1 binding, with some variants undergoing a predicted decrease of almost 2 orders of magnitude. C1 [Raghuram, Nikhil; Hendzel, Michael J.] Univ Alberta, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. [Carrero, Gustavo] Athabasca Univ, Ctr Sci, Edmonton, AB T5J 3S8, Canada. [Stasevich, Timothy J.; McNally, James G.] NCI, NIH, Bethesda, MD 20892 USA. [Th'ng, John] No Ontario Sch Med, Div Med Sci, Thunder Bay Reg Hlth Sci Ctr, Reg Canc Ctr, Thunder Bay, ON P7B 5E1, Canada. RP Hendzel, MJ (reprint author), Univ Alberta, Dept Oncol, 11560 Univ Ave NW, Edmonton, AB T6G 1Z2, Canada. EM mhendzel@ualberta.ca OI Hendzel, Michael/0000-0002-9603-7945 FU Alberta Cancer Research Institute; Canadian Cancer Society Research Institute; Athabasca University; Endowed Graduate Studentship in Oncology; CIHR FX This work was supported by grants from the Alberta Cancer Research Institute and the Canadian Cancer Society Research Institute. M.J.H. is a senior scholar of the Alberta Heritage Foundation for Medical Research. G.C. has been supported by the Athabasca University Research Incentive Grant. N.R. is supported by the Endowed Graduate Studentship in Oncology and CIHR Graduate Studentship (Masters). NR 73 TC 9 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 2010 VL 49 IS 21 BP 4420 EP 4431 DI 10.1021/bi100296z PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 599KX UT WOS:000277912100002 PM 20411992 ER PT J AU Ananthaswamy, N Rutledge, R Sauna, ZE Ambudkar, SV Dine, E Nelson, E Xia, D Golin, J AF Ananthaswamy, Neeti Rutledge, Robert Sauna, Zuben E. Ambudkar, Suresh V. Dine, Elliot Nelson, Emily Xia, Di Golin, John TI The Signaling Interface of the Yeast Multidrug Transporter Pdr5 Adopts a Cis Conformation, and There Are Functional Overlap and Equivalence of the Deviant and Canonical Q-Loop Residues SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING DOMAIN; ABC TRANSPORTER; P-GLYCOPROTEIN; ATP HYDROLYSIS; EFFLUX; MECHANISM; ARCHITECTURE; MUTATIONS; CASSETTE; COMPLEX AB ABC transporters are polytopic proteins. ATP hydrolysis and substrate transport take place in separate domains, and these activities must he coordinated through a signal interface. We previously characterized a mutation (S558Y) in the yeast multidrug transporter Pdr5 that uncouples ATP hydrolysis and drug transport. To characterize the transmission interface, we used a genetic screen to isolate second-site mutations of S558Y that restore drug transport. We recovered suppressors that restore drug resistance; their locations provide functional evidence for an interface in the cis rather than the trans configuration indicated by structural and cross-linking studies of bacterial and eukaryotic efflux transporters. One mutation, E244G, defines the Q-loop of the deviant portion of NBD1, which is the hallmark of this group of fungal transporters. When moved to an otherwise wild-type background, this mutation and its counterpart in the canonical ATP-binding site Q951G show a similar reduction in drug resistance and in the very high basal-level ATP hydrolysis characteristic of Pdr5. A double E244G. Q951G mutant is considerably more drug sensitive than either of the single mutations. Surprisingly, then, the deviant and canonical Q-loop residues are functionally overlapping and equivalent in a strikingly asymmetric ABC transporter. C1 [Ananthaswamy, Neeti; Dine, Elliot; Nelson, Emily; Golin, John] Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. [Rutledge, Robert; Ambudkar, Suresh V.; Xia, Di] NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Sauna, Zuben E.] US FDA, Bethesda, MD 20892 USA. RP Golin, J (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. EM golin@cua.edu FU NIH [GM07721]; NIH, National Cancer Institute, Center for Cancer Research; FDA FX This work was supported by NIH Grant GM07721 to J.G., the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (R.R., D.X., S.V.A.), and the FDA (Z.E.S.) NR 27 TC 19 Z9 19 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 1 PY 2010 VL 49 IS 21 BP 4440 EP 4449 DI 10.1021/bi100394j PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 599KX UT WOS:000277912100004 PM 20426485 ER PT J AU Arias, HR Rosenberg, A Feuerbach, D Targowska-Duda, KM Maciejewski, R Jozwiak, K Moaddel, R Glick, SD Wainer, IW AF Arias, Hugo R. Rosenberg, Avraham Feuerbach, Dominik Targowska-Duda, Katarzyna M. Maciejewski, Ryszard Jozwiak, Krzysztof Moaddel, Ruin Glick, Stanley D. Wainer, Irving W. TI Interaction of 18-methoxycoronaridine with nicotinic acetylcholine receptors in different conformational states SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Nicotinic acetylcholine receptor; Conformational state; Noncompetitive antagonist; lbogaine analog; 18-Methoxycoronaridine ID ANTAGONIST BINDING-SITES; ION-CHANNEL; NONCOMPETITIVE INHIBITORS; AFFINITY-CHROMATOGRAPHY; MOLECULAR-MECHANISMS; ALPHA-3-BETA-4; PHENCYCLIDINE; ALPHA-4-BETA-2; CONGENERS; BUPROPION AB The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) was compared with that for ibogaine and phencyclidine (PCP). The results established that 18-MC: (a) is more potent than ibogaine and PCP inhibiting (+/-)-epibatidine-induced AChR Ca(2+) influx. The potency of 18-MC is increased after longer pre-incubation periods, which is in agreement with the enhancement of [(3)H]cytisine binding to resting but activatable Torpedo AChRs, (b) binds to a single site in the Torpedo AChR with high affinity and inhibits [(3)H]TCP binding to desensitized AChRs in a steric fashion, suggesting the existence of overlapping sites. This is supported by our docking results indicating that 18-MC interacts with a domain located between the serine (position 6') and valine (position 13') rings, and (c) inhibits [(3)H]TCP, [(3)H] ibogaine, and [(3)H]18-MC binding to desensitized AChRs with higher affinity compared to resting AChRs. This can be partially attributed to a slower dissociation rate from the desensitized AChR compared to that from the resting AChR. The enthalpic contribution is more important than the entropic contribution when 18-MC binds to the desensitized AChR compared to that for the resting AChR, and vice versa. lbogaine analogs inhibit the AChR by interacting with a luminal domain that is shared with PCP, and by inducing desensitization. (C) 2010 Elsevier B.V. All rights reserved. C1 [Arias, Hugo R.] Midwestern Univ, Dept Pharmaceut Sci, Coll Pharm, Glendale, AZ 85308 USA. [Rosenberg, Avraham; Moaddel, Ruin; Wainer, Irving W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Feuerbach, Dominik] Novartis Inst Biomed Res, Basel, Switzerland. [Targowska-Duda, Katarzyna M.; Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, Lublin, Poland. [Maciejewski, Ryszard] Med Univ Lublin, Lin Neuroengn Ctr, Lublin, Poland. [Glick, Stanley D.] Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. RP Arias, HR (reprint author), Midwestern Univ, Dept Pharmaceut Sci, Coll Pharm, 19555 N 59th Ave, Glendale, AZ 85308 USA. EM harias@midwestern.edu RI Targowska-Duda, Katarzyna/I-3434-2016 FU Science Foundation Arizona; Stardust Foundation; Office of Research and Sponsored Programs, Midwestern University; Polish Ministry of Science and Higher Education [NN 405297036]; Foundation for Polish Science; National Institute on Drug Addiction (NIDA) [DA016283]; NIH, National Institute on Aging; NIDA (NIH, Bethesda, Maryland, USA) FX This research was supported by grants from the Science Foundation Arizona and Stardust Foundation and from the Office of Research and Sponsored Programs, Midwestern University (to H.R.A.), by a grant from the Polish Ministry of Science and Higher Education (no. NN 405297036) and by the FOCUS and TEAM research subsidy from the Foundation for Polish Science (to K.J.), and by the National Institute on Drug Addiction (NIDA) grant DA016283 (to S.D.G.). This research was also supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The authors give thanks to NIDA (NIH, Bethesda, Maryland, USA) for the gift of [3H] lbogaine, ibogaine, and phencyclidine, and to Jorgelina L Arias Castillo and Paulina lacoban for their technical assistance. NR 39 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JUN PY 2010 VL 1798 IS 6 BP 1153 EP 1163 DI 10.1016/j.bbamem.2010.03.013 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 605BB UT WOS:000278321200016 PM 20303928 ER PT J AU Nwe, K Bryant, LH Brechbiel, MW AF Nwe, Kido Bryant, L. Henry, Jr. Brechbiel, Martin W. TI Poly(amidoamine) Dendrimer Based MRI Contrast Agents Exhibiting Enhanced Relaxivities Derived via Metal Preligation Techniques SO BIOCONJUGATE CHEMISTRY LA English DT Article ID NEPHROGENIC SYSTEMIC FIBROSIS; MAGNETIC-RESONANCE; MOLECULAR-WEIGHT; DRUG-DELIVERY; RENAL-FAILURE; GD-DOTA; GADOLINIUM; RELAXATION; PHARMACOKINETICS; COMPLEXES AB This report presents the preparation and characterization of three [Gd-C-DOTA](-1) dendrimer assemblies by way of analysis, NMRD spectroscopy, and photon correlation spectroscopy (PCS). The metal ligand chelates were preformed in alcohol media prior to conjugation to generation 4, 5, and 6 PAMAM dendrimers. The dendrimer-based agents were purified by Sephadex G-25 column chromatography. The combustion analysis, SE-HPLC, and UV-vis data indicated chelate to dendrimer ratios of 28:1, 61:1 and 115:1, respectively. Molar relaxivity measured at pH 7.4, 22 degrees C, and 3 T (29.6, 49.8, and 89.1 mM(-1) s(-1)) indicated the viability of conjugates as MRI contrast agents. 1/T(1) NMRD profiles were measured at 23 C and indicated that at 22 MHz the 1/T(1) reached a plateau at 60, 85, and 140 mM(-1) s(-1) for the generation 4, 5, and 6 dendrimer conjugates, respectively. The PCS data showed the respective sizes of 5.2, 6.5, and 7.8 nm for G-4, 5, and 6 conjugates. C1 [Nwe, Kido; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Bryant, L. Henry, Jr.] NIH, Lab Diagnost Radiol Res CC, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU National Institute of Health, National Cancer Institute, Center for Cancer Research; United States Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institute of Health, National Cancer Institute, Center for Cancer Research, and the United States Department of Health and Human Services. NR 40 TC 33 Z9 34 U1 2 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUN PY 2010 VL 21 IS 6 BP 1014 EP 1017 DI 10.1021/bc1000802 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 610LT UT WOS:000278734900003 PM 20462240 ER PT J AU Guyot, N Bergsson, G Butler, MW Greene, CM Weldon, S Kessler, E Levine, RL O'Neill, SJ Taggart, CC McElvaney, NG AF Guyot, Nicolas Bergsson, Gudmundur Butler, Marcus W. Greene, Catherine M. Weldon, Sinead Kessler, Efrat Levine, Rodney L. O'Neill, Shane J. Taggart, Clifford C. McElvaney, Noel G. TI Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases SO BIOLOGICAL CHEMISTRY LA English DT Article DE antimicrobials; antiproteases; cleavage; microbial; proteases; transglutaminase ID ELASTASE-SPECIFIC INHIBITOR; MUCUS PROTEINASE-INHIBITOR; TRAPPIN-2 PRE-ELAFIN; ALPHA-1-PROTEINASE INHIBITOR; NEUTROPHIL ELASTASE; HUMAN KERATINOCYTES; EPITHELIAL-CELLS; KAPPA-B; SERINE PROTEINASES; CYSTIC-FIBROSIS AB Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect of Pseudomonas aeruginosa proteases on elafin function. We found that P aeruginosa PAO1-conditioned medium and two purified Pseudomonas metalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites by P aeruginosa metalloproteinases, which can affect different biological functions of elafin. C1 [Weldon, Sinead; Taggart, Clifford C.] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Infect & Immun, Belfast BT9 7BL, Antrim, North Ireland. [Guyot, Nicolas; Bergsson, Gudmundur; Butler, Marcus W.; Greene, Catherine M.; O'Neill, Shane J.; McElvaney, Noel G.] Beaumont Hosp, Royal Coll Surg Ireland, Pulm Res Div, Dept Med, Dublin 9, Ireland. [Kessler, Efrat] Tel Aviv Univ, Sackler Fac Med, Chaim Sheba Med Ctr, Goldschleger Eye Res Inst, IL-52621 Tel Hashomer, Israel. [Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Taggart, CC (reprint author), Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Infect & Immun, Whitla Med Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland. EM c.taggart@qub.ac.uk RI McElvaney, Noel/A-6809-2010; Greene, Catherine/D-3513-2012; Taggart, Clifford/G-4492-2014; Weldon, Sinead/J-5451-2014; Levine, Rodney/D-9885-2011 OI Greene, Catherine/0000-0003-2549-2569; Weldon, Sinead/0000-0001-5628-6624; FU Health Research Board, Alpha One Foundation FX This work was supported by the Health Research Board, Alpha One Foundation, Programme for Research in Third levels Institutes administered by Higher Education Authority, Science Foundation Ireland, Cystic Fibrosis Hope Source, Cystic Fibrosis Research Trust, Cystic Fibrosis Association of Ireland (awarded to C.T.) and the Royal College of Surgeons in Ireland. NR 41 TC 16 Z9 16 U1 0 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD JUN PY 2010 VL 391 IS 6 BP 705 EP 716 DI 10.1515/BC.2010.066 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607GG UT WOS:000278486500013 PM 20370321 ER PT J AU Chen, G Henter, ID Manji, HK AF Chen, Guang Henter, Ioline D. Manji, Husseini K. TI Presynaptic Glutamatergic Dysfunction in Bipolar Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID MESSENGER-RNA EXPRESSION; MOOD DISORDERS; TEMPORAL-LOBE; SCHIZOPHRENIA; PATHOPHYSIOLOGY; PLASTICITY; MARKER; BRAIN C1 [Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. [Chen, Guang] NIMH, Mol Pathophysiol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Henter, Ioline D.] NIMH, Mood & Anxiety Disorders Res Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), Johnson & Johnson, Pharmaceut Grp, 1125 Trenton Harbourton Rd,E32000, Titusville, NJ 08560 USA. EM hmanji@its.jnj.com RI Chen, Guang/A-2570-2017 FU Intramural NIH HHS [Z99 MH999999] NR 17 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2010 VL 67 IS 11 BP 1007 EP 1009 DI 10.1016/j.biopsych.2010.03.027 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 599MT UT WOS:000277918000001 PM 20457307 ER PT J AU Arabadzisz, D Diaz-Heijtz, R Knuesel, I Weber, E Pilloud, S Dettling, AC Feldon, J Law, AJ Harrison, PJ Pryce, CR AF Arabadzisz, Dimitrula Diaz-Heijtz, Rochellys Knuesel, Irene Weber, Elisabeth Pilloud, Sonia Dettling, Andrea C. Feldon, Joram Law, Amanda J. Harrison, Paul J. Pryce, Christopher R. TI Primate Early Life Stress Leads to Long-Term Mild Hippocampal Decreases in Corticosteroid Receptor Expression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Corticosteroid receptor; depression; early life stress; hippocampus; marker; neurodevelopment; neuropathology; primate ID MESSENGER-RNA; MINERALOCORTICOID RECEPTOR; MARMOSET MONKEY; GLUCOCORTICOID-RECEPTOR; PARENTAL DEPRIVATION; DISORDER; DEPRESSION; SCHIZOPHRENIA; CHILDREN; AXIS AB Background: Expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) genes are moderately reduced in several brain regions in depression. These reductions could be partly due to early life stress (ELS), which predicts emotional disorders. Controlled primate studies are important to test whether ELS sufficient to induce long-term emotional changes also induces long-term altered MR and/or GR brain expression. Methods: In the common marmoset, ELS of daily 30-120-min social isolation across month-1 resulted in some long-term changes in homeostasis and emotional behavior. In some of these same subjects, the aim of this study was to use marmoset-specific riboprobes to determine whether ELS produced long-term effects on brain MR and GR gene expression. Results: At adolescence, relative to control subjects, ELS marmosets exhibited mildly reduced messenger RNA signal for both MR (-15%, p = .05) and GR (-13%, p = .02) in hippocampus-primarily CA1-but not in prefrontal cortex, other cortical regions, or hypothalamus. Conclusions: In adolescent marmoset monkey brains, reduced hippocampal expression of MR and GR are consistent chronic-indicators of ELS. It is unlikely that these chronic, mild, specific reductions were acute-mediators of the observed long-term emotional effects of ELS. However, they do suggest involvement of hippocampal MR/GR in the neurodevelopmental effects of ELS. C1 [Arabadzisz, Dimitrula; Knuesel, Irene; Weber, Elisabeth; Pilloud, Sonia; Dettling, Andrea C.; Feldon, Joram; Pryce, Christopher R.] Swiss Fed Inst Technol, Lab Behav Neurobiol, Zurich, Switzerland. [Diaz-Heijtz, Rochellys] Karolinska Inst, Dept Neurosci, Stockholm, Sweden. [Law, Amanda J.; Harrison, Paul J.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Law, Amanda J.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Pryce, CR (reprint author), Psychiat Univ Hosp Zurich, Clin Affect Disorders & Gen Psychiat, August Forel Str 7, CH-8008 Zurich, Switzerland. EM Christopher.pryce@bli.uzh.ch RI Law, Amanda/G-6372-2012; OI Law, Amanda/0000-0002-2574-1564 FU Swiss Federal Institute of Technology (ETH) Zurich; Swiss National Science Foundation (SNSF) National Center for Competence in Research (NCCR); Swiss Etiological Study of Adjustment and Mental Health [51A240-104890]; SNSF [31-67791.02]; Wellcome Trust, United Kingdom; GlaxoSmithKline; NCCR Net Plasticity and Repair FX This research teas funded by the Swiss Federal Institute of Technology (ETH) Zurich, the Swiss National Science Foundation (SNSF) National Center for Competence in Research (NCCR), Swiss Etiological Study of Adjustment and Mental Health, Grant 51A240-104890, the NCCR Net Plasticity and Repair, a SNSF Project Grant 31-67791.02, and the Wellcome Trust, United Kingdom. We are extremely, grateful to Jean-Marc Fritschy for providing laboratory facilities: Corinne Sidler, Mary Walker, and Helen Gordon-Andrews for their expert technical assistance; and Sandor Vizi for and stimulating discussion.; Dr. Harrison reports having received. in the past 3 years. honoraria from AstraZeneca, Janssen Cilag, Merck, Novartis, Organon Sanofi, Schering Plough Servier, and Wyeth and an unrestricted educational grant from GlaxoSmithKline. Dr. Pryce has been an employee of Novartis. All other authors reported no biomedical financial interests or potential conflicts of interest. NR 20 TC 29 Z9 30 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2010 VL 67 IS 11 BP 1106 EP 1109 DI 10.1016/j.biopsych.2009.12.016 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 599MT UT WOS:000277918000014 PM 20132928 ER PT J AU Cairo, MS Jordan, CT Maley, CC Chao, C Melnick, A Armstrong, SA Shlomchik, W Molldrem, J Ferrone, S Mackall, C Zitvogel, L Bishop, MR Giralt, SA June, CH AF Cairo, Mitchell S. Jordan, Craig T. Maley, Carlo C. Chao, Clifford Melnick, Ari Armstrong, Scott A. Shlomchik, Warren Molldrem, Jeff Ferrone, Soldano Mackall, Crystal Zitvogel, Laurence Bishop, Michael R. Giralt, Sergio A. June, Carl H. TI NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biological Considerations of Hematological Relapse following Allogeneic Stem Cell Transplantation Unrelated to Graft-versus-Tumor Effects: State of the Science SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Relapse; Allogeneic stem cell transplant; Biology; Resistance; Cancer stem cells ID ACUTE MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HISTONE DEACETYLASE INHIBITORS; HEDGEHOG PATHWAY ACTIVATION; 2 IRRADIATION REGIMENS; TOTAL-BODY IRRADIATION; SELF-RENEWAL CAPACITY; HUMAN PROSTATE-CANCER AB Hematopoietic malignant relapse still remains the major cause of death following allogeneic hematopoietic stem cell transplantation (HSCT). Although there has been a large focus on the immunologic mechanisms responsible for the graft-versus-tumor (GVT) effect or lack thereof, there has been little attention paid to investigating the biologic basis of hematologic malignant disease relapse following allogeneic HSCT. There are a large number of factors that are responsible for the biologic resistance of hematopoietic tumors following allogeneic HSCT. We have focused on 5 major areas including clonal evolution of cancer drug resistance, cancer radiation resistance, genomic basis of leukemia resistance, cancer epigenetics, and resistant leukemia stem cells. We recommend increased funding to pursue 3 broad areas that will significantly enhance our understanding of the biologic basis of malignant relapse after allogeneic HSCT, including: ( I) genomic and epigenetic alterations, (2) cancer stem cell biology, and (3) clonal cancer drug and radiation resistance. Biol Blood Marrow Transplant 16: 709-728 (2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Cairo, Mitchell S.] Columbia Univ, Morgan Stanley Childrens Hosp, New York Presbyterian Hosp, Dept Pediat Med & Pathol, New York, NY 10032 USA. [Jordan, Craig T.] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA. [Jordan, Craig T.] Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. [Maley, Carlo C.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Chao, Clifford] Columbia Univ, Dept Radiat Oncol, New York, NY 10032 USA. [Melnick, Ari] Yeshiva Univ, Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shlomchik, Warren] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA. [Molldrem, Jeff] MD Anderson, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Surg, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA USA. [Ferrone, Soldano] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA USA. [Mackall, Crystal] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Zitvogel, Laurence] Inst Gustave Roussy, Rouen, France. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Giralt, Sergio A.] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [June, Carl H.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [June, Carl H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Cairo, MS (reprint author), Columbia Univ, Div Pediat Blood & Marrow Transplantat, 3959 Broadway,CHN 10-03, New York, NY 10032 USA. EM mc1310@columbia.edu FU National Cancer Institute FX This article was supported by the National Cancer Institute. NR 157 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2010 VL 16 IS 6 BP 709 EP 728 DI 10.1016/j.bbmt.2010.03.002 PG 20 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 601GQ UT WOS:000278046700001 PM 20227509 ER PT J AU Navath, RS Menjoge, AR Wang, B Romero, R Kannan, S Kannan, RM AF Navath, Raghavendra S. Menjoge, Anupa R. Wang, Bing Romero, Roberto Kannan, Sujatha Kannan, Rangaramanujam M. TI Amino Acid-Functionalized Dendrimers with Heterobifunctional Chemoselective Peripheral Groups for Drug Delivery Applications SO BIOMACROMOLECULES LA English DT Article ID RESONANCE CONTRAST AGENT; IN-VITRO; POLYAMIDOAMINE DENDRIMERS; BIFUNCTIONAL DENDRIMERS; ARTIFICIAL ENZYMES; PAMAM DENDRIMERS; MOLECULAR-WEIGHT; GUEST MOLECULES; CELLULAR ENTRY; ACETYLATION AB Dendrimers have emerged as multifunctional carriers for targeted drug delivery, gene delivery and imaging. Improving the functional versatility at the surface for carrying multiple conjugation reactions is becoming vital. Typically, generation four polyamidoamine (G4-PAMAM) dendrimers bear similar to 64 symmetrical end groups, often requiring different spacers to conjugate various functional groups (drugs and targeting moities), increasing the synthetic steps. In the present study, a simple one-step synthesis to convert each symmetrical end group of G4-PAMAM dendrimers into two reactive, distinct orthogonal and chemoselective groups is described. A near-complete end-capping of the dendrimers (87-93%) with amino acids results in heterobifunctional G4-PAMAM dendrimers bearing a very high (>= 110) diverse peripheral end groups (OH+NHBoc, OH+COOMe, SH+NHBoc, and COOH+NHBoc). Postfunctionalization ability of these dendrimers was evaluated. The heterobifunctional groups at the dendrimer periphery could be chemoselectively conjugated to multiple moities such as drugs (indomethacin and dexamethasone) and drugs and imaging agents (dexamethasone and FITC). These conjugations could be achieved in immediate succession without functional group conversions, eliminating the additional elaborate synthetic steps traditionally required to append specific linkers. Furthermore, one of the two functional handles at periphery was used to develop in situ forming hydrogels, whereas the other handle could be used for conjugating the drugs (e.g., dexamethasone). The heterobifunctional dendrimers with either "NH(2) or SH (thiopyridyl protected form)" terminations showed in situ hydrogel formation by cross-linking with N-hydroxysuccinimide or thiol-terminated multiarm polyethylene glycol (20 kDa). The choice of amino acids as versatile linkers would enable biocompatible dendrimer scaffolds for use in drug delivery. zeta-potential measurements showed drastic lowering of the charge on G4-PAMAM-NH(2) dendrimers by end-capping with amino acids, whereas in the ease of neutral G4-PAMAM-OH dendrimers, the charge did not increase or decrease substantially. The in vitro cytotoxicity and hemolysis assay showed that the heterobifunctional dendrimers were noncytotoxic in the 100 ng/mL to 1 mg/mL concentration range. With this study, we demonstrate the development of biocompatible dendrimers bearing multiple orthogonal surface groups, enabling the attachment of drugs, imaging agents, and gel formation using minimal synthetic steps. C1 [Navath, Raghavendra S.; Menjoge, Anupa R.; Wang, Bing; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. [Navath, Raghavendra S.; Menjoge, Anupa R.; Wang, Bing; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Biomed Engn, Detroit, MI 48202 USA. [Navath, Raghavendra S.; Menjoge, Anupa R.; Wang, Bing; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. [Navath, Raghavendra S.; Menjoge, Anupa R.; Wang, Bing; Romero, Roberto; Kannan, Sujatha; Kannan, Rangaramanujam M.] NICHD, Dept Hlth & Human Serv, NIH, Detroit, MI 48201 USA. [Kannan, Sujatha] Wayne State Univ, Dept Pediat Crit Care Med, Childrens Hosp Michigan, Detroit, MI 48201 USA. RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. EM rkannan.wsu@gmail.com FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH/DHHS); Pediatric Critical Care Scientist Development Program FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services (NICHD/NIH/DHHS), and the Pediatric Critical Care Scientist Development Program. NR 54 TC 43 Z9 44 U1 2 U2 60 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD JUN PY 2010 VL 11 IS 6 BP 1544 EP 1563 DI 10.1021/bm100186b PG 20 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 608VD UT WOS:000278613200016 PM 20415504 ER PT J AU Menjoge, AR Navath, RS Asad, A Kannan, S Kim, CJ Romero, R Kannan, RM AF Menjoge, Anupa R. Navath, Raghavendra S. Asad, Abbas Kannan, Sujatha Kim, Chong J. Romero, Roberto Kannan, Rangaramanujam M. TI Transport and biodistribution of dendrimers across human fetal membranes: Implications for intravaginal administration of dendrimer-drug conjugates SO BIOMATERIALS LA English DT Article DE Dendrimers; Transplacental transport; Membrane permeability; Chorioamnion; Biodistribution; Topical intravaginal; Nanotoxicology ID POLYAMIDOAMINE PAMAM DENDRIMERS; SEXUALLY-TRANSMITTED INFECTIONS; HUMAN TERM PLACENTA; IN-VITRO; POLY(AMIDOAMINE) DENDRIMERS; ANTIMICROBIAL ACTIVITY; TRANSDERMAL DELIVERY; POLY(VINYL ALCOHOL); BACTERIAL VAGINOSIS; AMNIOTIC-FLUID AB Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size similar to 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (similar to 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than <3%, whereas the transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 x 10(-7) cm(2)/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother without affecting the fetus. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Menjoge, Anupa R.; Navath, Raghavendra S.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci & Biomed Engn, Detroit, MI 48202 USA. [Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kim, Chong J.; Romero, Roberto; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver NICHHD, Perinatol Res Branch, NIH, Detroit, MI 48201 USA. [Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kim, Chong J.; Romero, Roberto; Kannan, Rangaramanujam M.] US Dept HHS, Detroit, MI 48201 USA. [Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA. RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. EM rkannan@eng.wayne.edu FU National Institute of Child Health and Human Development, NIH, DHHS FX This study was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS. NR 70 TC 30 Z9 30 U1 0 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 2010 VL 31 IS 18 BP 5007 EP 5021 DI 10.1016/j.biomaterials.2010.02.075 PG 15 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 597SY UT WOS:000277783100027 PM 20346497 ER PT J AU Teng, CT AF Teng, Christina T. TI Lactoferrin: the path from protein to gene SO BIOMETALS LA English DT Article; Proceedings Paper CT 9th International Conference on Lactoferrin, Structure, Function and Application CY OCT 18-22, 2009 CL Beijing, PEOPLES R CHINA SP Feed Res Inst, Chinese Acad Agr Sci, freisland Foods Domo, DMV, Natl Nat Sci Fdn China, Nat Sci Fdn Beijing, Shanghai Genon Bioengn Co, Shanghai Transgen Res Ctr, China Agr Univ, State Key Lab Agrobiotechnol DE Gene; Estrogen regulation; Reproduction; Cancer; Methylation and SNPs; Promoter ID EPIDERMAL-GROWTH-FACTOR; ESTROGEN-RECEPTOR-ALPHA; LACTOTRANSFERRIN GENE; PRENATAL EXPOSURE; MOUSE UTERUS; COUP-TF; MOLECULAR-MECHANISM; REPRODUCTIVE-TRACT; RESPONSE-ELEMENT; SEMINAL-VESICLE AB This review focuses on the basic research that was performed on the lactoferrin protein and gene that was conducted in my laboratory over the past 25 years. This manuscript will outline how we discovered that lactoferrin is a target gene for estrogen, and how the first mouse lactoferrin cDNA, promoter and gene was cloned. Additionally, study was further extended to investigating the human lactoferrin protein and gene. Lastly the expression of lactoferrin in various tissues of both human and rodent under various physiological conditions were examined. C1 NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, MD K202,POB 12233, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov FU Intramural NIH HHS NR 55 TC 17 Z9 17 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0966-0844 J9 BIOMETALS JI Biometals PD JUN PY 2010 VL 23 IS 3 SI SI BP 359 EP 364 DI 10.1007/s10534-010-9310-8 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 595RP UT WOS:000277630400002 PM 20221787 ER PT J AU Berger, VW AF Berger, Vance W. TI "Exact permutation tests for correlated binomial variables" SO BIOMETRICAL JOURNAL LA English DT Letter C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, 6130 Execut Blvd EPN,MSC 7354,Suite 3131, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD JUN PY 2010 VL 52 IS 3 BP 436 EP 437 DI 10.1002/bimj.201000012 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 626NF UT WOS:000279972000009 PM 20535744 ER PT J AU Qin, J Shen, Y AF Qin, Jing Shen, Yu TI Statistical Methods for Analyzing Right-Censored Length-Biased Data under Cox Model SO BIOMETRICS LA English DT Article DE Cox model; Dependent censoring; Estimating equation; Length biased ID PREVALENT COHORT DATA; TRUNCATED DATA; NONPARAMETRIC-ESTIMATION; EMPIRICAL DISTRIBUTIONS; HAZARDS REGRESSION; SURVIVAL-DATA; LARGE SAMPLE; DURATION; TIMES; UNEMPLOYMENT AB Length-biased time-to-event data are commonly encountered in applications ranging from epidemiological cohort studies or cancer prevention trials to studies of labor economy. A longstanding statistical problem is how to assess the association of risk factors with survival in the target population given the observed length-biased data. In this article, we demonstrate how to estimate these effects under the semiparametric Cox proportional hazards model. The structure of the Cox model is changed under length-biased sampling in general. Although the existing partial likelihood approach for left-truncated data can be used to estimate covariate effects, it may not be efficient for analyzing length-biased data. We propose two estimating equation approaches for estimating the covariate coefficients under the Cox model. We use the modern stochastic process and martingale theory to develop the asymptotic properties of the estimators. We evaluate the empirical performance and efficiency of the two methods through extensive simulation studies. We use data, from a. dementia study to illustrate the proposed methodology, and demonstrate the computational algorithms for point estimates, which can be directly linked to the existing functions in S-PLUS or R. C1 [Qin, Jing] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Qin, J (reprint author), NIAID, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM yshen@mdanderson.org OI Shen, Yu/0000-0002-3899-7868 FU National Institutes of Health [CA79466, CA016672]; National Health Research and Development Program (NHRDP) of Health Canada [6606-3954-MC(S)]; Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada; NHRDP [6603-1417-302(R)]; Bayer Incorporated; British Columbia Health Research Foundation [38 (93-2), 34 (96-1)] FX We thank Professor David Zucker, the associate editor, and the referee for their constructive comments. This work was supported in part by grants CA79466 and CA016672 from the National Institutes of Health. We thank Professor Masoud Asgharian and the investigators from the CSHA for providing us with the dementia data from the CSHA. The data reported in the example were collected as part of the CSHA. The CSHA study was funded by the Seniors' Independence Research Program through the National Health Research and Development Program (NHRDP) of Health Canada (Project 6606-3954-MC(S)). Additional funding was provided by Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program, NHRDP Project 6603-1417-302(R), Bayer Incorporated, and the British Columbia Health Research Foundation Projects 38 (93-2) and 34 (96-1). The study was coordinated through the University of Ottawa. and the Division of Aging and Seniors, Health Canada. NR 25 TC 37 Z9 38 U1 3 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2010 VL 66 IS 2 BP 382 EP 392 DI 10.1111/j.1541-0420.2009.01287.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 613FL UT WOS:000278964200007 PM 19522872 ER PT J AU Sinha, S Mallick, BK Kipnis, V Carroll, RJ AF Sinha, Samiran Mallick, Bani K. Kipnis, Victor Carroll, Raymond J. TI Semiparametric Bayesian Analysis of Nutritional Epidemiology Data in the Presence of Measurement Error SO BIOMETRICS LA English DT Article DE B-splines; Dirichlet process prior; Gibbs sampling; Measurement error; Metropolis-Hastings algorithm; Partly linear model ID NONPARAMETRIC REGRESSION; IN-VARIABLES; NATIONAL-INSTITUTES; SPLINES; MODEL; INFERENCE; DENSITY; COHORT; HEALTH; DIET AB We propose a semiparametric Bayesian method for handling measurement error in nutritional epidemiological data. Our goal is to estimate nonparametrically the form of association between a disease and exposure variable while the true values of the exposure are never observed. Motivated by nutritional epidemiological data, we consider the setting where a surrogate covariate is recorded in the primary data, and a calibration data set contains information on the surrogate variable and repeated measurements of an unbiased instrumental variable of the true exposure. We develop a flexible Bayesian method where not only is the relationship between the disease and exposure variable treated semiparametrically, but also the relationship between the surrogate and the true exposure is modeled semiparametrically. The two nonparametric functions are modeled simultaneously via B-splines. In addition, we model the distribution of the exposure variable as a Dirichlet process mixture of normal distributions, thus making its modeling essentially nonparametric and placing this work into the context of functional measurement error modeling. We apply our method to the NIH-AARP Diet and Health Study and examine its performance in a simulation study. C1 [Sinha, Samiran; Mallick, Bani K.; Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Kipnis, Victor] NCI, Biometry Res Grp, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Sinha, S (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. EM sinha@stat.tamu.edu; bmallick@stat.tamu.edu; kipnisv@mail.nih.gov; carroll@stat.tamu.edu FU National Cancer Institute [CA57030,, CA 104620]; King Abdullah University of Science and Technology (KAUST) [KUS-CI-016-04] FX The research of BKM and RJC was supported by grants from the National Cancer Institute (CA57030, CA 104620) and in part by Award Number KUS-CI-016-04, made by King Abdullah University of Science and Technology (KAUST). NR 22 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2010 VL 66 IS 2 BP 444 EP 454 DI 10.1111/j.1541-0420.2009.01309.x PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 613FL UT WOS:000278964200013 PM 19673858 ER PT J AU Guo, WG Sarkar, SK Peddada, SD AF Guo, Wenge Sarkar, Sanat K. Peddada, Shyamal D. TI Controlling False Discoveries in Multidimensional Directional Decisions, with Applications to Gene Expression Data on Ordered Categories SO BIOMETRICS LA English DT Article DE Benjamini-Hochberg procedure; Directional FDR; Dose-response; Microarray; Multiple testing; Ordered categories; Time course ID MULTIPLE TEST PROCEDURES; RESPONSE MICROARRAY EXPERIMENTS; INFERENCE; ERRORS; HYPOTHESIS; STATISTICS AB Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell line is exposed to different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles Over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions is tested and further directional decisions are made if it is rejected. Sloth of the existing multiple testing procedures are devised ha controlling the usual false discovery rate (FDR) rather than the mixed directional FUR (mdFDR), the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005, Journal of the American Statistical Association 100, 71-93) proved that an augmentation of the usual Benjamini Hochberg (1:111) procedure can control the rndFDR. while testing simple null hypotheses against; two-sided alternatives in terms of one-dimensional parameters. Ill this article. we consider the problem of controlling the mdFDR, involving multidimensional parameters. To deal with this problem. we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mdFDR)R. control when the underlying test statistics are independent across the genes. The results of a simulation Study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a tune-course microarray data obtained by Lobenhofer et al. (2002, Molecular Endocrinology 16. 1215-1229). We identified several important cell-cycle genus, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenholer et al. (2002) and Peddada et al. (2003, Bioinformatics 19, 834-841). Although some of our findings overlap with previous findings; we identify several other genes that; complement the results of Lobenhofer et al. (2002). C1 [Guo, Wenge; Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Sarkar, Sanat K.] Temple Univ, Dept Stat, Philadelphia, PA 19122 USA. RP Guo, WG (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM wenge.guo@gmail.com; sanat@temple.edu; peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; OI Guo, Wenge/0000-0003-3777-2058 FU NIH; National Institute of Environmental Health Sciences [Z01 ES101744-04]; U.S. National Science Foundation [DMS-0603868] FX The research of the first and third authors is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES101744-04) and the research of the second author is supported by a grant from U.S. National Science Foundation (DMS-0603868). We thank Grace Kissling and David Dunson for several useful comments that led to improved presentation of the manuscript. We also thank the editor, the associate editor (AE), and the referees for their comments that have led to substantial improvement in the presentation of the manuscript. We are particularly thankful to the AE for spotting an error in the proof of Theorem 1, for providing an interesting example showing that Procedure 2 cannot control the mdFDR. (described in Remark 3), and for making several other important comments that led to improved simulation studies and better exposition of the article. NR 20 TC 24 Z9 24 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2010 VL 66 IS 2 BP 485 EP 492 DI 10.1111/j.1541-0420.2009.01292.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 613FL UT WOS:000278964200017 PM 19645703 ER PT J AU Li, HL Graubard, BI Gail, MH AF Li, Huilin Graubard, Barry I. Gail, Mitchell H. TI Covariate Adjustment and Ranking Methods to Identify Regions with High and Low Mortality Rates SO BIOMETRICS LA English DT Article DE Incidence rate maps; Mortality rate maps; Poisson-Gamma model; Ranking procedures Standardized incidence; ratio; Standardized mortality ratio AB Identifying regions with the highest and lowest mortality rates and producing the corresponding color-coded maps help epidemiologists identify promising areas for analytic etiological studies. Based on a two-stage Poisson Gainina model with covariates, we use information on known risk factors, such as smoking prevalence, to adjust mortality rates and reveal residual variation in relative risks that may reflect; previously masked etiological associations. In addition to covariate adjustment. we study rankings based on standardized mortality ratios (SMRs), empirical Bayes (ER) estimates, and a posterior percentile ranking (PPR) method and indicate circumstances that. warrant the more complex procedures in order to obtain a high probability of correctly classifying the regions with the upper 100 gamma% and lower 100 gamma% of relative risks for gamma = 0.05, 0.1, and 0.2. We also give analytic approximations to the probabilities of correctly classifying regions in the upper 1007% of relative risks for these three ranking methods. Using data on mortality from heart disease, we found that, adjustment for smoking prevalence has an important impact on which regions are classified as high and low risk. With such a common disease, all three ranking methods performed comparably. However, for diseases with smaller event counts, such as cancers, and wide variation in event counts among regions, ER and PPR methods outperform ranking based on Ski RS. C1 [Li, Huilin; Graubard, Barry I.; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Li, HL (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Execut Plaza S,RM 8034, Bethesda, MD 20892 USA. EM lih5@nih.gov FU Division of Cancer Epidemiology and Genetics of the National Cancer Institute FX The authors thank Professor Thomas A. Louis for pointing out some key references and providing reprints, and the reviewers for helpful suggestions. This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute. NR 11 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2010 VL 66 IS 2 BP 613 EP 620 DI 10.1111/j.1541-0420.2009.01284.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 613FL UT WOS:000278964200031 PM 19508235 ER PT J AU Hu, ZH Follmann, DA Qin, J AF Hu, Zonghui Follmann, Dean A. Qin, Jing TI Semiparametric dimension reduction estimation for mean response with missing data SO BIOMETRIKA LA English DT Article DE Dimension reduction; Inverse probability weighting; Kernel regression; Missing at random; Robustness to model misspecification ID LIKELIHOOD-BASED INFERENCE; GENERALIZED LINEAR-MODELS; BANDWIDTH SELECTION; REGRESSION; IMPUTATION; DESIGN AB Model misspecification can be a concern for high-dimensional data. Nonparametric regression obviates model specification but is impeded by the curse of dimensionality. This paper focuses on the estimation of the marginal mean response when there is missingness in the response and multiple covariates are available. We propose estimating the mean response through nonparametric functional estimation, where the dimension is reduced by a parametric working index. The proposed semiparametric estimator is robust to model misspecification: it is consistent for any working index if the missing mechanism of the response is known or correctly specified up to unknown parameters; even with misspecification in the missing mechanism, it is consistent so long as the working index can recover E(Y vertical bar X), the conditional mean response given the covariates. In addition, when the missing mechanism is correctly specified, the semiparametric estimator attains the optimal efficiency if E(Y vertical bar X) is recoverable through the working index. Robustness and efficiency of the proposed estimator is further investigated by simulations. We apply the proposed method to a clinical trial for HIV. C1 [Hu, Zonghui; Follmann, Dean A.; Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Hu, ZH (reprint author), NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. EM huzo@niaid.nih.gov; dfollmann@niaid.nih.gov; jqin@niaid.nih.gov NR 24 TC 12 Z9 13 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2010 VL 97 IS 2 BP 305 EP 319 DI 10.1093/biomet/asq005 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 634DM UT WOS:000280559700004 ER PT J AU Tang, J Maddali, K Pommier, Y Sham, YY Wang, ZQ AF Tang, Jing Maddali, Kasthuraiah Pommier, Yves Sham, Yuk Y. Wang, Zhengqiang TI Scaffold rearrangement of dihydroxypyrimidine inhibitors of HIV integrase: Docking model revisited SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV; Integrase; Inhibitor design; Docking model; Binding mechanism ID DYNAMIC PHARMACOPHORE MODEL; DIKETO ACID PHARMACOPHORE; CATALYTIC DOMAIN; STRAND-TRANSFER; CRYSTAL-STRUCTURE; DISCOVERY; POTENT; COMPLEX; DESIGN; IDENTIFICATION AB A series of dihydroxypyrimidine (DHP) derivatives were designed as inhibitors of HIV integrase (IN) based on known homology models. Through chemical synthesis and biochemical assays it was found that the activity profile of these compounds largely deviates from predictions with existing models. With the recently disclosed IN crystal structure of prototype foamy virus (PFV), a new HIV IN homology model was constructed featuring a critical IN/DNA interface previously lacking. With this new model, docking results completely corroborated observed biological activities. This new model should provide a more accurate and improved platform for the design of new inhibitors of HIV IN. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Tang, Jing; Sham, Yuk Y.; Wang, Zhengqiang] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. [Maddali, Kasthuraiah; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Sham, YY (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, 516 Delaware St SE, Minneapolis, MN 55455 USA. EM shamx002@umn.edu; wangx472@umn.edu RI Sham, Yuk/A-6472-2011 FU Center for Drug Design at the University of Minnesota; Center for Cancer Research, National Cancer Institute, NIH FX This research was supported by the Center for Drug Design at the University of Minnesota and by the Center for Cancer Research, National Cancer Institute, NIH. We thank Professor Robert Vince for discussion and the University of Minnesota Supercomputing Institute for providing computational resources. NR 40 TC 24 Z9 25 U1 0 U2 0 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 JUN 1 PY 2010 VL 20 IS 11 BP 3275 EP 3279 DI 10.1016/j.bmcl.2010.04.048 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 597UY UT WOS:000277788900017 PM 20457521 ER PT J AU Jiang, JK Boxer, MB Vander Heiden, MG Shen, M Skoumbourdis, AP Southall, N Veith, H Leister, W Austin, CP Park, HW Inglese, J Cantley, LC Auld, DS Thomas, CJ AF Jiang, Jian-kang Boxer, Matthew B. Vander Heiden, Matthew G. Shen, Min Skoumbourdis, Amanda P. Southall, Noel Veith, Henrike Leister, William Austin, Christopher P. Park, Hee Won Inglese, James Cantley, Lewis C. Auld, Douglas S. Thomas, Craig J. TI Evaluation of thieno[3,2-b]pyrrole[3,2-d]pyridazinones as activators of the tumor cell specific M2 isoform of pyruvate kinase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Warburg effect; Pyruvate kinase; Cellular metabolism; Anti-cancer strategies; Small molecule activators ID CANCER CELLS; M-GENE; GROWTH; RAT; IDENTIFICATION; METABOLISM; INHIBITORS; ISOZYMES; HALIDES; M2-PK AB Cancer cells have distinct metabolic needs that are different from normal cells and can be exploited for development of anti-cancer therapeutics. Activation of the tumor specific M2 form of pyruvate kinase (PKM2) is a potential strategy for returning cancer cells to a metabolic state characteristic of normal cells. Here, we describe activators of PKM2 based upon a substituted thieno[3,2-b]pyrrole[3,2-d]pyridazinone scaffold. The synthesis of these agents, structure-activity relationships, analysis of activity at related targets (PKM1, PKR and PKL) and examination of aqueous solubility are investigated. These agents represent the second reported chemotype for activation of PKM2. Published by Elsevier Ltd. C1 [Jiang, Jian-kang; Boxer, Matthew B.; Shen, Min; Skoumbourdis, Amanda P.; Southall, Noel; Veith, Henrike; Leister, William; Austin, Christopher P.; Inglese, James; Auld, Douglas S.; Thomas, Craig J.] NHGRI, Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Vander Heiden, Matthew G.] MIT, Robert Koch Inst, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.; Cantley, Lewis C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vander Heiden, Matthew G.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Park, Hee Won] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L5, Canada. [Park, Hee Won] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. [Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. RP Thomas, CJ (reprint author), NHGRI, Chem Genom Ctr, NIH, 9800 Med Ctr Dr,Bldg B,Room 3005,MSC 3370, Bethesda, MD 20892 USA. EM craigt@nhgri.nih.gov RI Southall, Noel/H-8991-2012; Cantley, Lewis/D-1800-2014 OI Southall, Noel/0000-0003-4500-880X; Cantley, Lewis/0000-0002-1298-7653 FU National Institutes of Health Roadmap for Medical Research; National Human Genome Research Institute, National Institutes of Health [R03MH085679]; Canadian Institutes for Health Research; Canadian Foundation for Innovation; Genome Canada through the Ontario Genomics Institute; GlaxoSmithKline; Karolinska Institutet; Knut and Alice Wallenberg Foundation; Ontario Innovation Trust; Ontario Ministry for Research and Innovation; Merck Co., Inc.; Novartis Research Foundation; Swedish Agency for Innovation Systems; Swedish Foundation for Strategic Research; Wellcome Trust FX The authors thank Jeremy Smith, Paul Shinn, and Danielle van Leer for assistance with compound management. We thank Ms. Allison Mandich for critical reading of this manuscript. This research was supported by the Molecular Libraries Program 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 and R03MH085679. The Structural Genomics Consortium is a registered charity (No. 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co., Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. NR 34 TC 48 Z9 51 U1 0 U2 18 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 JUN 1 PY 2010 VL 20 IS 11 BP 3387 EP 3393 DI 10.1016/j.bmcl.2010.04.015 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 597UY UT WOS:000277788900042 PM 20451379 ER PT J AU Graham, A Brender, JD Sharkey, JR Zhu, L Felkner, M Suarez, L Canfield, MA AF Graham, Anna Brender, Jean D. Sharkey, Joseph R. Zhu, Li Felkner, Marilyn Suarez, Lucina Canfield, Mark A. TI Dietary Methionine Intake and Neural Tube Defects in Mexican-American Women SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE neural tube defects; methionine; vitamin B12; birth defects; dietary intake ID AFFECTED PREGNANCIES; BORDER POPULATION; UNITED-STATES; SPINA-BIFIDA; RAT EMBRYOS; RISK; HOMOCYSTEINE; SERUM; CLOSURE; FOLATE AB BACKGROUND: Nutrients other than maternal folic acid are also thought to play a role in preventing neural tube defects (NTDs). Evidence suggests that methionine interacts with folic acid and vitamin 13,2 in the methylation of contractile proteins involved in closing the neural folds. The role of dietary intake of methionine in NTD risk has not been specifically studied among Mexican Americans, a population with one of the highest prevalences of NTDs in the United States. METHODS: We conducted a case control study of 184 Mexican American women with NTD-affected pregnancies (case women) and 225 women with normal offspring (control women) who resided along the Texas-Mexico border. The average daily intakes of methionine were calculated from periconceptional food frequency questionnaire data. Women were categorized according to quartiles of daily methionine intake, based on the control mothers' distribution, and the risk for an NTD-affected pregnancy was calculated using the lowest quartile of intake as the referent. RESULTS: With adjustment for income, body mass index, hyperinsulinemia, and diarrhea, the odds ratios for increasing quartile of methionine intake were: 0.95 (95% confidence interval [CI], 0.48,1.90), 0.92 (95% CI, 0.46,1.84), and 0.66 (95% CI, 0.30,1.45). Some evidence of interaction between dietary methionine and serum vitamin B-12 was noted particularly at higher levels of both components. CONCLUSIONS: This study was limited by a small sample size but examined this association in an exclusively Hispanic population. Results were suggestive of a potential protective effect for NTDs with increasing maternal dietary methionine intake. Birth Defects Research (Part A) 88:451-457, (C) 2010 Wiley-Liss, Inc. C1 [Graham, Anna] Sch Rural Publ Hlth, Texas A&M Hlth Sci Ctr, Off Special Programs, College Stn, TX USA. [Brender, Jean D.] Sch Rural Publ Hlth, Texas A&M Hlth Sci Ctr, Dept Epidemiol & Biostat, College Stn, TX USA. [Sharkey, Joseph R.] Sch Rural Publ Hlth, Texas A&M Hlth Sci Ctr, Dept Social & Behav Hlth, College Stn, TX USA. [Zhu, Li] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Felkner, Marilyn] Dept State Hlth Serv, Emerging & Acute Infect Dis Branch, Austin, TX USA. [Suarez, Lucina] Texas Dept State Hlth Serv, Environm Epidemiol & Dis Registries Sect, Austin, TX USA. [Canfield, Mark A.] Texas Dept State Hlth Serv, Birth Defects Epidemiol & Surveillance Branch, Austin, TX USA. RP Graham, A (reprint author), 1266 TAMU, College Stn, TX 77843 USA. EM acgraham@srph.tamhsc.edu NR 24 TC 5 Z9 5 U1 1 U2 3 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 JUN PY 2010 VL 88 IS 6 BP 451 EP 457 DI 10.1002/bdra.20672 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 623DA UT WOS:000279716900001 PM 20589914 ER PT J AU Gaso-Sokac, D Josic, D AF Gaso-Sokac, Dajana Josic, Djuro TI The role of proteomics in plasma fractionation and quality control of plasma-derived therapeutic proteins SO BLOOD TRANSFUSION LA English DT Article; Proceedings Paper CT Conference on Blood Proteomics - Applications Relevant to Transfusion Medicine CY OCT 12-14, 2009 CL Viterbo, ITALY DE proteomics; quality control; plasma fractionation; Factor VIII ID VON-WILLEBRAND-FACTOR; TRANSFUSION MEDICINE; FACTOR-VIII; FACTOR-IX; ALPHA-INHIBITOR; CONCENTRATE; TOOL; GLYCOSYLATION; ANTITHROMBIN; SEPARATION C1 [Gaso-Sokac, Dajana] JJ Strossmayer Univ, Dept Chem, Osijek, Croatia. [Josic, Djuro] Rhode Isl Hosp, COBRE, Ctr Canc Res Dev, Providence, RI USA. [Josic, Djuro] Brown Univ, Providence, RI 02912 USA. RP Josic, D (reprint author), CORO W, COBRE Ctr Canc Res Dev, Prote Core, Suite 4-206,1 Hoppkin St, Providence, RI 02903 USA. EM Djuro_Josic@brown.edu NR 29 TC 8 Z9 8 U1 0 U2 5 PU SIMITI SERVIZI SRL PI MILAN PA VIALE BEATRICE D ESTE 5, MILAN, 20122, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD JUN PY 2010 VL 8 SU 3 BP S86 EP S91 DI 10.2450/2010.014S PG 6 WC Hematology SC Hematology GA 687VL UT WOS:000284806200014 PM 20606756 ER PT J AU Parisi, MJ Gupta, V Sturgill, D Warren, JT Jallon, JM Malone, JH Zhang, Y Gilbert, LI Oliver, B AF Parisi, Michael J. Gupta, Vaijayanti Sturgill, David Warren, James T. Jallon, Jean-Marc Malone, John H. Zhang, Yu Gilbert, Lawrence I. Oliver, Brian TI Germline-dependent gene expression in distant non-gonadal somatic tissues of Drosophila SO BMC GENOMICS LA English DT Article ID LSP-2 GENE; ECDYSTEROID TITERS; LIFE-SPAN; MELANOGASTER; PROTEINS; HYBRIDIZATION; REPRODUCTION; OOGENESIS; COMMUNITY; DATABASE AB Background: Drosophila females commit tremendous resources to egg production and males produce some of the longest sperm in the animal kingdom. We know little about the coordinated regulation of gene expression patterns in distant somatic tissues that support the developmental cost of gamete production. Results: We determined the non-gonadal gene expression patterns of Drosophila females and males with or without a germline. Our results show that germline-dependent expression in the non-gonadal soma is extensive. Interestingly, gene expression patterns and hormone titers are consistent with a hormone axis between the gonads and non-gonadal soma. Conclusions: The germline has a long-range influence on gene expression in the Drosophila sexes. We suggest that this is the result of a germline/soma hormonal axis. C1 [Parisi, Michael J.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Gupta, Vaijayanti; Sturgill, David; Malone, John H.; Zhang, Yu; Oliver, Brian] NIDDK, Cellular & Dev Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Warren, James T.; Gilbert, Lawrence I.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. Univ Paris 11, CNPS, UMR, UPS CNRS, Orsay, France. RP Parisi, MJ (reprint author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. EM mparisi@sas.upenn.edu FU National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health FX We thank Dr. S. Kobayashi for providing gs(1)N441/FM7c and gs(1)N26/FM7c flies and the Bloomington Drosophila Stock Center for supplying tud1 bw1 sp1/CyO-DTS flies. The Lsp-2 antisera was a gift from Dr. Helen Benes. We thank members of the lab and LCDB for stimulating discussions. This research was supported by the Intramural Research Program of the National Institute of Diabetes Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. NR 53 TC 11 Z9 11 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 1 PY 2010 VL 11 AR 346 DI 10.1186/1471-2164-11-346 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 625BU UT WOS:000279867700002 PM 20515475 ER PT J AU Zimon, M Baets, J Auer-Grumbach, M Berciano, J Garcia, A Lopez-Laso, E Merlini, L Hilton-Jones, D McEntagart, M Crosby, AH Barisic, N Boltshauser, E Shaw, CE Landoure, G Ludlow, CL Gaudet, R Houlden, H Reilly, MM Fischbeck, KH Sumner, CJ Timmerman, V Jordanova, A De Jonghe, P AF Zimon, Magdalena Baets, Jonathan Auer-Grumbach, Michaela Berciano, Jose Garcia, Antonio Lopez-Laso, Eduardo Merlini, Luciano Hilton-Jones, David McEntagart, Meriel Crosby, Andrew H. Barisic, Nina Boltshauser, Eugen Shaw, Christopher E. Landoure, Guida Ludlow, Christy L. Gaudet, Rachelle Houlden, Henry Reilly, Mary M. Fischbeck, Kenneth H. Sumner, Charlotte J. Timmerman, Vincent Jordanova, Albena De Jonghe, Peter TI Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies SO BRAIN LA English DT Article DE transient receptor potential vanilloid 4 gene; hereditary motor and sensory neuropathy type 2C; scapuloperoneal spinal muscular atrophy; congenital distal spinal muscular atrophy; skeletal dysplasia ID SPINAL MUSCULAR-ATROPHY; MARIE-TOOTH-DISEASE; VOCAL CORD PARALYSIS; HEREDITARY MOTOR; SENSORY NEUROPATHY; PHENOTYPIC SPECTRUM; ANKYRIN REPEAT; TRPV4 CHANNEL; GDAP1 GENE; LOCALIZATION AB Hereditary neuropathies form a heterogeneous group of disorders for which over 40 causal genes have been identified to date. Recently, dominant mutations in the transient receptor potential vanilloid 4 gene were found to be associated with three distinct neuromuscular phenotypes: hereditary motor and sensory neuropathy 2C, scapuloperoneal spinal muscular atrophy and congenital distal spinal muscular atrophy. Transient receptor potential vanilloid 4 encodes a cation channel previously implicated in several types of dominantly inherited bone dysplasia syndromes. We performed DNA sequencing of the coding regions of transient receptor potential vanilloid 4 in a cohort of 145 patients with various types of hereditary neuropathy and identified five different heterozygous missense mutations in eight unrelated families. One mutation arose de novo in an isolated patient, and the remainder segregated in families. Two of the mutations were recurrent in unrelated families. Four mutations in transient receptor potential vanilloid 4 targeted conserved arginine residues in the ankyrin repeat domain, which is believed to be important in protein-protein interactions. Striking phenotypic variability between and within families was observed. The majority of patients displayed a predominantly, or pure, motor neuropathy with axonal characteristics observed on electrophysiological testing. The age of onset varied widely, ranging from congenital to late adulthood onset. Various combinations of additional features were present in most patients including vocal fold paralysis, scapular weakness, contractures and hearing loss. We identified six asymptomatic mutation carriers, indicating reduced penetrance of the transient receptor potential vanilloid 4 defects. This finding is relatively unusual in the context of hereditary neuropathies and has important implications for diagnostic testing and genetic counselling. C1 [Zimon, Magdalena; Baets, Jonathan; Jordanova, Albena; De Jonghe, Peter] Univ Antwerp VIB, Dept Mol Genet, Neurogenet Grp, B-2610 Antwerp, Belgium. [Zimon, Magdalena; Baets, Jonathan; Timmerman, Vincent; Jordanova, Albena; De Jonghe, Peter] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, B-2610 Antwerp, Belgium. [Baets, Jonathan; De Jonghe, Peter] Univ Antwerp Hosp, Div Neurol, B-2650 Antwerp, Belgium. [Auer-Grumbach, Michaela] Med Univ Graz, Inst Med Biol, A-8010 Graz, Austria. [Auer-Grumbach, Michaela] Med Univ Graz, Dept Internal Med Diabet & Metab, A-8010 Graz, Austria. [Berciano, Jose; Garcia, Antonio] Univ Cantabria, Santander 39008, Spain. [Berciano, Jose] Univ Hosp Marque de Valdecilla, CIBERNED, Serv Neurol, Santander 39008, Spain. [Garcia, Antonio] Univ Hosp Marque de Valdecilla, CIBERNED, Serv Clin Neurophysiol, Santander 39008, Spain. [Lopez-Laso, Eduardo] Univ Cordoba, Univ Hosp Reina Sofia, Dept Paediat, Paediat Neurol Unit, Cordoba 14005, Spain. [Merlini, Luciano] Univ Ferrara, Dept Expt & Diagnost Med, Muscle Unit, Div Med Genet, I-44100 Ferrara, Italy. [Merlini, Luciano] IOR IRCCS, Lab Musculoskeletal Cell Biol, I-40136 Bologna, Italy. [Hilton-Jones, David] John Radcliffe Hosp, Dept Neurol, Oxford OX3 9DU, England. [McEntagart, Meriel; Crosby, Andrew H.] St George Hosp, Sch Med, Dept Med Genet, London SW17 0RE, England. [Barisic, Nina] Univ Zagreb, Sch Med, Univ Hosp Ctr Zagreb, Dept Paediat, Zagreb 10000, Croatia. [Boltshauser, Eugen] Univ Zurich, Childrens Hosp, Dept Paediat Neurol, CH-8032 Zurich, Switzerland. [Shaw, Christopher E.] Kings Coll London, Dept Clin Neurosci, MRC Ctr Neurodegenerat Res, Inst Psychiat, London SE5 8AF, England. [Landoure, Guida] UCL, Dept Med & Neurosci, London WC1N 3BG, England. [Landoure, Guida] NINDS, Neurogenet Branch, NIH, Bethesda, MD USA. [Ludlow, Christy L.] James Madison Univ, Lab Neural Bases Commun & Swallowing, Harrisonburg, VA 22807 USA. [Gaudet, Rachelle] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Houlden, Henry; Reilly, Mary M.] UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England. [Sumner, Charlotte J.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Timmerman, Vincent] Univ Antwerp, VIB Dept Mol Genet, Peripheral Neuropathy Grp, B-2610 Antwerp, Belgium. RP De Jonghe, P (reprint author), Univ Antwerp VIB, Dept Mol Genet, Neurogenet Grp, Univ Pl 1, B-2610 Antwerp, Belgium. EM peter.dejonghe@molgen.vib-ua.be RI Houlden, Henry/C-1532-2008; Lopez-Laso, Eduardo/B-8700-2014; Gaudet, Rachelle/I-4133-2014; Crosby, Andrew/E-2218-2015; Jordanova, Albena/H-8323-2015; OI Houlden, Henry/0000-0002-2866-7777; Lopez-Laso, Eduardo/0000-0001-7732-6277; Gaudet, Rachelle/0000-0002-9177-054X; Jordanova, Albena/0000-0002-3833-3754; Zimon, Magdalena/0000-0001-7255-6639; MERLINI, LUCIANO/0000-0002-1108-1198; Ludlow, Christy/0000-0002-2015-6171 FU Genetic Service Facility (VIB) FX The authors are grateful to the patients and their families for their willingness to cooperate in this research project. The authors also wish to thank the Genetic Service Facility (VIB) for the sequencing support (http://www.vibgeneticservicefacility.be/)and Dr Robert Kleta for support and encouragement. NR 46 TC 72 Z9 72 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2010 VL 133 BP 1798 EP 1809 DI 10.1093/brain/awq109 PN 6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 603RW UT WOS:000278226700022 PM 20460441 ER PT J AU Filbey, FM Chen, G Sunderland, T Cohen, RM AF Filbey, Francesca M. Chen, Gang Sunderland, Trey Cohen, Robert M. TI Failing Compensatory Mechanisms During Working Memory in Older Apolipoprotein E-epsilon 4 Healthy Adults SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE fMRI; APOE; Alzheimer's disease; Working memory; Compensation ID MILD COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE RISK; APOE EPSILON-4 ALLELE; MIDDLE-AGED ADULTS; GENETIC RISK; BRAIN ACTIVATION; FMRI EVIDENCE; FEATURE BINDING; INTACT ADULTS; E GENOTYPE AB How and when the known genetic risk allele, apolipoprotein E-epsilon 4 (APOE epsilon 4), confers risk to Alzheimer's disease has yet to be determined. We studied older adults and found that APOE epsilon 4 carriers had greater neural activation in the medial frontal and parahippocampal gyrus during a memory task (cluster-corrected p < .01). When compared to a group of younger adults, interactive effects of age and APOE epsilon 4 were found in the inferior frontal-anterior temporal region, one of the first areas to develop amyloid plaques in patients with Alzheimer's disease, and, in the posterior cingulate, one of the earliest areas to show decreased cerebral metabolism in Alzheimer's disease. Thus, abnormally high activation in fronto-temporal areas are present in both younger and older APOE epsilon 4 carriers confronted with a working memory task when compared to non-APOE epsilon 4 carriers. This effect, however, appears to diminish with age. C1 [Filbey, Francesca M.] Mind Res Network, Albuquerque, NM 87106 USA. [Filbey, Francesca M.; Sunderland, Trey; Cohen, Robert M.] NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Cohen, Robert M.] Cedars Sinai Med Ctr, Dept Psychiat & Behav Neurosci, Los Angeles, CA 90048 USA. [Cohen, Robert M.] Cedars Sinai Med Ctr, S Mark Taper Dept Imaging, Los Angeles, CA 90048 USA. RP Filbey, FM (reprint author), Mind Res Network, 1101 Yale Blvd, Albuquerque, NM 87106 USA. EM ffilbey@mrn.org FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [ZO1 MH00330-14] NR 54 TC 17 Z9 17 U1 5 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2010 VL 4 IS 2 BP 177 EP 188 DI 10.1007/s11682-010-9097-9 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA 606HJ UT WOS:000278413200006 PM 20502990 ER PT J AU Dunn, BK Agurs-Collins, T Browne, D Lubet, R Johnson, KA AF Dunn, Barbara K. Agurs-Collins, Tanya Browne, Doris Lubet, Ronald Johnson, Karen A. TI Health disparities in breast cancer: biology meets socioeconomic status SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Review DE Breast cancer; Estrogen receptor negative; Health disparities; Epidemiology; Risk factors; Targeted therapy ID AFRICAN-AMERICAN WOMEN; HORMONE-RECEPTOR STATUS; TRIPLE-NEGATIVE PHENOTYPE; RECREATIONAL PHYSICAL-ACTIVITY; BASAL-LIKE PHENOTYPE; ESTROGEN-RECEPTOR; POSTMENOPAUSAL WOMEN; TRANSGENIC MICE; RISK-FACTORS; SOUTHWEST-ONCOLOGY AB Breast cancer is the most common cancer in women worldwide, accounting for just over 1 million new cases annually. Population-based statistics show that globally, when compared to whites, women of African ancestry (AA) tend to have more aggressive breast cancers that present more frequently as estrogen receptor negative (ERneg) tumors. ERneg tumors fail to respond to current established targeted therapies, whether for treatment or prevention. Subsets of the ERneg phenotype include those that are also negative for the progesterone receptor (PR) and HER2; these are called "triple negative'' (TN) breast cancers. TN tumors frequently have pathological characteristics resembling "basal-like'' breast cancers. Hence, the latter two terms are often used interchangeably; yet, despite extensive overlap, they are not synonymous. The ERneg, TN, and basal-like phenotypic categories are important because they carry worse prognoses than ER-positive (ERpos) tumors, in addition to lacking obvious molecular targets, such as HER2 and the ER, for known therapies. Furthermore, among premenopausal women the three subsets occur more frequently in women of African descent compared to white women with breast cancer. The contribution of these three subtypes of poor-prognosis tumors to the higher breast cancer mortality in black women is the focus of this review. We will attempt to clarify some of the issues, including risk factors, in terms of their contribution to that component of health disparities that involves biological differences in breast cancer between women of AA and white women. C1 [Dunn, Barbara K.] NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Browne, Doris] Browne & Associates Inc, Washington, DC USA. RP Dunn, BK (reprint author), NCI, Basic Prevent Sci Res Grp, Canc Prevent Div, 6130 Execut Blvd,Room 2056, Bethesda, MD 20892 USA. EM dunnb@mail.nih.gov NR 108 TC 41 Z9 41 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2010 VL 121 IS 2 BP 281 EP 292 DI 10.1007/s10549-010-0827-x PG 12 WC Oncology SC Oncology GA 599JC UT WOS:000277906500003 PM 20437200 ER PT J AU Figueroa, JD Flanders, KC Garcia-Closas, M Anderson, WF Yang, XHR Matsuno, RK Duggan, MA Pfeiffer, RM Ooshima, A Cornelison, R Gierach, GL Brinton, LA Lissowska, J Peplonska, B Wakefield, LM Sherman, ME AF Figueroa, Jonine D. Flanders, Kathleen C. Garcia-Closas, Montserrat Anderson, William F. Yang, Xiaohong R. Matsuno, Rayna K. Duggan, Maire A. Pfeiffer, Ruth M. Ooshima, Akira Cornelison, Robert Gierach, Gretchen L. Brinton, Louise A. Lissowska, Jolanta Peplonska, Beata Wakefield, Lalage M. Sherman, Mark E. TI Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Transforming growth factor beta; Breast cancer; Estrogen receptor ID PROGNOSTIC-SIGNIFICANCE; RISK-FACTORS; TGF-BETA-1; LOCALIZATION; RECEPTORS; TUMORIGENESIS; PROGRESSION; CARCINOMA; SURVIVAL; DISEASE AB The transforming growth factor beta (TGF-beta) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-beta signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case-control study conducted in Poland from 2000 to 2003. TGF-beta signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-beta 1 (78%), TGF-beta 2 (91%), TGF-beta 3 (93%), TGF-beta R2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-beta 1 was expressed in 32% of tumors. Expression of TGF-beta ligands (beta 1, beta 2, and beta 3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-beta R2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-beta. In addition, expression of extracellular-TGF-beta 1 (P = 0.005), TGF-beta R2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-beta signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment. C1 [Figueroa, Jonine D.; Garcia-Closas, Montserrat; Anderson, William F.; Yang, Xiaohong R.; Matsuno, Rayna K.; Pfeiffer, Ruth M.; Gierach, Gretchen L.; Brinton, Louise A.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Flanders, Kathleen C.; Ooshima, Akira; Wakefield, Lalage M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Duggan, Maire A.] Univ Calgary, Dept Pathol, Calgary, AB, Canada. [Duggan, Maire A.] Univ Calgary, Dept Lab Med, Calgary, AB, Canada. [Duggan, Maire A.] Calgary Lab Serv, Calgary, AB, Canada. [Cornelison, Robert] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Figueroa, JD (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM figueroaj@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Pfeiffer, Ruth /F-4748-2011; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS [ZIA CP010126-14] NR 27 TC 33 Z9 34 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2010 VL 121 IS 3 BP 727 EP 735 DI 10.1007/s10549-009-0590-z PG 9 WC Oncology SC Oncology GA 595TM UT WOS:000277636000021 PM 19937272 ER PT J AU Kingma, E AF Kingma, Elselijn TI Paracetamol, Poison, and Polio: Why Boorse's Account of Function Fails to Distinguish Health and Disease SO BRITISH JOURNAL FOR THE PHILOSOPHY OF SCIENCE LA English DT Article ID PSYCHIATRY; MEDICINE; ILLNESS AB Christopher Boorse's Bio Statistical Theory (BST) defines health as the absence of disease, and disease as the adverse departure from normal species functioning. This paper presents a two-pronged problem for this account. First I demonstrate that, in order to accurately account for dynamic physiological functions, Boorse's account of normal function needs to be modified to index functions against situations. I then demonstrate that if functions are indexed against situations, the BST can no longer account for diseases that result from specific environmental factors. The BST is impaled on either horn of this dilemma and therefore must be dismissed. C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Kingma, E (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,Room 1C118, Bethesda, MD 20892 USA. EM kingmae@cc.nih.gov FU Wellcome Trust [077887]; Department of Bioethics, Clinical Centre, National Institutes of Health FX I would like to thank Tim Lewens, Peter Lipton, Christopher Boorse, Martin Peterson, Matthew Drage, Danielle Bromwich, the 2007 Cambridge Philosophy Workshop, and an anonymous referee of this journal for helpful comments on this paper. The views herein are those of the author and do not represent the views or policies of the Department of Health and Human Services or the National Institutes of Health. Funding for this work was provided by the Wellcome Trust (077887), and the Intramural Research Program of the Department of Bioethics, Clinical Centre, National Institutes of Health. NR 37 TC 27 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0882 J9 BRIT J PHILOS SCI JI Br. J. Philos. Sci. PD JUN PY 2010 VL 61 IS 2 BP 241 EP 264 DI 10.1093/bjps/axp034 PG 24 WC History & Philosophy Of Science SC History & Philosophy of Science GA 600OK UT WOS:000277996300001 ER PT J AU Herishanu, Y Eshel, R Kay, S Rothman, R Njuguna, N Perry, C Shpringer, M Wiestner, A Polliack, A Naparstek, E AF Herishanu, Yair Eshel, Rinat Kay, Sigi Rothman, Rachel Njuguna, Ndegwa Perry, Chava Shpringer, Meirav Wiestner, Adrian Polliack, Aaron Naparstek, Elizabeth TI Unexpected detection of monoclonal B-cell lymphocytosis in a HLA-matched sibling donor on the day of allogeneic stem cell transplantation for a patient with chronic lymphocytic leukaemia: clinical outcome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE chronic lymphocytic leukaemia; transplantation; monoclonal B-cell lymphocytosis C1 [Herishanu, Yair; Eshel, Rinat; Kay, Sigi; Perry, Chava; Shpringer, Meirav; Polliack, Aaron] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Haematol, IL-69978 Tel Aviv, Israel. [Herishanu, Yair; Eshel, Rinat; Kay, Sigi; Perry, Chava; Shpringer, Meirav; Polliack, Aaron] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, BMT, IL-69978 Tel Aviv, Israel. [Rothman, Rachel] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Genet Inst, IL-69978 Tel Aviv, Israel. [Njuguna, Ndegwa; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Naparstek, Elizabeth] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RP Herishanu, Y (reprint author), Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Haematol, IL-69978 Tel Aviv, Israel. EM yairh@tasmc.health.gov.il NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2010 VL 149 IS 6 BP 905 EP 907 DI 10.1111/j.1365-2141.2010.08133.x PG 3 WC Hematology SC Hematology GA 600GN UT WOS:000277973400014 PM 20201940 ER PT J AU Yeh, S Li, Z Sen, HN Lim, WK Gill, F Perkins, K Rao, VK Nussenblatt, RB AF Yeh, S. Li, Z. Sen, H. N. Lim, W-K Gill, F. Perkins, K. Rao, V. K. Nussenblatt, R. B. TI Scleritis and multiple systemic autoimmune manifestations in chronic natural killer cell lymphocytosis associated with elevated TCR alpha/beta(+)CD3(+)CD4(-)CD8(-) double-negative T cells SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; NECROTIZING SCLERITIS; SJOGRENS-SYNDROME; NK CELLS; IN-VIVO; EXPRESSION; SCLEROSIS; IMMUNOPATHOLOGY; PSORIASIS; APOPTOSIS AB Background/aims Chronic natural killer lymphocytosis (CNKL) has been associated with systemic autoimmunity; however, its association with scleritis or ocular autoimmunity has not been characterised. The natural killer (NK) cell function and immunophenotype of a patient with CNKL who developed bilateral scleritis and multiple systemic autoimmune findings were evaluated. Methods The ophthalmic records of a patient with CNKL and scleritis were reviewed over a 6-year period. Flow cytometry was performed to evaluate T cell, NK and B cell populations. NK cellular functions (ie, NK cytotoxicity and cytokine/chemokine production following interleukin 2 (IL2) stimulation) were evaluated. Results A 56-year-old woman with vitiligo, psoriatic arthritis, thyroiditis, erythema nodosum, bilateral anterior scleritis and Sjogren syndrome was managed with multiple immunosuppressive medications, including prednisone, mycophenolate mofetil and methotrexate. Flow cytometry showed a persistent elevation of CD56(+)CD3(-) NK cells greater than 40%, which was consistent with CNKL. NK cell cytotoxicity assay identified a deficiency of K562 cell lysis in the patient (1.46 mean-fold greater in control vs patient). NK cytokine/chemokine production following IL2 stimulation was also deficient (2.5-32.5-fold greater in control). Cytokines/chemokines assessed included pro-inflammatory (interferon gamma, tumor necrosis factor alpha, IL1, monocyte chemotactic protein 1) and immunoregulatory cytokines (IL4, IL5 and IL10). An abnormal elevation of TCR alpha/beta(+) CD3(+)CD4(-)CD8(-) T cells suggestive of autoimmune lymphoproliferative syndrome was observed; however, apoptosis dysfunction was not found. Conclusion The association of increased but dysfunctional NK cells in the context of multiple systemic and ocular manifestations suggests a role of NK cells in the pathogenesis of our patient's disease. Further studies regarding NK cell dysfunction and ocular autoimmunity are needed. C1 [Yeh, S.; Li, Z.; Sen, H. N.; Lim, W-K; Nussenblatt, R. B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Gill, F.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Perkins, K.; Rao, V. K.] NIAID, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,10N112,10 Ctr Dr, Bethesda, MD 20892 USA. FU National Eye Institute, National Institutes of Health; National Institute for Allergy and Infectious Disease, National Institutes of Health; Heed Ophthalmic Foundation; NIH FX This research is supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health and the National Institute for Allergy and Infectious Disease, National Institutes of Health. Dr Steven Yeh has received support from the Heed Ophthalmic Foundation. Other Funders: NIH. NR 24 TC 4 Z9 5 U1 1 U2 1 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 JUN PY 2010 VL 94 IS 6 BP 748 EP 752 DI 10.1136/bjo.2009.171264 PG 5 WC Ophthalmology SC Ophthalmology GA 601VK UT WOS:000278093200017 PM 20508050 ER PT J AU Ferre, S Lluis, C Justinova, Z Quiroz, C Orru, M Navarro, G Canela, EI Franco, R Goldberg, SR AF Ferre, Sergi Lluis, Carme Justinova, Zuzana Quiroz, Cesar Orru, Marco Navarro, Gemma Canela, Enric I. Franco, Rafael Goldberg, Steven R. TI Adenosine-cannabinoid receptor interactions. Implications for striatal function SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE adenosine A(2A) receptor; cannabinoid CB(1) receptor; dopamine D(2) receptor; receptor heteromers; striatum; basal ganglia disorders; drug addiction ID PROTEIN-COUPLED RECEPTORS; DOPAMINE D2 RECEPTORS; BIOLUMINESCENCE ENERGY-TRANSFER; RAT NUCLEUS-ACCUMBENS; A(2A) RECEPTORS; BASAL GANGLIA; CB1 RECEPTOR; ULTRASTRUCTURAL-LOCALIZATION; ENDOCANNABINOID RELEASE; CONCURRENT STIMULATION AB This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x. C1 [Ferre, Sergi; Justinova, Zuzana; Quiroz, Cesar; Orru, Marco; Goldberg, Steven R.] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224 USA. [Lluis, Carme; Navarro, Gemma; Canela, Enric I.; Franco, Rafael] Univ Barcelona, Fac Biol, CIBERNED, Dept Biochem & Mol Biol, Barcelona, Spain. [Justinova, Zuzana] Univ Maryland, MPRC, Dept Psychiat, Baltimore, MD 21201 USA. [Franco, Rafael] CIMA Neurociencias, Pamplona, Spain. RP Ferre, S (reprint author), Natl Inst Drug Abuse, IRP, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011; Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015 OI Justinova, Zuzana/0000-0001-5793-7484; Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919 FU National Institute on Drug Abuse; NIH; DHHS; Spanish 'Ministerio de Ciencia y Tecnologia' [SAF2008-00146, SAF2008-03229-E/]; 'Fundacio La Marato de TV3' [060110] FX Work supported by the intramural funds of the National Institute on Drug Abuse, NIH, DHHS and by Grants from Spanish 'Ministerio de Ciencia y Tecnologia' (SAF2008-00146 and SAF2008-03229-E/ for ERA-NET Coordination of Research Activities) and grant 060110 from 'Fundacio La Marato de TV3'. NR 95 TC 44 Z9 45 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2010 VL 160 IS 3 BP 443 EP 453 DI 10.1111/j.1476-5381.2010.00723.x PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599LR UT WOS:000277914700003 PM 20590556 ER PT J AU Panlilio, LV Justinova, Z Goldberg, SR AF Panlilio, Leigh V. Justinova, Zuzana Goldberg, Steven R. TI Animal models of cannabinoid reward SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Review DE addiction; anandamide; conditioned place preference; drug discrimination; drug self-administration; electrical brain reward; FAAH; gateway hypothesis; microdialysis; rimonabant; withdrawal ID ACID AMIDE HYDROLASE; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS SHELL; CB1 RECEPTOR AGONIST; ENDOCANNABINOID SYSTEM; SQUIRREL-MONKEYS; RHESUS-MONKEYS; REINFORCING EFFICACY; SEEKING BEHAVIOR; BRAIN REWARD AB This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x. C1 [Panlilio, Leigh V.; Justinova, Zuzana; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland FX The preparation of this manuscript was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services and Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland. NR 116 TC 18 Z9 18 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2010 VL 160 IS 3 BP 499 EP 510 DI 10.1111/j.1476-5381.2010.00775.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599LR UT WOS:000277914700007 PM 20590560 ER PT J AU Mukhopadhyay, P Pan, H Rajesh, M Batkai, S Patel, V Harvey-White, J Mukhopadhyay, B Hasko, G Gao, B Mackie, K Pacher, P AF Mukhopadhyay, Partha Pan, Hao Rajesh, Mohanraj Batkai, Sandor Patel, Vivek Harvey-White, Judith Mukhopadhyay, Bani Hasko, Gyoergy Gao, Bin Mackie, Ken Pacher, Pal TI CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE nephropathy; endocannabinoids; cannabinoid receptors ID CISPLATIN-INDUCED NEPHROTOXICITY; ISCHEMIA-REPERFUSION INJURY; HEPATIC ISCHEMIA/REPERFUSION INJURY; INDUCED RENAL INJURY; ENDOCANNABINOID SYSTEM; NITRIC-OXIDE; CARDIOVASCULAR-DISEASE; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; LIVER-DISEASES AB Background and purpose: Accumulating recent evidence suggests that cannabinoid-1 (CB1) receptor activation may promote inflammation and cell death and its pharmacological inhibition is associated with anti-inflammatory and tissue-protective effects in various preclinical disease models, as well as in humans. Experimental approach: In this study, using molecular biology and biochemistry methods, we have investigated the effects of genetic deletion or pharmacological inhibition of CB1 receptors on inflammation, oxidative/nitrosative stress and cell death pathways associated with a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Results: Cisplatin significantly increased endocannabinoid anandamide content, activation of p38 and JNK mitogen-activated protein kinases (MAPKs), apoptotic and poly (ADP-ribose)polymerase-dependent cell death, enhanced inflammation (leucocyte infiltration, tumour necrosis factor-alpha and interleukin-1 beta) and promoted oxidative/nitrosative stress [increased expressions of superoxide-generating enzymes (NOX2(gp91phox), NOX4), inducible nitric oxide synthase and tissue 4-hydroxynonenal and nitrotyrosine levels] in the kidneys of mice, accompanied by marked histopathological damage and impaired renal function (elevated creatinine and serum blood urea nitrogen) 3 days following its administration. Both genetic deletion and pharmacological inhibition of CB1 receptors with AM281 or SR141716 markedly attenuated the cisplatin-induced renal dysfunction and interrelated oxidative/nitrosative stress, p38 and JNK MAPK activation, cell death and inflammatory response in the kidney. Conclusions and implications: The endocannabinoid system through CB1 receptors promotes cisplatin-induced tissue injury by amplifying MAPK activation, cell death and interrelated inflammation and oxidative/nitrosative stress. These results also suggest that inhibition of CB1 receptors may exert beneficial effects in renal (and most likely other) diseases associated with enhanced inflammation, oxidative/nitrosative stress and cell death. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Pan, Hao] Zhejiang Univ, Dept Urol, Affiliated Hosp 1, Coll Med, Hangzhou 310003, Zhejiang, Peoples R China. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Mackie, Ken] Indiana Univ, Gill Ctr, Bloomington, IN USA. [Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Mackie, Kenneth/B-7358-2011; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Ji, Haofeng/G-6206-2012; Mackie, Ken/E-3715-2013; Batkai, Sandor/H-7983-2014 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199; FU NIH/NIAAA; NIH/NIDA [DA11322, DA21696] FX This study was supported by the Intramural Research Program of NIH/NIAAA (to PP) and NIH/NIDA (DA11322 & DA21696 to KM). Authors are indebted to Dr George Kunos for the endocannabinoid measurements. PP dedicates this study to his beloved mother Iren Bolfert, who died from the complications of chemotherapy. NR 67 TC 53 Z9 55 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2010 VL 160 IS 3 BP 657 EP 668 DI 10.1111/j.1476-5381.2010.00769.x PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599LR UT WOS:000277914700021 PM 20590569 ER PT J AU Rajesh, M Mukhopadhyay, P Hasko, G Liaudet, L Mackie, K Pacher, P AF Rajesh, Mohanraj Mukhopadhyay, Partha Hasko, Gyoergy Liaudet, Lucas Mackie, Ken Pacher, Pal TI Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE endothelial cells; atherosclerosis; vascular dysfunction; endocannabinoids; cannabinoid receptors ID ISCHEMIA-REPERFUSION INJURY; OBESE ZUCKER RATS; ENDOCANNABINOID SYSTEM; INFLAMMATORY BIOMARKERS; OXIDATIVE STRESS; CEREBRAL-ISCHEMIA; ATHEROSCLEROSIS; ANTAGONIST; DYSFUNCTION; DISEASE AB Background and purpose: Impaired endothelial activity and/or cell death play a critical role in the development of vascular dysfunction associated with congestive heart failure, diabetic complications, hypertension, coronary artery disease and atherosclerosis. Increasing evidence suggests that cannabinoid 1 (CB(1)) receptor inhibition is beneficial in atherosclerosis and cardiovascular inflammation both in experimental models, as well as in humans. Here, we investigated the effects of CB(1) receptor activation with the endocannabinoid anandamide (AEA) or synthetic agonist HU210 on cell death and interrelated signal transduction pathways in human primary coronary artery endothelial cells (HCAECs). Experimental approach: Cell death, CB(1) receptor expression, reactive oxygen species (ROS) generation and activation of signal transduction pathways in HCAECs were determined by flow cytometry and molecular biology tools. Key results: In HCAECs expressing CB(1) receptors (demonstrated by Western immunoblot and flow cytometry) AEA (5-15 mu M) or HU210 (30-1000 nM) triggered concentration- and time-dependent activation of p38 and c-Jun NH(2)-terminal protein kinase (JNK)-mitogen-activated protein kinases (MAPKs), cell death and ROS generation. The AEA- or HU210-induced cell death and MAPK activation were attenuated by CB(1) antagonists [SR141716 (rimonabant) and AM281], inhibitors of p38 and JNK-MAPKs or the antioxidant N-acetylcysteine. N-acetylcysteine alone prevented AEA- or HU210-induced ROS generation, but only partially attenuated MAPK activation and cell death. In contrast, in combination with CB(1) antagonists, N-acetylcysteine completely prevented these effects. Conclusions and implications: CB(1) receptor activation in endothelial cells may amplify the ROS-MAPK activation-cell death pathway in pathological conditions when the endocannabinoid synthetic or metabolic pathways are dysregulated by excessive inflammation and/or oxidative/nitrosative stress, thereby contributing to the development of endothelial dysfunction and pathophysiology of multiple cardiovascular diseases. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x. C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. [Liaudet, Lucas] Univ Med Ctr, Dept Intens Care Med, Lausanne, Switzerland. [Liaudet, Lucas] Fac Biol & Med, Lausanne, Switzerland. [Mackie, Ken] Indiana Univ, Gill Ctr, Bloomington, IN USA. [Mackie, Ken] Indiana Univ, Dept Psychol & Brain Sci, Bloomington, IN USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI Mackie, Ken/E-3715-2013; Liaudet, Lucas/E-1322-2017; MUKHOPADHYAY, PARTHA/G-3890-2010; Mackie, Kenneth/B-7358-2011; Pacher, Pal/B-6378-2008 OI Mackie, Ken/0000-0001-8501-6199; Liaudet, Lucas/0000-0003-2670-4930; MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU NIH/NIAAA; [DA11322]; [DA21696] FX This study was supported by the Intramural Research Program of NIH/NIAAA (P.P.), and DA11322 and DA21696 (K.M.). NR 62 TC 41 Z9 43 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 2010 VL 160 IS 3 BP 688 EP 700 DI 10.1111/j.1476-5381.2010.00712.x PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599LR UT WOS:000277914700024 PM 20590572 ER PT J AU Scarinci, IC Garcia, FAR Kobetz, E Partridge, EE Brandt, HM Bell, MC Dignan, M Ma, GX Daye, JL Castle, PE AF Scarinci, Isabel C. Garcia, Francisco A. R. Kobetz, Erin Partridge, Edward E. Brandt, Heather M. Bell, Maria C. Dignan, Mark Ma, Grace X. Daye, Jane L. Castle, Philip E. TI Cervical Cancer Prevention New Tools and Old Barriers SO CANCER LA English DT Review DE cervical cancer; human papillomavirus testing; human papillomavirus vaccination; cervical cancer prevention ID RANDOMIZED CONTROLLED-TRIAL; HUMAN-PAPILLOMAVIRUS DNA; VIETNAMESE-AMERICAN WOMEN; LIQUID-BASED CYTOLOGY; DEEP SOUTH NETWORK; UNITED-STATES; QUADRIVALENT VACCINE; HEALTH DISPARITIES; PARTICLE VACCINE; HPV VACCINATION AB Cervical cancer is the second most common female tumor worldwide, and its incidence is disproportionately high (>80%) in the developing world. In the United States, in which Papanicolaou (Pap) tests have reduced the annual incidence to approximately 11,000 cervical cancers, >60% of cases are reported to occur in medically underserved populations as part of a complex of diseases linked to poverty, race/ethnicity, and/or health disparities. Because carcinogenic human papillomavirus (HPV) infections cause virtually all cervical cancer, 2 new approaches for cervical cancer prevention have emerged: 1) HPV vaccination to prevent infections in younger women (aged <= 18 years) and 2) carcinogenic HPV detection in older women (aged >= 30 years). Together, HPV vaccination and testing, if used in an age-appropriate manner, have the potential to transform cervical cancer prevention, particularly among underserved populations. Nevertheless, significant barriers of access, acceptability, and adoption to any cervical cancer prevention strategy remain. Without understanding and addressing these obstacles, these promising new tools for cervical cancer prevention may be futile. In the current study, the delivery of cervical cancer prevention strategies to these US populations that experience a high cervical cancer burden (African-American women in South Carolina, Alabama, and Mississippi; Haitian immigrant women in Miami; Hispanic women in the US-Mexico Border; Sioux/Native American women in the Northern Plains; white women in the Appalachia; and Vietnamese-American women in Pennsylvania and New Jersey) is reviewed. The goal was to inform future research and outreach efforts to reduce the burden of cervical cancer in underserved populations. Cancer 2010;116:2531-42. (C) 2070 American Cancer Society. C1 [Scarinci, Isabel C.] Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. [Garcia, Francisco A. R.] Univ Arizona, Dept Obstet & Gynecol, Tucson, AZ USA. [Kobetz, Erin] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Partridge, Edward E.] Univ S Carolina, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Bell, Maria C.] Sanford Clin, Sioux Falls, SD USA. [Dignan, Mark] Univ Kentucky, Prevent Res Ctr, Lexington, KY USA. [Ma, Grace X.] Temple Univ, Ctr Asian Hlth, Philadelphia, PA 19122 USA. [Daye, Jane L.] NCI, Ctr Reducing Canc Hlth Dispar, NIH, Bethesda, MD 20892 USA. [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Scarinci, Isabel C.; Partridge, Edward E.] Univ Alabama, Univ Alabama Birmingham Comprehens Canc, Birmingham, AL 35294 USA. RP Scarinci, IC (reprint author), Univ Alabama, Div Prevent Med, 1530 3rd Ave S MT 609, Birmingham, AL 35294 USA. EM scarinci@uab.edu FU Westat Corporation, Rockville, Maryland; National Institutes of Health/National Cancer Institute (NCI); NCI Center for Reducing Cancer Health Disparities; NCI [U01 CA114619, R21CA-11, 981, U01 CA86098-04, R01 CA120606, R01 CA111570, U01 CA114582, U01 CA114601, U01CA114601-03S4]; American Cancer Society (ACS) [MRSGT-07-159-01-CPHPS]; Dr. John T. Macdonald Foundation [98218]; Women's Fund of Miami-Dade County [M0600284]; Centers for Disease Control and Prevention [U58 DP001044-01] FX We acknowledge the support of Tameka Walls, Vanessa Olivio, Kerrygrace Morrissey, and Shelly Niwa of Westat Corporation, Rockville, Maryland.; Dr. Castle was supported by the intramural program of the National Institutes of Health/National Cancer Institute (NCI) and the NCI Center for Reducing Cancer Health Disparities. The following grants supported this work: NCI U01 CA114619 (Drs. Scarinci and Partridge); NCI R21CA-11, 981, the American Cancer Society (ACS) (MRSGT-07-159-01-CPHPS), the Dr. John T. Macdonald Foundation (98218), and the Women's Fund of Miami-Dade County (M0600284) (Dr. Kobetz); ACS and NCI U01 CA86098-04 (Dr. Bell); NCI R01 CA120606 (Dr. Dignan); NCI R01 CA111570 and U01 CA114582 (Dr. Ma); NCI U01 CA114601 and U01CA114601-03S4 (Dr. Brandt); and Centers for Disease Control and Prevention U58 DP001044-01(Dr. Garcia). NR 77 TC 120 Z9 128 U1 5 U2 23 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2010 VL 116 IS 11 BP 2531 EP 2542 DI 10.1002/cncr.25065 PG 12 WC Oncology SC Oncology GA 600LZ UT WOS:000277989100006 PM 20310056 ER PT J AU Sinclair, S Swain, SM AF Sinclair, Sarah Swain, Sandra M. TI Primary Systemic Chemotherapy for Inflammatory Breast Cancer SO CANCER LA English DT Article; Proceedings Paper CT 1st International Inflammatory Breast Cancer Conference CY DEC 05-07, 2008 CL Houston, TX DE inflammatory breast cancer; neoadjuvant chemotherapy; multimodality therapy; bevacizumab ID STEM-CELL TRANSPLANTATION; CARCINOMA; SURVIVAL; THERAPY; BEVACIZUMAB; DOXORUBICIN; EXPRESSION; DISEASE; TRIAL; ANGIOGENESIS AB The advent of multimodality therapy for patients with inflammatory breast cancer (IBC), consisting of neoadjuvant chemotherapy, particularly taxanes, surgery, radiotherapy, and hormonal therapy, has improved survival. A pathologic complete response to neoadjuvant chemotherapy in locally advanced breast cancer and IBC improves outcomes, which suggests that obtaining a pathologic complete response to neoadjuvant chemotherapy has prognostic significance. The benefit of high-dose chemotherapy has shown encouraging results; however, this approach needs to be prospectively evaluated and to date remains experimental. Vascular endothelial growth factor, a promoter of angiogenesis, is highly expressed in IBC, making the angiogenesis pathway an attractive therapeutic target. A better understanding of the complex biology of IBC is needed for the development of additional targeted agents to further improve outcomes for patients with this aggressive form of breast cancer. Cancer 2010;116(11 suppl):2821-8. (C) 2010 American Cancer Society. C1 [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. [Sinclair, Sarah] NCI, Dept Oncol, NIH, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA. EM Sandra.M.Swain@Medstar.net OI Swain, Sandra/0000-0002-1320-3830 NR 44 TC 12 Z9 15 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2010 VL 116 IS 11 SU S BP 2821 EP 2828 DI 10.1002/cncr.25166 PG 8 WC Oncology SC Oncology GA 600MA UT WOS:000277989200015 PM 20503414 ER PT J AU Yang, L AF Yang, Li TI TGF beta and cancer metastasis: an inflammation link SO CANCER AND METASTASIS REVIEWS LA English DT Review DE TGF beta; Tumor suppressor; Metastasis; Immune; Inflammation; Tumor microenvironment ID GROWTH-FACTOR-BETA; T-CELL; MYELOID CELLS; COLON-CANCER; TUMOR PROGRESSION; SUPPRESSOR-CELLS; IMMUNE-SYSTEM; PROMOTE METASTASIS; MAMMARY CARCINOMAS; GENE-EXPRESSION AB Dysregulated transforming growth factor beta (TGF beta) signaling is observed in a variety of human cancers. TGF beta is produced in large quantities by many tumor types and is known to be pro-oncogenic. Therapeutic strategies directed against TGF beta signaling using neutralizing antibodies and small molecular inhibitors have been developed. However, TGF beta is also found to function as a tumor suppressor. This switch from a tumor suppressor in premalignant stages of tumorigenesis to a tumor promoter in later stages of the disease poses great challenges in TGF beta-targeted cancer therapy. It remains unclear what mechanisms underlie the dual role of TGF beta and what factors mediate the switch. In the past, most work on dissecting underlying mechanisms was focused on differential regulation of signaling pathways by tumor cell autonomous TGF beta signaling. Recent progress in elucidating TGF beta effects on host immune/inflammatory reactions in the tumor microenvironment and distant organs brings exciting new perspectives to the field. C1 NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA. RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 3134C,37 Convent Dr,MSC 4258, Bethesda, MD 20876 USA. EM yangl3@mail.nih.gov NR 87 TC 29 Z9 29 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2010 VL 29 IS 2 SI SI BP 263 EP 271 DI 10.1007/s10555-010-9226-3 PG 9 WC Oncology SC Oncology GA 592WC UT WOS:000277411300004 PM 20437081 ER PT J AU Platz, EA Sutcliffe, S De Marzo, AM Drake, CG Rifai, N Hsing, AW Hoque, A Neuhouser, ML Goodman, PJ Kristal, AR AF Platz, Elizabeth A. Sutcliffe, Siobhan De Marzo, Angelo M. Drake, Charles G. Rifai, Nader Hsing, Ann W. Hoque, Ashraful Neuhouser, Marian L. Goodman, Phyllis J. Kristal, Alan R. TI Intra-individual variation in serum C-reactive protein over 4 years: an implication for epidemiologic studies SO CANCER CAUSES & CONTROL LA English DT Article DE C-reactive protein; Variability; Relative risk ID CORONARY-HEART-DISEASE; VARIABILITY; RISK; HEALTHY; TIME; INFLAMMATION; BIOMARKERS; INTERVALS; CANCER; COHORT AB Data on long-term intra-individual variability in high-sensitivity C-reactive protein (hsCRP) are needed to determine whether one measurement adequately reflects usual levels in prospective studies of on the etiology of cancer and other chronic diseases; when not reflective, the ability to statistically detect modest to moderate associations is reduced. The authors estimated the size of this source of variability and consequent attenuation of the relative risk (RR). High-sensitivity C-reactive protein (hsCRP) concentration was measured using a high-sensitivity immunoturbidometric assay in sera collected at years 2, 4, and 6 from 50 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). After natural logarithm-transformation of hsCRP, analysis of variance was used to estimate the within- and between-individual variances from which the intra-class correlation coefficient (ICC) was calculated. The observed RR due to an ICC < 1 was calculated by e((ln true RR*ICC)) for a range of true RRs. The 4-year ICC was 0.66. Measuring hsCRP once and assuming no other error, if the true RRs were 1.50, 2.00, and 3.00 when comparing high with low concentration, then the observed RRs would be 1.31, 1.58, and 2.06, respectively. Investigators planning to measure hsCRP only once should design adequately sized studies to preserve inferences for hypothesized modest to moderate RRs. C1 [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Platz, Elizabeth A.; De Marzo, Angelo M.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Platz, Elizabeth A.; De Marzo, Angelo M.; Drake, Charles G.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [De Marzo, Angelo M.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Drake, Charles G.] Johns Hopkins Med Inst, Dept Immunol, Baltimore, MD 21205 USA. [Rifai, Nader] Childrens Hosp Boston, Boston, MA USA. [Rifai, Nader] Harvard Univ, Sch Med, Boston, MA USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. [Neuhouser, Marian L.; Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Seattle, WA 98104 USA. [Kristal, Alan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Rm E6132, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu OI Sutcliffe, Siobhan/0000-0002-4613-8107; Kristal, Alan/0000-0002-7329-1617 FU National Cancer Institute, National Institutes of Health [CCOP2016, P01 CA 108964] FX We thank Gary Bradwin at Children's Hospital Boston, Bob Dayton at the University of Colorado, and Anna DeNooyer at the Johns Hopkins Bloomberg School of Public Health. This work was supported by the National Cancer Institute, National Institutes of Health (CCOP2016, P01 CA 108964). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 20 TC 18 Z9 18 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2010 VL 21 IS 6 BP 847 EP 851 DI 10.1007/s10552-010-9511-z PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 596UA UT WOS:000277709800006 PM 20135215 ER PT J AU Bonner, MR Williams, BA Rusiecki, JA Blair, A Freeman, LEB Hoppin, JA Dosemeci, M Lubin, J Sandler, DP Alavanja, MCR AF Bonner, Matthew R. Williams, Brent A. Rusiecki, Jennifer A. Blair, Aaron Freeman, Laura E. Beane Hoppin, Jane A. Dosemeci, Mustafa Lubin, Jay Sandler, Dale P. Alavanja, Michael C. R. TI Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer incidence; Terbufos; Organophosphate insecticides ID NON-HODGKINS-LYMPHOMA; PESTICIDE USE; PROSTATE-CANCER; RISK-FACTORS; ORGANOPHOSPHOROUS PESTICIDES; COHORT; APPLICATORS; IOWA; MEN; INFORMATION AB Terbufos is the fourth most commonly used organophosphate insecticide (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic in rodents, although non-arsenical insecticides, including OPs, have been associated with excess cancer in epidemiologic studies. We investigated associations between use of terbufos and the incidence of cancer. The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Terbufos intensity-weighted lifetime exposure-days were defined as (lifetime exposure-days) x (exposure intensity score). Cases include all first primary cancers diagnosed between enrollment and December 31, 2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards models, adjusting for potential confounders. Overall cancer risk was slightly increased among terbufos users [HR 1.21 (1.06-1.37)]. Suggestive associations were observed between terbufos use and cancers of the prostate (HR(highest tertile) = 1.21; 95% CI = 0.99-1.47) and lung (HR(middle tertile) = 1.45; 95% CI = 0.95-2.22) and leukemia (HR(middle tertile) = 2.38; 95% CI = 1.35-4.21) and non-Hodgkin's lymphoma (HR(middle tertile) = 1.94; 95% CI = 1.16-3.22), although the exposure-response gradients were non-monotonic and p for trends were not significant. We found suggestive associations between occupational terbufos use and several cancer sites. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos. C1 [Bonner, Matthew R.; Williams, Brent A.] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Rusiecki, Jennifer A.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Blair, Aaron; Freeman, Laura E. Beane; Dosemeci, Mustafa; Alavanja, Michael C. R.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hoppin, Jane A.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Lubin, Jay] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bonner, MR (reprint author), SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, 270 Farber Hall, Buffalo, NY 14260 USA. EM mrbonner@buffalo.edu RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU National Institutes of Health, the National Institute of Environmental Health Sciences [Z01-ES049030-11]; National Cancer Institute [Z01-CP010119] FX This work was supported [in part] by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences (Z01-ES049030-11), and National Cancer Institute (Z01-CP010119). NR 30 TC 41 Z9 43 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2010 VL 21 IS 6 BP 871 EP 877 DI 10.1007/s10552-010-9514-9 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 596UA UT WOS:000277709800009 PM 20155313 ER PT J AU Kilfoy, BA Ward, MH Zheng, TZ Holford, TR Boyle, P Zhao, P Dai, M Leaderer, B Zhang, YW AF Kilfoy, Briseis A. Ward, Mary H. Zheng, Tongzhang Holford, Theodore R. Boyle, Peter Zhao, Ping Dai, Min Leaderer, Brian Zhang, Yawei TI Risk of non-Hodgkin lymphoma and nitrate and nitrite from the diet in Connecticut women SO CANCER CAUSES & CONTROL LA English DT Article DE Non-Hodgkin lymphoma; Nitrate and nitrite; Diet ID N-NITROSO COMPOUNDS; DRINKING-WATER NITRATE; GASTRIC-CANCER RISK; UNITED-STATES; FLAVONOID INTAKE; HEALTH; CLASSIFICATION AB It has been estimated that 65,980 individuals were diagnosed with non-Hodgkin lymphoma (NHL) and 19,500 died from NHL in the United States in 2009. Although established risk factors such as immunodeficiency and viral infections may be responsible for a portion of the cases, the majority of NHL cases remain unexplained. Dietary nitrate and nitrite intake are exposures of particular interest for NHL risk as they are precursors in the endogenous formation of N-nitroso compounds, which cause lymphomas in animal studies. We investigated NHL risk overall and by histologic type in relation to dietary nitrate and nitrite intake in a population-based case-control study of 1,304 women in Connecticut. Nitrate and nitrite intake were assessed using a 120-item food frequency questionnaire. We found no association between risk of NHL overall and dietary nitrate and a slightly increased risk of NHL with higher dietary nitrite intake (highest vs. lowest intake quartile OR = 1.4; 95% CI: 0.9-2.2). When we evaluated intake by subtype, a significant positive trend was observed for follicular lymphoma and nitrate (p-trend = 0.04) and nitrite (p-trend < 0.01) with an over twofold risk in the highest nitrite intake quartile (OR = 2.3; 95% CI: 1.1-4.9). An increased risk in the highest quartile of nitrite intake was also observed for T-cell lymphoma (OR = 3.4; 95% CI: 1.0-11.9). Animal products containing nitrite were more strongly associated with risk of follicular lymphoma; whereas, both animal and plant sources of nitrite were associated with elevated ORs for T-cell lymphoma. Our results confirm a previous finding for nitrite intake and NHL risk and highlight the importance of evaluating histologic type. We conclude that these results should be replicated in a larger study with data on drinking water as well as dietary sources of nitrate intake. C1 [Kilfoy, Briseis A.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH,EPS, Rockville, MD 20852 USA. [Zheng, Tongzhang; Holford, Theodore R.; Leaderer, Brian; Zhang, Yawei] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA. [Boyle, Peter] Int Prevent Res Inst, Lyon, France. [Zhao, Ping; Dai, Min] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100021, Peoples R China. RP Kilfoy, BA (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH,EPS, Room 8111,6120 Execut Blvd, Rockville, MD 20852 USA. EM kilfoyb@mail.nih.gov RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU National Cancer Institute (NCI) [CA62006]; National Institutes of Health (NIH) [1D43TW008323-01]; National Center for Research Resources (NCRR) [UL1 RR024139] FX This research was supported by grant CA62006 from the National Cancer Institute (NCI), the Intramural Research Program of the NCI, National Institutes of Health (NIH) and Fogarty training grant 1D43TW008323-01 from the NIH. This publication was made possible by CTSA Grant number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the NIH, and NHL roadmap for medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR. NR 29 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2010 VL 21 IS 6 BP 889 EP 896 DI 10.1007/s10552-010-9517-6 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 596UA UT WOS:000277709800011 PM 20204494 ER PT J AU Geller, AC Greinert, R Sinclair, C Weinstock, MA Aitken, J Boniol, M Capellaro, M Dore, JF Elwood, M Fletcher, SW Gallagher, R Gandini, S Halpern, AC Katalinic, A Lucas, R Marghoob, AA Nolte, S Schuz, J Tucker, MA Volkmer, B Breitbart, E AF Geller, Alan C. Greinert, Ruediger Sinclair, Craig Weinstock, Martin A. Aitken, Joanne Boniol, Mathieu Capellaro, Marcus Dore, Jean-Francois Elwood, Mark Fletcher, Suzanne W. Gallagher, Richard Gandini, Sara Halpern, Allan C. Katalinic, Alexander Lucas, Robin Marghoob, Ashfag A. Nolte, Sandra Schuez, Joachim Tucker, Margaret A. Volkmer, Beate Breitbart, Eckhard TI A nationwide population-based skin cancer screening in Germany: Proceedings of the first meeting of the International Task Force on Skin Cancer Screening and Prevention (September 24 and 25, 2009) SO CANCER EPIDEMIOLOGY LA English DT Article DE Melanoma; Skin cancer; Germany; Screening; Early detection; Cancer ID CUTANEOUS MELANOMA; TRENDS AB Skin cancer incidence is increasing worldwide in white populations and mortality rates have not declined throughout most of the world. An extraordinarily high proportion of at-risk individuals have yet to be screened for melanoma but guidelines from esteemed bodies do not currently endorse population-based screening. Evidence for the effectiveness of skin cancer screening is imperative. To this end, scientists in Germany have launched a nationwide skin cancer screening campaign. Herein, we review pilot screening data from Schleswig-Holstein, discuss the launch of the major new national initiative, review issues related to evaluation of that program, and propose seven recommendations from the International Task Force on Skin Cancer Screening and Prevention that was held in Hamburg, Germany, on September 24 and 25, 2009. Published by Elsevier Ltd. C1 [Geller, Alan C.] Boston Univ, Sch Med, Harvard Univ, Sch Publ Hlth,Div Publ Hlth Practice, Boston, MA 02118 USA. [Greinert, Ruediger; Volkmer, Beate; Breitbart, Eckhard] Elbe Klinikum Buxtehude, Ctr Dermatol, D-21614 Buxtehude, Germany. [Greinert, Ruediger; Boniol, Mathieu; Nolte, Sandra; Volkmer, Beate; Breitbart, Eckhard] EUROSKIN eV, Elbe Klinikum Buxtehude, D-21614 Buxtehude, Germany. [Sinclair, Craig] Canc Council Victoria, Canc Prevent Ctr, Carlton, Vic 3053, Australia. [Sinclair, Craig] WHO, Collaborat Ctr UV Radiat, New York, NY 10017 USA. [Sinclair, Craig] Canc Council Australia, Skin Canc Comm, Carlton, Vic 3053, Australia. [Weinstock, Martin A.] Brown Univ, Dermatoepidemiol Unit, VA Med Ctr, Providence, RI 02908 USA. [Katalinic, Alexander] Med Univ Lubeck, Inst Canc Epidemiol eV, Dept Registrat Canc Registry Schleswig Holstein, D-23538 Lubeck, Germany. [Aitken, Joanne] Canc Council Queensland, Fortitude Valley, Qld 4006, Australia. [Boniol, Mathieu] Int Prevent Res Inst, F-69006 Lyon, France. [Greinert, Ruediger; Capellaro, Marcus; Volkmer, Beate; Breitbart, Eckhard] ADP, D-20457 Hamburg, Germany. [Dore, Jean-Francois] Ctr Leon Berard, INSERM, U590, F-69373 Lyon 08, France. [Dore, Jean-Francois] IARC, F-69372 Lyon, France. [Elwood, Mark] BC Canc Agcy, Family & Community Oncol, Vancouver, BC V5Z 1G1, Canada. [Fletcher, Suzanne W.] Harvard Univ, Sch Med, Chapel Hill, NC 27516 USA. [Gallagher, Richard] Univ British Columbia, Canc Control Res BC Canc Agcy, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1L3, Canada. [Gandini, Sara] Inst Europe Oncol, Div Epidemiol & Biostat, I-20141 Milan, Italy. [Halpern, Allan C.; Marghoob, Ashfag A.] Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10065 USA. [Halpern, Allan C.; Marghoob, Ashfag A.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Lucas, Robin] Australian Natl Univ, NCEPH, Canberra, ACT 0200, Australia. [Schuez, Joachim] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Tucker, Margaret A.] NCI, Human Genet Program, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Harvard Univ, Sch Publ Hlth,Div Publ Hlth Practice, Boston, MA 02118 USA. EM ageller@hsph.harvard.edu RI Katalinic, Alexander/D-2512-2010; Mavoa, Suzanne/B-5372-2010; Boniol, Mathieu/F-9623-2011; Nolte, Sandra/B-7498-2008; Tucker, Margaret/B-4297-2015 OI Gandini, Sara/0000-0002-1348-4548; Katalinic, Alexander/0000-0003-0490-1554; Boniol, Mathieu/0000-0003-1052-5604; Nolte, Sandra/0000-0001-6185-9423; NR 13 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD JUN PY 2010 VL 34 IS 3 BP 355 EP 358 DI 10.1016/j.canep.2010.03.006 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 615PX UT WOS:000279148300022 PM 20381443 ER PT J AU Bobe, G Murphy, G Rogers, CJ Hance, KW Albert, PS Laiyemo, AO Sansbury, LB Lanza, E Schatzkin, A Cross, AJ AF Bobe, Gerd Murphy, Gwen Rogers, Connie J. Hance, Kenneth W. Albert, Paul S. Laiyemo, Adeyinka O. Sansbury, Leah B. Lanza, Elaine Schatzkin, Arthur Cross, Amanda J. TI Serum Adiponectin, Leptin, C-Peptide, Homocysteine, and Colorectal Adenoma Recurrence in the Polyp Prevention Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VISCERAL FAT ACCUMULATION; COLON-CANCER; HIGH-FIBER; PLASMA ADIPONECTIN; CELL-PROLIFERATION; INSULIN-RESISTANCE; FOLATE STATUS; WEIGHT-LOSS; HIGH-FRUIT; RISK AB Background: Serum adiponectin, leptin, C-peptide, and homocysteine are indicators for obesity, hyperinsulinemia, and chronic inflammation, which have all been associated with colorectal cancer. Aims: To determine whether serum adiponectin, leptin, C-peptide, and homocysteine are associated with fat, fiber, fruit and vegetable, flavonol, or dry bean intake and colorectal adenoma recurrence. Methods: Using logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (95% CI) for adenoma recurrence in 627 participants from the control arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Results: Serum concentrations of C-peptide and homocysteine were inversely related to fiber, fruit and vegetable, and flavonol intake and positively related to percentage of calories from fat (all P(trend) = <= 0.01). High homocysteine concentrations were associated with any (4th versus 1st quartile: OR, 2.26; 95% CI, 1.30-3.94) and more than one adenoma recurrence (OR, 2.11; 95% CI, 1.01-4.40). Individuals in the highest, versus lowest, tertile of serum leptin concentration had a decreased risk of advanced adenoma recurrence (OR, 0.22; 95% CI, 0.06-0.79). Conclusion: Our results suggest that serum homocysteine may serve as an indicator of dietary exposure, including a low-fat and high-fiber, high-fruit and vegetable, and high-flavonol diet, as well as colorectal adenoma recurrence. Impact: Discovering biomarkers that are both modifiable and can predict cancer risk is critical. We identified serum homocysteine as a novel indicator that is modified by diet and predicts risk of adenoma recurrence. Cancer Epidemiol Biomarkers Prev; 19(6); 1441-52. (C) 2010 AACR. C1 [Bobe, Gerd; Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Rogers, Connie J.; Hance, Kenneth W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Murphy, Gwen] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Schatzkin, Arthur; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Albert, Paul S.] NICHHD, Biostat & Bioinformat Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] NCI, Biometry Res Grp, Canc Prevent Div, NIH,DHHS, Bethesda, MD 20892 USA. [Sansbury, Leah B.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA. RP Bobe, G (reprint author), Oregon State Univ, 112 Withycombe Hall, Corvallis, OR 97331 USA. EM gerd.bobe@oregonstate.edu RI Murphy, Gwen/G-7443-2015 FU National Cancer Institute, NIH, DHHS (Bethesda, MD) FX Intramural Research Program, National Cancer Institute, NIH, DHHS (Bethesda, MD). NR 59 TC 17 Z9 17 U1 1 U2 8 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 JUN PY 2010 VL 19 IS 6 BP 1441 EP 1452 DI 10.1158/1055-9965.EPI-09-1082 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300006 PM 20501764 ER PT J AU Altekruse, SF Huang, L Cucinelli, JE McNeel, TS Wells, KM Oliver, MN AF Altekruse, Sean F. Huang, Lan Cucinelli, James E. McNeel, Timothy S. Wells, Kristen M. Oliver, M. Norman TI Spatial Patterns of Localized-Stage Prostate Cancer Incidence Among White and Black Men in the Southeastern United States, 1999-2001 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SOCIOECONOMIC-STATUS; DIAGNOSIS; RACE; MORTALITY; ILLINOIS; IMPACT AB Background: In the United States, prostate cancer incidence is higher among black than among white males, with a higher proportion of blacks diagnosed with advanced-stage cancer. Methods: Prostate cancer incidence (1999-2001) and census tract data were obtained for 66,468 cases in four states that account for 20% of U.S. blacks: Georgia, Florida, Alabama, and Tennessee. Spatial clusters of localized-stage prostate cancer incidence were detected by spatial scan. Clusters were examined by relative risk, population density, and socioeconomic and racial attributes. Results: Overall prostate cancer incidence rates were higher in black than in white men, and a lower proportion of black cases were diagnosed with localized-stage cancer. Strong associations were seen between urban residence and high relative risk of localized-stage cancer. The highest relative risks generally occurred in clusters with a lower percent black population than the national average. Conversely, of eight nonurban clusters with significantly elevated relative risk of localized-disease, seven had a higher proportion of blacks than the national average. Furthermore, positive correlations between percent black population and relative risk of localized-stage cancer were seen in Alabama and Georgia. Conclusion: Association between urban residence and high relative risk of localized-stage disease (favorable prognosis) persisted after spatial clusters were stratified by percent black population. Unexpectedly, seven of eight nonurban clusters with high relative risk of localized-stage disease had a higher percentage of blacks than the U. S. population. Impact: Although evidence of racial disparity in prostate cancer was found, there were some encouraging findings. Studies of community-level factors that might contribute to these findings are recommended. Cancer Epidemiol Biomarkers Prev; 19( 6); 1460-7. (C) 2010 AACR. C1 [Altekruse, Sean F.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Huang, Lan] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cucinelli, James E.; McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. [Wells, Kristen M.] Univ Virginia, Sch Med, Dept Family Med, Charlottesville, VA 22908 USA. [Oliver, M. Norman] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA. RP Altekruse, SF (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Room 5003, Rockville, MD 20852 USA. EM altekrusesf@mail.nih.gov FU NCI NIH HHS [HHSN261200900022C]; PHS HHS [HHSN261200900022C] NR 22 TC 11 Z9 11 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2010 VL 19 IS 6 BP 1460 EP 1467 DI 10.1158/1055-9965.EPI-09-1310 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300008 PM 20501756 ER PT J AU Chaturvedi, AK Gaydos, CA Agreda, P Holden, JP Chatterjee, N Goedert, JJ Caporaso, NE Engels, EA AF Chaturvedi, Anil K. Gaydos, Charlotte A. Agreda, Patricia Holden, Jeffrey P. Chatterjee, Nilanjan Goedert, James J. Caporaso, Neil E. Engels, Eric A. TI Chlamydia pneumoniae Infection and Risk for Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEAT-SHOCK-PROTEIN; PELVIC-INFLAMMATORY-DISEASE; ANTIBODY-RESPONSE; EPIDEMIOLOGIC EVIDENCE; IMMUNOGLOBULIN-A; HEAT-SHOCK-PROTEIN-60; ASSOCIATION; TRACHOMATIS; WOMEN AB Background: We evaluated the relationship of Chlamydia pneumoniae infection with prospective lung cancer risk using traditional serologic markers [microimmunoflourescence (MIF) IgG and IgA antibodies] and Chlamydia heat shock protein-60 (CHSP-60) antibodies, a marker for chronic chlamydial infection. Methods: We conducted a nested case-control study (593 lung cancers and 671 controls) within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 77,464). Controls were matched to cases by age, sex, randomization year, follow-up time, and smoking (pack-years of smoking, time since quitting). We assessed C. pneumoniae seropositivity and endpoint antibody titers (IgG and IgA against C. pneumoniae elementary bodies and IgG against CHSP-60). Results: C. pneumoniae seropositivity by microimmunoflourescence IgG or IgA antibodies was not associated with lung cancer [ odds ratio of 0.88 and 95% confidence interval (95% CI) of 0.69-1.13 for IgG; odds ratio of 0.98 and 95% CI of 0.75-1.27 for IgA]. In contrast, individuals seropositive for CHSP-60 IgG antibodies had significantly increased lung cancer risk (odds ratio, 1.30; 95% CI, 1.02-1.67), and risk increased with increasing antibody titers (P trend = 0.006). CHSP-60-related risk did not differ significantly by lung cancer histology, follow-up time, or smoking. CHSP-60 seropositivitywas associated with increased risk 2 to 5 years before lung cancer diagnosis (odds ratio, 1.77; 95% CI, 1.16-2.71; P trend = 0.006), thus arguing against reverse causality. Conclusions: CHSP-60 seropositivity and elevated antibody titers were associated with significantly increased risk for subsequent lung cancer, supporting an etiologic role for C. pneumoniae infection in lung carcinogenesis. Impact: Our results highlight the potential for lung cancer risk reduction through treatments targeted toward C. pneumoniae infections and chronic pulmonary inflammation. Cancer Epidemiol Biomarkers Prev; 19(6); 1498-505. (C) 2010 AACR. C1 [Chaturvedi, Anil K.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Gaydos, Charlotte A.; Agreda, Patricia; Holden, Jeffrey P.] Johns Hopkins Univ, Baltimore, MD USA. RP Chaturvedi, AK (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Execut Plaza S,Rm 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Gaydos, Charlotte/E-9937-2010; Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. NR 33 TC 26 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2010 VL 19 IS 6 BP 1498 EP 1505 DI 10.1158/1055-9965.EPI-09-1261 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300014 PM 20501758 ER PT J AU Berstad, P Coates, RJ Bernstein, L Folger, SG Malone, KE Marchbanks, PA Weiss, LK Liff, JM McDonald, JA Strom, BL Simon, MS Deapen, D Press, MF Burkman, RT Spirtas, R Ursin, G AF Berstad, Paula Coates, Ralph J. Bernstein, Leslie Folger, Suzanne G. Malone, Kathleen E. Marchbanks, Polly A. Weiss, Linda K. Liff, Jonathan M. McDonald, Jill A. Strom, Brian L. Simon, Michael S. Deapen, Dennis Press, Michael F. Burkman, Ronald T. Spirtas, Robert Ursin, Giske TI A Case-Control Study of Body Mass Index and Breast Cancer Risk in White and African-American Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGESTERONE-RECEPTOR STATUS; PHYSICAL-ACTIVITY; WEIGHT CHANGE; BLACK-WOMEN; REPRODUCTIVE FACTORS; PROSPECTIVE COHORT; FAT DISTRIBUTION; PREMENOPAUSAL WOMEN; HORMONE-RECEPTOR; MENSTRUAL-CYCLE AB Objective: Large body size has been associated with decreased risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. Limited information is available about African-American women and differences by estrogen and progesterone receptor status. Methods: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study among 3,997 white and African-American breast cancer case patients diagnosed in 1994 to 1998 and 4,041 control participants ages 35 to 64 years. We calculated multivariate odds ratios (OR) as measures of relative risk of breast cancer associated with self-reported body mass index (BMI) at age 18 and 5 years before diagnosis (recent BMI). Results: Risk tended to decrease with increasing BMI at age 18 years in all women [OR(BMI) (>= 25 kg/m2 versus <) (20 kg/m2) = 0.76; 95% confidence interval (CI), 0.63-0.90; P(trend) = 0.005] and with recent BMI in premenopausal women (OR(BMI) (>=) (35 kg/m2 versus < 25 kg/m2) = 0.81; 95% CI, 0.61-1.06; P(trend) = (0.05)), unmodified by race. Among postmenopausal white but not African-American women, there was an inverse relation between recent BMI and risk. High recent BMI was associated with increased risk of estrogen receptor-and progesterone receptor-positive tumors among postmenopausal African-American women (OR(BMI >= 35 kg/m2 versus < 25 kg/m2) = 1.83; 95% CI, 1.08-3.09; P(trend) = 0.03). Conclusion: Among women at age 35 to 64 years, BMI at age 18 years is inversely associated with risk of breast cancer, but association with recent BMI varies by menopause status, race, and hormone receptor status. Impact: Our findings indicate that studies of BMI and breast cancer should consider breast cancer subtypes. Cancer Epidemiol Biomarkers Prev; 19(6); 1532-44. (C) 2010 AACR. C1 [Berstad, Paula; Ursin, Giske] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway. [Coates, Ralph J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Folger, Suzanne G.; Marchbanks, Polly A.; McDonald, Jill A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Liff, Jonathan M.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Weiss, Linda K.] NCI, Off Canc Ctr, Bethesda, MD 20892 USA. [Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. [Deapen, Dennis; Ursin, Giske] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Burkman, Ronald T.] Tufts Univ, Sch Med, Baystate Med Ctr, Dept Obstet & Gynecol,Div Gen Obstet & Gynecol, Springfield, MA 01199 USA. [Spirtas, Robert] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC USA. RP Berstad, P (reprint author), Akershus Univ Hosp, Res Ctr, Box 95, N-1478 Lorenskog, Norway. EM p.m.berstad@medisin.uio.no FU Norwegian Cancer Society [04055/001]; National Institute of Child Health and Human Development; National Cancer Institute; NIH [N01-HD-3-3168]; Fred Hutchinson Cancer Research Center [N01-HD-2-3166]; Karmanos Cancer Institute at Wayne State University [N01-HD-3-3174]; University of Pennsylvania [NO1-HD-3-3176]; University of Southern California [N01-HD-3-3175]; Interagency Agreement with Centers for Disease Control and Prevention [Y01-HD-7022]; California Department of Health Services; Centers for Disease Control and Prevention [1U58DP000807-03]; [N01-PC-67006]; [N01-CN-65064]; [N01-PC-67010]; [N01-CN-0532] FX Grant 04055/001 from Norwegian Cancer Society. Data collection for the Women's CARE study was supported by the National Institute of Child Health and Human Development and by the National Cancer Institute, NIH, through contracts with Emory University (N01-HD-3-3168), the Fred Hutchinson Cancer Research Center (N01-HD-2-3166), the Karmanos Cancer Institute at Wayne State University (N01-HD-3-3174), the University of Pennsylvania (NO1-HD-3-3176), the University of Southern California (N01-HD-3-3175), and the Interagency Agreement with Centers for Disease Control and Prevention (Y01-HD-7022). Collection of cancer incidence data in Los Angeles County by the University of Southern California was supported by the California Department of Health Services as part of a statewide cancer reporting program mandated by the California Health and Safety Code, Section 103885 and by contract 1U58DP000807-03 from the Centers for Disease Control and Prevention. Support for use of Surveillance, Epidemiology, and End Results cancer registries were through contracts N01-PC-67006 (Atlanta), N01-CN-65064 (Detroit), N01-PC-67010 (Los Angeles), and N01-CN-0532 (Seattle). NR 53 TC 43 Z9 45 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2010 VL 19 IS 6 BP 1532 EP 1544 DI 10.1158/1055-9965.EPI-10-0025 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300018 PM 20501755 ER PT J AU Dorgan, JF Liu, L Klifa, C Hylton, N Shepherd, JA Stanczyk, FZ Snetselaar, LG Van Horn, L Stevens, VJ Robson, A Kwiterovich, PO Lasser, NL Himes, JH Gabriel, KP Kriska, A Ruder, EH Fang, CY Barton, BA AF Dorgan, Joanne F. Liu, Lea Klifa, Catherine Hylton, Nola Shepherd, John A. Stanczyk, Frank Z. Snetselaar, Linda G. Van Horn, Linda Stevens, Victor J. Robson, Alan Kwiterovich, Peter O., Jr. Lasser, Norman L. Himes, John H. Gabriel, Kelley Pettee Kriska, Andrea Ruder, Elizabeth H. Fang, Carolyn Y. Barton, Bruce A. TI Adolescent Diet and Subsequent Serum Hormones, Breast Density, and Bone Mineral Density in Young Women: Results of the Dietary Intervention Study in Children Follow-up Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PREMENOPAUSAL WOMEN; CANCER RISK; LOW-FAT; POSTMENOPAUSAL WOMEN; LIPOPROTEIN CHOLESTEROL; PARENCHYMAL PATTERNS; MAMMOGRAPHIC DENSITY; SATURATED FAT; SEX-HORMONES AB Background: Adolescent diet is hypothesized to influence breast cancer risk. We evaluated the long-term effects of an intervention to lower fat intake among adolescent girls on biomarkers that are related to breast cancer risk in adults. Methods: A follow-up study was conducted on 230 girls who participated in the Dietary Intervention Study in Children (DISC), in which healthy, prepubertal, 8 to 10 year olds were randomly assigned to usual care or to a behavioral intervention that promoted a reduced fat diet. Participants were 25 to 29 years old at follow-up visits. All tests of statistical significance are two-sided. Results: In analyses that did not take account of diet at the time of the follow-up visit, the only statistically significant treatment group difference was higher bone mineral content in intervention group participants compared with usual care group participants; their mean bone mineral contents were 2,444 and 2,377 g, respectively. After adjustment for current diet, the intervention group also had statistically significantly higher bone mineral density and luteal phase serum estradiol concentrations. Serum progesterone concentrations and breast density did not differ by treatment group in unadjusted or adjusted analyses. Conclusions: Results do not support the hypothesis that consumption of a lower fat diet during adolescence reduces breast cancer risk via effects on subsequent serum estradiol and progesterone levels, breast density, or bone mineral density. It remains unclear, however, if the results are specific to the DISC intervention or are more broadly applicable. Impact: Modest reductions in fat intake during adolescence are unlikely to lower later breast cancer risk via long-term effects on the biomarkers measured. Cancer Epidemiol Biomarkers Prev; 19(6); 1545-56. (C) 2010 AACR. C1 [Dorgan, Joanne F.; Fang, Carolyn Y.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Liu, Lea; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. [Kwiterovich, Peter O., Jr.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Klifa, Catherine; Hylton, Nola; Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Stanczyk, Frank Z.] Univ So Calif, Los Angeles, CA USA. [Snetselaar, Linda G.] Univ Iowa, Iowa City, IA USA. [Van Horn, Linda] Northwestern Univ, Chicago, IL 60611 USA. [Stevens, Victor J.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Robson, Alan] Childrens Hosp, New Orleans, LA USA. [Lasser, Norman L.] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Himes, John H.] Univ Minnesota, Minneapolis, MN USA. [Gabriel, Kelley Pettee] Univ Nebraska Med Ctr, Omaha, NE USA. [Kriska, Andrea] Univ Pittsburgh, Pittsburgh, PA USA. [Ruder, Elizabeth H.] NCI, Rockville, MD USA. RP Dorgan, JF (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM joanne.dorgan@fccc.edu RI Kattelmann, Kendra/E-8225-2013; Fang, Carolyn/A-2324-2008; OI Fang, Carolyn/0000-0002-0575-3867; Kriska, Andrea/0000-0002-3522-0869; Barton, Bruce/0000-0001-7878-8895 FU National Cancer Institute [R01CA104670] FX National Cancer Institute grant R01CA104670 (J. F. Dorgan). NR 63 TC 19 Z9 19 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2010 VL 19 IS 6 BP 1545 EP 1556 DI 10.1158/1055-9965.EPI-09-1259 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607MD UT WOS:000278507300019 PM 20501774 ER PT J AU Vogel, VG Costantino, JP Wickerham, DL Cronin, WM Cecchini, RS Atkins, JN Bevers, TB Fehrenbacher, L Pajon, ER Wade, JL Robidoux, A Margolese, RG James, J Runowicz, CD Ganz, PA Reis, SE McCaskill-Stevens, W Ford, LG Jordan, VC Wolmark, N AF Vogel, Victor G. Costantino, Joseph P. Wickerham, D. Lawrence Cronin, Walter M. Cecchini, Reena S. Atkins, James N. Bevers, Therese B. Fehrenbacher, Louis Pajon, Eduardo R. Wade, James L., III Robidoux, Andre Margolese, Richard G. James, Joan Runowicz, Carolyn D. Ganz, Patricia A. Reis, Steven E. McCaskill-Stevens, Worta Ford, Leslie G. Jordan, V. Craig Wolmark, Norman CA Natl Surgical Adjuvant Breast Bowe TI Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing Breast Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID MAMMARY-CARCINOMA MODEL; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIALS; RISK-FACTORS; FOLLOW-UP; OUTCOMES; MUTATIONS; ESTROGEN; SURVIVAL; NSABP AB The selective estrogen-receptor modulator (SERM) tamoxifen became the first U. S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene: tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene: tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer. Cancer Prev Res; 3(6); 696-706. (C) 2010 AACR. C1 [Costantino, Joseph P.; Cronin, Walter M.; Cecchini, Reena S.] NSABP, Ctr Biostat, Pittsburgh, PA USA. [Vogel, Victor G.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Wickerham, D. Lawrence; Wolmark, Norman] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Reis, Steven E.] Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA. [Vogel, Victor G.] Amer Canc Soc, Atlanta, GA 30329 USA. [Atkins, James N.] SE Canc Control Consortium CCOP, Winston Salem, NC USA. [Bevers, Therese B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fehrenbacher, Louis] Kaiser Permanente No Calif, Vallejo, CA USA. [Pajon, Eduardo R.] Colorado Canc Res Program, Denver, CO USA. [Wade, James L., III] Cent Illinois CCOP, Decatur, IL USA. [Robidoux, Andre] CHUM Hot Dieu, Montreal, PQ, Canada. [Margolese, Richard G.] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [James, Joan; Jordan, V. Craig] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Runowicz, Carolyn D.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA. [McCaskill-Stevens, Worta; Ford, Leslie G.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Wickerham, DL (reprint author), Four Allegheny Ctr, 5th Floor, Pittsburgh, PA 15212 USA. EM larry.wickerham@nsabp.org RI Jordan, V. Craig/H-4491-2011; Reis, Steven/J-3957-2014; OI Cecchini, Reena/0000-0002-9075-9357 FU National Cancer Institute, Department of Health and Human Services [U10-CA-12027, U10-CA-69651, U10-CA37377, U10-CA-69974] FX Public Health Service grants U10-CA-12027, U10-CA-69651, U10-CA37377, and U10-CA-69974 from the National Cancer Institute, Department of Health and Human Services. NR 27 TC 271 Z9 280 U1 2 U2 20 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 JUN PY 2010 VL 3 IS 6 BP 696 EP 706 DI 10.1158/1940-6207.CAPR-10-0076 PG 11 WC Oncology SC Oncology GA 605VK UT WOS:000278374900005 PM 20404000 ER PT J AU Wright, ME Groshong, SD Husgafvel-Pursiainen, K Genova, E Lucia, MS Wolff, H Virtamo, J Albanes, D AF Wright, Margaret E. Groshong, Steve D. Husgafvel-Pursiainen, Kirsti Genova, Erin Lucia, M. Scott Wolff, Henrik Virtamo, Jarmo Albanes, Demetrius TI Effects of beta-Carotene Supplementation on Molecular Markers of Lung Carcinogenesis in Male Smokers SO CANCER PREVENTION RESEARCH LA English DT Article ID RETINOIC ACID RECEPTOR; BRONCHIAL EPITHELIUM; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; CIGARETTE-SMOKE; CYCLIN D1; CANCER; FERRETS; INDEX; IMMUNOHISTOCHEMISTRY AB Two primary prevention trials unexpectedly showed adverse effects of supplemental beta-carotene on lung cancer incidence in cigarette smokers. To elucidate the molecular mechanisms that might underlie these effects, we studied the immunohistochemical expression of cytochrome P450 1A1, 1A2, and 2E1, retinoic acid receptor beta, activated protein-1 elements, cyclin D1, and Ki67 in lung tumors and, when available, adjacent normal tissues obtained from incident cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Archival lung tissue was available from 52 men randomized to receive 20 mg of beta-carotene per day and 30 men randomized to the placebo arm, all of whom were diagnosed with incident non-small-cell lung carcinoma during the course of the trial and subsequently underwent radical pulmonary resection. In normal-appearing bronchial epithelium, positive staining for cyclin D1 was observed in 23% of cases in the beta-carotene group and 0% of cases in the placebo group (based on only 3 of 13 versus 0 of 11 cases staining positively, however; P = 0.04), with no differences in expression noted in lung tumor tissue (P = 0.48). There were no statistically significant differences in Ki67 expression in normal or cancerous lung tissue between intervention groups, although a small increase in staining in tumors was noted among cases in the beta-carotene versus placebo group (88% versus 71% of cases stained positive, respectively; P = 0.13). Contrary to expectation, beta-carotene supplementation had no apparent effect on retinoic acid receptor-beta expression. These findings suggest that male smokers supplemented with beta-carotene may have had an increased risk of lung cancer due to aberrant cell growth, although our results are based on a relatively small number of cases and require confirmation in other completed trials of beta-carotene supplementation. Cancer Prev Res; 3(6); 745-52. (C) 2010 AACR. C1 [Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wright, Margaret E.] Univ Illinois, Dept Pathol, Chicago, IL USA. [Groshong, Steve D.] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. [Husgafvel-Pursiainen, Kirsti; Wolff, Henrik] Finnish Inst Occupat Hlth, Helsinki, Finland. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Genova, Erin; Lucia, M. Scott] Univ Colorado Denver, Dept Pathol, Aurora, CO USA. RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 3044, Bethesda, MD 20892 USA. EM daa@nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Cancer Institute, NIH FX Intramural Research Program of the National Cancer Institute, NIH.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 32 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD JUN PY 2010 VL 3 IS 6 BP 745 EP 752 DI 10.1158/1940-6207.CAPR-09-0107 PG 8 WC Oncology SC Oncology GA 605VK UT WOS:000278374900010 PM 20484175 ER PT J AU Bobe, G Albert, PS Sansbury, LB Lanza, E Schatzkin, A Colburn, NH Cross, AJ AF Bobe, Gerd Albert, Paul S. Sansbury, Leah B. Lanza, Elaine Schatzkin, Arthur Colburn, Nancy H. Cross, Amanda J. TI Interleukin-6 as a Potential Indicator for Prevention of High-Risk Adenoma Recurrence by Dietary Flavonols in the Polyp Prevention Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID C-REACTIVE PROTEIN; COLORECTAL-CANCER; INFLAMMATORY MARKERS; CIRCULATING LEVELS; HIGH-FIBER; US ADULTS; LOW-FAT; SERUM; CELLS; INTERVENTION AB Serum interleukin-6 (IL-6), a proinflammatory cytokine, is considered an indicator of inflammation and may be an indicator of colorectal carcinogenesis given that inflammation can promote carcinogenesis. Flavonols, which can be found in fruits and vegetables, may inhibit colorectal carcinogenesis partly by inhibiting inflammation. We estimated odds ratios and 95% confidence intervals (95% CI) to determine whether serum IL-6 was associated with colorectal adenoma recurrence and flavonol intake and thus may serve as a risk indicator and as a response indicator to dietary flavonols. Serum IL-6 concentrations at baseline, year 1, and year 3 were measured in 872 participants from the intervention arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Intake of flavonols, especially of isorhamnetin, kaempferol, and quercetin, was inversely associated with serum IL-6 concentrations (highest versus lowest flavonol intake quartile, 1.80 versus 2.20 pg/mL) and high-risk (OR, 0.51; 95% CI, 0.26-0.98) and advanced adenoma recurrence (OR, 0.17; 95% CI, 0.06-0.50). A decrease in IL-6 concentration during the trial was inversely associated with high-risk (OR, 0.44; 95% CI, 0.23-0.84) and advanced adenoma recurrence (OR, 0.47; 95% CI, 0.19-1.18). Individuals with above median flavonol intake and equal or below median IL-6 change after baseline had the lowest risk of recurrence of high- risk and advanced adenoma. Our results suggest that serum IL-6 may serve as a risk indicator and as a response indicator to dietary flavonols for colorectal cancer prevention. Cancer Prev Res; 3(6); 764-75. (C) 2010 AACR. C1 [Bobe, Gerd; Lanza, Elaine; Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bobe, Gerd] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Sansbury, Leah B.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Schatzkin, Arthur; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bobe, G (reprint author), Oregon State Univ, Dept Anim Sci, 112 Withycombe Hall, Corvallis, OR 97331 USA. EM gerd.bobe@oregonstate.edu FU Intramural Research Program, National Cancer Institute, NIH, Bethesda, MD FX Office of Dietary Supplements and the Intramural Research Program, National Cancer Institute, NIH, Bethesda, MD. NR 46 TC 27 Z9 27 U1 0 U2 3 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 JUN PY 2010 VL 3 IS 6 BP 764 EP 775 DI 10.1158/1940-6207.CAPR-09-0161 PG 12 WC Oncology SC Oncology GA 605VK UT WOS:000278374900012 PM 20484173 ER PT J AU Nagahara, LA Lee, JSH Molnar, LK Panaro, NJ Farrell, D Ptak, K Alper, J Grodzinski, P AF Nagahara, Larry A. Lee, Jerry S. H. Molnar, Linda K. Panaro, Nicholas J. Farrell, Dorothy Ptak, Krzysztof Alper, Joseph Grodzinski, Piotr TI Strategic Workshops on Cancer Nanotechnology SO CANCER RESEARCH LA English DT Editorial Material AB Nanotechnology offers the potential for new approaches to detecting, treating, and preventing cancer. To determine the current status of the cancer nanotechnology field and the optimal path forward, the National Cancer Institute's Alliance for Nanotechnology in Cancer held three strategic workshops, covering the areas of in vitro diagnostics and prevention, therapy and post-treatment, and in vivo diagnosis and imaging. At each of these meetings, a wide range of experts from academia, industry, the nonprofit sector, and the U.S. government discussed opportunities in the field of cancer nanotechnology and barriers to its implementation. Cancer Res; 70(11); 4265-8. (C)2010 AACR. C1 [Nagahara, Larry A.; Lee, Jerry S. H.; Farrell, Dorothy; Ptak, Krzysztof; Grodzinski, Piotr] NCI, Ctr Strateg Sci Initiat, Bethesda, MD 20892 USA. [Panaro, Nicholas J.] NCI Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD USA. [Alper, Joseph] Parrotfish Consulting, Louisville, CO USA. RP Grodzinski, P (reprint author), NCI, Ctr Strateg Sci Initiat, 31 Ctr Dr,MSC2580,Bldg 31,Room 10A52, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [HHSN261200800001E] NR 10 TC 6 Z9 6 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 JUN 1 PY 2010 VL 70 IS 11 BP 4265 EP 4268 DI 10.1158/0008-5472.CAN-09-3716 PG 4 WC Oncology SC Oncology GA V25EM UT WOS:000208461300001 PM 20460532 ER PT J AU Makareeva, E Han, SJ Vera, JC Sackett, DL Holmbeck, K Phillips, CL Visse, R Nagase, H Leikin, S AF Makareeva, Elena Han, Sejin Vera, Juan Carlos Sackett, Dan L. Holmbeck, Kenn Phillips, Charlotte L. Visse, Robert Nagase, Hideaki Leikin, Sergey TI Carcinomas Contain a Matrix Metalloproteinase-Resistant Isoform of Type I Collagen Exerting Selective Support to Invasion SO CANCER RESEARCH LA English DT Article ID CANCER-CELL-LINES; EXTRACELLULAR-MATRIX; OSTEOGENESIS IMPERFECTA; BREAST-CARCINOMA; EPITHELIAL-CELLS; TRIMER COLLAGEN; BIOPSY FRAGMENTS; DANLOS-SYNDROME; OSTEO-SARCOMA; TRIPLE-HELIX AB Collagen fibers affect metastasis in two opposing ways, by supporting invasive cells but also by generating a barrier to invasion. We hypothesized that these functions might be performed by different isoforms of type I collagen. Carcinomas are reported to contain alpha 1(I)(3) homotrimers, a type I collagen isoform normally not present in healthy tissues, but the role of the homotrimers in cancer pathophysiology is unclear. In this study, we found that these homotrimers were resistant to all collagenolytic matrix metalloproteinases (MMP). MMPs are massively produced and used by cancer cells and cancer-associated fibroblasts for degrading stromal collagen at the leading edge of tumor invasion. The MMP-resistant homotrimers were produced by all invasive cancer cell lines tested, both in culture and in tumor xenografts, but they were not produced by cancer-associated fibroblasts, thereby comprising a specialized fraction of tumor collagen. We observed the homotrimer fibers to be resistant to pericellular degradation, even upon stimulation of the cells with proinflammatory cytokines. Furthermore, we confirmed an enhanced proliferation and migration of invasive cancer cells on the surface of homotrimeric versus normal (heterotrimeric) type I collagen fibers. In summary, our findings suggest that invasive cancer cells may use homotrimers for building MMP-resistant invasion paths, supporting local proliferation and directed migration of the cells whereas surrounding normal stromal collagens are cleaved. Because the homotrimers are universally secreted by cancer cells and deposited as insoluble, MMP-resistant fibers, they offer an appealing target for cancer diagnostics and therapy. Cancer Res; 70(11); 4366-74. (C) 2010 AACR. C1 [Makareeva, Elena; Han, Sejin; Vera, Juan Carlos; Sackett, Dan L.; Leikin, Sergey] Eunice Kennedy Shriver NICHHD, NIH, Bethesda, MD 20892 USA. [Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Phillips, Charlotte L.] Univ Missouri, Dept Biochem, Columbia, MO USA. [Visse, Robert; Nagase, Hideaki] Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Div Rheumatol, London, England. RP Leikin, S (reprint author), Eunice Kennedy Shriver NICHHD, NIH, Bldg 9,Room 1N-111, Bethesda, MD 20892 USA. EM leikins@mail.nih.gov RI Makareeva, Elena/F-5183-2011; Leikin, Sergey/A-5518-2008; OI Leikin, Sergey/0000-0001-7095-0739; Phillips, Charlotte/0000-0002-7761-3783 FU Wellcome Trust [075473]; NIH/NIDDK [DK069522]; NICHD, NIDCR, NIH FX Intramural Research Programs of NICHD (S. Leikin) and NIDCR (K. Holmbeck), NIH; Wellcome Trust Programme grant 075473 (H. Nagase); and NIH/NIDDK grant DK069522 (C.L. Phillips). NR 49 TC 40 Z9 40 U1 0 U2 8 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 JUN 1 PY 2010 VL 70 IS 11 BP 4366 EP 4374 DI 10.1158/0008-5472.CAN-09-4057 PG 9 WC Oncology SC Oncology GA 607GF UT WOS:000278486400014 PM 20460529 ER PT J AU Menashe, I Maeder, D Garcia-Closas, M Figueroa, JD Bhattacharjee, S Rotunno, M Kraft, P Hunter, DJ Chanock, SJ Rosenberg, PS Chatterjee, N AF Menashe, Idan Maeder, Dennis Garcia-Closas, Montserrat Figueroa, Jonine D. Bhattacharjee, Samsiddhi Rotunno, Melissa Kraft, Peter Hunter, David J. Chanock, Stephen J. Rosenberg, Philip S. Chatterjee, Nilanjan TI Pathway Analysis of Breast Cancer Genome-Wide Association Study Highlights Three Pathways and One Canonical Signaling Cascade SO CANCER RESEARCH LA English DT Article ID SUSCEPTIBILITY GENE; C-MET; SYNDECAN-1 EXPRESSION; MUTATIONS; ALLELES; RISK; BRCA2; TWINS; ANGIOGENESIS; THERAPY AB Genome-wide association studies (GWAS) focus on relatively few highly significant loci, whereas less attention is given to other genotyped markers. Using pathway analysis to study existing GWAS data may shed light on relevant biological processes and illuminate new candidate genes. We applied a pathway-based approach to the breast cancer GWAS data of the National Cancer Institute (NCI) Cancer Genetic Markers of Susceptibility project that includes 1,145 cases and 1,142 controls. Pathways were retrieved from three databases: KEGG, BioCarta, and NCI Protein Interaction Database. Genes were represented by their most strongly associated SNP, and an enrichment score reflecting the overrepresentation of gene-based association signals in each pathway was calculated by using a weighted Kolmogorov-Smirnov procedure. Finally, hierarchical clustering was used to identify pathways with overlapping genes, and clusters with an excess of association signals were determined by the adaptive rank-truncated product (ARTP) method. A total of 421 pathways containing 3,962 genes was included in our study. Of these, three pathways (syndecan-1-mediated signaling, signaling of hepatocyte growth factor receptor, and growth hormone signaling) were highly enriched with association signals [P(ES) < 0.001, false discovery rate (FDR) = 0.118]. Our clustering analysis revealed that pathways containing key components of the RAS/RAF/mitogen-activated protein kinase canonical signaling cascade were significantly more likely to have an excess of association signals than expected by chance (P(ARTP) = 0.0051, FDR = 0.07). These results suggest that genetic alterations associated with these three pathways and one canonical signaling cascade may contribute to breast cancer susceptibility. Cancer Res; 70(11); 4453-9. (C) 2010 AACR. C1 [Menashe, Idan; Maeder, Dennis; Garcia-Closas, Montserrat; Figueroa, Jonine D.; Bhattacharjee, Samsiddhi; Rotunno, Melissa; Chanock, Stephen J.; Rosenberg, Philip S.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. RP Menashe, I (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Room 8047,Execut Plaza S,6120 Execut Blvd, Rockville, MD 20852 USA. EM menashei@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU National Institute of Health (NIH); NIH/NCI FX This study was partly supported by the Gene Environment Initiative program of the National Institute of Health.; Intramural Research Program of the NIH/NCI and the Gene Environment Initiative program of the NIH. NR 39 TC 60 Z9 62 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2010 VL 70 IS 11 BP 4453 EP 4459 DI 10.1158/0008-5472.CAN-09-4502 PG 7 WC Oncology SC Oncology GA 607GF UT WOS:000278486400023 PM 20460509 ER PT J AU Conti, C Leo, E Eichler, GS Sordet, O Martin, MM Fan, A Aladjem, MI Pommier, Y AF Conti, Chiara Leo, Elisabetta Eichler, Gabriel S. Sordet, Olivier Martin, Melvenia M. Fan, Angela Aladjem, Mirit I. Pommier, Yves TI Inhibition of Histone Deacetylase in Cancer Cells Slows Down Replication Forks, Activates Dormant Origins, and Induces DNA Damage SO CANCER RESEARCH LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; SACCHAROMYCES-CEREVISIAE; CHROMATIN CHALLENGES; SINGLE-CELL; INITIATION; BREAKS; ACETYLATION; DYNAMICS; STRESS; H2AX AB Protein acetylation is a reversible process regulated by histone deacetylases (HDAC) that is often altered in human cancers. Suberoylanilide hydroxamic acid (SAHA) is the first HDAC inhibitor to be approved for clinical use as an anticancer agent. Given that histone acetylation is a key determinant of chromatin structure, we investigated how SAHA may affect DNA replication and integrity to gain deeper insights into the basis for its anticancer activity. Nuclear replication factories were visualized with confocal immunofluorescence microscopy and single-replicon analyses were conducted by genome-wide molecular combing after pulse labeling with two thymidine analogues. We found that pharmacologic concentrations of SAHA induce replication-mediated DNA damage with activation of histone gamma H2AX. Single DNA molecule analyses indicated slowdown in replication speed along with activation of dormant replication origins in response to SAHA. Similar results were obtained using siRNA-mediated depletion of HDAC3 expression, implicating this HDAC member as a likely target in the SAHA response. Activation of dormant origins was confirmed by molecular analyses of the beta-globin locus control region. Our findings demonstrate that SAHA produces profound alterations in DNA replication that cause DNA damage, establishing a critical link between robust chromatin acetylation and DNA replication in human cancer cells. Cancer Res; 70(11); 4470-80. (C) 2010 AACR. C1 [Conti, Chiara; Leo, Elisabetta; Eichler, Gabriel S.; Sordet, Olivier; Martin, Melvenia M.; Fan, Angela; Aladjem, Mirit I.; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Aladjem, Mirit/G-2169-2010; Sordet, Olivier/M-3271-2014 OI Aladjem, Mirit/0000-0002-1875-3110; FU Center for Cancer Research, National Cancer Institute, NIH [Z01 BC 006150-19LMP, 1Z01BC010411-09]; University College London FX NIH Intramural Program, Center for Cancer Research, National Cancer Institute, NIH grants Z01 BC 006150-19LMP and 1Z01BC010411-09. E. Leo was partially supported by the Bogue Fellowship (University College London). NR 49 TC 72 Z9 73 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2010 VL 70 IS 11 BP 4470 EP 4480 DI 10.1158/0008-5472.CAN-09-3028 PG 11 WC Oncology SC Oncology GA 607GF UT WOS:000278486400025 PM 20460513 ER PT J AU Li, LW Shukla, S Lee, A Garfield, SH Maloney, DJ Ambudkar, SV Yuspa, SH AF Li, Luowei Shukla, Suneet Lee, Andrew Garfield, Susan H. Maloney, David J. Ambudkar, Suresh V. Yuspa, Stuart H. TI The Skin Cancer Chemotherapeutic Agent Ingenol-3-Angelate (PEP005) Is a Substrate for the Epidermal Multidrug Transporter (ABCB1) and Targets Tumor Vasculature SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; P-GLYCOPROTEIN; INGENOL 3-ANGELATE; INDUCED APOPTOSIS; CELL CARCINOMAS; MDR1 ABCB1; IN-VITRO; DELTA; KERATINOCYTES; RESISTANCE AB Ingenol-3-angelate (Ing3A), extracted from Euphorbia peplus, is currently in clinical trials for eradicating basal cell carcinoma, actinic keratosis, and squamous cell carcinoma (SCC) in situ by topical application. Although structurally related to phorbol esters and a protein kinase C activator, topical Ing3A, but not phorbol 12-myristate 13-acetate (PMA), inhibited the growth of subcutaneous tumors derived from PAM212 (mouse SCC) and B16 (mouse melanoma). Ing3A and PMA both induced acute neutrophilic inflammation on mouse skin, but only Ing3A caused subcutaneous hemorrhage and vascular damage. Both Ing3A and PMA activated extracellular signal-regulated kinase 1/2 (ERK1/2) in epidermis, but Ing3A also activated ERK1/2 in skin dermal fibroblasts and endothelial cells. Pretreatment with topical cyclosporin A (CsA), verapamil, or XR9576, modulators of P-glycoprotein (P-gp), prevented Ing3A-induced hemorrhage but not neutrophil infiltration. CsA also impaired the anticancer activity of Ing3A, whereas the anti-inflammatory dexamethasone did not. Ing3A, but not PMA, blocked photoaffinity labeling of human P-gp with [(125)I]iodoaryazidoprazosin and inhibited P-gp-mediated drug resistance to HCT-15 cells. The intracellular levels of Ing3A were significantly lower in P-gp-expressing cells, and treatment with XR9576 increased the levels to those of cells that do not express P-gp, showing that Ing3A binds to and is transported by P-gp. Taken together, our results suggest that P-gp-mediated absorptive transport, dermal penetration, and vascular damage contribute to the anticancer activity of Ing3A in vivo. Cancer Res; 70(11); 4509-19. (c) 2010 AACR. C1 [Li, Luowei] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Garfield, Susan H.] NCI, Confocal Core Facil, Ctr Canc Res, Bethesda, MD 20892 USA. [Maloney, David J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 4068,37 Convent Dr, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov RI shukla, suneet/B-4626-2012 FU Center for Cancer Research, NCI, NIH FX Intramural Research Program of the Center for Cancer Research, NCI, NIH. NR 45 TC 37 Z9 37 U1 1 U2 8 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 JUN 1 PY 2010 VL 70 IS 11 BP 4509 EP 4519 DI 10.1158/0008-5472.CAN-09-4303 PG 11 WC Oncology SC Oncology GA 607GF UT WOS:000278486400029 PM 20460505 ER PT J AU Meyer, MJ Fleming, JM Lin, AF Hussnain, SA Ginsburg, E Vonderhaar, BK AF Meyer, Matthew J. Fleming, Jodie M. Lin, Amy F. Hussnain, S. Amal Ginsburg, Erika Vonderhaar, Barbara K. TI CD44(pos)CD49f(hi)CD133/2(hi) Defines Xenograft-Initiating Cells in Estrogen Receptor-Negative Breast Cancer SO CANCER RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; METHYLATION PATTERNS; GENE-EXPRESSION; MAMMARY-GLAND; SELF-RENEWAL; IN-VIVO; CD44; SURVIVAL; TUMORS; GROWTH AB Defining the populations of tumor-initating cells that are present in tumors is a first step in developing therapeutics to target these cells. We show here that both CD44(pos)CD24(neg) and CD44(pos)CD24(pos) cell populations in estrogen receptor (ER) alpha-negative breast tumors are tumorigenic in murine xenograft models. We also describe a third population of xenograft-initiating cells (XIC) enriched in CD44(pos)CD49f(hi)CD133/2(hi) cells that display heightened tumorigenicity, self-renewal in vivo, and the capacity to give rise to functional and molecular heterogeneity. Consistent with their capacity for self-renewal, these cells express elevated levels of Sox2, Bmi-1, and/or Nanog and their CpG islands are hypermethylated relative to nontumorigenic cells. These differences in methylome regulation may be responsible for the dramatic functional differences between the two populations. The identification of CD44(pos)CD49f(hi)CD133/2(hi) XIC in ER-negative tumors may lead to expanded understanding of these tumors and ultimately the development of therapeutics designed to specifically target the cells. Cancer Res; 70(11); 4624-33. (c) 2010 AACR. C1 [Meyer, Matthew J.; Fleming, Jodie M.; Lin, Amy F.; Hussnain, S. Amal; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Meyer, MJ (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 1108, Bethesda, MD 20892 USA. EM meyerm@mail.nih.gov; bv10w@nih.gov FU NCI FX Center for Cancer Research, an Intramural Research Program of the NCI, and Breast Cancer Research Stamp proceeds awarded through competitive peer review. NR 48 TC 76 Z9 77 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2010 VL 70 IS 11 BP 4624 EP 4633 DI 10.1158/0008-5472.CAN-09-3619 PG 10 WC Oncology SC Oncology GA 607GF UT WOS:000278486400040 PM 20484027 ER PT J AU Kwon, MJ Kim, SS Choi, YL Jung, HS Balch, C Kim, SH Song, YS Marquez, VE Nephew, KP Shin, YK AF Kwon, Mi Jeong Kim, Sung-Su Choi, Yoon-La Jung, Hun Soon Balch, Curt Kim, Su-Hyeong Song, Yong-Sang Marquez, Victor E. Nephew, Kenneth P. Shin, Young Kee TI Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications SO CARCINOGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENES; CANCER-CELLS; DNA METHYLATION; COLORECTAL-CANCER; EPITHELIAL-CELLS; STEM-CELLS; EZH2; CLAUDIN-4; DIFFERENTIATION; HYPOMETHYLATION AB Unlike epigenetic silencing of tumor suppressor genes, the role of epigenetic derepression of cancer-promoting genes or oncogenes in carcinogenesis remains less well understood. The tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer and their overexpression was previously reported to promote the migration and invasion of ovarian epithelial cells. Here, we show that the expression of claudin-3 and claudin-4 is repressed in ovarian epithelial cells in association with promoter 'bivalent' histone modifications, containing both the activating trimethylated histone H3 lysine 4 (H3K4me3) mark and the repressive mark of trimethylated histone H3 lysine 27 (H3K27me3). During ovarian tumorigenesis, derepression of CLDN3 and CLDN4 expression correlates with loss of H3K27me3 in addition to trimethylated histone H4 lysine 20 (H4K20me3), another repressive histone modification. Although CLDN4 repression was accompanied by both DNA hypermethylation and repressive histone modifications, DNA methylation was not required for CLDN3 repression in immortalized ovarian epithelial cells. Moreover, activation of both CLDN3 and CLDN4 in ovarian cancer cells was associated with simultaneous changes in multiple histone modifications, whereas H3K27me3 loss alone was insufficient for their derepression. CLDN4 repression was robustly reversed by combined treatment targeting both DNA demethylation and histone acetylation. Our study strongly suggests that in addition to the well-known chromatin-associated silencing of tumor suppressor genes, epigenetic derepression by the conversely related loss of repressive chromatin modifications also contributes to ovarian tumorigenesis via activation of cancer-promoting genes or candidate oncogenes. C1 [Kwon, Mi Jeong; Kim, Sung-Su; Jung, Hun Soon; Shin, Young Kee] Seoul Natl Univ, Coll Pharm, Dept Pharm, Lab Mol Pathol, Seoul 151742, South Korea. [Choi, Yoon-La] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol, Seoul 135710, South Korea. [Balch, Curt; Nephew, Kenneth P.] Indiana Univ, Sch Med, Dept Cellular & Integrat Physiol, Bloomington, IN 47405 USA. [Kim, Su-Hyeong; Song, Yong-Sang] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110744, South Korea. [Song, Yong-Sang] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Shin, YK (reprint author), Seoul Natl Univ, Coll Pharm, Dept Pharm, Lab Mol Pathol, 599 Gwanak Ro, Seoul 151742, South Korea. EM ykeeshin@snu.ac.kr RI Shin, Young Kee/C-8929-2011; Song, Yong Sang/E-7824-2012 FU National Research Foundation of Korea, Korea government [20090083533]; Industry University Research Cooperation Program, Seoul Metropolitan Government [10541]; National Institutes of Health, National Cancer Institute, Center for Cancer Research, USA; National Cancer Institute [CA085289, CA113001] FX National Research Foundation of Korea, Korea government (20090083533); Industry University Research Cooperation Program, Seoul Metropolitan Government (10541); Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, USA; and National Cancer Institute Awards (CA085289 and CA113001). NR 51 TC 30 Z9 32 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2010 VL 31 IS 6 BP 974 EP 983 DI 10.1093/carcin/bgp336 PG 10 WC Oncology SC Oncology GA 603OS UT WOS:000278218500004 PM 20053926 ER PT J AU Perez-Lorenzo, R Markell, LM Hogan, KA Yuspa, SH Glick, AB AF Perez-Lorenzo, Rolando Markell, Lauren Mordasky Hogan, Kelly A. Yuspa, Stuart H. Glick, Adam B. TI Transforming growth factor beta 1 enhances tumor promotion in mouse skin carcinogenesis SO CARCINOGENESIS LA English DT Article ID KERATINOCYTE DIFFERENTIATION; CHEMICAL CARCINOGENESIS; INFLAMMATORY RESPONSE; NEUTROPHIL CHEMOTAXIS; MESSENGER-RNA; RAS ONCOGENE; C-FOS; PROTEIN; TGF-BETA-1; MICE AB Transforming growth factor beta 1 (TGF beta 1) expression is elevated by tumor promoters in the mouse skin, but its role in tumor promotion has not been well defined. To investigate this, we have compared TGF beta 1+/+ and +/- mice in a two-stage skin chemical carcinogenesis protocol. Surprisingly, TGF beta 1+/- mice had fewer number and incidence of benign papillomas, reduced epidermal and tumor cell proliferation and reduced epidermal TGF beta 1 and nuclear p-Smad2 localization in response to the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) compared with TGF beta 1+/+ mice. Maximal TPA activation of protein kinase C (PKC alpha) as measured by activity assays and activation of target genes and induction of cornified envelopes correlated with TGF beta 1 gene dosage in keratinocytes and addition of exogenous TGF beta 1 restored the cornification defect in TGF beta 1+/- keratinocytes. Similarly, inhibition of ALK5-suppressed TPA-mediated PKC alpha activation suggesting that physiological levels of TGF beta 1 are required for maximal activation of PKC-dependent mitogenic responses. Paradoxically, the TPA-induced inflammatory response was greater in TGF beta 1+/- skin, but TGF beta 1+/+ papillomas had more tumor infiltrating myeloperoxidase-positive cells and pro-inflammatory gene expression was elevated in v-ras(Ha)-transduced TGF beta 1+/+ but not TGF beta 1+/- keratinocytes. Thus, ras activation switches TGF beta 1 to a pro-inflammatory cytokine. Despite this differential proliferative and inflammatory response to TPA and enhanced papilloma formation in the TGF beta 1+/+ mice, the frequency of malignant conversion was reduced compared with TGF beta 1+/- mice. Therefore, TGF beta 1 promotes benign tumors by modifying tumor promoter-induced cell proliferation and inflammation but retains a suppressive function for malignant conversion. C1 [Perez-Lorenzo, Rolando; Markell, Lauren Mordasky; Hogan, Kelly A.; Glick, Adam B.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Perez-Lorenzo, Rolando] Univ Autonoma Campeche, Campeche 24030, Mexico. [Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. RP Glick, AB (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, 201 Life Sci Bldg, University Pk, PA 16802 USA. EM abg11@psu.edu FU National Institutes of Health [RO1 CA117957, CA122109]; National Cancer Institute FX National Institutes of Health (RO1 CA117957, CA122109) to A. B. G; intramural program of the National Cancer Institute. NR 50 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2010 VL 31 IS 6 BP 1116 EP 1123 DI 10.1093/carcin/bgq041 PG 8 WC Oncology SC Oncology GA 603OS UT WOS:000278218500022 PM 20172950 ER PT J AU Wang, HX Teh, MT Ji, YM Patel, V Firouzabadian, S Patel, AA Gutkind, JS Yeudall, WA AF Wang, Huixin Teh, Muy-Teck Ji, Youngmi Patel, Vyomesh Firouzabadian, Shahrzad Patel, Anisha A. Gutkind, J. Silvio Yeudall, W. Andrew TI EPS8 upregulates FOXM1 expression, enhancing cell growth and motility SO CARCINOGENESIS LA English DT Article ID TRANSCRIPTION FACTOR FOXM1; SQUAMOUS CARCINOMA-CELLS; FACTOR RECEPTOR KINASE; FACTOR-KAPPA-B; CHEMOKINE RECEPTOR; SIGNALING PATHWAYS; EPITHELIAL-CELLS; PROSTATE-CANCER; MALIGNANT-TRANSFORMATION; DOWN-REGULATION AB Previous studies from our laboratory have indicated that overexpression of the epidermal growth factor receptor pathway substrate 8 (EPS8) enhances cell proliferation, migration and tumorigenicity in vivo, although the mechanisms involved remain unexplored. A microarray screen to search for potential mediators of EPS8 identified upregulation of multiple cell cycle-related targets such as the transcription factor FOXM1 and several of its reported downstream mediators, including cdc20, cyclin B1, cyclin A, aurora-B kinase and cdc25C in cells with elevated EPS8, as well as matrix metalloproteinase-9, which we reported previously to be upregulated by EPS8-dependent mechanisms. Cells engineered to overexpress FOXM1 showed increased proliferation, similar to EPS8-overexpressing cells. Conversely, targeted knockdown of FOXM1 in EPS8-overexpressing cells reduced proliferation. Cotransfection of EPS8 with a FOXM1-luciferase reporter plasmid into 293-T- or SVpgC2a-immortalized buccal keratinocytes demonstrated that EPS8 enhances FOXM1 promoter activity, whereas chromatin immunoprecipitation assays revealed elevated levels of acetylated histone H3 associated with the FOXM1 promoter in cells expressing high levels of EPS8. Treatment of EPS8-overexpressing cells with inhibitors of phosphoinositide 3-OH kinase or AKT reduced expression of FOXM1 and aurora-B kinase, a transcriptional target of FOXM1. Overexpression of EPS8 induced expression of the chemokine ligands CXCL5 and CXCL12 in a FOXM1-dependent manner, which was blocked by LY294002 or a dominant-negative form of AKT. Additionally, overexpression of FOXM1 enhanced cell migration, whereas targeted knockdown of CXCL5 or inhibition of AKT reduced migration of EPS8-expressing cells. These data suggest that EPS8 enhances cell proliferation and migration in part by deregulating FOXM1 activity and inducing CXC-chemokine expression, mediated by PI3K- and AKT-dependent mechanisms. C1 [Wang, Huixin; Firouzabadian, Shahrzad; Patel, Anisha A.; Yeudall, W. Andrew] Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA. [Teh, Muy-Teck] Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Dent, Ctr Clin & Diagnost Oral Sci, London E1 2AD, England. [Ji, Youngmi] NIAMSD, Clin & Expt Orthoped Branch, Bethesda, MD 20892 USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Yeudall, W. Andrew] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. RP Yeudall, WA (reprint author), Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, POB 980566,521 N 11th St, Richmond, VA 23298 USA. EM wayeudall@vcu.edu RI Gutkind, J. Silvio/A-1053-2009; Teh, Muy-Teck/B-9284-2016 OI Teh, Muy-Teck/0000-0002-7725-8355 FU Commonwealth Health Research Board of the State Council of Higher Education for Virginia; National Institute of Dental and Craniofacial Research FX Supported in part by the Commonwealth Health Research Board of the State Council of Higher Education for Virginia through a grant to W.A.Y. and by the intramural programs of the National Institute of Dental and Craniofacial Research. NR 64 TC 26 Z9 27 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 JUN PY 2010 VL 31 IS 6 BP 1132 EP 1141 DI 10.1093/carcin/bgq058 PG 10 WC Oncology SC Oncology GA 603OS UT WOS:000278218500024 PM 20351091 ER PT J AU Torres, SM Divi, RL Walker, DM McCash, CL Carter, MM Campen, MJ Einem, TL Chu, Y Seilkop, SK Kang, HN Poirier, MC Walker, VE AF Torres, Salina M. Divi, Rao L. Walker, Dale M. McCash, Consuelo L. Carter, Meghan M. Campen, Matthew J. Einem, Tracey L. Chu, Yvonne Seilkop, Steven K. Kang, Huining Poirier, Miriam C. Walker, Vernon E. TI In Utero Exposure of Female CD-1 Mice to AZT and/or 3TC: II. Persistence of Functional Alterations in Cardiac Tissue SO CARDIOVASCULAR TOXICOLOGY LA English DT Article DE AZT; 3TC; Cardiotoxicity; Echocardiography; Mitochondrial DNA content; Mitochondrial DNA mutation; Mitochondrial dysfunction; Mitochondrial toxicity; OXPHOS; Transplacental exposure ID REVERSE-TRANSCRIPTASE INHIBITORS; MITOCHONDRIAL-DNA GENOME; TO-CHILD TRANSMISSION; PERINATAL EXPOSURE; PATAS MONKEYS; CORD BLOOD; ANTIRETROVIRAL THERAPY; NUCLEOSIDE ANALOGS; INFECTED PATIENTS; UMBILICAL-CORD AB To delineate temporal changes in the integrity and function of mitochondria/cardiomyocytes in hearts from mice exposed in utero to commonly used nucleoside analogs (NRTIs), CD-1 mice were exposed in utero to 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during days 12-18 of gestation and hearts from female mouse offspring were examined at 13 and 26 weeks postpartum. Alterations in cardiac mitochondrial DNA (mtDNA) content, oxidative phosphorylation (OXPHOS) enzyme activities, mtDNA mutations, and echocardiography of NRTI-exposed mice were assessed and compared with findings in vehicle-exposed control mice. A hybrid capture-chemiluminescence assay showed significant twofold increases in mtDNA levels in hearts from AZT- and AZT/3TC-exposed mice at 13 and 26 weeks postpartum, consistent with near doubling in mitochondrial numbers over time compared with vehicle-exposed mice. Echocardiographic measurements at 13 and 26 weeks postpartum indicated progressive thinning of the left ventricular posterior wall in NRTI-exposed mice, relative to controls, with differences becoming statistically significant by 26 weeks. Overall, progressive functional changes occurred in mouse mitochondria and cardiac tissue several months after in utero NRTI exposures; AZT and 3TC acted in concert to cause additive cardiotoxic effects of AZT/3TC compared with either drug alone. C1 [Walker, Vernon E.] Univ Vermont, Genet Toxicol Lab, Burlington, VT 05405 USA. [Torres, Salina M.; Walker, Vernon E.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA. [Torres, Salina M.; McCash, Consuelo L.; Carter, Meghan M.; Campen, Matthew J.; Walker, Vernon E.] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. [Divi, Rao L.; Einem, Tracey L.; Chu, Yvonne; Poirier, Miriam C.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Walker, Dale M.; Seilkop, Steven K.] SKS Consulting Serv, Siler City, NC 27344 USA. [Kang, Huining] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87106 USA. [Walker, Vernon E.] BioMosaics Inc, Burlington, VT 05405 USA. [Walker, Vernon E.] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. RP Walker, VE (reprint author), Univ Vermont, Genet Toxicol Lab, 665 Spear St,Bldg C, Burlington, VT 05405 USA. EM vwalker@uvm.edu FU NIH [R01 HL 72727, F31 HL081928] FX We wish to thank Mr. Steve Randock, Ms. Cynthia Herrera, and Ms. Wendy Piper (LRRI) for technical assistance in preparing figures and the manuscript; Dr. Beth Goens (University of New Mexico) for assistance with the echocardiography. This work was supported, in part, by NIH grant R01 HL 72727 to VEW and 1 F31 HL081928 to SMT from the National Heart, Lung, and Blood Institute and in part by the intramural program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 40 TC 9 Z9 9 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1530-7905 J9 CARDIOVASC TOXICOL JI Cardiovasc. Toxicol. PD JUN PY 2010 VL 10 IS 2 BP 87 EP 99 DI 10.1007/s12012-010-9065-z PG 13 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA 596UB UT WOS:000277709900002 PM 20155331 ER PT J AU Fliedner, SMJ Breza, J Kvetnansky, R Powers, JF Tischler, AS Wesley, R Merino, M Lehnert, H Pacak, K AF Fliedner, Stephanie M. J. Breza, Jan Kvetnansky, Richard Powers, James F. Tischler, Arthur S. Wesley, Robert Merino, Maria Lehnert, Hendrik Pacak, Karel TI Tyrosine hydroxylase, chromogranin A, and steroidogenic acute regulator as markers for successful separation of human adrenal medulla SO CELL AND TISSUE RESEARCH LA English DT Article DE Adrenal medulla; Chromogranin A; Steroidogenic acute regulator; Pheochromocytoma; Chromaffin cell; Human ID HUMAN CHROMAFFIN CELLS; PRO-OPIOMELANOCORTIN; NEURITE OUTGROWTH; CANCER-PATIENTS; IN-VITRO; PHEOCHROMOCYTOMA; EXPRESSION; PEPTIDES; WEIGHT; PAIN AB Progress in high throughput "-omic" techniques now allows the simultaneous measurement of expression levels of thousands of genes and promises the improved understanding of the molecular biology of diseases such as cancer. Detection of the dysfunction of molecular pathways in diseases requires healthy control tissue. This is difficult to obtain from pheochromocytomas (PHEOs), rare chromaffin tumors derived from adrenal medulla. The two options for obtaining adrenal tissue are: (1) whole organ removal post-mortem or during radical nephrectomy; (2) removal during PHEO surgery. Access to high quality normal adrenal tissue is limited. Removal of whole adrenals during nephrectomy is rare, because of improved surgical techniques. For adrenals removed post-mortem, the lag time to proper organ perfusion causes uncontrolled tissue degradation. Adjacent normal adrenal tissue can almost never be obtained from resected PHEOs, because they often replace the entire medulla or are well-encapsulated. If a margin of normal adrenal is attached to a resected PHEO, it seldom contains any medulla. The clean separation of medulla and cortex is further complicated, because their border is convoluted, and because adult adrenal consists of similar to 90% cortex. Thus, the quality of separation has to be evaluated with specific medullary and cortical markers. We describe the successful dissection of highly pure, medullary tissue from adrenals snap-frozen upon resection during radical nephrectomy or after brain death. Separation quality has been verified by quantitative reverse transcription with polymerase chain reaction for the medullary enzymes, tyrosine hydroxylase, and chromogranin A, and for the cortical enzyme, steroidogenic acute regulator. C1 [Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Fliedner, Stephanie M. J.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Breza, Jan] Comenius Univ, Dept Urol, Sch Med, Bratislava 84248, Slovakia. [Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. [Powers, James F.; Tischler, Arthur S.] Tufts Med Ctr, Dept Pathol, Boston, MA 02111 USA. [Wesley, Robert] NIH, Dept Hlth & Human Serv, Ctr Clin, Bethesda, MD 20892 USA. [Merino, Maria] NCI, Lab Surg Pathol, NIH, Bethesda, MD 20892 USA. [Lehnert, Hendrik] Med Univ Lubeck, Dept Med 1, D-23538 Lubeck, Germany. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Fliedner, Stephanie/D-3406-2012 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA; Pheo Para Alliance FX This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md., USA and, in part, by a grant from the Pheo Para Alliance (to A.S.T). NR 29 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD JUN PY 2010 VL 340 IS 3 BP 607 EP 612 DI 10.1007/s00441-010-0965-9 PG 6 WC Cell Biology SC Cell Biology GA 607QH UT WOS:000278520900019 PM 20440513 ER PT J AU Liu, XB Ong, HL Pani, B Johnson, K Swaim, WB Singh, B Ambudkar, I AF Liu, Xibao Ong, Hwei Ling Pani, Biswaranjan Johnson, Katherine Swaim, William B. Singh, Brij Ambudkar, Indu TI Effect of cell swelling on ER/PM junctional interactions and channel assembly involved in SOCE SO CELL CALCIUM LA English DT Article DE SOCE; ER-PM junctional domains; STIM1; TRPC1; Orai1; Cell volume; Hypotonic stress ID OPERATED CA2+ ENTRY; PLASMA MEMBRANE JUNCTIONS; TRPC CHANNELS; SALIVARY-GLANDS; CRAC CHANNELS; ION CHANNELS; STIM1; STORE; ACTIVATION; CALCIUM AB Store-operated calcium entry (SOCE) regulates critical cellular functions and is determined by precise ER/plasma membrane (PM) junctional interactions. Here we have assessed the effect of hypotonic cell volume increase on SOCE in a salivary gland epithelial cell line (HSG). Thapsigargin (Tg) activated a 2APB- and 1 mu M Gd(3+)-sensitive, inwardly rectifying, cation current, I(SOC), while hypotonic solution (150 mOsm) induced cell swelling and activated an outwardly rectifying cation current that was blocked by 100 mu M Gd(3+) but not by 2APB. HTS addition before or after Tg attenuated the sensitivity of Ca(2+) influx to 2APB and 1 mu M Gd(3+). After HTS-induced volume increase, while stimulation of cells with Tg resulted in intracellular Ca(2+) release without Ca(2+) influx, stimulation with CCh caused neither internal Ca(2+) release nor Ca(2+) influx. Importantly, HTS caused the ER to recede from the plasma membrane which prevented Tg-stimulated clustering of STIM1 in the ER/PM region and association of STIM1 with TRPC1 and Orai1. Disruption of SOCE was dependent on the level of hypotonic stress as 225 mOsm HTS induced relatively less cell swelling or disruption of SOCE. These results demonstrate that epithelial cells can tolerate small increases (up to 5%) in cell volume while larger increases lead to disruption of ER PM interactions that are critical for activation of SOCE. We suggest that loss of SOCE could impact cell function and contribute to the deleterious effects of severe hypotonic stress. Published by Elsevier Ltd. C1 [Liu, Xibao; Ong, Hwei Ling; Johnson, Katherine; Swaim, William B.; Ambudkar, Indu] Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. [Pani, Biswaranjan; Singh, Brij] Univ N Dakota, Dept Biochem & Mol Biol, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. RP Ambudkar, I (reprint author), Bldg 10,Room 1N113,10 Ctr Dr, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov OI Singh, Brij/0000-0003-0535-5997 FU NIDCR-DIR; University of North Dakota; ND-EPSCoR FX We acknowledge NIDCR-DIR funding for ISA, and University of North Dakota and ND-EPSCoR Student fellowships awarded to BP. We would also like to thank the following for kindly giving us their DNAs: Dr. Tobias Meyer (Stanford University, CA) for the CFP- and YFP-STIM1, and Dr. Tamas Balla (NICHD, NIH, MD) for Orai1-CFP. NR 40 TC 8 Z9 8 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JUN PY 2010 VL 47 IS 6 BP 491 EP 499 DI 10.1016/j.ceca.2010.04.002 PG 9 WC Cell Biology SC Cell Biology GA 627GE UT WOS:000280026700003 PM 20488539 ER PT J AU Ajiro, K Scoltock, AB Smith, LK Ashasima, M Cidlowski, JA AF Ajiro, K. Scoltock, A. B. Smith, L. K. Ashasima, M. Cidlowski, J. A. TI Reciprocal epigenetic modification of histone H2B occurs in chromatin during apoptosis in vitro and in vivo SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE chromatin structure; lymphocyte apoptosis; histone modification; glucocorticoid ID DNA FRAGMENTATION; STERILE-20 KINASE; PHOSPHORYLATION; CELLS; H3; CONDENSATION; ACETYLATION; THYMOCYTES; CLEAVAGE; DEACETYLATION AB Histone H2B phosphorylation at Serine 14 (phosS14) has been proposed as an epigenetic marker of apoptotic cells, whereas acetylation at the adjacent Lysine 15 (acK15) is a property of non-dying cells. We investigated the relationship and the potential regulatory mechanisms between these two epigenetic histone modifications and internucleosomal DNA degradation during apoptosis. Using rat primary thymocytes induced to undergo apoptosis with glucocorticoids we found that H2B phosphorylated at Ser14 was associated with soluble, cleaved DNA in apoptotic nuclei. In contrast acK15 was prevalent in non-apoptotic nuclei and scarce in apoptotic nuclei. This switch between K15 acetylation and S14 phosphorylation on H2B was also observed in apoptotic thymocytes from animals treated in vivo with glucocorticoids and in a rat hepatoma cell line (HTC) induced to die by UV-C or Fas ligand. It is interesting to note that the combined use of a histone deacetylase inhibitor and glucocorticoid suppressed both S14 phosphorylation and internucleosomal DNA degradation without inhibiting apoptosis in thymocytes. Using synthetic peptides and a PKC phosphorylation assay system, we show that the deacetylation of K15 was necessary to allow the S14 phosphorylation. These findings suggest that selective chromatin post-translational modifications are associated with DNA degradation during apoptosis. Cell Death and Differentiation (2010) 17, 984-993; doi:10.1038/cdd.2009.199; published online 8 January 2010 C1 [Ajiro, K.; Scoltock, A. B.; Smith, L. K.; Ashasima, M.; Cidlowski, J. A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU NIEHS, NIH [1Z01ES090057] FX We thank Tiwanda Marsh for the assistance in histochemical analysis. We thank the members of our laboratory for useful discussion. This research was supported by grant number 1Z01ES090057 of the Intramural Research Program of the NIEHS, NIH. NR 34 TC 10 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 2010 VL 17 IS 6 BP 984 EP 993 DI 10.1038/cdd.2009.199 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 593FA UT WOS:000277436800009 PM 20057502 ER PT J AU Jirmanova, L Ashwell, JD AF Jirmanova, Ludmila Ashwell, Jonathan D. TI T cell priming: let there be light SO CELL RESEARCH LA English DT Editorial Material ID IMMUNE FUNCTION; ACTIVATION; PHOSPHORYLATION; INFECTION; P38-ALPHA; NAIVE C1 [Jirmanova, Ludmila; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 15 TC 2 Z9 2 U1 0 U2 0 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JUN PY 2010 VL 20 IS 6 BP 608 EP 610 DI 10.1038/cr.2010.72 PG 3 WC Cell Biology SC Cell Biology GA 610IX UT WOS:000278726600003 PM 20502440 ER PT J AU Gardner, MK Sprague, BL Pearson, CG Cosgrove, BD Bicek, AD Bloom, K Salmon, ED Odde, DJ AF Gardner, Melissa K. Sprague, Brian L. Pearson, Chad G. Cosgrove, Benjamin D. Bicek, Andrew D. Bloom, Kerry Salmon, E. D. Odde, David J. TI Model Convolution: A Computational Approach to Digital Image Interpretation SO CELLULAR AND MOLECULAR BIOENGINEERING LA English DT Article DE Model-convolution; Fluorescence; Deconvolution; Modeling; Microscopy ID FIELD FLUORESCENCE MICROSCOPY; SACCHAROMYCES-CEREVISIAE; OPTICAL SECTIONS; SPINDLE; DECONVOLUTION; MICROTUBULES; YEAST; CONGRESSION; RESOLUTION; DYNAMICS AB Digital fluorescence microscopy is commonly used to track individual proteins and their dynamics in living cells. However, extracting molecule-specific information from fluorescence images is often limited by the noise and blur intrinsic to the cell and the imaging system. Here we discuss a method called "model-convolution," which uses experimentally measured noise and blur to simulate the process of imaging fluorescent proteins whose spatial distribution cannot be resolved. We then compare model-convolution to the more standard approach of experimental deconvolution. In some circumstances, standard experimental deconvolution approaches fail to yield the correct underlying fluorophore distribution. In these situations, model-convolution removes the uncertainty associated with deconvolution and therefore allows direct statistical comparison of experimental and theoretical data. Thus, if there are structural constraints on molecular organization, the model-convolution method better utilizes information gathered via fluorescence microscopy, and naturally integrates experiment and theory. C1 [Gardner, Melissa K.; Cosgrove, Benjamin D.; Bicek, Andrew D.; Odde, David J.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. [Bloom, Kerry; Salmon, E. D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Sprague, Brian L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Pearson, Chad G.] Univ Colorado, MCD Biol, Boulder, CO 80309 USA. RP Odde, DJ (reprint author), Univ Minnesota, Dept Biomed Engn, 7-132 Nils Hasselmo Hall,312 Church St SE, Minneapolis, MN 55455 USA. EM oddex002@umn.edu RI Odde, David/H-4925-2011; Cosgrove, Benjamin/A-9810-2016; OI Cosgrove, Benjamin/0000-0003-2164-350X; Bloom, Kerry/0000-0002-3457-004X; Odde, David/0000-0001-7731-2799 FU Whitaker Foundation; National Science Foundation; National Institutes of Health FX This work was supported by the Whitaker Foundation, the National Science Foundation, and the National Institutes of Health. The authors thank John Condeelis and James McNally for stimulating discussions. NR 31 TC 19 Z9 19 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1865-5025 J9 CELL MOL BIOENG JI Cell. Mol. Bioeng. PD JUN PY 2010 VL 3 IS 2 BP 163 EP 170 DI 10.1007/s12195-010-0101-7 PG 8 WC Cell & Tissue Engineering; Biophysics; Cell Biology SC Cell Biology; Biophysics GA 592HK UT WOS:000277368900007 PM 20461132 ER PT J AU Park, JE Soung, NK Johmura, Y Kang, YH Liao, C Lee, KH Park, CH Nicklaus, MC Lee, KS AF Park, Jung-Eun Soung, Nak-Kyun Johmura, Yoshikazu Kang, Young H. Liao, Chenzhong Lee, Kyung H. Park, Chi Hoon Nicklaus, Marc C. Lee, Kyung S. TI Polo-box domain: a versatile mediator of polo-like kinase function SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Polo kinase; Plk1; Polo-box domain; Mitosis; Cell proliferation ID CELL-CYCLE PROGRESSION; PROTEIN-SERINE/THREONINE KINASE; TOPOISOMERASE-II-ALPHA; KINESIN-LIKE PROTEIN; PLK1 PHOSPHORYLATION; PLK1-DEPENDENT PHOSPHORYLATION; SUBCELLULAR-LOCALIZATION; NUCLEAR TRANSLOCATION; CENTRIOLE DUPLICATION; MITOTIC PROGRESSION AB Members of the polo subfamily of protein kinases have emerged as important regulators in diverse aspects of the cell cycle and cell proliferation. A large body of evidence suggests that a highly conserved polo-box domain (PBD) present in the C-terminal non-catalytic region of polo kinases plays a pivotal role in the function of these enzymes. Recent advances in our comprehension of the mechanisms underlying mammalian polo-like kinase 1 (Plk1)-dependent protein-protein interactions revealed that the PBD serves as an essential molecular mediator that brings the kinase domain of Plk1 into proximity with its substrates, mainly through phospho-dependent interactions with its target proteins. In this review, current understanding of the structure and functions of PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other phospho-independent functions of PBD are discussed. C1 [Park, Jung-Eun; Soung, Nak-Kyun; Johmura, Yoshikazu; Kang, Young H.; Lee, Kyung H.; Park, Chi Hoon; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Liao, Chenzhong; Nicklaus, Marc C.] NCI Frederick, Biol Chem Lab, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov RI Nicklaus, Marc/N-4183-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU Intramural NIH HHS [ZIA BC010681-05] NR 130 TC 71 Z9 74 U1 3 U2 15 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUN PY 2010 VL 67 IS 12 BP 1957 EP 1970 DI 10.1007/s00018-010-0279-9 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 602AV UT WOS:000278111400001 PM 20148280 ER PT J AU Cook, NL AF Cook, Nakela L. TI Disparities in Cardiovascular Care Does a Rising Tide Lift All Boats? SO CIRCULATION LA English DT Editorial Material DE Editorials; health disparities; quality of care ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-IMPROVEMENT PROGRAM C1 NHLBI, Bethesda, MD 20892 USA. RP Cook, NL (reprint author), NHLBI, Rockledge 2,Ste 10018,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM cookn2@nhlbi.nih.gov NR 7 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 1 PY 2010 VL 121 IS 21 BP 2253 EP 2254 DI 10.1161/CIRCULATIONAHA.110.956961 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 603MQ UT WOS:000278213100001 PM 20479149 ER PT J AU Ping, PP Chan, DW Srinivas, P AF Ping, Peipei Chan, Daniel W. Srinivas, Pothur TI Advancing Cardiovascular Biology and Medicine via Proteomics Opportunities and Present Challenges of Cardiovascular Proteomics SO CIRCULATION LA English DT Article DE biology; biomedical technologies; medicine; proteomics ID MYOCARDIAL-INFARCTION; OUTCOMES; ST2 C1 [Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Dept Physiol, Los Angeles, CA 90095 USA. [Chan, Daniel W.] Johns Hopkins Univ Hosp, Dept Pathol, Div Clin Chem, Baltimore, MD 21287 USA. [Srinivas, Pothur] NHLBI, Prote Program, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Ping, PP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Dept Physiol, 675 Charles E Young Dr,MRL Bldg,Suite 1-619, Los Angeles, CA 90095 USA. EM pping@mednet.ucla.edu OI Ping, Peipei/0000-0003-3583-3881 FU National Institutes of Health/NHLBI FX This work was supported by the National Institutes of Health/NHLBI. NR 11 TC 7 Z9 7 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 1 PY 2010 VL 121 IS 21 BP 2326 EP 2328 DI 10.1161/CIRCULATIONAHA.110.949230 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 603MQ UT WOS:000278213100010 PM 20516387 ER PT J AU Lubitz, SA Ozcan, C Magnani, JW Kaab, S Benjamin, EJ Ellinor, PT AF Lubitz, Steven A. Ozcan, Cevher Magnani, Jared W. Kaeaeb, Stefan Benjamin, Emelia J. Ellinor, Patrick T. TI Genetics of Atrial Fibrillation Implications for Future Research Directions and Personalized Medicine SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial flutter; atrium; electrophysiology; epidemiology; fibrillation; genetics; ion channels; risk factors ID OF-FUNCTION MUTATION; CONGESTIVE-HEART-FAILURE; LEFT-RIGHT ASYMMETRY; SHORT QT SYNDROME; DILATED CARDIOMYOPATHY; FAMILIAL AGGREGATION; CHROMOSOME 4Q25; COMMON VARIANTS; ISCHEMIC-STROKE; SODIUM-CHANNEL C1 [Ozcan, Cevher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lubitz, Steven A.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Benjamin, Emelia J.] Boston Univ, Framingham, MA USA. [Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Magnani, Jared W.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Ellinor, PT (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM pellinor@partners.org OI Benjamin, Emelia/0000-0003-4076-2336 FU NIH [T32HL007575, HL092577, AG028321, RC1-HL01056, DA027021]; Fondation Leducq [07-CVD 03]; Bundesministerium fur Bildung und Forschung (BMBF), in the context of the German National Genome Research Network (NGFN) [01GS0838]; German AF-Net [01 GI 0204/N]; Exzellen-zinitiative at Ludwig-Maximilians University, Munich FX Dr Lubitz is supported by an NIH training grant in the Epidemiology of Cardiovascular Disease (T32HL007575). Dr Magnani is supported by an AHA grant (09FTF2190028). This work was supported by grants from the NIH to Drs Benjamin and Ellinor (HL092577), Dr Benjamin (AG028321, RC1-HL01056), and Dr Ellinor (DA027021). Drs Benjamin, Ellinor, and Kaab are supported by a grant from the Fondation Leducq (07-CVD 03). Dr Kaab is supported by Bundesministerium fur Bildung und Forschung (BMBF) in the context of the German National Genome Research Network (NGFN, 01GS0838), the German AF-Net (01 GI 0204/N), and the Exzellen-zinitiative at Ludwig-Maximilians University, Munich. NR 100 TC 43 Z9 43 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3149 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JUN PY 2010 VL 3 IS 3 BP 291 EP 299 DI 10.1161/CIRCEP.110.942441 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 611EB UT WOS:000278793000012 PM 20551423 ER PT J AU Morrison, AC Felix, JF Cupples, LA Glazer, NL Loehr, LR Dehghan, A Demissie, S Bis, JC Rosamond, WD Aulchenko, YS Wang, YA Haritunians, T Folsom, AR Rivadeneira, F Benjamin, EJ Lumley, T Couper, D Stricker, BH O'Donnell, CJ Rice, KM Chang, PP Hofman, A Levy, D Rotter, JI Fox, ER Uitterlinden, AG Wang, TJ Psaty, BM Willerson, JT van Duijn, CM Boerwinkle, E Witteman, JCM Vasan, RS Smith, NL AF Morrison, Alanna C. Felix, Janine F. Cupples, L. Adrienne Glazer, Nicole L. Loehr, Laura R. Dehghan, Abbas Demissie, Serkalem Bis, Joshua C. Rosamond, Wayne D. Aulchenko, Yurii S. Wang, Ying A. Haritunians, Talin Folsom, Aaron R. Rivadeneira, Fernando Benjamin, Emelia J. Lumley, Thomas Couper, David Stricker, Bruno H. O'Donnell, Christopher J. Rice, Kenneth M. Chang, Patricia P. Hofman, Albert Levy, Daniel Rotter, Jerome I. Fox, Ervin R. Uitterlinden, Andre G. Wang, Thomas J. Psaty, Bruce M. Willerson, James T. van Duijn, Cornelia M. Boerwinkle, Eric Witteman, Jacqueline C. M. Vasan, Ramachandran S. Smith, Nicholas L. TI Genomic Variation Associated With Mortality Among Adults of European and African Ancestry With Heart Failure The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE heart failure; all-cause mortality; genetics; genome-wide variation; mortality ID CORONARY SMOOTH-MUSCLE; QT INTERVAL DURATION; WIDE ASSOCIATION; ATHEROSCLEROSIS RISK; COMMON VARIANTS; EXPRESSION; DESIGN; CHANNELS; SUBUNIT; DISEASE AB Background-Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2 366 858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results-Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance. Conclusions-This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF. (Circ Cardiovasc Genet. 2010;3:248-255.) C1 [Morrison, Alanna C.; Willerson, James T.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77225 USA. [Chang, Patricia P.] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Rosamond, Wayne D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Loehr, Laura R.; Rosamond, Wayne D.] Nat Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Dept Med, University, MS 38677 USA. [Fox, Ervin R.] NHLBI, Jackson Heart Study, Houston, TX USA. [Willerson, James T.] Texas Heart Inst, Houston, TX 77025 USA. [Felix, Janine F.; Dehghan, Abbas; Aulchenko, Yurii S.; Stricker, Bruno H.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Felix, Janine F.; Witteman, Jacqueline C. M.] Netherlands Consortium Healthy Aging, Leiden, Netherlands. [Cupples, L. Adrienne; Demissie, Serkalem; Wang, Ying A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med & Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Cupples, L. Adrienne; Benjamin, Emelia J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.] Natl Heart Lung Blood Inst, Framingham Heart Study, Framingham, MA USA. [O'Donnell, Christopher J.; Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Psaty, Bruce M.; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Glazer, Nicole L.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Lumley, Thomas; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Psaty, Bruce M.; Smith, Nicholas L.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. RP Morrison, AC (reprint author), Univ Texas Houston Hlth Sci Ctr, Ctr Human Genet, 1200 Herman Pressler,Suite 453E, Houston, TX 77030 USA. EM Alanna.C.Morrison@uth.tmc.edu RI Rice, Kenneth/A-4150-2013; Aulchenko, Yurii/M-8270-2013; Rivadeneira, Fernando/O-5385-2015; OI Rice, Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira, Fernando/0000-0001-9435-9441; Felix, Janine/0000-0002-9801-5774; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Dehghan, Abbas/0000-0001-6403-016X FU National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C]; National Institutes of Health, National Institutes of Environmental Health Sciences; National Heart Lung and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC-25195]; National Center for Research Resources [M01RR00425-39]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; National Heart Lung Blood Institute [2K24HL04334, R01HL077477, R01HL093328]; Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Heart Foundation; Ministry of Health, Welfare and Sports; Ministry of Education, Culture and Science; European Commission; Municipality of Rotterdam; Netherlands Organization for Scientific Research (NWO) [918-76-619]; Netherlands Organization for Scientific Research [175.010.2005.011, 911.03.012]; Research Institute for Diseases; Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-60-810]; [UL1RR025005] FX The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694); National Human Genome Research Institute (U01HG004402); and National Institutes of Health (HHSN268200625226C). Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This research was supported in part by the intramural research program of the National Institutes of Health, National Institutes of Environmental Health Sciences. The Cardiovascular Health Study is 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 HL080295, and R01 HL 087652 from National Heart Lung and Blood Institute with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal Cardiovascular Health Study 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 M01RR00425-39 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The Framingham Heart Study was supported by National Heart Lung and Blood Institute (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). This work was also supported in part by grants from the National Heart Lung Blood Institute 2K24HL04334, R01HL077477, and R01HL093328 (all to Dr Vasan). This study is based on analyses by Framingham Heart Study investigators participating in the SNP Health Association Resource project. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Health, Welfare and Sports; the Ministry of Education, Culture and Science; the European Commission (DG XII); and the Municipality of Rotterdam. Abbas Dehghan and Janine Felix are supported by a VICI grant from the Netherlands Organization for Scientific Research (NWO) no. 918-76-619. The GWAS database of the Rotterdam study was funded through Netherlands Organization for Scientific Research (175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly. This study was supported by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research, project number 050-60-810. NR 28 TC 48 Z9 52 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 248 EP U64 DI 10.1161/CIRCGENETICS.109.895995 PG 10 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900006 PM 20400778 ER PT J AU Smith, NL Felix, JF Morrison, AC Demissie, S Glazer, NL Loehr, LR Cupples, LA Dehghan, A Lumley, T Rosamond, WD Lieb, W Rivadeneira, F Bis, JC Folsom, AR Benjamin, E Aulchenko, YS Haritunians, T Couper, D Murabito, J Wang, YA Stricker, BH Gottdiener, JS Chang, PP Wang, TJ Rice, KM Hofman, A Heckbert, SR Fox, ER O'Donnell, CJ Uitterlinden, AG Rotter, JI Willerson, JT Levy, D van Duijn, CM Psaty, BM Witteman, JCM Boerwinkle, E Vasan, RS AF Smith, Nicholas L. Felix, Janine F. Morrison, Alanna C. Demissie, Serkalem Glazer, Nicole L. Loehr, Laura R. Cupples, L. Adrienne Dehghan, Abbas Lumley, Thomas Rosamond, Wayne D. Lieb, Wolfgang Rivadeneira, Fernando Bis, Joshua C. Folsom, Aaron R. Benjamin, Emelia Aulchenko, Yurii S. Haritunians, Talin Couper, David Murabito, Joanne Wang, Ying A. Stricker, Bruno H. Gottdiener, John S. Chang, Patricia P. Wang, Thomas J. Rice, Kenneth M. Hofman, Albert Heckbert, Susan R. Fox, Ervin R. O'Donnell, Christopher J. Uitterlinden, Andre G. Rotter, Jerome I. Willerson, James T. Levy, Daniel van Duijn, Cornelia M. Psaty, Bruce M. Witteman, Jacqueline C. M. Boerwinkle, Eric Vasan, Ramachandran S. TI Association of Genome-Wide Variation With the Risk of Incident Heart Failure in Adults of European and African Ancestry A Prospective Meta-Analysis From the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE epidemiology; genetics; heart failure; genome; wide variation; incidence ID ATHEROSCLEROSIS RISK; LIFETIME RISK; FRAMINGHAM; DISEASE; COMMUNITIES; PREVALENCE; ROTTERDAM; DESIGN; CARDIOMYOPATHY; DYSFUNCTION AB Background-Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2 478 304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Methods and Results-Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximate to 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age-and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0 x 10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4 x 10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7 x 10-(8)), which was 6.3 kb from LRIG3. Conclusions-We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF. (Circ Cardiovasc Genet. 2010;3:256-266.) C1 [Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Study, Seattle, WA 98195 USA. [Glazer, Nicole L.; Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Lumley, Thomas; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Smith, Nicholas L.] Dept Vet Affairs, Seattle Epidemiol Res & Informat Ctr, Off Res & Dev, Seattle, WA USA. [Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Gottdiener, John S.] Univ Maryland, Dept Cardiol, Baltimore, MD 21201 USA. [Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Morrison, Alanna C.; Benjamin, Emelia; Willerson, James T.] Univ Texas Houston Hlth Sci Ctr, Artherosclerosis Risk Communities Study, Houston, TX USA. [Loehr, Laura R.; Chang, Patricia P.] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. [Loehr, Laura R.; Rosamond, Wayne D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Loehr, Laura R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Willerson, James T.] Texas Heart Inst, Houston, TX 77025 USA. [Demissie, Serkalem; Cupples, L. Adrienne; Wang, Ying A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham Heart Study, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Bethesda, MD 20892 USA. [Wang, Thomas J.; O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cupples, L. Adrienne; Lieb, Wolfgang; Benjamin, Emelia; Murabito, Joanne; Wang, Thomas J.; O'Donnell, Christopher J.; Levy, Daniel; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Felix, Janine F.; Dehghan, Abbas; Aulchenko, Yurii S.; Stricker, Bruno H.; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam Study, Rotterdam, Netherlands. RP Smith, NL (reprint author), Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98105 USA. EM nlsmith@u.washington.edu RI Lieb, Wolfgang/C-1990-2012; Rice, Kenneth/A-4150-2013; Aulchenko, Yurii/M-8270-2013; Rivadeneira, Fernando/O-5385-2015; OI Dehghan, Abbas/0000-0001-6403-016X; Rice, Kenneth/0000-0001-5779-4495; Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira, Fernando/0000-0001-9435-9441; Murabito, Joanne/0000-0002-0192-7516; Felix, Janine/0000-0002-9801-5774; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute (NHLBI) [N01HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; NIH, National Institutes of Environmental Health Sciences; NHLBI [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC25195, 2K24HL04334, R01HL077477, R01HL093328]; National Center for Research Resources [M01RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; NWO [175.010.2005.011, 911.03.012]; Netherlands Genomics Initiative (NGI)/NWO [050-060-810]; Netherlands Foundation for Scientific Research (NWO, VICI) [918-76-619]; [UL1RR025005] FX We acknowledge the essential role of the CHARGE Consortium in developing this article and for the support. CHARGE members include National Heart, Lung, and Blood Institute's ARIC Study, NIA's Iceland Age, Gene/Environment Susceptibility Study, National Heart, Lung, and Blood Institute's Cardiovascular Health Study and Framingham Heart Study, and the Netherland's Rotterdam Study. The authors also acknowledge the thousands of study participants who volunteered their time to help advance science and the scores of research staff and scientists who have made this research possible. The Rotterdam Study authors thank Mila Jhamai, Pascal Arp, Dr Michael J. Moorhouse, Marijn Verkerk, and Sander Bervoets for their help in creating the database and Maxim Struchalin for his contributions to the imputations of the data.; The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01HC- 55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health (NIH) contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This research was supported in part by the intramural research program of the NIH, National Institutes of Environmental Health Sciences.; The CHS is supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, grant numbers U01 HL080295 and R01 HL 087652 from NHLBI with additional contribution from the National Institute of Neurological 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, National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center, and Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR).; The FHS was supported by NHLBI (Contract No. N01-HC25195) and its contract with Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278). This work was also supported in part by grants from the NHLBI 2K24HL04334, R01HL077477, and R01HL093328 (all to RSV). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The analyses reflect intellectual input and resource development from the FHS investigators participating in the SNP Health Association Resource (SHARe) project.; The RS is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Heart Foundation (Nederlandse hartstichting); the Ministry of Health Welfare and Sports; the Ministry of Education, Culture and Science; the European Commission (DG XII); and the Municipality of Rotterdam. Support for genotyping was given by NWO (175.010.2005.011, 911.03.012) and RIDE. This study was supported by the Netherlands Genomics Initiative (NGI)/NWO project number 050-060-810 (Netherlands Consortium for Healthy Ageing). The Netherlands Foundation for Scientific Research (NWO, VICI no. 918-76-619) also provided investigator support (A.D., and J.F.F.); The funding sources had no role in the study design, analyses, or drafting of the article. The NHLBI reviews all articles submitted for publication but it was not involved in the decision to publish. Drs NL Smith, JF Felix, AC Morrison, and S Demissie had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 49 TC 72 Z9 74 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 256 EP U79 DI 10.1161/CIRCGENETICS.109.895763 PG 13 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900007 PM 20445134 ER PT J AU Musunuru, K Lettre, G Young, T Farlow, DN Pirruccello, JP Ejebe, KG Keating, BJ Yang, Q Chen, MH Lapchyk, N Crenshaw, A Ziaugra, L Rachupka, A Benjamin, EJ Cupples, LA Fornage, M Fox, ER Heckbert, SR Hirschhorn, JN Newton-Cheh, C Nizzari, MM Paltoo, DN Papanicolaou, GJ Patel, SR Psaty, BM Rader, DJ Redline, S Rich, SS Rotter, JI Taylor, HA Tracy, RP Vasan, RS Wilson, JG Kathiresan, S Fabsitz, RR Boerwinkle, E Gabriel, SB AF Musunuru, Kiran Lettre, Guillaume Young, Taylor Farlow, Deborah N. Pirruccello, James P. Ejebe, Kenechi G. Keating, Brendan J. Yang, Qiong Chen, Ming-Huei Lapchyk, Nina Crenshaw, Andrew Ziaugra, Liuda Rachupka, Anthony Benjamin, Emelia J. Cupples, L. Adrienne Fornage, Myriam Fox, Ervin R. Heckbert, Susan R. Hirschhorn, Joel N. Newton-Cheh, Christopher Nizzari, Marcia M. Paltoo, Dina N. Papanicolaou, George J. Patel, Sanjay R. Psaty, Bruce M. Rader, Daniel J. Redline, Susan Rich, Stephen S. Rotter, Jerome I. Taylor, Herman A., Jr. Tracy, Russell P. Vasan, Ramachandran S. Wilson, James G. Kathiresan, Sekar Fabsitz, Richard R. Boerwinkle, Eric Gabriel, Stacey B. CA NHLBI Candidate Gene Assoc TI Candidate Gene Association Resource (CARe) Design, Methods, and Proof of Concept SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics; lipids; epidemiology ID DENSITY-LIPOPROTEIN CHOLESTEROL; ATHEROSCLEROSIS; RECRUITMENT; HEART; POLYMORPHISMS; OBJECTIVES; HAPLOTYPE; ALLELES; DISEASE AB Background-The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe), a planned cross-cohort analysis of genetic variation in cardiovascular, pulmonary, hematologic, and sleep-related traits, comprises >40 000 participants representing 4 ethnic groups in 9 community-based cohorts. The goals of CARe include the discovery of new variants associated with traits using a candidate gene approach and the discovery of new variants using the genome-wide association mapping approach specifically in African Americans. Methods and Results-CARe has assembled DNA samples for >40 000 individuals self-identified as European American, African American, Hispanic, or Chinese American, with accompanying data on hundreds of phenotypes that have been standardized and deposited in the CARe Phenotype Database. All participants were genotyped for 7 single-nucleotide polymorphisms (SNPs) selected based on prior association evidence. We performed association analyses relating each of these SNPs to lipid traits, stratified by sex and ethnicity, and adjusted for age and age squared. In at least 2 of the ethnic groups, SNPs near CETP, LIPC, and LPL strongly replicated for association with high-density lipoprotein cholesterol concentrations, PCSK9 with low-density lipoprotein cholesterol levels, and LPL and APOA5 with serum triglycerides. Notably, some SNPs showed varying effect sizes and significance of association in different ethnic groups. Conclusions-The CARe Pilot Study validates the operational framework for phenotype collection, SNP genotyping, and analytic pipeline of the CARe project and validates the planned candidate gene study of approximate to 2000 biological candidate loci in all participants and genome-wide association study in similar to 8000 African American participants. CARe will serve as a valuable resource for the scientific community. ( Circ Cardiovasc Genet. 2010;3:267-275.) C1 [Musunuru, Kiran; Lettre, Guillaume; Young, Taylor; Farlow, Deborah N.; Pirruccello, James P.; Ejebe, Kenechi G.; Lapchyk, Nina; Crenshaw, Andrew; Ziaugra, Liuda; Rachupka, Anthony; Hirschhorn, Joel N.; Newton-Cheh, Christopher; Kathiresan, Sekar; Gabriel, Stacey B.] Broad Inst, Cambridge, MA 02142 USA. [Musunuru, Kiran; Pirruccello, James P.; Ejebe, Kenechi G.; Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Musunuru, Kiran; Hirschhorn, Joel N.; Newton-Cheh, Christopher; Kathiresan, Sekar] Harvard Univ, Sch Med, Boston, MA USA. [Musunuru, Kiran; Pirruccello, James P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Lettre, Guillaume] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada. [Yang, Qiong; Chen, Ming-Huei; Benjamin, Emelia J.; Cupples, L. Adrienne; Vasan, Ramachandran S.] Boston Univ, Boston, MA USA. [Yang, Qiong; Chen, Ming-Huei; Benjamin, Emelia J.; Cupples, L. Adrienne; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Ervin R.; Taylor, Herman A., Jr.; Wilson, James G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77225 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Seattle, WA 98195 USA. [Hirschhorn, Joel N.] Childrens Hosp, Boston, MA 02115 USA. [Farlow, Deborah N.; Papanicolaou, George J.; Fabsitz, Richard R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Patel, Sanjay R.; Redline, Susan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Patel, Sanjay R.; Redline, Susan] Univ Hosp Cleveland, Case Med Ctr, Cleveland, OH 44106 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Rich, Stephen S.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Tracy, Russell P.] Univ Vermont, Coll Med, Burlington, VT USA. RP Gabriel, SB (reprint author), Broad Inst, 5 Cambridge Ctr, Cambridge, MA 02142 USA. EM stacey@broadinstitute.org; stacey@broadinstitute.org RI Yang, Qiong/G-5438-2014; Ejebe, Kenechi/I-9238-2016; OI Ejebe, Kenechi/0000-0002-6090-8657; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336; Patel, Sanjay/0000-0002-9142-5172 FU DNA [N01-HC-65226]; University of North Carolina at Chapel Hill [N01-HC-55015, N01-HC-55018]; Baylor Medical College [N01-HC-55016]; University of Mississippi Medical Center [N01-HC-55021]; University of Minnesota [N01-HC-55019, N01-HC-48048]; Johns Hopkins University [N01-HC-55020, N01-HC-85081, N01-HC-15103]; University of Texas, Houston [N01-HC-55022]; Cardiovascular Health Study: University of Washington [N01-HC-85079, N01-HC-55222, U01-HL-080295]; Wake Forest University [N01-HC-85080, N01-HC-05187]; University of Pittsburgh [N01HC-85082]; University of California [N01-HC-85083, N01-HC-85084, N01-HC-45134, N01-HC-95100]; New England Medical Center [N01-HC-85085]; University of Vermont [N01-HC-85086]; Georgetown University [N01-HC-35129]; University of Wisconsin [N01-HC-75150]; Cleveland Family Study: Case Western Reserve University [R01-HL-46380, M01-RR-00080]; Cooperative Study of Sickle Cell Disease: University of Illinois [N01-HB-72982, N01HB- 97062]; Howard University [N01-HB-72991, N01-HB-97061]; University of Miami [N01-HB-72992, N01-HB-97064]; Duke University [N01-HB-72993]; George Washington University [N01-HB72994]; University of Tennessee [N01-HB-72995, N01-HB-97070]; Yale University [N01-HB-72996, N01-HB-97072]; Children's Hospital-Philadelphia [N01-HB-72997, N01-HB-97056]; University of Chicago [N01-HB-72998, N01-HB-97053]; Medical College of Georgia [N01-HB-73000, N01-HB-97060]; Washington University [N01-HB-73001, N01-HB-97071]; Jewish Hospital and Medical Center of Brooklyn [N01-HB-73002]; Trustees of Health and Hospitals of the City of Boston, Inc [N01-HB-73003]; Children's Hospital-Oakland [N01-HB-73004, N01-HB-97054]; University of Mississippi [N01-HB-73005]; St Luke's Hospital-New York [N01HB- 73006]; Alta Bates-Herrick Hospital [N01-HB-97051]; Columbia University [N01-HB-97058]; St Jude's Children's Research Hospital [N01-HB-97066]; Research Foundation, State University of New York-Albany [N01-HB-97068, N01-HB-97069]; New England Research Institute [N01-HB-97073]; Interfaith Medical CenterBrooklyn [N01-HB-97085]; Coronary Artery Risk in Young Adults: University of Alabama at Birmingham [N01-HC-48047, N01-HC95095]; Northwestern University [N01-HC-48049]; Kaiser Foundation Research Institute [N01-HC-48050]; Tufts-New England Medical Center [N01-HC45204]; Harbor-UCLA Research and Education Institute [N01-HC-05187]; Framingham Heart Study: Boston University [N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321]; Jackson Heart Study: Jackson State University FX The following 9 parent studies, funded by the listed National Institutes of Health grants, have contributed parent study data, ancillary study data, and samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: Atherosclerotic Risk in Communities: University of North Carolina at Chapel Hill (N01-HC-55015, N01-HC-55018), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55022); Cardiovascular Health Study: University of Washington (N01-HC-85079, N01-HC-55222, U01-HL-080295), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081, N01-HC-15103), University of Pittsburgh (N01HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), University of Wisconsin (N01-HC-75150); Cleveland Family Study: Case Western Reserve University (R01-HL-46380, M01-RR-00080); Cooperative Study of Sickle Cell Disease: University of Illinois (N01-HB-72982, N01HB- 97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children's Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc (N01-HB-73003), Children's Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke's Hospital-New York (N01HB- 73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude's Children's Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical CenterBrooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults: University of Alabama at Birmingham (N01-HC-48047, N01-HC95095), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), Tufts-New England Medical Center (N01-HC45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study: Boston University (N01-HC-25195, R01-HL-092577, R01-HL-076784, R01-AG-028321); Jackson Heart Study: Jackson State University (N01-HC-95170), University of Mississippi (N01HC- 95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis: University of Washington (N01-HC95159), University of California, Los Angeles (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162, N01-HC-95168), University of Minnesota (N01HC- 95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01HC- 95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC-95169), Cedars-Sinai Medi; al Center (R01-HL-071205), University of Virginia (subcontract to R01-HL-071205); Sleep Heart Health Study: Johns Hopkins University (U01-HL-064360), Case Western University (U01-HL-063463), University of California, Davis (U01-HL053916), University of Arizona (U01-HL-053938, U01-HL053934), University of Pittsburgh (U01-HL-077813), Boston University (U01-HL-053941), MedStar Research Institute (U01-HL063429), Johns Hopkins University (U01-HL-053937). NR 24 TC 98 Z9 100 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD JUN PY 2010 VL 3 IS 3 BP 267 EP U94 DI 10.1161/CIRCGENETICS.109.882696 PG 13 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 611GH UT WOS:000278799900008 PM 20400780 ER PT J AU Burbelo, PD Issa, AT Ching, KH Cohen, JI Iadarola, MJ Marques, A AF Burbelo, Peter D. Issa, Alexandra T. Ching, Kathryn H. Cohen, Jeffrey I. Iadarola, Michael J. Marques, Adriana TI Rapid, Simple, Quantitative, and Highly Sensitive Antibody Detection for Lyme Disease SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; IMMUNODOMINANT CONSERVED REGION; BORRELIA-BURGDORFERI; 4-ANTIGEN MIXTURE; PROTEIN-A; C-6 TEST; DIAGNOSIS; INFECTION; PEPTIDE AB There is currently a need for improved serological tests for the diagnosis and monitoring of Lyme disease, an infection caused by Borrelia burgdorferi. In the present study, we evaluated luciferase immunoprecipitation systems (LIPSs) for use for profiling of the antibody responses to a panel of B. burgdorferi proteins for the diagnosis of Lyme disease. Initially, serum samples from a cohort of patients and controls (n = 46) were used for training and were profiled by the use of 15 different B. burgdorferi antigen constructs. For the patient sera, the antibody responses to several B. burgdorferi antigens, including VlsE, flagellin (FlaB), BmpA, DbpA, and DbpB, indicated that the antigens had high levels of immunoreactivity. However, the best diagnostic performance was achieved with a synthetic protein, designated VOVO, consisting of a repeated antigenic peptide sequence, VlsE-OspC-VlsE-OspC, Analysis of an independent set of serum samples (n = 139) used for validation showed that the VOVO LIPS test had 98% sensitivity (95% confidence interval [CI], 93% to 100%; P < 0.0001) and 100% specificity (95% CI, 94% to 100%; P < 0.0001). Similarly, the C6 peptide enzyme-linked immunosorbent assay (ELISA) also had 98% sensitivity (95% CI, 93% to 100%; P < 0.0001) and 98% specificity (95% CI, 90% to 100%; P < 0.0001). Receiver operating characteristic analysis revealed that the rates of detection of Lyme disease by the LIPS test and the C6 ELISA were not statistically different. However, the VOVO LIPS test displayed a wide dynamic range of antibody detection spanning over 10,000-fold without the need for serum dilution. These results suggest that screening by the LIPS test with VOVO and other B. burgdorferi antigens offers an efficient quantitative approach for evaluation of the antibody responses in patients with Lyme disease. C1 [Burbelo, Peter D.; Issa, Alexandra T.; Ching, Kathryn H.; Iadarola, Michael J.] NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Cohen, Jeffrey I.; Marques, Adriana] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, 49 Convent Dr,Bldg 49,Room 1C20, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 30 TC 29 Z9 30 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JUN PY 2010 VL 17 IS 6 BP 904 EP 909 DI 10.1128/CVI.00476-09 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 603MG UT WOS:000278212100003 PM 20392886 ER PT J AU Miller, WG Myers, GL Sakurabayashi, I Bachmann, LM Caudill, SP Dziekonski, A Edwards, S Kimberly, MM Korzun, WJ Leary, ET Nakajima, K Nakamura, M Nilsson, G Shamburek, RD Vetrovec, GW Warnick, GR Remaley, AT AF Miller, W. Greg Myers, Gary L. Sakurabayashi, Ikunosuke Bachmann, Lorin M. Caudill, Samuel P. Dziekonski, Andrzej Edwards, Selvin Kimberly, Mary M. Korzun, William J. Leary, Elizabeth T. Nakajima, Katsuyuki Nakamura, Masakazu Nilsson, Goeran Shamburek, Robert D. Vetrovec, George W. Warnick, G. Russell Remaley, Alan T. TI Seven Direct Methods for Measuring HDL and LDL Cholesterol Compared with Ultracentrifugation Reference Measurement Procedures SO CLINICAL CHEMISTRY LA English DT Article ID HOMOGENEOUS ASSAYS; PRECIPITATION; PERFORMANCE AB BACKGROUND: Methods from 7 manufacturers and 1 distributor for directly measuring HDL cholesterol (C) and LDL-C were evaluated for imprecision, trueness, total error, and specificity in nonfrozen serum samples. METHODS: We performed each direct method according to the manufacturer's instructions, using a Roche/Hitachi 917 analyzer, and compared the results with those obtained with reference measurement procedures for HDL-C and LDL-C. Imprecision was estimated for 35 runs performed with frozen pooled serum specimens and triplicate measurements on each individual sample. Sera from 37 individuals without disease and 138 with disease (primarily dyslipidemic and cardiovascular) were measured by each method. Trueness and total error were evaluated from the difference between the direct methods and reference measurement procedures. Specificity was evaluated from the dispersion in differences observed. RESULTS: Imprecision data based on 4 frozen serum pools showed total CVs <3.7% for HDL-C and <4.4% for LDL-C. Bias for the nondiseased group ranged from -5.4% to 4.8% for HDL-C and from -6.8% to 1.1% for LDL-C, and for the diseased group from -8.6% to 8.8% for HDL-C and from -11.8% to 4.1% for LDL-C. Total error for the nondiseased group ranged from -13.4% to 13.6% for HDL-C and from -13.3% to 13.5% for LDL-C, and for the diseased group from -19.8% to 36.3% for HDL-C and from -26.6% to 31.9% for LDL-C. CONCLUSIONS: Six of 8 HDL-C and 5 of 8 LDL-C direct methods met the National Cholesterol Education Program total error goals for nondiseased individuals. All the methods failed to meet these goals for diseased individuals, however, because of lack of specificity toward abnormal lipoproteins. (C) 2010 American Association for Clinical Chemistry C1 [Miller, W. Greg; Bachmann, Lorin M.; Dziekonski, Andrzej; Korzun, William J.; Vetrovec, George W.] Virginia Commonwealth Univ, Richmond, VA USA. [Myers, Gary L.; Caudill, Samuel P.; Edwards, Selvin; Kimberly, Mary M.] US Ctr Dis Control & Prevent, Atlanta, GA USA. [Sakurabayashi, Ikunosuke] Jichi Med Univ, Shimotsuke, Tochigi, Japan. [Leary, Elizabeth T.] Pacific Biometr & Pacific Biometr Res Fdn, Seattle, WA USA. [Nakajima, Katsuyuki] Otsuka Pharmceut, Tokyo, Japan. [Nakamura, Masakazu] Osaka Med Ctr Hlth Sci & Promot, Osaka, Japan. [Nilsson, Goeran] Nilsson Measurement Qual, Uppsala, Sweden. [Shamburek, Robert D.; Remaley, Alan T.] NIH, Bethesda, MD 20892 USA. [Warnick, G. Russell] Hlth Diagnost Lab, Richmond, VA USA. RP Miller, WG (reprint author), POB 980286, Richmond, VA 23298 USA. EM gmiller@vcu.edu FU US distributors Genzyme; Pacific Biometrics Research Foundation; Merck; Pfizer; Abbott; Schering Plough; NIH; Gilead (CV Therapeutics); Lilly/Daiichi Sankyo; Cordis FX W. G. Miller, PI for this investigation, sources acknowledged in manuscript; G. W. Vetrovec, Merck, Pfizer, Abbott, and Schering Plough; A. T. Remaley, NIH.; G.W. Vetrovec, Pfizer, Gilead (CV Therapeutics), Lilly/Daiichi Sankyo, Cordis (all 4 are speaker bureau related), Cordis-Johnson & Johnson and Corindus (both relate to grants for education or research under discussion at time of declaration).; The authors are grateful to each of the Japanese manufacturers mentioned in the Methods section, who provided financial support, reagents, calibrators, and controls for this evaluation, and to US distributors Genzyme, who provided their HDL-C calibrator, and Pointe Scientific, who provided financial support. We thank Roche Diagnostics for providing reagents, calibrators, and controls, plus the loan of a Hitachi 917 instrument for use in this investigation. We thank Pacific Biometrics Research Foundation for financial support, and T. Mallory for arranging the support from the US distributors. We appreciate the assistance of Drs. T. Gehr, D. Carl, A. Vinnikova, and V. Luketic, along with C. Sargeant, for recruiting patients at VCU. We also thank K. Dobbin and E. Monsell at CDC for performing the cholesterol RMP measurements and statistical calculations, respectively. NR 22 TC 89 Z9 91 U1 2 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2010 VL 56 IS 6 BP 977 EP 986 DI 10.1373/clinchem.2009.142810 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 602NB UT WOS:000278145000019 PM 20378768 ER PT J AU Schwope, DM Milman, G Huestis, MA AF Schwope, David M. Milman, Garry Huestis, Marilyn A. TI Validation of an Enzyme Immunoassay for Detection and Semiquantification of Cannabinoids in Oral Fluid SO CLINICAL CHEMISTRY LA English DT Article ID METABOLITE 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; DELTA(9)-TETRAHYDROCANNABINOL THC; COLLECTION DEVICE; MARIJUANA; SPECIMENS AB BACKGROUND: Oral fluid (OF) is gaining prominence as an alternative matrix for monitoring drugs of abuse in the workplace, criminal justice, and driving under the influence of drugs programs. It is important to characterize assay performance and limitations of screening techniques for Delta(9)-tetrahydrocannabinol (THC) in OF. METHODS: We collected OF specimens by use of the Quantisal (TM) OF collection device from 13 daily cannabis users after controlled oral cannabinoid administration. All specimens were tested with the Immunalysis Sweat/OF THC Direct ELISA and confirmed by 2-dimensional GC-MS. RESULTS: The limit of detection was <1 mu g/L THC equivalent, and the assay demonstrated linearity from 1 to 50 mu g/L, with semiquantification to 200 mu g/L. Intraplate imprecision (n = 7) ranged from 2.9% to 7.7% CV, and interplate imprecision (n = 20) was 3.0%-9.1%. Cross-reactivities at 4 mu g/L were as follows: 11-hydroxy-THC, 198%; Delta(8)-tetrahydrocannabinol (Delta(8)-THC), 128%; 11-nor-9-carboxy-THC (THCCOOH), 121%; THC (target), 98%; cannabinol, 87%; THCCOOH-glucuronide, 11%; THC-glucuronide, 10%; and cannabidiol, 2.4%. Of 499 tested OF specimens, 52 confirmed positive (THC 2.0-290 mu g/L), with 100% diagnostic sensitivity at the proposed Substance Abuse and Mental Health Services Administration screening cutoff of 4 mu g/L cannabinoids and GC-MS cutoff of 2 mu g/L THC. Forty-seven specimens screened positive but were not confirmed by 2D-GC-MS, yielding 89.5% diagnostic specificity and 90.6% diagnostic efficiency. Thirty-one of 47 unconfirmed immunoassay positive specimens were from 1 individual and contained >400 ng/L THCCOOH, potentially contributing to cross-reactivity. CONCLUSIONS: The Immunalysis Sweat/OF THC Direct ELISA is an effective screening procedure for detecting cannabinoids in OF. (C) 2010 American Association for Clinical Chemistry C1 [Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health; Immunalysis Corporation FX This work was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health.; D. M. Schwope, Immunalysis Corporation. (It sponsored an open competition for a travel grant; this author won the competition and has received travel funding from Immunalysis Corporation to present this research at a scientific meeting.) NR 17 TC 11 Z9 11 U1 5 U2 16 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2010 VL 56 IS 6 BP 1007 EP 1014 DI 10.1373/clinchem.2009.141754 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 602NB UT WOS:000278145000022 PM 20360126 ER PT J AU Bimpaki, EI Iliopoulos, D Moraitis, A Stratakis, CA AF Bimpaki, Eirini I. Iliopoulos, Dimitrios Moraitis, Andreas Stratakis, Constantine A. TI MicroRNA signature in massive macronodular adrenocortical disease and implications for adrenocortical tumourigenesis SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CUSHINGS-SYNDROME; ADRENAL-HYPERPLASIA; GENE-EXPRESSION; BREAST-CANCER; RECEPTORS; LEUKEMIA; HYPOXIA; TUMORS AB Purpose Massive macronodular adrenocortical disease (MMAD) may be caused by aberrant microRNA expression. To determine the microRNA profile in MMAD and identify putative microRNA-gene target pairs involved in adrenal tumourigenesis. Experimental design We performed microRNA microarray analysis in 10 patients with ACTH-independent Cushing syndrome caused by MMAD (ages 39-60 years) and four normal adrenal cortex samples were used as controls. Microarray data were validated by real-time polymerase chain reaction (qRT-PCR). Identification of potential microRNA-gene target pairs implicated in MMAD pathogenesis has been performed by integrating our microRNA data with previously obtained cDNA microarray data. Experimental validation of specific microRNA gene targets was performed by transfection experiments and luciferase assay. Results A total of 37 microRNAs were differentially expressed between MMAD and normal tissues; 16 microRNAs were down-regulated, including miR-200b and miR-203, whereas 21 microRNAs were up-regulated, miR-210 and miR-484 among them. Comparison of microRNA data with different clinicopathological parameters revealed miR-130a and miR-382 as putative diagnostic MMAD markers. Interestingly, we detected miR-200b targeting directly Matrin 3 (MATR3) expression in an adrenocortical cancer cell line (H295R). Conclusions MicroRNAs appear to have distinct regulatory effects in MMAD, including an association with clinical presentation and severity of the disease, expressed by the degree of hyper-cortisolism. This is the first investigation of microRNAs in MMAD, a disease with complex pathogenesis; the data indicate that specific microRNAs such as miR-200b may play a significant role in MMAD formation and/or progression. C1 [Stratakis, Constantine A.] NICHD, SEGEN PDEGEN, NIH, CRC East Labs, Bethesda, MD 20892 USA. [Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Stratakis, CA (reprint author), NICHD, SEGEN PDEGEN, NIH, CRC East Labs, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU NIH [Z01-HD-000642-04]; University of Crete, School of Medicine FX This work was supported by NIH intramural project Z01-HD-000642-04 to Dr C. A. Stratakis and, in part, by the University of Crete, School of Medicine, Post-Graduate Program (to Drs Bimpaki and Stratakis). We would like to thank Dr Maya Lodish for her assistance in formatting the tables. NR 33 TC 28 Z9 30 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUN PY 2010 VL 72 IS 6 BP 744 EP 751 DI 10.1111/j.1365-2265.2009.03725.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 598VD UT WOS:000277866200005 PM 19849700 ER PT J AU Gordon, A Saborio, S Videa, E Lopez, R Kuan, G Balmaseda, A Harris, E AF Gordon, Aubree Saborio, Saira Videa, Elsa Lopez, Roger Kuan, Guillermina Balmaseda, Angel Harris, Eva TI Clinical Attack Rate and Presentation of Pandemic H1N1 Influenza versus Seasonal Influenza A and B in a Pediatric Cohort in Nicaragua SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; INFECTION; FEATURES; CHILDREN; VIRUS AB Background. Little is known about the clinical presentation and epidemiology of influenza A H1N1pdm in children in developing countries. We assessed the severity of influenza A H1N1pdm in children in Nicaragua by comparing H1N1pdm cases to seasonal influenza cases in an ongoing cohort study. Methods. The Nicaraguan Influenza Cohort Study was established in June 2007 to study the burden and seasonality of pediatric influenza in a tropical developing country. During the period from June 2007 through November 2009, a total of 4391 children aged 2-14 years participated in the cohort. We examined the attack rate of clinical influenza and assessed symptoms at first presentation in febrile patients with H1N1pdm versus those with seasonal influenza A or B. Results. The estimated clinical attack rate of H1N1pdm in the cohort was 20.1%, compared to 11.7% and 15.1% for seasonal influenza A and 11.9% and 24.2% for seasonal influenza A and B in 2007 and 2008, respectively. Symptoms significantly associated with H1N1pdm cases versus seasonal influenza A cases were sore throat (adjusted odds ratio [OR], 1.7; 95% confidence interval [CI], 1.2-2.5), wheezing (OR, 5.1; 95% CI, 1.3-19.0), rhonchi (OR, 4.6; 95% CI, 1.4-15.0), crepitations (OR, 16.2; 95% CI, 2.1-128.7), pneumonia (OR, 8.0; 95% CI, 1.7-37.3), nausea (OR, 2.8; 95% CI, 1.5-5.1), and loss of appetite (OR, 2.1; 95% CI, 1.4-3.1). In addition, 3 concurrent influenza and dengue virus coinfections were identified. Conclusions. Children with influenza A H1N1pdm presented with significantly more symptoms of lower respiratory infection and gastrointestinal symptoms than children with seasonal influenza. The clinical influenza attack rate was high in both pandemic and seasonal years. C1 [Gordon, Aubree; Harris, Eva] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA. [Gordon, Aubree] Univ Calif Berkeley, Sch Publ Hlth, Dept Epidemiol, Berkeley, CA 94720 USA. [Gordon, Aubree] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Kuan, Guillermina] Minist Hlth, Ctr Salud Socrates Flores Vivas, Managua, Nicaragua. [Saborio, Saira; Lopez, Roger; Balmaseda, Angel] Ctr Nacl Diagnost & Referencia, Dept Virol, Managua, Nicaragua. [Videa, Elsa] Sustainable Sci Inst, Managua, Nicaragua. RP Gordon, A (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, 1 Barker Hall 416, Berkeley, CA 94720 USA. EM aubree@berkeley.edu OI Gordon, Aubree/0000-0002-9352-7877 FU National Institutes of Health; Pediatric Dengue Vaccine Initiative; US National Institute of Allergy and Infectious Diseases; Centers for Disease Control and Prevention FX The Fogarty International Center of the National Institutes of Health, the Pediatric Dengue Vaccine Initiative, the US National Institute of Allergy and Infectious Diseases, and the Centers for Disease Control and Prevention. The sponsors of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. NR 20 TC 39 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2010 VL 50 IS 11 BP 1462 EP 1467 DI 10.1086/652647 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 590AF UT WOS:000277194800006 PM 20420502 ER PT J AU Khalsa, JH Elkashef, A AF Khalsa, Jag H. Elkashef, Ahmed TI Interventions for HIV and Hepatitis C Virus Infections in Recreational Drug Users SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; METHADONE-MAINTENANCE TREATMENT; POTENT ANTIRETROVIRAL THERAPY; SEXUAL TRANSMISSION; HCV INFECTION; SAN-FRANCISCO; LIVER-DISEASE; INJECTION; MANAGEMENT; COINFECTION AB Recreational drug use and infections are 2 of the major problems in the world today. Both cause serious health problems, such as immunologic impairment leading to opportunistic infections and medical comorbidity, including medical complications associated with, for example, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Effective and safe interventions (prevention and pharmacologic treatment) are possible for drug-dependent patients with single or dual infections with HIV and HCV if patients in drug treatment programs are closely monitored for adherence and compliance to treatment regimens. C1 [Khalsa, Jag H.] NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Elkashef, Ahmed] NIDA, Clin Trials Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Khalsa, JH (reprint author), NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4137,MSC 9551, Bethesda, MD 20892 USA. EM jk98p@nih.gov NR 87 TC 5 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2010 VL 50 IS 11 BP 1505 EP 1511 DI 10.1086/652447 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 590AF UT WOS:000277194800013 PM 20415569 ER PT J AU Althoff, KN Gange, SJ Klein, MB Brooks, JT Hogg, RS Bosch, RJ Horberg, MA Saag, MS Kitahata, MM Justice, AC Gebo, KA Eron, JJ Rourke, SB Gill, MJ Rodriguez, B Sterling, TR Calzavara, LM Deeks, SG Martin, JN Rachlis, AR Napravnik, S Jacobson, LP Kirk, GD Collier, AC Benson, CA Silverberg, MJ Kushel, M Goedert, JJ McKaig, RG Van Rompaey, SE Zhang, JB Moore, RD AF Althoff, Keri N. Gange, Stephen J. Klein, Marina B. Brooks, John T. Hogg, Robert S. Bosch, Ronald J. Horberg, Michael A. Saag, Michael S. Kitahata, Mari M. Justice, Amy C. Gebo, Kelly A. Eron, Joseph J. Rourke, Sean B. Gill, M. John Rodriguez, Benigno Sterling, Timothy R. Calzavara, Liviana M. Deeks, Steven G. Martin, Jeffrey N. Rachlis, Anita R. Napravnik, Sonia Jacobson, Lisa P. Kirk, Gregory D. Collier, Ann C. Benson, Constance A. Silverberg, Michael J. Kushel, Margot Goedert, James J. McKaig, Rosemary G. Van Rompaey, Stephen E. Zhang, Jinbing Moore, Richard D. CA N Amer AIDS Cohort Collaboration R TI Late Presentation for Human Immunodeficiency Virus Care in the United States and Canada SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; HIV-INFECTION; MEDICAL-CARE; HETEROSEXUAL TRANSMISSION; RISK; POPULATION; ADULTS; RECOMMENDATIONS; ASSOCIATION; GUIDELINES AB Background. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. Methods. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. Results. Median age at first presentation for HIV care increased over time (range, 40-43 years; P<.01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P<.01) and heterosexual transmission risk increased (from 16% to 23%; P<.01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135517 cells/mm(3)) from 1997 to 2007 (P<.01). The percentage of patients with a CD4 count >= 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P<.01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). Conclusion. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment. C1 [Althoff, Keri N.; Gange, Stephen J.; Gebo, Kelly A.; Jacobson, Lisa P.; Kirk, Gregory D.; Zhang, Jinbing; Moore, Richard D.] Johns Hopkins Univ Hosp, Sch Med, Baltimore, MD 21287 USA. [Goedert, James J.; McKaig, Rosemary G.] NIH, Bethesda, MD 20892 USA. [Brooks, John T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Bosch, Ronald J.] Harvard Univ, Boston, MA 02115 USA. [Horberg, Michael A.; Silverberg, Michael J.] Kaiser Permanente No Calif, Oakland, CA USA. [Deeks, Steven G.; Martin, Jeffrey N.; Kushel, Margot] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Benson, Constance A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Saag, Michael S.] Univ Alabama, Birmingham, AL USA. [Kitahata, Mari M.; Collier, Ann C.; Van Rompaey, Stephen E.] Univ Washington, Seattle, WA 98195 USA. [Justice, Amy C.] Yale Univ, New Haven, CT USA. [Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. [Eron, Joseph J.; Napravnik, Sonia] Univ N Carolina Chapel Hill, Chapel Hill, NC USA. [Rodriguez, Benigno] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sterling, Timothy R.] Vanderbilt Univ, Nashville, TN USA. [Klein, Marina B.] McGill Univ Montreal, Quebec City, PQ, Canada. [Hogg, Robert S.] Simon Fraser Univ, Vancouver, BC, Canada. [Hogg, Robert S.] British Columbia Ctr Excellence & HIV AIDS, Vancouver, BC, Canada. [Rourke, Sean B.; Calzavara, Liviana M.; Rachlis, Anita R.] Univ Toronto, Toronto, ON, Canada. [Gill, M. John] Univ Calgary, Calgary, AB, Canada. RP Moore, RD (reprint author), Johns Hopkins Univ Hosp, Sch Med, 1830 E Monument St,Ste 8059, Baltimore, MD 21287 USA. EM rdmoore@jhmi.edu RI Hogg, Robert/B-2783-2012; Rodriguez, Benigno/C-3365-2009; Gill, John/G-7083-2016; OI Rodriguez, Benigno/0000-0001-9736-7957; Gill, John/0000-0002-8546-8790; Gange, Stephen/0000-0001-7842-512X; Hogg, Robert/0000-0003-3463-5488 FU National Institutes of Health [U01-AI069918, U10-AA013566, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-HD32632, M01-RR00071, M01-RR00079, M01-RR00083, M01-RR00722, P30-AI27757, P30-AI27767, P30-AI50410, P30-AI54999, R01-DA04334, R01-DA12568, R01-MH54907, R24-AI067039, Z01-CP010176, N02-CP55504, R01-DA11602, AI-69432, K01-AI071754, R01-AA16893, K24-DA00432, K23-AI610320, R01-AI069434]; Agency for Healthcare Research and Quality [HS 290-01-0012]; Ardea Biosciences; Avexa; Boehringer-Ingelheim; Bristol-Myers Squibb; Gilead Sciences; GlaxoSmithKline; Merck; Monogram Biosciences; Pain Therapeutics; Panacos; Pfizer; Progenics; Roche Laboratories; Tibotec; Tobira Therapeutics; Vicro; Achillion Pharmaceuticals; Theratechnologies; Roche; Gilead; Abbott; Canadian Institutes of Health Research; Fonds de la recherche en sante du Quebec; Canadian HIV Trials Network; Ontario HIV Treatment Network; Schering Plough Canada; Universitywide AIDS Research Program; Community Benefit/Kaiser Permanente; Johns Hopkins University; Schering-Plough; Koronis; Achillion; Steris FX We are grateful to all patients, physicians, investigators, and staff involved in the NA-ACCORD. This work was supported by grants from the National Institutes of Health (U01-AI069918, U10-AA013566, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-HD32632, M01-RR00071, M01-RR00079, M01-RR00083, M01-RR00722, P30-AI27757, P30-AI27767, P30-AI50410, P30-AI54999, R01-DA04334, R01-DA12568, R01-MH54907, R24-AI067039, Z01-CP010176, N02-CP55504, R01-DA11602, AI-69432, K01-AI071754, R01-AA16893, K24-DA00432, K23-AI610320, and R01-AI069434) and the Agency for Healthcare Research and Quality (HS 290-01-0012).; Potential conflicts of interest. M. S. S. reports that he has received consulting fees from Ardea Biosciences, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Monogram Biosciences, Pain Therapeutics, Panacos, Pfizer, Progenics, Roche Laboratories, Tibotec, Tobira Therapeutics, and Vicro and research support from Achillion Pharmaceuticals, Avexa, Boehringer-Ingelheim, GlaxoSmithKline, Merck, Panacos, Pfizer, Progenics, Theratechnologies, and Tibotec. S. G. D. reports that he has received consulting fees from GlaxoSmithKline, Roche, Gilead, and Boehringer-Ingelheim and grant support from Merck, Gilead, Bristol-Myers Squibb, and Pfizer. J.J.E. reports that he has received consulting fees from Tibotec, Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Pfizer, lecture fees from Roche, Bristol-Myers Squibb, Tibotec, and Merck, and grant support from GlaxoSmithKline, Merck, and Boehringer-Ingelheim. M.J.G. reports that he has received consulting fees from Gilead, GlaxoSmithKline, Abbott, Merck, Boehringer-Ingelheim, Tibotec, and Pfizer and grant support from GlaxoSmithKline, Abbott, Canadian Institutes of Health Research, Tibotec, and Pfizer. R. S. H. reports that he has received grant support from Merck. M. BK. reports that she has received consulting fees from GlaxoSmithKline, Abbott, Pfizer, and Boehringer-Ingelheim, lecture fees from Abbott, Gilead, Tibotec, Bristol-Myers Squibb, and GlaxoSmithKline, and research support from Canadian Institutes of Health Research/Fonds de la recherche en sante du Quebec, Canadian HIV Trials Network, Ontario HIV Treatment Network, and Schering Plough Canada. A. R. R. reports that she has received consulting and lecture fees from GlaxoSmithKline, Abbott, Merck, Pfizer, Bristol Myers Squibb, Gilead, and Tibotec and grant support from GlaxoSmithKline, Tibotec, Boehringer-Ingelheim, Abbott, Merck, Pfizer, and Roche. M. A. H. reports that he has received grant support from Gilead, Abbott, and Bristol-Myers Squibb. M.J.S. reports that he has received grant support from Pfizer, Merck, Gilead, Universitywide AIDS Research Program, and Community Benefit/Kaiser Permanente. K. A. G. reports that she has received consulting fees from Tibotec and grant support from the Johns Hopkins University Richard Ross Award. R. D. M. reports that he has received consulting fees from Bristol-Myers Squibb and GlaxoSmithKline, lecture fees from Gilead, and grant support from Pfizer, Merck, and Gilead. A. C. C. reports that she has received consulting fees from Merck, Pfizer, and GlaxoSmithKline, equity ownership/stock options in Bristol-Myers Squibb and Abbott, and grant support from Schering-Plough, Tibotec-Virco, Gilead, Koronis, and Merck. C. A. B. reports that she has received consulting fees from GlaxoSmithKline, Pfizer, Merck, and Achillion and grant support from Gilead. B. R. reports that he has received consulting fees from Gilead and Bristol-Myers Squibb, lecture fees from Bristol-Myers Squibb, and grant support from Steris. All other authors: no conflicts. NR 44 TC 113 Z9 115 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2010 VL 50 IS 11 BP 1512 EP 1520 DI 10.1086/652650 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 590AF UT WOS:000277194800014 PM 20415573 ER PT J AU Gunay-Aygun, M Font-Montgomery, E Lukose, L Tuchman, M Graf, J Bryant, JC Kleta, R Garcia, A Edwards, H Piwnica-Worms, K Adams, D Bernardini, I Fischer, RE Krasnewich, D Oden, N Ling, A Quezado, Z Zak, C Daryanani, KT Turkbey, B Choyke, P Guay-Woodford, LM Gahl, WA AF Gunay-Aygun, Meral Font-Montgomery, Esperanza Lukose, Linda Tuchman, Maya Graf, Jennifer Bryant, Joy C. Kleta, Robert Garcia, Angelica Edwards, Hailey Piwnica-Worms, Katie Adams, David Bernardini, Isa Fischer, Roxanne E. Krasnewich, Donna Oden, Neal Ling, Alex Quezado, Zenaide Zak, Colleen Daryanani, Kailash T. Turkbey, Baris Choyke, Peter Guay-Woodford, Lisa M. Gahl, William A. TI Correlation of Kidney Function, Volume and Imaging Findings, and PKHD1 Mutations in 73 Patients with Autosomal Recessive Polycystic Kidney Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CONGENITAL HEPATIC-FIBROSIS; CHILDREN; ARPKD; LIVER; SONOGRAPHY; EXPERIENCE; ENCODES; PROTEIN; GENE AB Background and objectives: Renal function and imaging findings have not been comprehensively and prospectively characterized in a broad age range of patients with molecularly confirmed autosomal recessive polycystic kidney disease (ARPKD). Design, setting, participants, & measurements: Ninety potential ARPKD patients were examined at the National Institutes of Health Clinical Center. Seventy-three fulfilled clinical diagnostic criteria, had at least one PKHD1 mutation, and were prospectively evaluated using magnetic resonance imaging (MRI), high-resolution ultrasonography (HR-USG), and measures of glomerular and tubular function. Results: Among 31 perinatally symptomatic patients, 25% required renal replacement therapy by age 11 years; among 42 patients who became symptomatic beyond 1 month (nonperinatal), 25% required kidney transplantation by age 32 years. Creatinine clearance (CrCl) for nonperinatal patients (103 +/- 54 ml/min/1.73 m(2)) was greater than for perinatal patients (62 +/- 33) (P = 0.002). Corticomedullary involvement on HR-USG was associated with a significantly worse mean CrCl (61 +/- 32) in comparison with medullary involvement only (131 +/- 46) (P < 0.0001). Among children with enlarged kidneys, volume correlated inversely with function, although with wide variability. Severity of PKHD1 mutations did not determine kidney size or function. In 35% of patients with medullary-only abnormalities, standard ultrasound was normal and the pathology was detectable with HR-USG. Conclusions: In ARPKD, perinatal presentation and corticomedullary involvement are associated with faster progression of kidney disease. Mild ARPKD is best detected by HR-USG. Considerable variability occurs that is not explained by the type of PKHD1 mutation. Clin J Am Soc Nephrol 5: 972-984, 2010. doi: 10.2215/CJN.07141009 C1 [Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Graf, Jennifer; Ling, Alex; Quezado, Zenaide; Daryanani, Kailash T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Oden, Neal; Turkbey, Baris; Choyke, Peter] EMMES Corp, Rockville, MD USA. [Oden, Neal; Turkbey, Baris; Choyke, Peter] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Zak, Colleen] Autosomal Recess Polycyst Kidney Dis Congenital H, Kirkwood, PA USA. [Guay-Woodford, Lisa M.] Univ Alabama, Birmingham, AL USA. RP Gunay-Aygun, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU ARPKD/CHF Alliance; National Human Genome Research Institute; National Cancer Institute; NIH FX We thank the ARPKD/CHF Alliance for their extensive support and the patients and their families who generously participated in this investigation. The Intramural Research Programs of the National Human Genome Research Institute, the National Cancer Institute, and the NIH Clinical Center supported this study. NR 35 TC 32 Z9 35 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JUN PY 2010 VL 5 IS 6 BP 972 EP 984 DI 10.2215/CJN.07141009 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 608OY UT WOS:000278596200005 PM 20413436 ER PT J AU Dunleavy, K Shapiro, G Disinski, M Chirieac, L Pittaluga, S Jaffe, ES Janik, JE Wiestner, A Wilson, WH AF Dunleavy, Kieron Shapiro, Geoff Disinski, Megan Chirieac, Lucian Pittaluga, Stefania Jaffe, Elaine S. Janik, John E. Wiestner, Adrian Wilson, Wyndham H. TI A Phase I/II Study of a Hybrid Schedule of Flavopiridol in Relapsed/Refractory Mantle Cell Lymphoma and Diffuse Large B-Cell Lymphoma SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Meeting Abstract C1 [Dunleavy, Kieron; Disinski, Megan; Pittaluga, Stefania; Jaffe, Elaine S.; Janik, John E.; Wiestner, Adrian; Wilson, Wyndham H.] NCI, Bethesda, MD 20892 USA. [Shapiro, Geoff; Chirieac, Lucian] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2010 VL 10 IS 3 MA 2 BP E27 EP E27 DI 10.3816/CLML.2010.n.037 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 602DX UT WOS:000278119800013 ER PT J AU Hsu, AL Khachikyan, I Stratton, P AF Hsu, Albert L. Khachikyan, Izabella Stratton, Pamela TI Invasive and Noninvasive Methods for the Diagnosis of Endometriosis SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE endometriosis; diagnosis; laparoscopy; ultrasound; magnetic resonance imaging; endometrioma; deep infiltrating endometriosis ID TRANSVAGINAL SONOGRAPHY; NERVE-FIBERS; LAPAROSCOPY; ACCURACY; CA-125; WOMEN AB Endometriosis has been associated with pain and infertility. The gold standard for the diagnosis of endometriosis has been visual inspection by laparoscopy, preferably with histologic confirmation. Because there is no good noninvasive test for endometriosis, there is often a significant delay in diagnosis of this disease. Imaging that confirms an endometriotic cyst or deep infiltrating endometriosis may help guide surgical therapeutic approaches. No serum marker has been found to diagnose endometriosis with adequate sensitivity and specificity. There has been a recent focus on the presence of nerve fibers in the eutopic endometrium of patients with endometriosis. C1 [Hsu, Albert L.; Khachikyan, Izabella; Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 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 USA. EM strattop@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Funding for this work was provided exclusively by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. No pharmaceutical or industry funding was accepted in the preparation of this manuscript. NR 18 TC 25 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2010 VL 53 IS 2 BP 413 EP 419 DI 10.1097/GRF.0b013e3181db7ce8 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 631TC UT WOS:000280369900016 PM 20436318 ER PT J AU Freidlin, B Korn, EL Gray, R AF Freidlin, Boris Korn, Edward L. Gray, Robert TI A general inefficacy interim monitoring rule for randomized clinical trials SO CLINICAL TRIALS LA English DT Article ID CELL LUNG-CANCER; METASTATIC BREAST-CANCER; PHASE-III TRIAL; ONCOLOGY-GROUP; FUTILITY; PACLITAXEL; PLUS; BEVACIZUMAB; CARBOPLATIN; COMBINATION AB Background The ultimate goal of a phase III randomized clinical trial designed to demonstrate superiority of a new versus standard therapy is to provide sufficiently compelling evidence to affect clinical practice. To balance patient interests against the need for acquiring evidence it is desirable to stop a study for inefficacy as soon as convincing evidence that the new therapy is not beneficial becomes available. Purpose To discuss potential deficiencies in some commonly used inefficacy monitoring rules and to propose a comprehensive inefficacy monitoring procedure. Methods The proposed approach is developed using clinical, logistical, and statistical considerations. The new approach is compared to the commonly used inefficacy rules in a simulation study. Results Some of the commonly used inefficacy rules are suboptimal with respect to the strength of evidence required for stopping throughout the trial: too conservative in the middle and/or too aggressive at the end. Our approach allows timely stopping (a) if the new therapy is harmful, and (b) if the interim data provides convincing evidence that the new therapy has no tangible benefit. Relative to common inefficacy rules, our procedure is shown to result in potentially fewer treated patients and shorter study duration under the null hypothesis with only a minor loss of power under the alternative hypothesis. Limitations The proposed procedure is applicable to superiority designs with well-defined clinical objectives. Conclusions The proposed inefficacy approach is attractive from statistical, clinical, and logistical standpoints. By decreasing average stopping times relative to the commonly used boundaries, our rule lessens patient exposure to inactive treatments, improves resource utilization, and accelerates dissemination of important clinical information. At the same time, the proposed rule provides a clear benchmark for providing compelling evidence that the new therapy is not beneficial. Clinical Trials 2010; 7: 197-208. http://ctj.sagepub.com. C1 [Freidlin, Boris; Korn, Edward L.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Gray, Robert] Harvard Univ, Sch Publ Hlth, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA. EM freidlinb@ctep.nci.nih.gov NR 36 TC 17 Z9 17 U1 5 U2 10 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2010 VL 7 IS 3 BP 197 EP 208 DI 10.1177/1740774510369019 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 598TM UT WOS:000277861400001 PM 20423925 ER PT J AU Cizza, G Marincola, P Mattingly, M Williams, L Mitler, M Skarulis, M Csako, G AF Cizza, Giovanni Marincola, Paula Mattingly, Megan Williams, Lyda Mitler, Merrill Skarulis, Monica Csako, Gyorgy TI Treatment of obesity with extension of sleep duration: a randomized, prospective, controlled trial SO CLINICAL TRIALS LA English DT Article ID PERSONALITY PROFILES; YOUNG-ADULTS; RISK; METAANALYSIS; ASSOCIATION; DISORDERS; HOSTILITY; US AB Background The prevalence of chronic sleep deprivation is increasing in modern societies with negative health consequences. Recently, an association between short sleep and obesity has been reported. Purpose Primary objectives: To assess the feasibility of increasing sleep duration to a healthy length (approximately 7A1/2 h) and to determine the effect of sleep extension on body weight. Secondary objectives: To examine the long-term effects of sleep extension on endocrine (leptin and ghrelin) and immune (cytokines) parameters, the prevalence of metabolic syndrome, body composition, psychomotor vigilance, mood, and quality of life. Methods One hundred-fifty obese participants who usually sleep less than 6A1/2 h, are being randomized at a 2:1 ratio to either an Intervention or to a Comparison Group. They are stratified by age (above and below 35) and the presence or absence of metabolic syndrome. During the first 12 months (Efficacy Phase) of the study, participants are evaluated at bi-monthly intervals: the Intervention Group is coached to increase sleep by at least 30-60 min/night, while the Comparison Group maintains baseline sleep duration. In the second (Effectiveness) phase, participants converge into the same group and are asked to increase (Comparison Group) or maintain (Intervention Group) sleep duration and are evaluated at 6-month intervals for an additional 3 years. Non-pharmacological and behavior-based interventions are being utilized to increase sleep duration. Endocrine, metabolic, and psychological effects are monitored. The sleep, energy expenditure, and caloric intake are assessed by activity monitors and food recall questionnaires. At yearly intervals, body composition, abdominal fat, and basal metabolic rate are measured by dual energy X-ray absorptiometry (DXA), computerized tomography (CT), and indirect calorimetry, respectively. Results As of January 2010, 109 participants had been randomized, 64 to the Intervention Group and 45 to the Comparison Group (76% women, 62% minorities, average age: 40.8 years; BMI: 38.5 kg/m(2)). Average sleep duration at screening was less than 6 h/night, 40.3 h/week. A total of 28 Intervention and 22 Comparison participants had completed the Efficacy Phase. Limitations The study is not blinded and the sample size is relatively small. Conclusions This proof-of-concept study on a randomized sample will assess whether sleep extension is feasible and whether it influences BMI. Clinical Trials 2010; 7: 274-285. http://ctj.sagepub.com. C1 [Cizza, Giovanni; Marincola, Paula; Mattingly, Megan; Williams, Lyda; Skarulis, Monica] NIDDK, Clin Endocrinol Sect, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Mitler, Merrill] NINDS, Extramural Res Program, Bethesda, MD USA. [Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, DHHS, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), CRC, Bldg 10,Rm 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov OI Mitler, Merrill/0000-0002-7829-880X FU National Institute of Diabetes, Digestive, and Kidney Diseases; Warren Magnuson, National Institutes of Health Clinical Center FX This study is supported by the Intramural Program of the National Institute of Diabetes, Digestive, and Kidney Diseases, and the Warren Magnuson, National Institutes of Health Clinical Center. This study is conducted under the NIDDK protocol 06-DK-0036 and is listed in ClinicalTrials.gov (identifier: NCT00261898). Statistical expertise and a central sample-handling and assays facility are provided by the National Institute of Diabetes, Digestive and Kidney Disease Intramural Obesity Initiative of the National Institutes of Health Clinical Center. NR 31 TC 55 Z9 56 U1 5 U2 16 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2010 VL 7 IS 3 BP 274 EP 285 DI 10.1177/1740774510368298 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 598TM UT WOS:000277861400009 PM 20423926 ER PT J AU Alayash, AI AF Alayash, Abdu I. TI Setbacks in Blood Substitutes Research and Development: A Biochemical Perspective SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Blood substitutes; Hemoglobin toxicity; Oxygen transport ID ENDOTHELIAL-CELLS; NITRIC-OXIDE; HEMOGLOBIN; SCAVENGER; HIF-1-ALPHA; OXIDATION AB Recent setbacks in using Hb-based technology to develop oxygen carriers or blood substitutes may spur new and fundamentally different approaches for the development of a new generation of hemoglobin-based oxygen carriers (HBOCs). This article briefly details some underlying mechanisms that may have been responsible for the adverse-event profile associated with HBOCs, with a focus on the contribution of the author's laboratory toward identifying some of these biochemical pathways and some ways and means to control them. It is hoped that this will aid in the development of a safe and effective second generation of HBOCs. C1 NIH, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. [Alayash, Abdu I.] NIH, CBER, US FDA, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), NIH, Div Hematol, Lab Biochem & Vasc Biol, Bldg 29,Room 112,8800 Rickville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 23 TC 15 Z9 16 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2010 VL 30 IS 2 BP 381 EP + DI 10.1016/j.cll.2010.02.009 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 617BM UT WOS:000279255800003 PM 20513557 ER PT J AU Coward, J Germain, RN Altan-Bonnet, G AF Coward, Jesse Germain, Ronald N. Altan-Bonnet, Gregoire TI Perspectives for Computer Modeling in the Study of T Cell Activation SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID THYMOCYTE POSITIVE SELECTION; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; THYMIC SELECTION; LIGAND DISCRIMINATION; NEGATIVE SELECTION; FOREIGN ANTIGEN; DENDRITIC CELLS; KINASE CASCADE AB The T cell receptor (TCR) is responsible for discriminating between self- and foreign-derived peptides, translating minute differences in amino-acid sequence into large differences in response. Because of the great variability in the TCR and its ligands, activation of T cells by foreign peptides is a quantitative process, dependent on a mix of upstream signals and downstream integration. Accordingly, quantitative data and computational models have shed light on many important aspects of this process: molecular noise in ligand recognition, spatial dynamics in T cell-APC (antigen presenting cell) interactions, graded versus all-or-none decision making by the TCR apparatus, mechanisms of peptide antagonism and synergism, and the tunability and robustness of activation thresholds. Though diverse in their formalism, these studies together paint a picture of how modeling has shaped and will continue to shape understanding of T cell immunobiology. C1 [Coward, Jesse; Altan-Bonnet, Gregoire] Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Computat Biol, New York, NY 10065 USA. [Coward, Jesse; Altan-Bonnet, Gregoire] Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Immunol, New York, NY 10065 USA. [Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, Program Syst Immunol & Infect Dis Modeling,NIH,DH, Bethesda, MD 20892 USA. RP Altan-Bonnet, G (reprint author), Mem Sloan Kettering Canc Ctr, ImmunoDynam Grp, Program Computat Biol, New York, NY 10065 USA. EM altanbog@mskcc.org FU NIAID, National Institutes of Health (NIH); NSF [0848030]; NIH [R01-AI083408] FX This work was supported in part by funds from the Intramural Research Program, NIAID, National Institutes of Health (NIH). J.C. and G.A-B's research is supported by an NSF grant #0848030 and an NIH grant #R01-AI083408. G.A-B is the incumbent of a Bristol-Myers Squibb / James D. Robinson III junior faculty chair at MSKCC. J.C. and G.A-B wish to thank Matthew Hathorn and Karen Tkach for critical reading of the manuscript. NR 100 TC 5 Z9 5 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JUN PY 2010 VL 2 IS 6 AR a005538 DI 10.1101/cshperspect.a005538 PG 16 WC Cell Biology SC Cell Biology GA 625GJ UT WOS:000279882800015 PM 20516137 ER PT J AU Love, PE Hayes, SM AF Love, Paul E. Hayes, Sandra M. TI ITAM-mediated Signaling by the T-Cell Antigen Receptor SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; PHOSPHORYLATED TCR-ZETA; GAMMA-DELTA LINEAGES; TANDEM SH2 DOMAINS; ALPHA-BETA; THYMOCYTE SELECTION; ACTIVATION MOTIFS; NEGATIVE SELECTION; POSITIVE SELECTION; MICE LACKING AB Signal transduction by the T-cell antigen receptor (TCR) is initiated by phosphorylation of conserved motifs (ITAMs) contained within the cytoplasmic domains of the invariant subunits. TCR complexes contain a total of 10 ITAMs and this unusual configuration has prompted studies of the role of specific ITAMs, or of ITAM multiplicity, in regulating TCR-directed developmental and effector responses. Here, we summarize data generated during the past two decades and discuss how these findings have in some cases resolved, and in others complicated, outstanding questions relating to the function of TCR ITAMs. C1 [Love, Paul E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Hayes, Sandra M.] SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. RP Love, PE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM lovep@mail.nih.gov NR 73 TC 34 Z9 34 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JUN PY 2010 VL 2 IS 6 AR a002485 DI 10.1101/cshperspect.a002485 PG 11 WC Cell Biology SC Cell Biology GA 625GJ UT WOS:000279882800010 PM 20516133 ER PT J AU Staudt, LM AF Staudt, Louis M. TI Oncogenic Activation of NF-kappa B SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID PLASMA-CELL DIFFERENTIATION; BRUTONS TYROSINE KINASE; TUMOR-NECROSIS-FACTOR; HODGKIN/REED-STERNBERG CELLS; LYMPHOID-TISSUE LYMPHOMAS; LYMPHOTOXIN-BETA RECEPTOR; TNF-INDUCED APOPTOSIS; MULTIPLE-MYELOMA; GENE-EXPRESSION; MALT LYMPHOMA AB Recent genetic evidence has established a pathogenetic role for NF-kappa B signaling in cancer. NF-kappa B signaling is engaged transiently when normal B lymphocytes respond to antigens, but lymphomas derived from these cells accumulate genetic lesions that constitutively activate NF-kappa B signaling. Many genetic aberrations in lymphomas alter CARD11, MALT1, or BCL10, which constitute a signaling complex that is intermediate between the B-cell receptor and I kappa B kinase. The activated B-cell-like subtype of diffuse large B-cell lymphoma activates NF-kappa B by a variety of mechanisms including oncogenic mutations in CARD11 and a chronic active form of B-cell receptor signaling. Normal plasma cells activate NF-kappa B in response to ligands in the bone marrow microenvironment, but their malignant counterpart, multiple myeloma, sustains a variety of genetic hits that stabilize the kinase NIK, leading to constitutive activation of the classical and alternative NF-kappa B pathways. Various oncogenic abnormalities in epithelial cancers, including mutant K-ras, engage unconventional IkB kinases to activate NF-kappa B. Inhibition of constitutive NF-kappa B signaling in each of these cancer types induces apoptosis, providing a rationale for the development of NF-kappa B pathway inhibitors for the treatment of cancer. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 211 TC 220 Z9 229 U1 0 U2 13 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JUN PY 2010 VL 2 IS 6 AR a000109 DI 10.1101/cshperspect.a000109 PG 30 WC Cell Biology SC Cell Biology GA 625GJ UT WOS:000279882800001 PM 20516126 ER PT J AU Wheeler, DC Hickson, DA Waller, LA AF Wheeler, David C. Hickson, DeMarc A. Waller, Lance A. TI Assessing local model adequacy in Bayesian hierarchical models using the partitioned deviance information criterion SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Bayesian statistics; DIC; Spatial statistics; Hierarchical models; Linear models; HIV; Rwanda ID HIV-1 INFECTION; RWANDA; WOMEN; PREVALENCE; KIGALI; VIRUS; URBAN AB Many diagnostic tools and goodness-of-fit measures, such as the Akaike information criterion (AIC) and the Bayesian deviance information criterion (DIC), are available to evaluate the overall adequacy of linear regression models. In addition, visually assessing adequacy in models has become an essential part of any regression analysis. In this paper, we focus on a spatial consideration of the local DIC measure for model selection and goodness-of-fit evaluation. We use a partitioning of the DIC into the local DIC, leverage, and deviance residuals to assess the local model fit and influence for both individual observations and groups of observations in a Bayesian framework. We use visualization of the local DIC and differences in local DIC between models to assist in model selection and to visualize the global and local impacts of adding covariates or model parameters. We demonstrate the utility of the local DIC in assessing model adequacy using HIV prevalence data from pregnant women in the Butare province of Rwanda during the period 1989-1993 using a range of linear model specifications, from global effects only to spatially varying coefficient models, and a set of covariates related to sexual behavior. Results of applying the diagnostic visualization approach include more refined model selection and greater understanding of the models as applied to the data. Published by Elsevier B.V. C1 [Wheeler, David C.] Natl Canc Inst, Bethesda, MD 20892 USA. [Hickson, DeMarc A.] Univ Mississippi, Med Ctr, Sch Med, Dept Med, Jackson, MS 39213 USA. [Waller, Lance A.] Emmy Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA 30322 USA. RP Wheeler, DC (reprint author), Natl Canc Inst, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM wheelerdc@mail.nih.gov FU NIEHS NIH HHS [R01 ES015525, R01 ES015525-04] NR 44 TC 6 Z9 6 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 EI 1872-7352 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JUN 1 PY 2010 VL 54 IS 6 BP 1657 EP 1671 DI 10.1016/j.csda.2010.01.025 PG 15 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 581OV UT WOS:000276534500023 PM 21243121 ER PT J AU Patel, M Jiang, QF Woodgate, R Cox, MM Goodman, MF AF Patel, Meghna Jiang, Qingfei Woodgate, Roger Cox, Michael M. Goodman, Myron F. TI A new model for SOS-induced mutagenesis: how RecA protein activates DNA polymerase V SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Translesion synthesis; RecA nucleoprotein filament; polymerase transactivation; mutational mechanisms ID SINGLE-STRANDED-DNA; ERROR-PRONE REPAIR; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; UV MUTAGENESIS; TRANSLESION SYNTHESIS; ULTRAVIOLET-LIGHT; CRYSTAL-STRUCTURE; Y-FAMILY; BIOCHEMICAL BASIS AB In Escherichia coli, cell survival and genomic stability after UV radiation depends on repair mechanisms induced as part of the SOS response to DNA damage. The early phase of the SOS response is mostly dominated by accurate DNA repair, while the later phase is characterized with elevated mutation levels caused by error-prone DNA replication. SOS mutagenesis is largely the result of the action of DNA polymerase V (pol V), which has the ability to insert nucleotides opposite various DNA lesions in a process termed translesion DNA synthesis (TLS). Pol V is a low-fidelity polymerase that is composed of UmuD'(2)C and is encoded by the umuDC operon. Pol V is strictly regulated in the cell so as to avoid genomic mutation overload. RecA nucleoprotein filaments (RecA*), formed by RecA binding to single-stranded DNA with ATP, are essential for pol V-catalyzed TLS both in vivo and in vitro. This review focuses on recent studies addressing the protein composition of active DNA polymerase V, and the role of RecA protein in activating this enzyme. Based on unforeseen properties of RecA*, we describe a new model for pol V-catalyzed SOS-induced mutagenesis. C1 [Patel, Meghna; Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. [Patel, Meghna; Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. [Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Cox, Michael M.] Univ Wisconsin, Dept Biochem, Madison, WI 53705 USA. RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA. EM mgoodman@usc.edu RI JIANG, QINGFEI/K-3492-2012 FU National Institute of Health [ES12259, R37GM21422, GM32335]; NICHD/NIH FX Work described in this article from the authors' laboratories was supported by National Institute of Health grants to M.F.G. (ES12259; R37GM21422) and to M.M.C. (GM32335) and funds from the NICHD/NIH Intramural Research Program to R. W. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 91 TC 50 Z9 51 U1 0 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD JUN PY 2010 VL 45 IS 3 BP 171 EP 184 DI 10.3109/10409238.2010.480968 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 615CB UT WOS:000279107800001 PM 20441441 ER PT J AU Rotow, J Gameiro, SR Madan, RA Gulley, JL Schlom, J Hodge, JW AF Rotow, Julia Gameiro, Sofia R. Madan, Ravi A. Gulley, James L. Schlom, Jeffrey Hodge, James W. TI Vaccines as Monotherapy and in Combination Therapy for Prostate Cancer SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Review DE prostate cancer; immunotherapy; poxviral vaccines; radiation ID PHASE-I TRIAL; TUMOR-CELLS; ANTITUMOR-ACTIVITY; ACID-PHOSPHATASE; CARCINOEMBRYONIC ANTIGEN; CELLULAR IMMUNOTHERAPY; RADIATION-THERAPY; IMMUNE-RESPONSES; MEMBRANE ANTIGEN; CERVICAL-CANCER AB Prostate cancer is the second leading cause of cancer death among men in the United States. Standard-of-care chemotherapy for metastatic castration-resistant prostate cancer is associated with significant but modest survival benefit, indicating a need for alternative and/or additional approaches. The use of therapeutic cancer vaccines for the treatment of prostate cancer represents a novel targeted therapeutic approach. Whereas vaccine strategies are being developed for the treatment of various stages of prostate cancer, this article focuses on novel vaccine strategies for castration-resistant prostate cancer that have been translated into late-stage clinical studies. C1 [Rotow, Julia; Gameiro, Sofia R.; Madan, Ravi A.; Gulley, James L.; Schlom, Jeffrey; Hodge, James W.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016 OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX The authors thank Bonnie L. Casey for editorial assistance in the preparation of this manuscript. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 68 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD JUN PY 2010 VL 3 IS 3 BP 116 EP 122 DI 10.1111/j.1752-8062.2010.00186.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 615TP UT WOS:000279160700016 PM 20590682 ER PT J AU Mu, JB Seydel, KB Bates, A Su, XZ AF Mu, Jianbing Seydel, Karl B. Bates, Adam Su, Xin-Zhuan TI Recent Progress in Functional Genomic Research in Plasmodium falciparum SO CURRENT GENOMICS LA English DT Article DE Malaria; microarray; genome diversity; SNP; recombination; comparative genomics ID HUMAN MALARIA PARASITE; ANTIGENIC VARIATION; PROTEOME ANALYSIS; GENE-EXPRESSION; LIFE-CYCLE; CHLOROQUINE RESISTANCE; TRANSCRIPTION FACTORS; POPULATION-STRUCTURE; POSITIVE SELECTION; HUMAN ERYTHROCYTES AB With the completion and near completion of many malaria parasite genome-sequencing projects, efforts are now being directed to a better understanding of gene functions and to the discovery of vaccine and drug targets. Inter- and intraspecies comparisons of the parasite genomes will provide invaluable insights into parasite evolution, virulence, drug resistance, and immune invasion. Genome-wide searches for loci under various selection pressures may lead to discovery of genes conferring drug resistance or encoding for protective antigens. In addition, the Plasmodium falciparum genome sequence provides the basis for the development of various microarrays to monitor gene expression and to detect nucleotide substitution and deletion/amplification. Genome-wide profiling of the parasite proteome, chromatin modification, and nucleosome position also depend on availability of the parasite genome. In this brief review, we will highlight some recent advances and studies in characterizing gene function and related phenotype in P. falciparum that were made possible by the genome sequence, particularly the development of a genome-wide diversity map and various high-throughput genotyping methods for genome-wide association studies (GWAS). C1 [Mu, Jianbing; Bates, Adam; Su, Xin-Zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Seydel, Karl B.] Michigan State Univ, E Lansing, MI 48824 USA. RP Mu, JB (reprint author), NIAID, LMVR, NIH, 12735 Twinbrook Pkwy,Room 3E-32C, Rockville, MD 20852 USA. EM jmu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall for assistance. NR 107 TC 12 Z9 12 U1 0 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD JUN PY 2010 VL 11 IS 4 BP 279 EP 286 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 599JV UT WOS:000277909000006 PM 21119892 ER PT J AU Yang, L AF Yang, L. TI TGF beta, a Potent Regulator of Tumor Microenvironment and Host Immune Response, Implication for Therapy SO CURRENT MOLECULAR MEDICINE LA English DT Review DE TGF beta; inflammation; tumor microenvironment; bone marrow; myeloid cells; breast tumor; metastasis; antagonism ID GROWTH-FACTOR-BETA; ENDOTHELIAL PROGENITOR CELLS; MESENCHYMAL STEM-CELLS; KAPPA-B ACTIVATION; MYELOID CELLS; COLON-CANCER; T-CELLS; STROMAL FIBROBLASTS; SIGNALING PATHWAYS; SUPPRESSOR-CELLS AB Alterations in TGF beta signaling are common in human cancers. TGF beta has significant impact on tumor initiation and progression. Therapeutic strategies including neutralizing antibodies and small molecular inhibitors have been developed to target TGF beta signaling. However, TGF beta can work as both a tumor suppressor and a tumor promoter. A significant challenge to the development of successful TGF beta antagonism treatment is understanding how and when TGF beta switches its function from a tumor suppressor to a tumor promoter. Recent studies demonstrate that TGF beta regulates the infiltration of inflammatory cells and cancer associated fibroblasts into the tumor microenvironment, resulting in changes in signaling cascade in tumor cells. Additionally, TGF beta exerts systemic immune suppression and significantly inhibits host tumor immune surveillance. Neutralizing TGF beta in preclinical mouse models enhances CD8+ T-cell and natural killer cell-mediated anti-tumor immune response. This new understanding of TGF beta signaling in regulation of tumor microenvironment and immune response may provide useful information, particularly for patient selection and inflammation/immune biomarkers for TGF beta antagonism therapy in clinical trials. C1 NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20876 USA. RP Yang, L (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bldg 37,Room 3134C,37 Convent Dr,MSC 4258, Bethesda, MD 20876 USA. EM yangl3@mail.nih.gov NR 66 TC 25 Z9 28 U1 0 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD JUN PY 2010 VL 10 IS 4 BP 374 EP 380 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 599KC UT WOS:000277909700005 PM 20455854 ER PT J AU Myslobodsky, M Eldan, A AF Myslobodsky, M. Eldan, A. TI Winning a Won Game: Caffeine Panacea for Obesity Syndemic SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Caffeine targets; obesity; reactive oxygen species; networks; polypharmacy ID OBSTRUCTIVE SLEEP-APNEA; ENDOTHELIAL GROWTH-FACTOR; BLOOD-PRESSURE RHYTHM; TNF-ALPHA PRODUCTION; BODY-MASS INDEX; ADIPOSE-TISSUE; SUBSTANCE-P; ADENOSINE RECEPTORS; COFFEE CONSUMPTION; CIRCADIAN PATTERNS AB Over the past decades, chronic sleep reduction and a concurrent development of obesity have been recognized as a common problem in the industrialized world. Among its numerous untoward effects, there is a possibility that insomnia is also a major contributor to obesity. This attribution poses a problem for caffeine, an inexpensive, "natural" agent that is purported to improve a number of conditions and is often indicated in a long-term pharmacotherapy in the context of weight management. The present study used the "common target" approach by exploring the tentative shared molecular networks of insomnia and adiposity. It discusses caffeine targets beyond those associated with adenosine signaling machinery, phosphodiesterases, and calcium release channels. Here, we provide a view suggesting that caffeine could exert some of its effects by acting on several signaling complexes composed of HIF-1 alpha/VEGF/IL-8 along with NO, TNF-alpha, IL1, and GHRH, among others. Although the relevance of these targets to the reported therapeutic effects of caffeine has remained difficult to assess, the utilization of caffeine efficacies and potencies recommend its repurposing for development of novel therapeutic approaches. Among indications mentioned, are neuroprotective, nootropic, antioxidant, proliferative, anti-fibrotic, and anti-angiogenic that appear under a variety of dissimilar diagnostic labels comorbid with obesity. In the absence of safe and efficacious antiobesity agents, caffeine remains an attractive adjuvant. C1 [Myslobodsky, M.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Myslobodsky, M.] Howard Univ, Grad Sch, Washington, DC 20059 USA. RP Myslobodsky, M (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. EM myslobom@mail.nih.gov NR 157 TC 0 Z9 0 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD JUN PY 2010 VL 8 IS 2 BP 149 EP 160 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 599KE UT WOS:000277910000010 PM 21119886 ER PT J AU Hakim, O Sung, MH Hager, GL AF Hakim, Ofir Sung, Myong-Hee Hager, Gordon L. TI 3D shortcuts to gene regulation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID BETA-GLOBIN LOCUS; LONG-RANGE INTERACTIONS; CHROMOSOME CONFORMATION CAPTURE; IMPRINTING CONTROL REGION; GLUCOCORTICOID-RECEPTOR; ACTIVE GENES; TRANSCRIPTION REQUIRES; NUCLEAR ARCHITECTURE; SPATIAL-ORGANIZATION; DNA INTERACTIONS AB Recent technologies have allowed high-resolution genome-wide binding profiles of numerous transcription factors and other proteins. A widespread observation has emerged from studies in diverse mammalian systems: most binding events are located at great distances from gene promoters. It is becoming apparent that the traditional one-dimensional view of gene regulation via the proximal cis regulatory elements is oversimplified. True proximity and functional relevance can be revealed by studying the three-dimensional structure of the genome packaged inside the nucleus. Thus the spatial architecture of the genome has attracted a lot of interest and has intensified its significance in modern cell biology. Here we discuss current methods, concepts, and controversies in this rapidly evolving field. C1 [Hakim, Ofir; Sung, Myong-Hee; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov RI Hakim, Ofir/A-6239-2012 FU Intramural NIH HHS [Z01 BC005450-25, Z99 CA999999] NR 80 TC 28 Z9 29 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2010 VL 22 IS 3 BP 305 EP 313 DI 10.1016/j.ceb.2010.04.005 PG 9 WC Cell Biology SC Cell Biology GA 614MU UT WOS:000279064200007 PM 20466532 ER PT J AU Dalai, Y Bui, M AF Dalai, Yamini Bui, Minh TI Down the rabbit hole of centromere assembly and dynamics SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID CENP-A CHROMATIN; INNER KINETOCHORE PROTEINS; HISTONE H3-LIKE PROTEINS; FISSION YEAST SCM3; LIVING HUMAN-CELLS; SACCHAROMYCES-CEREVISIAE; CHROMOSOME SEGREGATION; TERMINAL DOMAIN; BUDDING YEAST; FOLD DOMAIN AB The centromere is perhaps the most iconic feature on a eukaryotic chromosome. An amateur enthusiast equipped with a light microscope can easily identify the center of each metacentric chromosome, marking the spot responsible for accurate genome segregation. This review will highlight findings that provide novel insights into how centromeres are assembled and disassembled, the role centromeric proteins play in repair, epigenetic features uniquely found at the centromere, and the three dimensional organization of centromeres caught in the act of mitosis. These advances have unveiled a veritable wonderland of non-canonical features that drive centromere function. C1 [Dalai, Yamini; Bui, Minh] NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Dalai, Y (reprint author), NCI, Chromatin Struct & Epigenet Mech Unit, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM dalaly@mail.nih.gov OI Dalal, Yamini/0000-0002-7655-6182 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX YD thanks Kerry Bloom for sharing the concept of CENH3 dynamic instability, Ali Hamiche, Ariel Prunell, Carl Wu, Gary Karpen, Stephan Deikmann, and Steve Henikoff for sharing unpublished observations, Nathan Morris for graphical input, and Sam John for critical comments on the manuscript. We apologize to colleagues whose important findings could not be cited due to space constraints. YD and MB are supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 91 TC 18 Z9 19 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2010 VL 22 IS 3 BP 392 EP 402 DI 10.1016/j.ceb.2010.02.005 PG 11 WC Cell Biology SC Cell Biology GA 614MU UT WOS:000279064200018 PM 20303726 ER PT J AU Mueller, F Mazza, D Stasevich, TJ McNally, JG AF Mueller, Florian Mazza, Davide Stasevich, Timothy J. McNally, James G. TI FRAP and kinetic modeling in the analysis of nuclear protein dynamics: what do we really know? SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID FLUORESCENCE CORRELATION SPECTROSCOPY; RNA-POLYMERASE-II; LASER-SCANNING MICROSCOPES; SINGLE-MOLECULE LEVEL; IN-VIVO; LIVING CELLS; TRANSCRIPTION FACTOR; DNA-BINDING; LIVE CELLS; ANOMALOUS DIFFUSION AB The binding of nuclear proteins to chromatin in live cells has been analyzed by kinetic modeling procedures applied to experimental data from fluorescence recovery after photobleaching (FRAP). The kinetic models have yielded a number of important biological predictions about transcription, but concerns have arisen about the accuracy of these predictions. First, different studies using different kinetic models have arrived at very different predictions for the same or similar proteins. Second, some of these divergent predictions have been shown to arise from technical issues rather than biological differences. For confidence and accuracy, gold standards for the measurement of in vivo binding must be established by extensive cross validation using both different experimental methods and different kinetic modeling procedures. C1 [Mueller, Florian; Mazza, Davide; Stasevich, Timothy J.; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM mcnallyj@mail.nih.gov RI Mazza, Davide/F-9536-2011; Mueller, Florian/C-9075-2012; Mazza, Davide/R-5340-2016 OI Mueller, Florian/0000-0002-9622-4396; Mazza, Davide/0000-0003-2776-4142 FU Intramural NIH HHS [Z01 BC010561-05, ZIA BC010561-06, Z01 BC010561-04] NR 55 TC 85 Z9 87 U1 1 U2 21 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2010 VL 22 IS 3 BP 403 EP 411 DI 10.1016/j.ceb.2010.03.002 PG 9 WC Cell Biology SC Cell Biology GA 614MU UT WOS:000279064200019 PM 20413286 ER PT J AU Thorne, N Auld, DS Inglese, J AF Thorne, Natasha Auld, Douglas S. Inglese, James TI Apparent activity in high-throughput screening: origins of compound-dependent assay interference SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID RESONANCE ENERGY-TRANSFER; REPORTER-GENE ASSAYS; PROMISCUOUS INHIBITORS; FIREFLY LUCIFERASE; FALSE POSITIVES; CHEMICAL LIBRARIES; HYDROGEN-PEROXIDE; FLUORESCENCE; IDENTIFICATION; MECHANISM AB Expansive compound collections made up of structurally heterogeneous chemicals, the activities of which are largely undefined, present challenging problems for high-throughput screening (HTS). Foremost is differentiating whether the activity for a given compound in an assay is directed against the targeted biology, or is the result of surreptitious compound activity involving the assay detection system. Such compound interference can be especially difficult to identify if it is reproducible and concentration-dependent - characteristics generally attributed to compounds with genuine activity. While reactive chemical groups on compounds were once thought to be the primary source of compound interference in assays used in HIS, recent work suggests that other factors, such as compound aggregation, may play a more significant role in many assay formats. Considerable progress has been made to profile representative compound libraries in an effort to identify chemical classes susceptible to producing compound interference, such as compounds commonly found to inhibit the reporter enzyme firefly luciferase. Such work has also led to the development of practices that have the potential to significantly reduce compound interference, for example, through the addition of non-ionic detergent to assay buffer to reduce aggregation-based inhibition. C1 [Thorne, Natasha; Auld, Douglas S.; Inglese, James] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. RP Inglese, J (reprint author), NIH, NIH Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jinglese@mail.nih.gov FU NIH FX We would like to thank Ruili Huang for preparation and use of the SOM presented in Figure 2. We would also like to sincerely thank Anton Simeonov for data on aggregation-based inhibition used in Figure 2, as well as for critically reading the manuscript. The NIH Chemical Genomics Center is supported by funding from the Molecular Libraries Initiative of the NIH Roadmap for Medical Research. NR 62 TC 132 Z9 133 U1 0 U2 26 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD JUN PY 2010 VL 14 IS 3 BP 315 EP 324 DI 10.1016/j.cbpa.2010.03.020 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 616NQ UT WOS:000279216500005 PM 20417149 ER PT J AU Neary, N Nieman, L AF Neary, Nicola Nieman, Lynnette TI Adrenal insufficiency: etiology, diagnosis and treatment SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE ACTH stimulation; adrenal insufficiency; autoimmunity; glucocorticoids ID X-LINKED ADRENOLEUKODYSTROPHY; SUBJECTIVE HEALTH-STATUS; CORTICOTROPIN-STIMULATION TEST; IMPROVES ENDOTHELIAL FUNCTION; 1 MU-G; SEPTIC SHOCK; ADDISONS-DISEASE; FREE CORTISOL; DEHYDROEPIANDROSTERONE REPLACEMENT; PREMATURE MORTALITY AB Purpose of review Adrenal insufficiency, first codified in 1855 by Thomas Addison, remains relevant in 2010 because of its lethal nature. Recent findings Reports illuminate features of adrenal insufficiency cause, diagnosis and treatment, and the role of glucocorticoids in critical illness. Summary Progress has been made in identifying human leukocyte antigen and major histocompatability complex alleles that predispose to the development of adrenal insufficiency in patients with antibodies to 21-hydroxylase, but their role in clinical care is not established. Reports of HIV-associated infections and medication-induced hypocortisolism are reminders that autoimmune adrenal destruction does not underlie all cases. The diagnosis is adequately established by the 250 mu g adrenocortocotropin hormone stimulation test in most patients; the 1 mu g test carries the risk of misdiagnosis of healthy individuals as adrenally insufficient. Glucocorticoids provide life-saving treatment, but long-term quality of life is impaired, perhaps because therapy is not given in a physiologic way. The current recommended total daily dose is lower than that often prescribed. Dehydroepiandrosterone replacement may be useful in pubertal girls with hypopituitarism, but not in adults. Supraphysiologic hydrocortisone doses may aid in the reversal of septic shock independent of underlying adrenal function. C1 [Neary, Nicola; Nieman, Lynnette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. RP Nieman, L (reprint author), Bldg 10 CRC 1E Rm 3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@nih.gov RI Andrade, Hugo/M-6631-2013 OI Andrade, Hugo/0000-0001-6781-6125 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX The authors declare no conflicts of interest. This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 61 TC 38 Z9 42 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2010 VL 17 IS 3 BP 217 EP 223 DI 10.1097/MED.0b013e328338f608 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691EL UT WOS:000285063000007 PM 20375886 ER PT J AU Mueller, SN Hickman, HD AF Mueller, Scott N. Hickman, Heather D. TI In vivo imaging of the T cell response to infection SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HOST-PATHOGEN INTERACTIONS; DENDRITIC CELLS; LYMPH-NODES; ANTIGEN PRESENTATION; MIGRATION; MICROSCOPY; IMMUNITY; ACTIVATION; DYNAMICS; OCCURS AB The induction and execution of a successful anti-pathogen immune response requires a consecutive series of cellular interactions that begin in lymphoid environments and later extend into the periphery. Much of our current knowledge of these events has been gained using ex vivo approaches that yield important static information but do not convey the dynamic nature of cellular behavior in vivo. The application of multiphoton-laser based microscopic analysis to the ongoing immune response has provided new insight into cellular interactions leading to T cell activation and the behavior of primed immune effectors. Here we discuss recent insights on anti-pathogen immune responses revealed using live imaging of both lymphoid and non-lymphoid tissues. C1 [Mueller, Scott N.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. [Hickman, Heather D.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Mueller, SN (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. EM smue@unimelb.edu.au; hhickman@mail.nih.gov RI Mueller, Scott/B-1918-2012 OI Mueller, Scott/0000-0002-3838-3989 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Australian Research Council FX This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (HDH) and the Australian Research Council's Discovery Projects funding scheme (SNM). NR 36 TC 8 Z9 8 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2010 VL 22 IS 3 BP 293 EP 298 DI 10.1016/j.coi.2009.12.009 PG 6 WC Immunology SC Immunology GA 619JD UT WOS:000279425500005 PM 20080040 ER PT J AU Cuddapah, S Barski, A Zhao, KJ AF Cuddapah, Suresh Barski, Artem Zhao, Keji TI Epigenomics of T cell activation, differentiation, and memory SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CYTOKINE GENE-EXPRESSION; HUMAN GENOME; HISTONE MODIFICATIONS; CHROMATIN SIGNATURES; RNA-POLYMERASE; STEM-CELLS; TGF-BETA; CHIP-SEQ; PLASTICITY; TRANSCRIPTION AB Activation of T cells is an essential step in the immunological response to infection. Although activation of naIve T cells results in proliferation and slow differentiation into cytokine-producing effector cells, antigen engagement with memory cells leads to cytokine production immediately. Even though the cell surface signaling events are similar in both the cases, the outcome is different, suggesting that distinct regulatory mechanisms may exist downstream of the activation signals. Recent advances in the understanding of global epigenetic patterns in T cells have resulted in the appreciation of the role of epigenetic mechanisms in processes such as activation and differentiation. In this review we discuss recent data suggesting that naive T cell activation, differentiation, and lineage commitment result in epigenetic changes and a fine balance between different histone modifications is required. On the other hand, memory T cells are poised and do not require epigenetic changes for short-term activation. C1 [Cuddapah, Suresh; Barski, Artem; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Cuddapah, S (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM cuddapas@nhlbi.nih.gov; barskia@nhlbi.nih.gov; zhaok@nhlbi.nih.gov OI Barski, Artem/0000-0002-1861-5316 FU National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health [1K22HL098691] FX We thank Yrina Rochman for critical reading of this manuscript. This work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health. AB is additionally supported by Career Transition Award 1K22HL098691 from NHLBI, NIH. NR 66 TC 58 Z9 59 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2010 VL 22 IS 3 BP 341 EP 347 DI 10.1016/j.coi.2010.02.007 PG 7 WC Immunology SC Immunology GA 619JD UT WOS:000279425500012 PM 20226645 ER PT J AU Yewdell, JW AF Yewdell, Jonathan W. TI Designing CD8+T cell vaccines: it's not rocket science (yet) SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CD8(+) T-CELLS; COMPLEX CLASS-I; C-TYPE LECTIN; PLASMACYTOID DENDRITIC CELLS; ANTIGEN CROSS-PRESENTATION; HEAT-SHOCK PROTEINS; EXOGENOUS ANTIGENS; PRIMING CAPACITY; SOLUBLE-ANTIGENS; IMMUNE-RESPONSES AB CD8+ T cells play important roles in clearing viral infections and eradicating tumors. Designing vaccines that elicit effective CD8+ T cell responses requires a thorough knowledge of the pathways of antigen presentation in vivo. Here, I review recent progress in understanding the activation of naive CD8+ T cells in vivo, with particular emphasis on cross-priming, the presentation of protein antigens acquired by dendritic cells from their environment. With the rapid advances in this area of research, the dawn of rational vaccine design is at hand. C1 NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM JYEWDELL@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS [Z01 AI000542-20] NR 99 TC 34 Z9 37 U1 1 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2010 VL 22 IS 3 BP 402 EP 410 DI 10.1016/j.coi.2010.04.002 PG 9 WC Immunology SC Immunology GA 619JD UT WOS:000279425500021 PM 20447814 ER PT J AU Cheung, GYC Otto, M AF Cheung, Gordon Y. C. Otto, Michael TI Understanding the significance of Staphylococcus epidermidis bacteremia in babies and children SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE biofilm; neonates; nosocomial infections; sepsis; Staphylococcus epidermidis ID COAGULASE-NEGATIVE STAPHYLOCOCCI; INTENSIVE-CARE-UNIT; POLYSACCHARIDE INTERCELLULAR ADHESIN; BLOOD-STREAM INFECTIONS; BIRTH-WEIGHT INFANTS; QUORUM-SENSING SYSTEM; TOLL-LIKE RECEPTORS; INTRAVENOUS LIPID EMULSIONS; CATHETER-RELATED INFECTIONS; HOST INFLAMMATORY RESPONSE AB Purpose of review This article provides an overview of Staphylococcus epidermidis bacteremia/sepsis and coagulase-negative staphylococci (CoNS) infections in neonates and children. Recent findings The incidence of S. epidermidis and CoNS sepsis in neonates is still very high and preventing and treating disease remains difficult. There has been recent progress in understanding the pathogenesis of S. epidermidis infection, interaction of S. epidermidis with host defenses, and risk factors for the development of S. epidermidis disease. For example, we have gained more insight into the development of biofilm-associated catheter infections, which are responsible for recurrent CoNS infections in hospitalized premature neonates and are especially difficult to treat owing to intrinsic resistance of biofilms to antibiotics. Summary Biofilm-associated catheter infections by S. epidermidis occur frequently in neonates and adults. S. epidermidis bloodstream infections are particularly problematic in neonates. Prophylaxis in the form of eradicating colonizing S. epidermidis may be a double-edged sword, as S. epidermidis colonization may be beneficial to the host. New drugs may arise from a better understanding of S. epidermidis virulence and analysis of risk factors may help identify neonates susceptible to bacterial sepsis. However, reducing morbidity should always begin by increasing hygiene in hospital settings to reduce the introduction of potentially harmful opportunistic pathogens such as S. epidermidis on indwelling medical devices or during surgery. C1 [Cheung, Gordon Y. C.; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, 33 North Dr,Bldg 33,Room 1W10A, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov RI Cheung, Yiu Chong /K-3565-2012; OI Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH) FX This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH). NR 148 TC 46 Z9 51 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD JUN PY 2010 VL 23 IS 3 BP 208 EP 216 DI 10.1097/QCO.0b013e328337fecb PG 9 WC Infectious Diseases SC Infectious Diseases GA 597ZJ UT WOS:000277800900002 PM 20179594 ER PT J AU Nienborg, H Cumming, B AF Nienborg, Hendrikje Cumming, Bruce TI Correlations between the activity of sensory neurons and behavior: how much do they tell us about a neuron's causality? SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID VISUAL AREA MT; CORTICAL AREA; DECISION-MAKING; ACTIVITY FLUCTUATIONS; PERCEPTUAL DECISIONS; STEREOSCOPIC DEPTH; POPULATION CODE; NEURAL ACTIVITY; TASK STRATEGY; V2 NEURONS AB How the activity of sensory neurons elicits perceptions and guides behavior is central to our understanding of the brain and is a subject of intense investigation in neuroscience. Correlations between the activity of sensory neurons and behavior have been widely observed and are sometimes used to infer how neurons are used to guide a certain behavior. This view is challenged firstly by theoretical considerations that these correlations rely on the existence of correlated noise and its structure, and secondly by recent empirical observations suggesting that such correlated noise is not a fixed network property but that it depends on various sources, and varies with a subject's mental state. C1 [Nienborg, Hendrikje] Salk Inst Biol Studies, La Jolla, CA 92037 USA. [Cumming, Bruce] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nienborg, H (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM nienborg@salk.edu; bgc@lsr.nei.nih.gov FU Intramural NIH HHS [ZIA EY000404-08] NR 56 TC 46 Z9 46 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD JUN PY 2010 VL 20 IS 3 BP 376 EP 381 DI 10.1016/j.conb.2010.05.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 618OG UT WOS:000279364800016 PM 20545019 ER PT J AU Hill, MJ Levens, ED AF Hill, Micah J. Levens, Eric D. TI Is there a benefit in follicular flushing in assisted reproductive technology? SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY LA English DT Article DE assisted reproductive technologies; double-lumen retrieval needle; oocyte retrieval; ovarian follicle flushing; poor responders ID IN-VITRO FERTILIZATION; HUMAN MENOPAUSAL GONADOTROPIN; DIRECTED OOCYTE RECOVERY; INVITRO FERTILIZATION; RANDOMIZED-TRIAL; ASPIRATION; ULTRASOUND; RETRIEVAL; MATURATION; PROGRAM AB Purpose of review Follicular flushing utilizing double-lumen retrieval needles attempts to increase oocyte yield during transvaginal retrieval. The original work on this topic, now more than 2 decades old, examined its utility in normal-responding assisted reproductive technologies (ART) patients. Newer studies examining its utility have focused on special populations expected to demonstrate benefit: poor responders, natural cycle and minimal stimulation ART, and in-vitro maturation cycles. This review assesses the current evidence regarding the effectiveness of ovarian follicular flushing in improving oocyte yield. Recent findings Follicular flushing offers no substantive benefit in oocyte yield, fertilization rates, or pregnancy outcomes for normal and poor-responding ART patients. Patients undergoing natural cycle or minimal stimulation ART may benefit from follicular flushing resulting in more mature embryos but unclear effects on cycle outcome. Summary Randomized controlled trials consistently demonstrate no benefit and increased procedural time with follicular flushing in both normal and poor-responding ART patients. Nonrandomized data suggest a possible role for follicular flushing in natural cycle or minimal stimulation ART and in those undergoing in-vitro maturation IVF cycles; however, randomized controlled trials are needed to verify this finding. Presently, there is insufficient evidence to recommend the routine use of follicular flushing. C1 [Hill, Micah J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, NIH, Bethesda, MD 20892 USA. RP Levens, ED (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, CRC, NIH, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM levense@mail.nih.gov FU NICHD, NIH, Bethesda, MD FX This work was supported, in part, by the Program in Reproductive and Adult Endocrinology, NICHD, NIH, Bethesda, MD. NR 28 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-872X J9 CURR OPIN OBSTET GYN JI Curr. Opin. Obstet. Gynecol. PD JUN PY 2010 VL 22 IS 3 BP 208 EP 212 DI 10.1097/GCO.0b013e3283373bfe PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 603IB UT WOS:000278201000006 PM 20124897 ER PT J AU Znosko, WA Yu, SB Thomas, K Molina, GA Li, CJ Tsang, W Dawid, IB Moon, AM Tsang, M AF Znosko, Wade A. Yu, Shibin Thomas, Kirk Molina, Gabriela A. Li, Chengjian Tsang, Warren Dawid, Igor B. Moon, Anne M. Tsang, Michael TI Overlapping functions of Pea3 ETS transcription factors in FGF signaling during zebrafish development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE FGF; Pea3 ETS factors; Heart; Left/right patterning; Zebrafish; Kupffer's vesicle; Cilia; Dusp6 ID LEFT-RIGHT ASYMMETRY; HEART FIELD; CARDIOVASCULAR DEVELOPMENT; KUPFFERS VESICLE; MAP-KINASE; EMBRYONIC-DEVELOPMENT; HINDBRAIN BOUNDARY; INDUCED ANTAGONIST; VERTEBRATE LIMB; VISCERAL ORGANS AB Fibroblast growth factors (FGFs) are secreted molecules that activate the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. In zebrafish development, FGF signaling is responsible for establishing dorsal polarity, maintaining the isthmic organizer, and cardiac ventricle formation. Because several ETS factors are known transcriptional mediators of MAPK signaling, we hypothesized that these factors function to mediate FGF signaling processes. In zebrafish, the simultaneous knock-down of three Pea3 ETS proteins, Etv5, Erm, and Pea3, produced phenotypes reminiscent of embryos deficient in FGF signaling. Morphant embryos displayed both cardiac and left/right patterning defects as well as disruption of the isthmic organizer. Furthermore, the expression of FGF target genes was abolished in Pea3 ETS depleted embryos. To understand how FGF signaling and ETS factors control gene expression, transcriptional regulation of dusp6 was studied in mouse and zebrafish. Conserved Pea3 ETS binding sites were identified within the Dusp6 promoter, and reporter assays showed that one of these sites is required for dusp6 induction by FGFs. We further demonstrated the interaction of Pea3 ETS factors with the Dusp6 promoter both in vitro and in vivo. These results revealed the requirement of ETS factors in transducing FGF signals in developmental processes. (C) 2010 Elsevier Inc. All rights reserved. C1 [Znosko, Wade A.; Molina, Gabriela A.; Li, Chengjian; Tsang, Warren; Tsang, Michael] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15213 USA. [Znosko, Wade A.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15213 USA. [Yu, Shibin; Moon, Anne M.] Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. [Thomas, Kirk] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Dawid, Igor B.] NICHD, Program Genom Dev, NIH, Bethesda, MD 20892 USA. [Moon, Anne M.] Univ Utah, Dept Neurobiol & Anat, Salt Lake City, UT 84112 USA. [Moon, Anne M.] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. [Tsang, Michael] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA USA. RP Tsang, M (reprint author), Univ Pittsburgh, Dept Microbiol & Mol Genet, 3501 5th Ave,BST3-5062, Pittsburgh, PA 15213 USA. EM tsang@pitt.edu RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014 OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063 FU National Heart, Lung, and Blood Institute (NHLBI) [R01HL088016]; American Heart Association [0565400U]; NICHD, NIH; NICHD [HD044157] FX We are thankful to the Hukriede lab for assistance with the Xenopus experiments, R. Burdine, S. Sanker, and P.K. Umasankar for help in imaging cilia. We would like to thank D. Yelon, B. Roman, N. Bahary, and S.K. Hong for reagents, and to Michael Rebagliati for critical reading of the manuscript and experimental suggestions. The project described was supported in part by Award Number R01HL088016 to M.T. from the National Heart, Lung, and Blood Institute (NHLBI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI. This work was also supported by the American Heart Association (0565400U) to MT. University of Pittsburgh CMRF, and by the intramural program of the NICHD, NIH. AMM's laboratory is supported by NICHD HD044157. NR 89 TC 26 Z9 26 U1 2 U2 7 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 JUN 1 PY 2010 VL 342 IS 1 BP 11 EP 25 DI 10.1016/j.ydbio.2010.03.011 PG 15 WC Developmental Biology SC Developmental Biology GA 598DC UT WOS:000277812300002 PM 20346941 ER PT J AU Yamada, S Samtani, RR Lee, ES Lockett, E Uwabe, C Shiota, K Anderson, SA Lo, CW AF Yamada, Shigehito Samtani, Rajeev R. Lee, Elaine S. Lockett, Elizabeth Uwabe, Chigako Shiota, Kohei Anderson, Stasia A. Lo, Cecilia W. TI Developmental Atlas of the Early First Trimester Human Embryo SO DEVELOPMENTAL DYNAMICS LA English DT Article DE magnetic resonance imaging; episcopic fluorescence image capture; human embryo; web atlas; development; birth defect ID MAGNETIC-RESONANCE MICROSCOPY; MR MICROSCOPE; CHICK-EMBRYO; VESSELS AB Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies. Developmental Dynamics 239:1585-1595, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Yamada, Shigehito; Samtani, Rajeev R.; Lee, Elaine S.; Lo, Cecilia W.] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [Yamada, Shigehito; Uwabe, Chigako; Shiota, Kohei] Kyoto Univ, Grad Sch Med, Congenital Anomaly Res Ctr, Kyoto, Japan. [Lockett, Elizabeth] Natl Museum Hlth & Med, Human Dev Anat Ctr, Washington, DC USA. RP Lo, CW (reprint author), Univ Pittsburgh, Sch Med, Dept Dev Biol, 530 45th St, Pittsburgh, PA 15201 USA. EM cel36@pitt.edu FU National Institutes of Health [ZO1-HL005701]; The Japanese Ministry of Education, Culture, Sports, Science, and Technology [19390050, 21790180]; Japanese Ministry of Health, Labor, and Welfare [17A-6 19390050]; Japan Science Technology Agency; Kyoto University Foundation; Japan Spina Bifida and Hydrocephalus Research Foundation FX Grant sponsor: National Institutes of Health; Grant number: ZO1-HL005701; Grant sponsor: The Japanese Ministry of Education, Culture, Sports, Science, and Technology; Grant numbers: 19390050, 21790180; Grant sponsor: Japanese Ministry of Health, Labor, and Welfare; Grant number: 17A-6 19390050; Grant sponsor: Japan Science Technology Agency; Kyoto University Foundation; Grant sponsor: Japan Spina Bifida and Hydrocephalus Research Foundation. NR 28 TC 21 Z9 21 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUN PY 2010 VL 239 IS 6 BP 1585 EP 1595 DI 10.1002/dvdy.22316 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 610UB UT WOS:000278761700002 PM 20503356 ER PT J AU Guo, H Jin, DZ Zhang, YY Wright, W Bazuine, M Brockman, DA Bernlohr, DA Chen, XL AF Guo, Hong Jin, Daozhong Zhang, Yuanyuan Wright, Wendy Bazuine, Merlijn Brockman, David A. Bernlohr, David A. Chen, Xiaoli TI Lipocalin-2 Deficiency Impairs Thermogenesis and Potentiates Diet-Induced Insulin Resistance in Mice SO DIABETES LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; BROWN ADIPOSE-TISSUE; ENERGY-BALANCE; NEUTROPHIL GELATINASE; ADAPTIVE THERMOGENESIS; LEPTIN; COLD; OBESITY; PROTEIN; INFLAMMATION AB OBJECTIVE-Lipocalin (LCN) 2 belongs to the lipocalin subfamily of low-molecular mass-secreted proteins that bind small hydrophobic molecules. LCN2 has been recently characterized as an adipose-derived cytokine, and its expression is upregulated in adipose tissue in genetically obese rodents. The objective of this study was to investigate the role of LCN2 in diet-induced insulin resistance and metabolic homeostasis in vivo. RESEARCH DESIGN AND METHODS-Systemic insulin sensitivity, adaptive thermogenesis, and serum metabolic and lipid profile were assessed in LCN2-deficient mice fed a high-fat diet (HFD) or regular chow diet. RESULTS-The molecular disruption of LCN2 in mice resulted in significantly potentiated diet-induced obesity, dyslipidemia, fatty liver disease, and insulin resistance. LCN2(-/-) mice exhibit impaired adaptive thermogenesis and cold intolerance. Gene expression patterns in white and brown adipose tissue, liver, and muscle indicate that LCN2(-/-) mice have increased hepatic gluconeogenesis, decreased mitochondrial oxidative capacity, impaired lipid metabolism, and increased inflammatory state under the HFD condition. CONCLUSIONS-LCN2 has a novel role in adaptive thermoregulation and diet-induced insulin resistance. Diabetes 59:1376-1385, 2010 C1 [Guo, Hong; Jin, Daozhong; Zhang, Yuanyuan; Brockman, David A.; Chen, Xiaoli] Univ Minnesota, Dept Food Sci & Nutr, Minneapolis, MN 55455 USA. [Wright, Wendy; Bernlohr, David A.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Bazuine, Merlijn] NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Chen, XL (reprint author), Univ Minnesota, Dept Food Sci & Nutr, Minneapolis, MN 55455 USA. EM xlchen@umn.edu RI Zhang, Yuanyuan/M-9602-2014; Brockman, David/I-1451-2016 OI Zhang, Yuanyuan/0000-0002-5894-5387; Brockman, David/0000-0003-2666-7332 FU National Institute of Diabetes and Digestive and Kidney Diseases [R01DK080743] FX The project described was supported by grant no. R01DK080743 (to X.C.) from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 38 TC 61 Z9 64 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2010 VL 59 IS 6 BP 1376 EP 1385 DI 10.2337/db09-1735 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 611TC UT WOS:000278844700011 PM 20332347 ER PT J AU Chutkow, WA Birkenfeld, AL Brown, JD Lee, HY Frederick, DW Yoshioka, J Patwari, P Kursawe, R Cushman, SW Plutzky, J Shulman, GI Samuel, VT Lee, RT AF Chutkow, William A. Birkenfeld, Andreas L. Brown, Jonathan D. Lee, Hui-Young Frederick, David W. Yoshioka, Jun Patwari, Parth Kursawe, Romy Cushman, Samuel W. Plutzky, Jorge Shulman, Gerald I. Samuel, Varman T. Lee, Richard T. TI Deletion of the alpha-Arrestin Protein Tymip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity SO DIABETES LA English DT Article ID THIOREDOXIN-INTERACTING-PROTEIN; FAMILIAL PARTIAL LIPODYSTROPHY; UP-REGULATED PROTEIN-1; PPAR-GAMMA; GENE-EXPRESSION; OXIDATIVE STRESS; RESISTANCE; TISSUE; TXNIP; DEFICIENCY AB OBJECTIVE-Thioredoxin interacting protein (Txnip), a regulator of cellular oxidative stress, is induced by hyperglycemia and inhibits glucose uptake into fat and muscle, suggesting a role for Txnip in type 2 diabetes pathogenesis. Here, we tested the hypothesis that Txnip-null (knockout) mice are protected from insulin resistance induced by a high-fat diet. RESEARCH DESIGN AND METHODS-Txnip gene-deleted (knockout) mice and age-matched wild-type littermate control mice were maintained on a standard chow diet or subjected to 4 weeks of high-fat feeding. Mice were assessed for body composition, fat development, energy balance, and insulin responsiveness. Adipogenesis was measured from ex vivo fat preparations, and in mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes after forced manipulation of Txnip expression. RESULTS-Txnip knockout mice gained significantly more adipose mass than controls due to a primary increase in both calorie consumption and adipogenesis. Despite increased fat mass, Txrtip knockout mice were markedly more insulin sensitive than controls, and augmented glucose transport was identified in both adipose and skeletal muscle. RNA interference gene-silenced preadipocytes and Txnip(-/-) MEFs were markedly adipogenic, whereas Txnip overexpression impaired adipocyte differentiation. As increased adipogenesis and insulin sensitivity suggested aspects of augmented peroxisome proliferator-activated receptor-gamma (PPAR-gamma) response, we investigated Txnip's regulation of PPAR gamma function; manipulation of Txrtip expression directly regulated PPAR gamma expression and activity. CONCLUSIONS-Txnip deletion promotes adiposity in the face of high-fat caloric excess; however, loss of this a-arrestin protein simultaneously enhances insulin responsiveness in fat and skeletal muscle, revealing Txnip as a novel mediator of insulin resistance and a regulator of adipogenesis. Diabetes 59:1424-1434, 2010 C1 [Birkenfeld, Andreas L.; Lee, Hui-Young; Frederick, David W.; Samuel, Varman T.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Chutkow, William A.; Brown, Jonathan D.; Yoshioka, Jun; Patwari, Parth; Plutzky, Jorge; Lee, Richard T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Cambridge, MA USA. [Chutkow, William A.; Brown, Jonathan D.; Yoshioka, Jun; Patwari, Parth; Plutzky, Jorge; Lee, Richard T.] Harvard Univ, Sch Med, Cambridge, MA USA. [Chutkow, William A.; Brown, Jonathan D.] Vet Adm Med Ctr, W Roxbury, MA USA. [Kursawe, Romy] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Cushman, Samuel W.] NIDDKD, Expt Diabet Metab & Nutr Sect, Bethesda, MD 20892 USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Samuel, Varman T.] Vet Adm Med Ctr, West Haven, CT 06516 USA. RP Samuel, VT (reprint author), Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. EM varman.samuel@yale.edu FU U.S. Public Health Service [P0-1 HL-048743, R01 DK-40936, P30 DK-45735, K23 RR-17404, K08 HL-088977]; Deutsche Forschungsgemeinschaft (German Research Foundation); Schering-Plough; Veterans Administration Medical Center (West Haven, CT) FX This work was supported by grants from the U.S. Public Health Service (P0-1 HL-048743 to R.T.L., R01 DK-40936 and P30 DK-45735 to G.I.S., K23 RR-17404 to V.T.S., and K08 HL-088977 to W.A.C.) and the Deutsche Forschungsgemeinschaft (German Research Foundation) to A.L.B., and by the Leadership Council for Improving Cardiovascular Care (LCIC) Future Leaders in Cardiovascular Medicine Award (sponsored by Schering-Plough) to W.A.C. G.I.S. is an investigator of the Howard Hughes Medical Institute. V.T.S. also receives support from the Veterans Administration Medical Center (West Haven, CT). NR 47 TC 63 Z9 69 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2010 VL 59 IS 6 BP 1424 EP 1434 DI 10.2337/db09-1212 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 611TC UT WOS:000278844700016 PM 20299477 ER PT J AU Adeyemo, A Chen, GJ Zhou, J Shriner, D Doumatey, A Huang, HX Rotimi, C AF Adeyemo, Adebowale Chen, Guanjie Zhou, Jie Shriner, Daniel Doumatey, Ayo Huang, Hanxia Rotimi, Charles TI FTO Genetic Variation and Association With Obesity in West Africans and African Americans SO DIABETES LA English DT Article ID BODY-MASS INDEX; FAT MASS; EXTREME OBESITY; ADULT OBESITY; UNITED-STATES; VARIANTS; POPULATION; GENOME; CHILDREN; CHINESE AB OBJECTIVE-The FTO gene is one of the most consistently replicated loci for obesity. However, data from populations of African ancestry are limited. We evaluated genetic variation in the FTO gene and investigated associations with obesity in West Africans and African Americans. RESEARCH DESIGN AND METHODS-The study samples comprised 968 African Americans (59% female, mean age 49 years, mean BMI 30.8 kg/m(2)) and 517 West Africans (58% female, mean age 54 years, mean EMI 25.5 kg/m2). FTO genetic variation was evaluated by genotyping 262 tag single nucleotide polymorphisms (SNPs) across the entire gene. Association of each SNP with HMI, waist circumference, and percent fat mass was investigated under an additive model. RESULTS-As expected, both African-ancestry samples showed weaker linkage disequilibrium (I,D) patterns compared with other continental (e.g., European) populations. Several intron 8 SNPs, in addition to intron 1 SNPs, showed significant associations in both study samples. The combined effect size for HMI for the top SNPs from meta-analysis was 0.77 kg/m(2) (P = 0.009, rs9932411) and 0.70 kg/m(2) (P = 0.006, rs7191513). Two previously reported associations with introit 1 SNPs (rs1121980 and rs7204609, r(2) = 0.001) were replicated among the West Africans. CONCLUSIONS-The FTO gene shows significant differences in allele frequency and LD patterns in populations of African ancestry compared with other continental populations. Despite these differences, we observed evidence of associations with obesity in African Americans and West Africans, as well as evidence of heterogeneity in association. More studies of FTO in multiple ethnic groups are needed. Diabetes 59:1549-1554, 2010 C1 [Adeyemo, Adebowale; Chen, Guanjie; Zhou, Jie; Shriner, Daniel; Doumatey, Ayo; Huang, Hanxia; Rotimi, Charles] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Adeyemo, A (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. EM adeyemoa@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU NIGMS/MBRS [S06GM008016-380111, S06GM008016-320107]; National Institutes of Health (NIH), National Center for Minority Health and Health Disparities [3T37TW0041-0352]; NIH, NHGRI [DK-54001]; National Center for Research Resources (NCRR), NIH [2M01RR010284]; Center for Research on Genomics and Global Health (CRGGH); NIDDK [DK-54001]; Center for Information Technology; Office of the Director at the NIH [Z01HG200362] FX The Howard University Family Study (HUFS) was supported by grants S06GM008016-380111 to A.A. and S06GM008016-320107 to C.R., both from the NIGMS/MBRS/SCORE Program. Support for the Africa-America Diabetes Mellitus (AADM) study was provided by National Institutes of Health (NIH) Grant 3T37TW0041-0352 from the National Center for Minority Health and Health Disparities, as well as other NIH institutes (NHGRI and NIDDK through grant DK-54001). Participant enrollment for the HUFS was carried out at the Howard University General Clinical Research Center, which is supported by grant 2M01RR010284 from the National Center for Research Resources (NCRR), a component of the NIH. This research was supported in part by the Intramural Research Program of the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the NHGRI, the NIDDK, the Center for Information Technology, and the Office of the Director at the NIH (Z01HG200362). NR 25 TC 45 Z9 46 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2010 VL 59 IS 6 BP 1549 EP 1554 DI 10.2337/db09-1252 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 611TC UT WOS:000278844700030 PM 20299471 ER PT J AU Yeung, EH Zhang, CL Louis, GMB Willett, WC Hu, FB AF Yeung, Edwina H. Zhang, Cuilin Louis, Germaine M. Buck Willett, Walter C. Hu, Frank B. TI Childhood Size and Life Course Weight Characteristics in Association With the Risk of Incident Type 2 Diabetes SO DIABETES CARE LA English DT Article ID EXPERT COMMITTEE; BIRTH-WEIGHT; MELLITUS; OBESITY; ADULTHOOD; GLUCOSE; COHORT; WOMEN; CLASSIFICATION; PREDICTORS AB OBJECTIVE - To determine how childhood overweight, in conjunction with other life course weight characteristics, relates to the development of type 2 diabetes in adulthood. RESEARCH DESIGN AND METHODS - Among 109,172 women in the Nurses' Health Study II, body fatness at ages 5, 10, and 20 years was assessed by recall using 9-level pictorial diagrams (somatotypes) representing extreme thinness (category 1) to obesity (category 9). Recalled weights at age 18 years and adulthood were used to derive BMI. Self-reported cases of type 2 diabetes were confirmed by supplementary questionnaire. RESULTS - Somatotypes at ages 5 and 10 years were positively associated with diabetes risk (P(trend) < 0.0001). The adjusted relative risk (RR) of women with somatotype >= 6 (vs. 2) at age 5 years was 2.19 (95% CI 1.79-2.67) and at age 10 years was 2.57 (2.20-3.01). Increases in size by somatotype or by weight gain since age 18 were associated with increased risk. Compared with women who were never overweight at any age, women who were overweight as an adult (BMI >25 kg/m(2)) but not previously had an adjusted RR of 8.23 (7.41-9.15). The adjusted RR was 15.10 (13.21-17.26) for women who were also overweight at age 10 (somatotype >= 5) and 18 (BMI >25 kg/m(2)). Increased childhood size was not associated with risk among women who did not continue to be overweight in adulthood. CONCLUSIONS - Increased body size starting from childhood is associated with a greater risk of diabetes in adulthood. However, women who become lean in adulthood do not have an increased risk. C1 [Yeung, Edwina H.; Zhang, Cuilin; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Willett, Walter C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Willett, Walter C.; Hu, Frank B.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Willett, Walter C.; Hu, Frank B.] Harvard Univ, Sch Med, Boston, MA USA. RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. EM yeungedw@mail.nih.gov RI Yeung, Edwina/F-5992-2015; OI Yeung, Edwina/0000-0002-3851-2613; Buck Louis, Germaine/0000-0002-1774-4490 FU National Institutes of Health [CA50385, DK58845]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was funded by research grants CA50385 and DK58845 from the National Institutes of Health. E.H.Y., C.Z., and G.M.B.L. were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Funding sources had no role in data collection, analysis, interpretation, or article submission, and researchers acted independently from funders. NR 24 TC 18 Z9 20 U1 0 U2 2 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 JUN PY 2010 VL 33 IS 6 BP 1364 EP 1369 DI 10.2337/dc10-0100 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 617TI UT WOS:000279304300042 PM 20215459 ER PT J AU Kannan, P Brimacombe, KR Zoghbi, SS Liow, JS Morse, C Taku, AK Pike, VW Halldin, C Innis, RB Gottesman, MM Hall, MD AF Kannan, Pavitra Brimacombe, Kyle R. Zoghbi, Sami S. Liow, Jeih-San Morse, Cheryl Taku, Andrew K. Pike, Victor W. Halldin, Christer Innis, Robert B. Gottesman, Michael M. Hall, Matthew D. TI N-desmethyl-Loperamide Is Selective for P-Glycoprotein among Three ATP-Binding Cassette Transporters at the Blood-Brain Barrier SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID DRUG EFFLUX TRANSPORTERS; MULTIDRUG-RESISTANCE; SUBSTRATE; CANCER; INHIBITION; TARIQUIDAR; REVERSAL; DISEASES; XR9576; CELLS AB [(11)C] N-desmethyl-Loperamide ([(11)C]dLop) is used in positron emission tomography (PET) to measure the in vivo activity of efflux transporters that block the passage of drugs across the blood-brain barrier. The three most prevalent ATP-binding cassette efflux transporters at the blood-brain barrier are P-glycoprotein (P-gp), multidrug resistance protein 1 (Mrp1), and breast cancer resistance protein (BCRP). We sought to measure the selectivity of dLop among these three transporters. The selectivity of dLop at low concentrations (<= 1 nM) was measured both as the accumulation of [(3)H]dLop in human cells that overexpress each transporter and as the uptake of [(11)C] dLop in brains of mice that lack genes encoding P-gp, Mrp1, or BCRP. The selectivity of dLop at high concentrations (>= 20 mu M) was measured as the inhibition of uptake of a fluorescent substrate and the change in cytotoxicity of drugs effluxed at each transporter. Accumulation of [(3)H]dLop was lowest in cells overexpressing P-gp, and the uptake of [(11)C]dLop was highest in brains of mice lacking P-gp. At high concentrations, dLop selectively inhibited P-gp function and also decreased the resistance of only the P-gp-expressing cells to cytotoxic agents. dLop is selective for P-gp among these three transporters, but its activity is dependent on concentration. At low concentrations (<= 1 nM), dLop acts only as a substrate; at high concentrations (>= 20 mu M), it acts as both a substrate and an inhibitor (i.e., a competitive substrate). Because low concentrations of radiotracer are used for PET imaging, [(11)C] dLop acts selectively and only as a substrate for P-gp. C1 [Kannan, Pavitra; Zoghbi, Sami S.; Liow, Jeih-San; Morse, Cheryl; Taku, Andrew K.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Kannan, Pavitra; Halldin, Christer] Karolinska Inst, Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden. [Brimacombe, Kyle R.; Gottesman, Michael M.; Hall, Matthew D.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov OI Kannan, Pavitra/0000-0002-9170-6062 FU National Institutes of Health National Institute of Mental Health [Z01-MH002852-04]; National Cancer Institute [Z01-BC005598] FX This research was supported in part by the Intramural Research Programs of the National Institutes of Health National Institute of Mental Health [Project Z01-MH002852-04] and the National Cancer Institute [Project Z01-BC005598]. NR 31 TC 23 Z9 24 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUN PY 2010 VL 38 IS 6 BP 917 EP 922 DI 10.1124/dmd.109.031161 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 595OG UT WOS:000277620200005 PM 20212014 ER PT J AU Harris, CC AF Harris, C. C. TI Interweaving microRNA, inflammatory cytokine and p53 pathways in human cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Harris, C. C.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 26 BP 7 EP 8 PG 3 WC Oncology SC Oncology GA 737XF UT WOS:000288603100025 ER PT J AU Meltzer, P Zaidi, M De Fabo, E Davis, S Hornyak, T Fuchs, E Arnheiter, H Trinchieri, G Noonan, F Merlino, G AF Meltzer, P. Zaidi, M. De Fabo, E. Davis, S. Hornyak, T. Fuchs, E. Arnheiter, H. Trinchieri, G. Noonan, F. Merlino, G. TI Ultraviolet B-induced inflammatory microenvironment promotes melanocyte survival and melanoma susceptibility SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Meltzer, P.; Davis, S.] NCI, NIH, Genet Branch, Bethesda, MD 20892 USA. [Zaidi, M.; Merlino, G.] NCI, NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [De Fabo, E.; Noonan, F.] George Washington Univ, Med Ctr, Dept Environm & Occupat Hlth, Washington, DC 20037 USA. [Hornyak, T.] NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. [Fuchs, E.] Rockefeller Univ, Lab Mammalian Cell Biol & Dev, New York, NY 10021 USA. [Arnheiter, H.] NINDS, NIH, Mammalian Dev Sect, Bethesda, MD 20892 USA. [Trinchieri, G.] NCI, NIH, Canc & Inflammat Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 28 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100027 ER PT J AU Prokunina-Olsson, L Fu, YP Edvardsen, H Kaushiva, A Kohaar, I Porter-Gill, P Fossa, S Naume, B Borresen-Dale, AL Kristensen, VN AF Prokunina-Olsson, L. Fu, Y. P. Edvardsen, H. Kaushiva, A. Kohaar, I. Porter-Gill, P. Fossa, S. Naume, B. Borresen-Dale, A. L. Kristensen, V. Nedelcheva TI NOTCH2 in breast cancer: association of SNP rs11249433 with gene expression in ER-positive breast tumours without TP53 mutations SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Prokunina-Olsson, L.; Fu, Y. P.; Kaushiva, A.; Kohaar, I.; Porter-Gill, P.] NCI, Lab Translat Genom, Bethesda, MD 20892 USA. [Edvardsen, H.; Borresen-Dale, A. L.; Kristensen, V. Nedelcheva] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Oslo, Norway. [Fossa, S.] Univ Oslo, Norwegian Radium Hosp, Fac Div Med, Oslo, Norway. [Naume, B.] Oslo Univ Hosp, Radiumhosp, Dept Oncol, Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 41 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100039 ER PT J AU Milne, RL Gaudet, MM Garcia-Closas, M Pharoah, PDP Couch, FJ Fasching, PA Spurdle, AB Goode, EL Chang-Claude, J AF Milne, R. L. Gaudet, M. M. Garcia-Closas, M. Pharoah, P. D. P. Couch, F. J. Fasching, P. A. Spurdle, A. B. Goode, E. L. Chang-Claude, J. CA Breast Canc Assoc Consortium TI Assessing interaction between established breast cancer genetic susceptibility loci and selected non-genetic risk factors using data from the Breast Cancer Association Consortium SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Milne, R. L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Gaudet, M. M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA. [Garcia-Closas, M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Pharoah, P. D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Couch, F. J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Fasching, P. A.] Univ Hosp Erlangen, Univ Breast Ctr, Erlangen, Germany. [Spurdle, A. B.] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia. [Goode, E. L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Chang-Claude, J.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 53 BP 14 EP 14 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100051 ER PT J AU Czachorowski, M Real, FX Lloreta, J Silverman, DT Morente, M Kishore, S Kogevinas, M Malats, N AF Czachorowski, M. Real, F. X. Lloreta, J. Silverman, D. T. Morente, M. Kishore, S. Kogevinas, M. Malats, N. TI Cycloxygenase-2 (COX2) expression in transitional cell carcinoma of the bladder does not confer independent prognostic properties SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Czachorowski, M.; Malats, N.] CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Real, F. X.] CNIO, Eptithelial Carcinogenesis Grp, Madrid, Spain. [Lloreta, J.; Kishore, S.; Kogevinas, M.] IMIM, Barcelona, Spain. [Silverman, D. T.] NCI, Bethesda, MD 20892 USA. [Morente, M.] CNIO, Biobank Grp, Madrid, Spain. RI Lloreta, J/I-2112-2014; Kogevinas, Manolis/C-3918-2017 OI Lloreta, J/0000-0003-1644-9470; NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 99 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100096 ER PT J AU Regnier, DCL Yakoub, S El Chami, N Kaszas, K Malek, M Huber, AL Smith, C Baydoun, E Manie, S Tabone, E AF Regnier, D. C. L. Yakoub, S. El Chami, N. Kaszas, K. Malek, M. Huber, A. L. Smith, C. Baydoun, E. Manie, S. Tabone, E. TI The E3-Ubiquitine ligase c-Cbl protects cells against oxydative stress - usefulness as a prognostic marker and a possible therapeutic target SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Regnier, D. C. L.; Malek, M.; Huber, A. L.; Manie, S.] UCBL1, Ctr Leon Berard, CNRS, UMR 5201, Lyon, France. [Yakoub, S.] Ctr Clermont Ferrand, INRA, St Genes Champanelle, France. [El Chami, N.; Smith, C.; Baydoun, E.] AUB, Dept Biol, Beirut, Lebanon. [Tabone, E.] Ctr Leon Berard, Cytol Lab, F-69373 Lyon, France. [Kaszas, K.] NIDCR, NIH, Neurobiol & Pain Therapeut Lab Sensor Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 119 BP 31 EP 31 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100116 ER PT J AU Hendrix, A Westbroek, W Cocquyt, V Bracke, M De Wever, O AF Hendrix, A. Westbroek, W. Cocquyt, V. Bracke, M. De Wever, O. TI The secretory small GTPase Rab27B drives poor prognosis in ER-positive breast cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Hendrix, A.; Bracke, M.; De Wever, O.] Ghent Univ Hosp, Lab Expt Canc Res, B-9000 Ghent, Belgium. [Westbroek, W.] NHGRI, NIH, Bethesda, MD 20892 USA. RI de wever, olivier/J-3094-2013 OI de wever, olivier/0000-0002-5453-760X NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 363 BP 92 EP 93 PG 3 WC Oncology SC Oncology GA 737XF UT WOS:000288603100346 ER PT J AU Garbe, Y Dittfeld, C Peickert, S Waurig, J Dietrich, A Grade, M Ried, T Kunz-Schughart, LA AF Garbe, Y. Dittfeld, C. Peickert, S. Waurig, J. Dietrich, A. Grade, M. Ried, T. Kunz-Schughart, L. A. TI A story of complexity and discrepancy: CD133 expression and tumourigenicity of colon cancer cell line subpopulations SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Garbe, Y.; Dittfeld, C.; Peickert, S.; Waurig, J.; Dietrich, A.; Kunz-Schughart, L. A.] Tech Univ Dresden, OncoRay Ctr Radiat Res Oncol, Dresden, Germany. [Grade, M.] Univ Med Goettingen, Dept Gen & Visceral Surg, Gottingen, Germany. [Ried, T.] NCI, NIH, Sect Canc Genom, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 447 BP 114 EP 115 PG 3 WC Oncology SC Oncology GA 737XF UT WOS:000288603100430 ER PT J AU Tiffen, JC Bailey, CG Ng, C Watson, SL Loukinov, DI Lobanenkov, VV Holst, J Rasko, JEJ AF Tiffen, J. C. Bailey, C. G. Ng, C. Watson, S. L. Loukinov, D. I. Lobanenkov, V. V. Holst, J. Rasko, J. E. J. TI BORIS and its paralogue CTCF exhibit similar biological functions SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Tiffen, J. C.; Bailey, C. G.; Ng, C.; Watson, S. L.; Holst, J.; Rasko, J. E. J.] Centenary Inst, Sydney, NSW, Australia. [Loukinov, D. I.; Lobanenkov, V. V.] NIAID, Immunopathol Lab, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 700 BP 176 EP 177 PG 2 WC Oncology SC Oncology GA 737XF UT WOS:000288603100675 ER PT J AU Dahl, M Bouchelouche, P Kramer-Marek, G Capala, J Nordling, J Bouchelouche, K AF Dahl, M. Bouchelouche, P. Kramer-Marek, G. Capala, J. Nordling, J. Bouchelouche, K. TI Sarcosine induces up-regulation of HER2/neu in androgen dependent prostate cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Dahl, M.; Bouchelouche, P.] Univ Copenhagen, Koege Hosp, Canc & Mol Imaging Unit, Res Div Clin Biochem, Koege, Denmark. [Kramer-Marek, G.; Capala, J.] NCI, NIH, Mol Targeting Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Nordling, J.] Univ Copenhagen, Herlev Hosp, Dept Urol, DK-2730 Herlev, Denmark. [Bouchelouche, K.] Univ Copenhagen, Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark. NR 2 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 710 BP 179 EP 179 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100685 ER PT J AU Dahl, M Bouchelouche, P Kramer-Marek, G Capala, J Bouchelouche, K AF Dahl, M. Bouchelouche, P. Kramer-Marek, G. Capala, J. Bouchelouche, K. TI Effect of tumour necrosis factor (TNF) alpha on HER2/neu expression in ovarian cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 21st Meeting of the European-Association-for-Cancer-Research CY JUN 26-29, 2010 CL Oslo, NORWAY SP European Assoc Canc Res C1 [Dahl, M.; Bouchelouche, P.] Univ Copenhagen, Koge Hosp, Koge, Denmark. [Kramer-Marek, G.; Capala, J.] NCI, NIH, Mol Targeting Sect, Radiat Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Bouchelouche, K.] Univ Copenhagen, Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark. NR 2 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2010 VL 8 IS 5 MA 715 BP 180 EP 180 PG 1 WC Oncology SC Oncology GA 737XF UT WOS:000288603100690 ER PT J AU Morens, DM Burke, DS Halstead, SB AF Morens, David M. Burke, Donald S. Halstead, Scott B. TI The Wages of Original Antigenic Sin SO EMERGING INFECTIOUS DISEASES LA English DT Article ID H1N1 INFLUENZA; ANTIBODIES; VIRUSES; VACCINATION; RESPONSES C1 [Morens, David M.] NIAID, NIH, Bethesda, MD 20892 USA. [Burke, Donald S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Halstead, Scott B.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Rm 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA. EM dm270q@nih.gov OI /0000-0002-5704-8094 NR 17 TC 28 Z9 28 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUN PY 2010 VL 16 IS 6 BP 1023 EP 1024 DI 10.3201/eid1606.100453 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 602UJ UT WOS:000278164000025 PM 20507764 ER PT J AU Perez-Edgar, K Bar-Haim, Y McDermott, JM Chronis-Tuscano, A Pine, DS Fox, NA AF Perez-Edgar, Koraly Bar-Haim, Yair McDermott, Jennifer Martin Chronis-Tuscano, Andrea Pine, Daniel S. Fox, Nathan A. TI Attention Biases to Threat and Behavioral Inhibition in Early Childhood Shape Adolescent Social Withdrawal SO EMOTION LA English DT Article DE temperament; behavioral inhibition; social withdrawal; attention biases ID GENERALIZED ANXIETY DISORDER; PREFRONTAL CORTEX ACTIVATION; SHY CHILDREN; ANGRY FACES; TEMPERAMENTAL CONTRIBUTIONS; EXPERIMENTAL MANIPULATION; SELECTIVE ATTENTION; PERSONALITY-TRAITS; RESPONSES; AMYGDALA AB Behavioral inhibition (BI) is a temperament characterized in young children by a heightened sensitivity to novelty, social withdrawal, and anxious behaviors. For many children, these social difficulties dissipate over time. For others, patterns of social withdrawal continue into adolescence. Over time, attention biases to threat may influence the stability of BI and its association with social withdrawal, ultimately modulating the risk for anxiety disorders in BI children. However, we know relatively little about the cognitive processes that accompany BI and shape later socioemotional functioning. We examined the relations among BI in childhood, attention biases to threat in adolescence, and adolescent social withdrawal in a longitudinal study (N = 126, Mean age = 15 years). As has been reported in anxious adults, adolescents who were behaviorally inhibited as toddlers and young children showed heightened attention bias to threat. In addition, attention bias to threat moderated the relation between childhood BI and adolescent social withdrawal. C1 [Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, Tel Aviv, Israel. [McDermott, Jennifer Martin] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. [Chronis-Tuscano, Andrea] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Perez-Edgar, K (reprint author), George Mason Univ, Dept Psychol, MS 3F5,4400 Univ Dr, Fairfax, VA 22030 USA. EM kperezed@gmu.edu OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU NICHD NIH HHS [HD17899, R01 HD017899, R37 HD017899]; NIMH NIH HHS [K01 MH073569, MH073569, MH074454, R01 MH074454, R01 MH074454-01A2, U01 MH074454] NR 72 TC 81 Z9 81 U1 4 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2010 VL 10 IS 3 BP 349 EP 357 DI 10.1037/a0018486 PG 9 WC Psychology, Experimental SC Psychology GA 605WI UT WOS:000278378200005 PM 20515224 ER PT J AU King, KS Darmani, NA Hughes, MS Adams, KT Pacak, K AF King, Kathryn S. Darmani, Nissar A. Hughes, Marybeth S. Adams, Karen T. Pacak, Karel TI Exercise-induced nausea and vomiting: another sign and symptom of pheochromocytoma and paraganglioma SO ENDOCRINE LA English DT Article DE Nausea; Vomiting; Pheochromocytoma; Paraganglioma; Norepinephrine; Epinephrine; Catecholamine ID BIOCHEMICAL-DIAGNOSIS; CLONIDINE; SURGERY; DISEASE; HEALTH AB A cohort of nine patients, mostly young adults, presented with a new sign/symptom of pheochromocytoma/paraganglioma: exercise-induced nausea and vomiting. The aims of this article are to introduce this sign/symptom and offer a possible hypothesis for the observation. Following a 2000 report from a paraganglioma patient experiencing exercise-induced nausea and vomiting, we began asking patients about instances of nausea and vomiting with exercise. A total of nine patients, 4.4% of our pheochromocytoma/paraganglioma population, presented with reports of exercise-induced nausea and vomiting, initially with moderate-to-intense levels of exercise, at the first presentation of their disease. All of these patients reported a cessation of exercise-induced nausea and vomiting following the removal of their primary tumor. Two patients with metastatic disease to the lungs reported a recurrence of exercise-induced nausea and vomiting. The majority of patients studied were young adults with mean onset age of 19.4 years (range of 9-51 years) and the mean age of diagnosis being 24.1 years (range of 11-53 years). Exercise-induced nausea and vomiting should be considered a sign/symptom of pheochromocytoma/paraganglioma and should be addressed in the clinical evaluation of these patients, especially in young adults. Whether exercise-induced elevated catecholamine levels could account for the induced nausea and vomiting via activation of adrenergic receptors in the area postrema remains to be established. C1 [King, Kathryn S.; Adams, Karen T.; Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Eunice Kennedy Shriver NICHHD,NIH, Bethesda, MD 20892 USA. [Darmani, Nissar A.] Western Univ Hlth Sci, Coll Osteopath Med Pacific, Dept Basic Med Sci, Pomona, CA 91766 USA. [Hughes, Marybeth S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, Eunice Kennedy Shriver NICHHD,NIH, Bldg 10,CRC,1 East,Room 1-3140,10 Ctr Dr,MSC-11, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU NIH, NICHD FX We would like to acknowledge the advice and suggestions provided by Professor Miklos Palkovits, M.D., Ph.D., D.Sc., in the preparation of this article. This research was supported, in part, by the Intramural Research Program of the NIH, NICHD. NR 19 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD JUN PY 2010 VL 37 IS 3 BP 403 EP 407 DI 10.1007/s12020-010-9319-3 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 590BY UT WOS:000277199600005 PM 20960160 ER PT J AU Panicker, LM Zhang, JH Dagur, PK Gastinger, MJ Simonds, WF AF Panicker, Leelamma M. Zhang, Jian-Hua Dagur, Pradeep K. Gastinger, Matthew J. Simonds, William F. TI Defective nucleolar localization and dominant interfering properties of a parafibromin L95P missense mutant causing the hyperparathyroidism-jaw tumor syndrome SO ENDOCRINE-RELATED CANCER LA English DT Article ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; RNA-POLYMERASE-II; UBIQUITIN-PROTEASOME PATHWAY; SPORADIC PARATHYROID TUMORS; SUPPRESSOR PROTEIN; HEREDITARY HYPERPARATHYROIDISM; GENETIC ANALYSES; HRPT2 MUTATION; HUMAN PAF1; GERMLINE AB The hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a familial cancer syndrome that can result from germline inactivation of HRPT2/CDC73, a putative tumor suppressor gene that encodes parafibromin, a component of the transcriptional regulatory PAF1 complex with homology to the yeast protein Cdc73p. The vast majority of HRPT2/CDC73 germline mutations identified have been truncation or frameshift mutations, and loss of function due to missense mutation is rare. We report here a kindred with HPT-JT due to a germline L95P missense mutation in parafibromin. The mutant parafibromin was studied in vitro to understand the basis of its presumed loss-of-function. When transfected in cultured cells, the L95P mutant was expressed to a lower level than wild-type (wt) parafibromin, a difference that was not overcome by inhibition of the proteasomal degradation pathway. The L95P mutant parafibromin retained the ability to assemble with endogenous PAF1 complex components as evidenced by co-immunoprecipitation. Analysis of subcellular localization showed that the L95P mutant was markedly deficient in nucleolar localization compared to the wt, an impairment likely resulting from disruption of a putative nucleolar localization signal immediately upstream of the L95P mutation. Transfection of the L95P parafibromin mutant, but not the wt, enhanced cell cycle progression and increased cell survival in NIH-3T3 and HEK 293 cells, resulting apparently from dominant interference with endogenous parafibromin action. The simultaneous loss of nucleolar localization and acquisition of a growth stimulatory phenotype with the L95P mutation raise the possibility that parafibromin must interact with targets in the nucleolus to fully execute its tumor suppressor functions. Endocrine-Related Cancer (2010) 17 513-524 C1 [Panicker, Leelamma M.; Zhang, Jian-Hua; Simonds, William F.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Dagur, Pradeep K.] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. [Gastinger, Matthew J.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C-101, Bethesda, MD 20892 USA. EM wfs@helix.nih.gov FU Division of Intramural Research of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA FX This research was funded by the Division of Intramural Research of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA. NR 31 TC 12 Z9 12 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2010 VL 17 IS 2 BP 513 EP 524 DI 10.1677/ERC-09-0272 PG 12 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 618HH UT WOS:000279341700022 PM 20304979 ER PT J AU Greene, MH Kratz, CP Mai, PL Mueller, C Peters, JA Bratslavsky, G Ling, A Choyke, PM Premkumar, A Bracci, J Watkins, RJ McMaster, ML Korde, LA AF Greene, Mark H. Kratz, Christian P. Mai, Phuong L. Mueller, Christine Peters, June A. Bratslavsky, Gennady Ling, Alex Choyke, Peter M. Premkumar, Ahalya Bracci, Janet Watkins, Rissah J. McMaster, Mary Lou Korde, Larissa A. TI Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype SO ENDOCRINE-RELATED CANCER LA English DT Review ID GENOME-WIDE ASSOCIATION; OF-THE-LITERATURE; SUSCEPTIBILITY GENE; CARCINOMA-INSITU; CANCER INCIDENCE; C-KIT; MEN; TESTIS; MICROLITHIASIS; MUTATIONS AB Familial aggregations of testicular germ cell tumor (FTGCT) have been well described, suggesting the existence of a hereditary TGCT subset. Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four-to sixfold and eight-to tenfold increases in TGCT risk respectively. Segregation analyses suggest an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest, although no high-penetrance cancer susceptibility gene has been mapped yet. These data suggest that the combined effects of multiple common alleles, each conferring modest risk, might underlie familial testicular cancer. Families display a mild phenotype: the most common number of affected families is 2. Age at diagnosis is 2-3 years younger for familial versus sporadic cases. The ratio of familial seminoma to nonseminoma is 1.0. FTGCT is more likely to be bilateral than sporadic TGCT. This syndrome is cancer site specific. Testicular microlithiasis is a newly recognized FTGCT component. Candidate gene-association studies have implicated the Y chromosome gr/gr deletion and PDE11A gene mutations as genetic modifiers of FTGCT risk. Two genomewide association studies of predominantly sporadic but also familial cases of TGCT have implicated the KIT-ligand, SPRY4, and BAK1 genes as TGCT risk modifiers. All five loci are involved in normal testicular development and/or male infertility. These genetic data provide a novel insight into the genetic basis of FTGCT, and an invaluable guide to future TGCT research. Endocrine-Related Cancer (2010) 17 R109-R121 C1 [Greene, Mark H.; Kratz, Christian P.; Mai, Phuong L.; Mueller, Christine; Peters, June A.; Korde, Larissa A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20852 USA. [Ling, Alex; Premkumar, Ahalya] NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20852 USA. [Choyke, Peter M.] NCI, Mol Imaging Program, Bethesda, MD 20852 USA. [Bracci, Janet; Watkins, Rissah J.] Westat Corp, Rockville, MD USA. [McMaster, Mary Lou] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. RP Greene, MH (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. EM greenem@mail.nih.gov FU US National Cancer Institute, National Institutes of Health; Westat, Inc., Rockville, MD, USA [N02-CP-11019-50, N02-CP-65504] FX This work was supported by the Intramural Research Program of the US National Cancer Institute, National Institutes of Health, and by support services contracts N02-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD, USA. NR 77 TC 34 Z9 34 U1 0 U2 0 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2010 VL 17 IS 2 BP R109 EP R121 DI 10.1677/ERC-09-0254 PG 13 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 618HH UT WOS:000279341700002 PM 20228134 ER PT J AU Alberobello, AT Congedo, V Liu, H Butler, PW Skarulis, MC Dubaz, O Luzon, J Forrest, D Celi, FS AF Alberobello, A. T. Congedo, V. Liu, H. Butler, P. W. Skarulis, M. C. Dubaz, O. Luzon, J. Forrest, D. Celi, F. S. TI SNPs in the Intronic Regulatory Region of the Thyroid Hormone Receptor Gene Are Associated with a Tissue-Specific over Expression of the R338W Mutation in a Pituitary Selective Form of Resistance to Thyroid Hormone SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Alberobello, A. T.; Liu, H.; Butler, P. W.; Skarulis, M. C.; Dubaz, O.; Luzon, J.; Forrest, D.; Celi, F. S.] NIH, Bethesda, MD 20892 USA. [Congedo, V.] Univ Gabriele DAnnunzio, Chieti, Italy. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2516 EP S2516 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400219 ER PT J AU Almeida, MQ Muchow, M Boikos, S Bauer, AJ Griffin, KJ Tsang, KM Cheadle, C Watkins, T Wen, F Starost, MF Bossis, I Nesterova, M Stratakis, CA AF Almeida, M. Q. Muchow, M. Boikos, S. Bauer, A. J. Griffin, K. J. Tsang, K. M. Cheadle, C. Watkins, T. Wen, F. Starost, M. F. Bossis, I. Nesterova, M. Stratakis, C. A. TI Mouse Prkar1a Haploinsufficiency Leads to an Increase in Tumors in the Trp53+/- or Rb1+/- Backgrounds and Chemically-Induced Skin Papillomas by Dysregulation of the Cell Cycle and Wnt Signaling. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Almeida, M. Q.; Muchow, M.; Boikos, S.; Bauer, A. J.; Griffin, K. J.; Tsang, K. M.; Wen, F.; Bossis, I.; Nesterova, M.; Stratakis, C. A.] NICHHD, NIH, Bethesda, MD 20892 USA. [Cheadle, C.; Watkins, T.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1663 EP S1663 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400118 ER PT J AU Andreopoulou, P Millo, CM Reynolds, JC Kelly, MH Brillante, BA Wodajo, FM Chang, R Chen, CC Collins, MT AF Andreopoulou, P. Millo, C. M. Reynolds, J. C. Kelly, M. H. Brillante, B. A. Wodajo, F. M. Chang, R. Chen, C. C. Collins, M. T. TI Multimodality Diagnosis and Treatment of Tumor-Induced Osteomalacia. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Andreopoulou, P.; Kelly, M. H.; Brillante, B. A.; Collins, M. T.] NIDCR, NIH, Bethesda, MD USA. [Wodajo, F. M.] Inova Fairfax Hosp, VCU Sch Med, Falls Church, VA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S49 EP S49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400049 ER PT J AU Bhattacharyya, N Wiench, M Patel, HV Andreopoulou, P Connolly, B Bugge, T Gafni, RI Collins, MT AF Bhattacharyya, N. Wiench, M. Patel, H. V. Andreopoulou, P. Connolly, B. Bugge, T. Gafni, R. I. Collins, M. T. TI Roles of O-Glycosylation and Furin in Cyclic AMP-Mediated Processing of FGF23 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Bhattacharyya, N.; Andreopoulou, P.; Connolly, B.; Bugge, T.; Gafni, R. I.; Collins, M. T.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Wiench, M.] NCI, NIH, Bethesda, MD 20892 USA. [Patel, H. V.] Natl Inst Diabet Digest & Kidney Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S826 EP S826 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400066 ER PT J AU Butler, PW Smith, SM Linderman, JD Brychta, RJ Alberobello, AT Dubaz, OM Luzon, JA Skarulis, MC Cochran, CS Wesley, RA Pucino, F Celi, FS AF Butler, P. W. Smith, S. M. Linderman, J. D. Brychta, R. J. Alberobello, A. T. Dubaz, O. M. Luzon, J. A. Skarulis, M. C. Cochran, C. S. Wesley, R. A. Pucino, F. Celi, F. S. TI Pharmacogenomic Response to Thyrotropin-Releasing Hormone Stimulation in Healthy Volunteers: The Influence of a Common Type 2 Deiodinase Gene Polymorphism on Serum T3 SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Butler, P. W.; Smith, S. M.; Linderman, J. D.; Brychta, R. J.; Alberobello, A. T.; Dubaz, O. M.; Luzon, J. A.; Skarulis, M. C.; Cochran, C. S.; Wesley, R. A.; Pucino, F.; Celi, F. S.] NIH, Bethesda, MD 20892 USA. [Pucino, F.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S22 EP S22 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400023 ER PT J AU King, KS Alexopoulos, DK Whatley, MA Reynolds, JC Adams, KT Xekouki, P Lando, HM Statakis, CA Chen, CC Pacak, K AF King, K. S. Alexopoulos, D. K. Whatley, M. A. Reynolds, J. C. Adams, K. T. Xekouki, P. Lando, H. M. Statakis, C. A. Chen, C. C. Pacak, K. TI Functional Imaging of Head and Neck Paragangliomas: Comparison of F-18-Fluorodihydroxyphenylalanine (F-18-FDOPA) Positron Emission Tomography (PET), F-18-Fluorodopamine (F-18-FDA) PET/Computed Tomography (CT), F-18-Fluoro-2-Deoxy-D-Glucose (F-18-FDG) PET/CT, I-123- Metaiodobenzylguanidine (I-123-MIBG) Scintigraphy, and In-111-Pentetreotide Scintigraphy SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [King, K. S.; Alexopoulos, D. K.; Whatley, M. A.; Reynolds, J. C.; Adams, K. T.; Xekouki, P.; Statakis, C. A.; Chen, C. C.; Pacak, K.] NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S841 EP S841 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400081 ER PT J AU Lee, HW Muniyappa, R Potti, K Harman, SM Sorkin, JD Blackman, MR AF Lee, Ho Won Muniyappa, Ranganath Potti, Karthya Harman, S. Mitchell Sorkin, John D. Blackman, Marc R. TI Gender Dimorphic Relationships of Adiposity, Fitness, and Physical Activity with Indices of Skeletal Muscle and Hepatic Insulin Sensitivity in Healthy Older Subjects SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lee, Ho Won; Muniyappa, Ranganath; Potti, Karthya] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Harman, S. Mitchell; Sorkin, John D.; Blackman, Marc R.] NIA, NIH, Baltimore, MD 21224 USA. [Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ USA. [Sorkin, John D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Sorkin, John D.] Baltimore VA Med Ctr, Baltimore, MD USA. [Blackman, Marc R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Blackman, Marc R.] Vet Affairs Med Ctr, Washington, DC 20422 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2547 EP S2547 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400250 ER PT J AU Lee, KY Gesta, S Boucher, J Wang, X Gonzalez, FJ Kahn, CR AF Lee, K. Y. Gesta, S. Boucher, J. Wang, X. Gonzalez, F. J. Kahn, C. R. TI Adipose Specific Ablation of Hif1b/Arnt and the Role of Hypoxia in Obesity and Adipose Vascular Function SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lee, K. Y.; Gesta, S.; Boucher, J.; Wang, X.; Kahn, C. R.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Gonzalez, F. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S836 EP S836 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400076 ER PT J AU Lui, JCK Baron, J AF Lui, Julian C. K. Baron, Jeffrey TI Changes in Histone Methylation during Postnatal Growth Deceleration. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lui, Julian C. K.; Baron, Jeffrey] NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1660 EP S1660 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400115 ER PT J AU Nemechek, NM Chen, M Mema, E Wang, J Kablan, A Weinstein, LS AF Nemechek, N. M. Chen, M. Mema, E. Wang, J. Kablan, A. Weinstein, L. S. TI G(s)alpha Deficiency in the Paraventricular Nucleus of the Hypothalamus Contibutes to the Parent-of-Origin Effect of G(s)alpha Mutations on Energy Metabolism SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Nemechek, N. M.; Chen, M.; Mema, E.; Wang, J.; Kablan, A.; Weinstein, L. S.] NIDDK, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2533 EP S2533 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400236 ER PT J AU Panel, V Hugendubler, L Mueller, E AF Panel, V. Hugendubler, L. Mueller, E. TI Global Analysis of Forkhead Proteins Reveals a Critical Role of FOXA3 in Adipogenesis SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Panel, V.; Hugendubler, L.; Mueller, E.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S835 EP S835 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400075 ER PT J AU Thearle, MS Pannacciulli, N Bonfiglio, S Krakoff, J AF Thearle, M. S. Pannacciulli, N. Bonfiglio, S. Krakoff, J. TI Effects of Macronutrient Manipulation on Short-Term Metabolic Response to Overfeeding. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Thearle, M. S.; Bonfiglio, S.; Krakoff, J.] NIDDK, NIH, Phoenix, AZ USA. [Pannacciulli, N.] Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S30 EP S30 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400030 ER PT J AU Tiano, JP Le May, C Korach, KS Mauvais-Jarvis, F AF Tiano, J. P. Le May, C. Korach, K. S. Mauvais-Jarvis, F. TI The Extranuclear Estrogen Receptor-alpha Improves Pancreatic Islet Lipid Homeostasis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Tiano, J. P.; Le May, C.; Mauvais-Jarvis, F.] Northwestern Univ, Chicago, IL 60611 USA. [Korach, K. S.] Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1654 EP S1654 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400109 ER PT J AU Vijayakumar, A Wu, Y Sun, H Liu, C Yakar, S LeRoith, D AF Vijayakumar, A. Wu, Y. Sun, H. Liu, C. Yakar, S. LeRoith, D. TI Targeted Ablation of Growth Hormone Receptors in the Skeletal Muscle Improves Metabolism and Protects Against Diet-Induced Obesity in Mice. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Vijayakumar, A.; Wu, Y.; Sun, H.; Yakar, S.; LeRoith, D.] Mt Sinai Sch Med, New York, NY USA. [Liu, C.] NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S2487 EP S2487 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400194 ER PT J AU Ward, Y Lake, RG Martin, P Lu, C Cheng, S Kelly, K AF Ward, Y. Lake, R. G. Martin, P. Lu, C. Cheng, S. Kelly, K. TI CD97 Promotes Cancer Progression in a Murine Model of Follicular Thyroid Cancer SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ward, Y.; Lake, R. G.; Martin, P.; Lu, C.; Cheng, S.; Kelly, K.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 BP S1677 EP S1677 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989400132 ER PT J AU Abel, BS Neary, NM Campbell, K Nieman, LK AF Abel, B. S. Neary, N. M. Campbell, K. Nieman, L. K. TI Post-Surgical Recovery in Patients with Cushing's Syndrome: Results of an Open-Ended Survey. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Abel, B. S.; Neary, N. M.; Nieman, L. K.] NIH, Bethesda, MD 20892 USA. [Campbell, K.] Cushings Support & Res Fdn, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403634 ER PT J AU Almeida, MQ Tsang, KM Wang, X Grivel, JC Nesterova, M Carney, JA Goldbach-Mansky, R Stratakis, CA AF Almeida, M. Q. Tsang, K. M. Wang, X. Grivel, J. C. Nesterova, M. Carney, J. A. Goldbach-Mansky, R. Stratakis, C. A. TI Protein Kinase A Regulates Caspase 1 Via Ets1 Proto-Oncogene Activation in Mouse and Human Bone Tumors Derived from Bone Stem Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Almeida, M. Q.; Tsang, K. M.; Grivel, J. C.; Nesterova, M.; Stratakis, C. A.] NICHHD, NIH, Bethesda, MD 20892 USA. [Wang, X.; Goldbach-Mansky, R.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Carney, J. A.] Mayo Clin, Rochester, MN USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403144 ER PT J AU Arao, Y Hamilton, K Ray, M Scott, G Korach, KS AF Arao, Y. Hamilton, K. Ray, M. Scott, G. Korach, K. S. TI Characterizing the In Vivo Physiological Roles for ER alpha AF-1 and AF-2 Using a Mutant AF-2 Knock-In Mouse Line. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Arao, Y.; Hamilton, K.; Ray, M.; Scott, G.; Korach, K. S.] Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401724 ER PT J AU Auchus, RJ Wichel, S White, PC Baker, LA Baratz, A Berebaum, SA Eugster, EA Geffner, ME Loechner, KJ Merke, D Nenadovich, T Poppas, DP Riepe, FG Rink, R Rivkees, SA Sandberg, DE Schaeffer, T Schlussel, RN VanRyzin, C Vogiatzi, MG Aisenberg, JE Bachega, T Lee, PA Miller, WL Quigley, CA Seely, E Azziz, R Fracassa, S Leight, K Lin, GA Snyder, D Matos, DM Schneck, FX Katz, AL Pass, K Lloyd-Puryear, MA Breault, D Kalro, B Harris, KB Therrell, BL AF Auchus, Richard J. Wichel, Selma White, Perrin C. Baker, Linda A. Baratz, Arlene Berebaum, Sheri A. Eugster, Erica A. Geffner, Mitchell E. Loechner, Karen J. Merke, Deborah Nenadovich, Tamara Poppas, Dix P. Riepe, Felix G. Rink, Richard Rivkees, Scott A. Sandberg, David E. Schaeffer, Traci Schlussel, Richard N. VanRyzin, Carol Vogiatzi, Maria G. Aisenberg, Javier E. Bachega, Tania Lee, Peter A. Miller, Walter L. Quigley, Charmian A. Seely, Ellen Azziz, Ricardo Fracassa, Stephanie Leight, Kelly Lin, Gretchen A. Snyder, Diane Matos, Dina M. Schneck, Francis X. Katz, Aviva L. Pass, Kenneth Lloyd-Puryear, Michele A. Breault, David Kalro, Brinda Harris, Katharine B. Therrell, Bradley L. CA CAH CCC Comm TI Development of Comprehensive Care Centers for Management of Patients with Congenital Adrenal Hyperplasia. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Auchus, Richard J.; White, Perrin C.; Baker, Linda A.] UT SW Med Ctr, Dallas, TX USA. [Wichel, Selma; Nenadovich, Tamara; Schneck, Francis X.] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Baratz, Arlene] USA, Androgen Insensit Syndrome Support Grp, Duncan, OK USA. [Berebaum, Sheri A.] Penn State Univ, University Pk, PA 16802 USA. [Eugster, Erica A.; Rink, Richard] Indiana Univ Sch Med, Indianapolis, IN USA. [Geffner, Mitchell E.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Loechner, Karen J.] Univ N Carolina, Chapel Hill, NC USA. [Merke, Deborah; VanRyzin, Carol] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Harris, Katharine B.] NYS Genet Serv Program, Albany, NY USA. [Poppas, Dix P.; Vogiatzi, Maria G.] Weill Cornell Med Coll, New York, NY USA. [Riepe, Felix G.] Univ Hosp Schleswig Holstein, Kiel, Germany. [Rivkees, Scott A.] Yale Univ, Sch Med, New Haven, CT USA. [Sandberg, David E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Schaeffer, Traci] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Schlussel, Richard N.] Columbia Univ, Med Ctr, New York, NY USA. [Aisenberg, Javier E.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Bachega, Tania] Univ Sao Paulo, Sao Paulo, Brazil. [Lee, Peter A.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Miller, Walter L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Quigley, Charmian A.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Seely, Ellen] Brigham & Womens Hosp, Boston, MA 02115 USA. [Azziz, Ricardo] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Fracassa, Stephanie; Leight, Kelly; Lin, Gretchen A.; Matos, Dina M.; CAH CCC Comm] Congenital Adrenal Hyperplasia Res Educ & Support, Union, NJ USA. [Katz, Aviva L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Pass, Kenneth] New York State Dept Hlth, Albany, NY USA. [Lloyd-Puryear, Michele A.] US Hlth Resources & Serv Adm, Rockville, MD USA. [Breault, David] Childrens Hosp Boston, Boston, MA USA. [Kalro, Brinda] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Snyder, Diane] Womens Hlth Specialists, Rockville, MD USA. [Therrell, Bradley L.] UT Hlth Scis Ctr, San Antonio, TX USA. RI Miller, Walter/J-3696-2012; Bachega, Tania/C-3361-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403722 ER PT J AU Azevedo, MF Bornstein, ER Horvath, A Kratz, C Nesterova, M Greene, M Stratakis, CA AF Azevedo, M. F. Bornstein, E. R. Horvath, A. Kratz, C. Nesterova, M. Greene, M. Stratakis, C. A. TI cAMP and KIT-KITLG Signaling Interact in Testicular Tissue and Possibly Cooperate in Predisposition to Testicular Germ Cell Tumors: A Novel Function of PDE11A in Testis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Azevedo, M. F.; Bornstein, E. R.; Horvath, A.; Kratz, C.; Nesterova, M.; Greene, M.; Stratakis, C. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403089 ER PT J AU Azevedo, MF Xekouki, P Patronas, N Lange, E Keil, MF Stratakis, CA AF Azevedo, M. F. Xekouki, P. Patronas, N. Lange, E. Keil, M. F. Stratakis, C. A. TI An Unusual Presentation of Cushing's Disease: A Recurrent ACTH-Producing Adenoma Located in the Posterior Pituitary Lobe. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Azevedo, M. F.; Xekouki, P.; Patronas, N.; Lange, E.; Keil, M. F.; Stratakis, C. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402319 ER PT J AU Barnes, KM Delaney, A Baron, J AF Barnes, K. M. Delaney, A. Baron, J. TI Changes in Gene Expression Occurring in Periosteum during Juvenile Growth Deceleration Resemble Those in Non-Skeletal Tissues. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Barnes, K. M.; Delaney, A.; Baron, J.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403147 ER PT J AU Ben Dor, R Marx, CE Rubinow, DR Schmidt, PJ AF Ben Dor, Rivi Marx, Christine E. Rubinow, David R. Schmidt, Peter J. TI Plasma Levels of the Neurosteroid Androsterone Increase after DHEA Therapy and Are Associated with Changes in Mood and Sexual Functioning in a Sexually Dimorphic Manner. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ben Dor, Rivi; Schmidt, Peter J.] NIMH, Bethesda, MD 20892 USA. [Marx, Christine E.] Duke Univ, Med Ctr, Durham, NC USA. [Marx, Christine E.] Durham VA Med Ctr, Durham, NC USA. [Rubinow, David R.] Univ N Carolina, Chapel Hill, NC USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403199 ER PT J AU Briassoulis, G Horvath, A Chrysostomou, P Lodish, MB Xekouki, P Azevedo, M Keil, M Lange, E Quezado, M Patronas, N Stratakis, CA AF Briassoulis, G. Horvath, A. Chrysostomou, P. Lodish, M. B. Xekouki, P. Azevedo, M. Keil, M. Lange, E. Quezado, M. Patronas, N. Stratakis, C. A. TI Lack of Mutations in the Gene Coding for the Glucocorticoid Receptor (NR3C1) in a Pediatric Patient with an ACTH-Secreting Pituitary Adenoma, Absence of Stigmata of Cushing Syndrome, and Unusual Histologic Features. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Briassoulis, G.; Horvath, A.; Chrysostomou, P.; Lodish, M. B.; Xekouki, P.; Azevedo, M.; Keil, M.; Lange, E.; Quezado, M.; Patronas, N.; Stratakis, C. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402318 ER PT J AU Chavan, NR Dwyer, AA Butler, PW Collins, MT Sykiotis, GP Keefe, KW Seminara, SB Plummer, L Crowley, WF Pitteloud, N AF Chavan, N. R. Dwyer, A. A. Butler, P. W. Collins, M. T. Sykiotis, G. P. Keefe, K. W. Seminara, S. B. Plummer, L. Crowley, W. F. Pitteloud, N. TI Male Functional Hypogonadotropic Hypogonadism (MFHH): A Distinct Clinical Entity?. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID AMENORRHEA C1 [Chavan, N. R.; Dwyer, A. A.; Sykiotis, G. P.; Keefe, K. W.; Seminara, S. B.; Plummer, L.; Crowley, W. F.; Pitteloud, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Butler, P. W.; Collins, M. T.] NIH, Bethesda, MD 20892 USA. RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; NR 4 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402462 ER PT J AU Chocron, ES Saelim, N Ibdah, JA Dong, LQ Zhu, X Cheng, SY Lechleiter, JD AF Chocron, E. S. Saelim, N. Ibdah, J. A. Dong, L. Q. Zhu, X. Cheng, S. Y. Lechleiter, J. D. TI Non-Transcriptional Stimulation of Mitochondrial Metabolism by Thyroid Hormone Can Be Attributed to Regulation of Fatty Acid Oxidation Via the Mitochondrial Trifunctional Protein. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Chocron, E. S.; Dong, L. Q.; Lechleiter, J. D.] UT Hlth Sci Ctr, San Antonio, TX USA. [Saelim, N.] Naresuan Univ, Fac Pharmaceut Scis, Phitsanulok, Thailand. [Ibdah, J. A.] Univ Missouri, Columbia, MO USA. [Zhu, X.; Cheng, S. Y.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402583 ER PT J AU Crocker, MK Mehta, SP Van Ryzin, CA Merke, DP AF Crocker, M. K. Mehta, S. P. Van Ryzin, C. A. Merke, D. P. TI Females with Congenital Adrenal Hyperplasia (CAH) and Hyperandrogenism Have Similar Measures of Insulin Sensitivity Compared to Females with CAH and Normal Androgen Levels. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Crocker, M. K.; Mehta, S. P.; Van Ryzin, C. A.; Merke, D. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402683 ER PT J AU DeBoer, MD Gurka, MJ Sumner, AE AF DeBoer, M. D. Gurka, M. J. Sumner, A. E. TI Inflammation Is Worse in Non-Hispanic Black Adolescents with Metabolic Syndrome Than Non-Hispanic Whites or Mexican Americans: NHANES 1999-2006. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [DeBoer, M. D.; Gurka, M. J.] Univ Virginia, Charlottesville, VA USA. [Sumner, A. E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402522 ER PT J AU Delaney, A Lui, JC Rezvani, G Forcinito, P Babich, T Padmanabhan, V Baron, J AF Delaney, A. Lui, J. C. Rezvani, G. Forcinito, P. Babich, T. Padmanabhan, V. Baron, J. TI Evolutionary Conservation and Modification of a Growth-Limiting Genetic Program. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Delaney, A.; Lui, J. C.; Rezvani, G.; Forcinito, P.; Babich, T.; Baron, J.] NICHD, NIH, Bethesda, MD USA. [Padmanabhan, V.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403693 ER PT J AU Duma, D Cidlowski, JA AF Duma, D. Cidlowski, J. A. TI Sexually Dimorphic Actions of Glucocorticoids: A Potential Link to Gender Prevalent Inflammatory Diseases. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Duma, D.; Cidlowski, J. A.] Natl Inst Environm Hlth Scis, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402120 ER PT J AU Durazo-Arvizu, RA Sempos, C Luke, A Kramer, H Yetley, E Dawson-Hughes, B Cao, G Bailey, RL Dawyer, JT Rovner, AJ Picciano, MF AF Durazo-Arvizu, R. A. Sempos, C. Luke, A. Kramer, H. Yetley, E. Dawson-Hughes, B. Cao, G. Bailey, R. L. Dawyer, J. T. Rovner, A. J. Picciano, M. F. TI Modeling the Association between 25[OH]D and All-Cause Mortality in a Representative US Population Sample. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Durazo-Arvizu, R. A.; Luke, A.; Kramer, H.; Cao, G.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Sempos, C.; Yetley, E.; Bailey, R. L.; Dawyer, J. T.; Rovner, A. J.; Picciano, M. F.] Natl Inst Hlth, Bethesda, MD USA. [Dawson-Hughes, B.] Tufts Univ, Boston, MA 02111 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402117 ER PT J AU Feng, H Leung, PK Krsmanovic, LZ Catt, KJ AF Feng, Hao Leung, Po Ki Krsmanovic, Lazar Z. Catt, Kevin J. TI GnRH-Mediated Activation of Protein Kinase D in Immortalized GnRH Neurons and Pituitary Gonadotrophs. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Feng, Hao; Leung, Po Ki; Krsmanovic, Lazar Z.; Catt, Kevin J.] NICHD, Sect Hormonal Regulat, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403209 ER PT J AU Fiori, JL Sanghvi, M Kole, S Moaddel, R Bernier, M AF Fiori, Jennifer L. Sanghvi, Mitesh Kole, Sutapa Moaddel, Ruin Bernier, Michel TI AM251 Induces Expression of EGF Receptor and Its Ligands through Inhibition of Estrogen Receptor-Related Receptor alpha SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Fiori, Jennifer L.; Sanghvi, Mitesh; Kole, Sutapa; Moaddel, Ruin; Bernier, Michel] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401003 ER PT J AU Fliedner, SMJ Kaludercic, N Jiang, XS Sedlakova, O Takacova, P Porter, FD Backlund, P Martiniova, L Yergey, AL Pastorekova, S Paolocci, N Lehnert, H Pacak, K AF Fliedner, S. M. J. Kaludercic, N. Jiang, X. S. Sedlakova, O. Takacova, P. Porter, F. D. Backlund, P. Martiniova, L. Yergey, A. L. Pastorekova, S. Paolocci, N. Lehnert, H. Pacak, K. TI Reactive Oxygen Species and HIF 2 alpha Stabilization in Aggressive Mouse Pheochromocytoma Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Fliedner, S. M. J.; Jiang, X. S.; Porter, F. D.; Backlund, P.; Martiniova, L.; Yergey, A. L.; Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Kaludercic, N.; Paolocci, N.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Sedlakova, O.; Takacova, P.; Pastorekova, S.] Slovak Acad Scis, Bratislava, Slovakia. [Lehnert, H.] Univ Lubeck, Lubeck, Germany. RI Fliedner, Stephanie/D-3406-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403620 ER PT J AU Forcinito, P Lui, JC Barnes, KM Marino, R Andrade, AC Baron, J Nilsson, O AF Forcinito, P. Lui, J. C. Barnes, K. M. Marino, R. Andrade, A. C. Baron, J. Nilsson, O. TI Growth Plate Senescence Is Not a Function of Time Per Se but of Growth. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Forcinito, P.; Lui, J. C.; Barnes, K. M.; Baron, J.] NIH, Bethesda, MD 20892 USA. [Andrade, A. C.; Nilsson, O.] Karolinska Univ Hosp, Stockholm, Sweden. [Marino, R.] Massachusetts Gen Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403148 ER PT J AU Fu, LZ Sun, GH Shi, YB AF Fu, Liezhen Sun, Guihong Shi, Yun-Bo TI Expression Profiles and Transgenic Study Suggest a Coordinating Function of MMPs and TIMPs during Thyroid Hormone-Dependent Frog Metamorphosis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Fu, Liezhen; Sun, Guihong; Shi, Yun-Bo] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402586 ER PT J AU Fukushima, M Tsai-Morris, CH Dufau, ML AF Fukushima, M. Tsai-Morris, C. H. Dufau, M. L. TI Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25), a Negative Regulator of LH/hCG Induced Steroidogenesis in Leydig Cells: A Central Role of StAR. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Fukushima, M.; Tsai-Morris, C. H.; Dufau, M. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402155 ER PT J AU Galia, AM Lim-Uy, SW Mamba, LAE Macaballug, AG Padua, ML Pacak, K Mercado-Asis, LB AF Galia, A. M. Lim-Uy, S. W. Mamba, L. A. E. Macaballug, A. G. Padua, M. L. Pacak, K. Mercado-Asis, L. B. TI Bilateral Pheochromocytoma in a Filipina Who Underwent Glucagon-Stimulated Bilateral Adrenal Venous Sampling and Genetic Testing: A Case Report. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Galia, A. M.; Lim-Uy, S. W.; Mamba, L. A. E.; Macaballug, A. G.; Padua, M. L.; Mercado-Asis, L. B.] Univ Santo Tomas Hosp, Manila, Philippines. [Pacak, K.] Natl Inst Child Hlth & Dev, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402700 ER PT J AU Glover, M Kelly, MH Brillante, BA Butman, JA Fitzgibbon, EJ Brewer, CC Zalewski, CK Cutler, CM Kim, HJ Collins, MT AF Glover, M. Kelly, M. H. Brillante, B. A. Butman, J. A. Fitzgibbon, E. J. Brewer, C. C. Zalewski, C. K. Cutler, C. M. Kim, H. J. Collins, M. T. TI Growth Hormone Excess in McCune-Albright Syndrome: Emphasis on Diagnosis and Treatment in Children. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Glover, M.; Kelly, M. H.; Brillante, B. A.; Butman, J. A.; Fitzgibbon, E. J.; Brewer, C. C.; Zalewski, C. K.; Cutler, C. M.; Kim, H. J.; Collins, M. T.] NIH, Bethesda, MD 20892 USA. [Kim, H. J.] Georgetown Univ Hosp, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403244 ER PT J AU Gravenstein, KS Ramachandran, R White, AA Carlson, OD Ferrucci, L Egan, JM Chia, CW AF Gravenstein, K. S. Ramachandran, R. White, A. A. Carlson, O. D. Ferrucci, L. Egan, J. M. Chia, C. W. TI Sex Hormone-Binding Globulin Attenuates the Age-Related Increase in Adiponectin Levels in the Baltimore Longitudinal Study of Aging. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Gravenstein, K. S.; Ramachandran, R.; White, A. A.; Carlson, O. D.; Ferrucci, L.; Egan, J. M.; Chia, C. W.] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402549 ER PT J AU Gravenstein, KS Napora, JK Short, RG Carlson, OD Metter, EJ Ferrucci, L Egan, JM Chia, CW AF Gravenstein, K. S. Napora, J. K. Short, R. G. Carlson, O. D. Metter, E. J. Ferrucci, L. Egan, J. M. Chia, C. W. TI The Interactions of Leptin, Osteocalcin, and Adiponectin with Indices of Insulin Resistance and beta Cell Function in the Baltimore Longitudinal Study of Aging. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Gravenstein, K. S.; Napora, J. K.; Short, R. G.; Carlson, O. D.; Metter, E. J.; Ferrucci, L.; Egan, J. M.; Chia, C. W.] NIA, NIH, Baltimore, MD 21224 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402181 ER PT J AU Han, JC Feuillan, PP Ng, D Sapp, JC Zheng, YC Yanovski, JA Biesecker, LG AF Han, J. C. Feuillan, P. P. Ng, D. Sapp, J. C. Zheng, Y. C. Yanovski, J. A. Biesecker, L. G. TI Differences in Metabolic Parameters in Patients with Bardet-Biedl Syndrome Compared with BMI-Z Matched Controls. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID OBESITY; MODEL C1 [Han, J. C.; Zheng, Y. C.; Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Feuillan, P. P.; Ng, D.; Sapp, J. C.; Biesecker, L. G.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402719 ER PT J AU He, JY Votruba, S Venti, C Krakoff, J AF He, Jianying Votruba, Susanne Venti, Colleen Krakoff, Jonathan TI Higher Incremental Insulin Area under the Curve in Response to an Oral Glucose Tolerance Test Predicts Lower Food Intake. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [He, Jianying; Votruba, Susanne; Venti, Colleen; Krakoff, Jonathan] NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402498 ER PT J AU Jefferson, WN Wagner, SM Padilla-Banks, E Williams, CJ AF Jefferson, W. N. Wagner, S. M. Padilla-Banks, E. Williams, C. J. TI Neonatal Genistein Exposure Permanently Disrupts Female Reproductive Tract Gene Expression and Tissue Architecture during Pregnancy. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Jefferson, W. N.; Wagner, S. M.; Padilla-Banks, E.; Williams, C. J.] Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. [Wagner, S. M.] Duke Univ, Sch Med, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402076 ER PT J AU Jewell, CM Cidlowski, JA AF Jewell, C. M. Cidlowski, J. A. TI The Human Glucocorticoid Receptor beta Single Nucleotide Polymorphism GR9 beta A3669G Alters Gene Expression SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Jewell, C. M.; Cidlowski, J. A.] Natl Inst Environm Hlth Scis, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401025 ER PT J AU Jumpertz, R Nelson, RG Hanson, RL Krakoff, J AF Jumpertz, Reiner Nelson, Robert G. Hanson, Robert L. Krakoff, Jonathan TI Increased Energy Expenditure Predicts Natural Mortality in Humans. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Jumpertz, Reiner; Nelson, Robert G.; Hanson, Robert L.; Krakoff, Jonathan] NIDDKD, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401441 ER PT J AU Kamran, F Cherqaoui, R Kemp, C Crocker, M Jailan, O Keil, M Lange, E Tsokos, M Merino, MJ Hughes, M Kebebew, E Stratakis, C AF Kamran, F. Cherqaoui, R. Kemp, C. Crocker, M. Jailan, O. Keil, M. Lange, E. Tsokos, M. Merino, M. J. Hughes, M. Kebebew, E. Stratakis, C. TI Ectopic CRH Production from Pancreatic Tumors May Mimic Cushing Disease Due to Pituitary Corticotroph Cell Hyperplasia: The First-Ever Cases in Young Children. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Kamran, F.; Kemp, C.; Crocker, M.; Jailan, O.; Keil, M.; Lange, E.; Tsokos, M.; Merino, M. J.; Hughes, M.; Kebebew, E.; Stratakis, C.] Natl Inst Hlth Bethesda, Bethesda, MD USA. [Cherqaoui, R.] Howard Univ Hosp Washington, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401081 ER PT J AU Kanamaluru, D Xiao, Z Veenstra, TD Kemper, JK AF Kanamaluru, D. Xiao, Z. Veenstra, T. D. Kemper, J. K. TI SHP Activity Is Positively Regulated by PRMT5 through Arginine Methylation at a Naturally-Occurring Mutation Site SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Kanamaluru, D.; Kemper, J. K.] Univ Illinois, Urbana, IL USA. [Xiao, Z.; Veenstra, T. D.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401004 ER PT J AU Keil, MF Gokarn, N Briassoulis, G Nesterova, M Wu, TJ Stratakis, CA AF Keil, M. F. Gokarn, N. Briassoulis, G. Nesterova, M. Wu, T. J. Stratakis, C. A. TI An Anxiety-Like Phenotype Is Present in Prkar1a Heterozygote Knock-Out Mice. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Keil, M. F.; Gokarn, N.; Briassoulis, G.; Nesterova, M.; Stratakis, C. A.] NICHD, Natl Inst Hlth, Bethesda, MD USA. [Keil, M. F.; Wu, T. J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401194 ER PT J AU Krug, AW Allenhoefer, L Monticone, R Spinetti, G Gekle, M Wang, M Lakatta, E AF Krug, A. W. Allenhoefer, L. Monticone, R. Spinetti, G. Gekle, M. Wang, M. Lakatta, E. TI Increased MR Activity in Aged Rat VSMCs Induces a Proinflammatory Phenotype SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Krug, A. W.; Allenhoefer, L.; Monticone, R.; Spinetti, G.; Wang, M.; Lakatta, E.] NIA, Baltimore, MD 21224 USA. [Gekle, M.] Univ Halle Wittenberg, Halle, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401029 ER PT J AU Kucka, M Kretschmannova, K Tomic, M Stojilkovic, SS AF Kucka, M. Kretschmannova, K. Tomic, M. Stojilkovic, S. S. TI Dependence of the Pacemaking on the Background TRP Channel Activity in Spontaneously Firing Pituitary Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Kucka, M.; Kretschmannova, K.; Tomic, M.; Stojilkovic, S. S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402297 ER PT J AU Larson, JK Carvan, MJ Klaper, R Hutz, RJ AF Larson, J. K. Carvan, M. J., III Klaper, R. Hutz, R. J. TI Gold Nanoparticles Alter Progesterone and Estradiol-17 Beta Accumulation In Vitro in a Rat Ovary Culture Model. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Larson, J. K.; Hutz, R. J.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Carvan, M. J., III; Klaper, R.] UWM Great Lakes Water Inst, Milwaukee, WI USA. [Larson, J. K.; Carvan, M. J., III; Klaper, R.; Hutz, R. J.] UWM NIEHS Childrens Environm Hlth Scis Core Ctr, Milwaukee, WI USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402083 ER PT J AU Lee, EE Nieman, LK Martinez, PE Harsh, VL Rubinow, DR Schmidt, PJ AF Lee, E. E. Nieman, L. K. Martinez, P. E. Harsh, V. L. Rubinow, D. R. Schmidt, P. J. TI ACTH & Cortisol Response to Dex/CRH Testing in Women with and without Premenstrual Dysphoria during GnRH Agonist-Induced Hypogonadism and Ovarian Steroid Replacement. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lee, E. E.; Martinez, P. E.; Schmidt, P. J.] NIMH, Bethesda, MD 20892 USA. [Nieman, L. K.] NICHHD, Bethesda, MD 20892 USA. [Harsh, V. L.] Univ Virginia, Charlottesville, VA USA. [Rubinow, D. R.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403398 ER PT J AU Legro, RS Schlaff, WD Diamond, MP Coutifaris, C Casson, PR Brzyski, RJ Christman, GM Trussell, JC Krawetz, SA Snyder, PJ Ohl, D Carson, SA Steinkampf, MP Carr, BR McGovern, PG Cataldo, NA Gosman, GG Nestler, JE Myers, ER Santoro, N Eisenberg, E Zhang, M Zhang, H AF Legro, R. S. Schlaff, W. D. Diamond, M. P. Coutifaris, C. Casson, P. R. Brzyski, R. J. Christman, G. M. Trussell, J. C. Krawetz, S. A. Snyder, P. J. Ohl, D. Carson, S. A. Steinkampf, M. P. Carr, B. R. McGovern, P. G. Cataldo, N. A. Gosman, G. G. Nestler, J. E. Myers, E. R. Santoro, N. Eisenberg, E. Zhang, M. Zhang, H. TI Total Testosterone Assays in Polycystic Ovary Syndrome: Is There a Gold Standard?. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Legro, R. S.; Trussell, J. C.] Penn State Univ, Hershey, PA USA. [Schlaff, W. D.; Santoro, N.] Univ Colorado, Denver, CO 80202 USA. [Zhang, H.] Yale Sch Publ Hlth, New Haven, CT USA. [Carr, B. R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Diamond, M. P.; Krawetz, S. A.] Wayne State Univ, Detroit, MI USA. [Carson, S. A.] Women & Infants Ctr Reprod & Infertil, Providence, RI USA. [Coutifaris, C.; Snyder, P. J.] Univ Penn, Philadelphia, PA 19104 USA. [McGovern, P. G.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Cataldo, N. A.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Gosman, G. G.] Univ Pittsburgh, Pittsburgh, PA USA. [Nestler, J. E.] Virginia Commonwealth Univ, Richmond, VA USA. [Myers, E. R.] Duke Univ, Med Ctr, Durham, NC USA. [Casson, P. R.] Univ Vermont, Burlington, VT USA. [Brzyski, R. J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Christman, G. M.; Ohl, D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Eisenberg, E.] NICHHD, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402402 ER PT J AU Li, WP Bakalov, VK AF Li, W. P. Bakalov, V. K. TI Transfer of Hashimoto's Thyroiditis by Donor Immune Cells during a Stem Cell Transplant. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Li, W. P.; Bakalov, V. K.] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402605 ER PT J AU Lim-Uy, SW Galia, AM Mamba, LAE Macaballug, AG Padua, ML Pacak, K Mercado-Asis, LB AF Lim-Uy, S. W. Galia, A. M. Mamba, L. A. E. Macaballug, A. G. Padua, M. L. Pacak, K. Mercado-Asis, L. B. TI Bilateral Adrenal Vein Sampling (BAVS) with Glucagon Stimulation and 18-Fluorodeoxyglucose Positron Emission Tomography Scanning ((18)FDG PET) in a Filipino Patient Suspected with Bilateral Pheochromocytoma. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Lim-Uy, S. W.; Galia, A. M.; Mamba, L. A. E.; Macaballug, A. G.; Padua, M. L.; Mercado-Asis, L. B.] Univ Santo Tomas Hosp, Manila, Philippines. [Pacak, K.] Natl Inst Child Hlth & Dev, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402699 ER PT J AU Liu, J Zhou, LA Xiong, KM Buettner, C Kunos, G AF Liu, Jie Zhou, Liang Xiong, Keming Buettner, Christoph Kunos, George TI Diet-Induced Hepatic Insulin Resistance Is Mediated by Endocannabinoids Via CB1 Receptor-Mediated Dephosphorylation of Akt-2 by PHLPP1. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc ID RANDOMIZED CONTROLLED-TRIAL; RISK-FACTORS; RIMONABANT; OVERWEIGHT; OBESITY C1 [Liu, Jie; Zhou, Liang; Xiong, Keming; Kunos, George] NIAAA, NIH, Bethesda, MD USA. [Buettner, Christoph] Mt Sinai Sch Med, New York, NY USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402510 ER PT J AU Liu, Y Kiss, A MacGregor, R Aguilera, G AF Liu, Y. Kiss, A. MacGregor, R. Aguilera, G. TI Differential Inhibitory Effects of Glucocorticoids on CRH and POMC Transcription. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Liu, Y.; MacGregor, R.; Aguilera, G.] NICHHD, Bethesda, MD 20892 USA. [Kiss, A.] Slovak Acad Sci, Bratislava, Slovakia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401617 ER PT J AU Lodish, MB Bornstein, E Sinaii, N Kim, A Gillespie, A Baldwin, A Reynolds, JC Stratakis, CA Widemann, B AF Lodish, M. B. Bornstein, E. Sinaii, N. Kim, A. Gillespie, A. Baldwin, A. Reynolds, J. C. Stratakis, C. A. Widemann, B. TI Bone Mineral Apparent Density and Vitamin D Status in Pediatric Neurofibromatosis Type I Patients. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Lodish, M. B.; Bornstein, E.; Sinaii, N.; Kim, A.; Gillespie, A.; Baldwin, A.; Reynolds, J. C.; Stratakis, C. A.; Widemann, B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403182 ER PT J AU Lodish, MB Kim, SY Janeway, K Ball, ER Raygada, M Huynh, T Faucz, F Horvath, A Pacak, K Carney, JA Gaal, J Rustin, P Gimenez-Roqueplo, A Helman, L Stratakis, CA AF Lodish, M. B. Kim, S. Y. Janeway, K. Ball, E. R. Raygada, M. Huynh, T. Faucz, F. Horvath, A. Pacak, K. Carney, J. A. Gaal, J. Rustin, P. Gimenez-Roqueplo, A. Helman, L. Stratakis, C. A. TI Succinate Dehydrogenase (SDH) Mutations in Patients with "Wild-Type" (Non-KIT, Non-PDGFRA-Mutated) Gastrointestinal Sarcomas. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID STROMAL TUMORS C1 [Lodish, M. B.; Kim, S. Y.; Ball, E. R.; Raygada, M.; Huynh, T.; Faucz, F.; Horvath, A.; Pacak, K.; Helman, L.; Stratakis, C. A.] NIH, Bethesda, MD 20892 USA. [Janeway, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carney, J. A.] Mayo Clin, Rochester, MN USA. [Gaal, J.] Univ Med Ctr, Rotterdam, Netherlands. [Rustin, P.] Hosp Robert Debre, Paris, France. [Gimenez-Roqueplo, A.] Paris Descartes Univ, Paris, France. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402094 ER PT J AU Maggio, M Lauretani, F Luci, M Vignali, A Cattabiani, C Ablondi, F Bandinelli, S Basaria, S Volpi, R Guralnik, JM Ferrucci, L Valenti, G Parrino, S Ceda, G AF Maggio, Marcello Lauretani, Fulvio Luci, Michele Vignali, Alessandro Cattabiani, Chiara Ablondi, Fabrizio Bandinelli, Stefania Basaria, Shehzad Volpi, Riccardo Guralnik, Jack M. Ferrucci, Luigi Valenti, Giorgio Parrino, Stefano Ceda, Gianpaolo TI Gonadal Status and Physical Performance in Older Men. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Maggio, Marcello; Luci, Michele; Vignali, Alessandro; Cattabiani, Chiara; Ablondi, Fabrizio; Volpi, Riccardo; Valenti, Giorgio; Parrino, Stefano; Ceda, Gianpaolo] Univ Parma, I-43100 Parma, Italy. [Maggio, Marcello; Lauretani, Fulvio] Univ Hosp Parma, Parma, Italy. [Bandinelli, Stefania] ASF, Florence, Italy. [Basaria, Shehzad] Boston Univ, Sch Med, Boston, MA 02118 USA. [Guralnik, Jack M.; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402454 ER PT J AU Maggio, M Lauretani, F Bandinelli, S Guralnik, JM Paolisso, G Semba, RD Nouvenne, A Borghi, L Ceresini, G Ablondi, F Benatti, M Ferrucci, L Ceda, G AF Maggio, Marcello Lauretani, Fulvio Bandinelli, Stefania Guralnik, Jack M. Paolisso, Giuseppe Semba, Richard D. Nouvenne, Antonio Borghi, Loris Ceresini, Graziano Ablondi, Fabrizio Benatti, Mario Ferrucci, Luigi Ceda, Gianpaolo TI Association between Plasma Selenium Concentration and Total IGF-1 in Older Adults. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Maggio, Marcello; Nouvenne, Antonio; Borghi, Loris; Ceresini, Graziano; Ablondi, Fabrizio; Ceda, Gianpaolo] Univ Parma, I-43100 Parma, Italy. [Maggio, Marcello; Lauretani, Fulvio; Ceresini, Graziano; Benatti, Mario; Ceda, Gianpaolo] Univ Hosp Parma, Parma, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. [Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA. [Paolisso, Giuseppe] Univ Naples 2, Naples, Italy. [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ferrucci, Luigi] Natl Inst Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402112 ER PT J AU Mason, PR Kubant, R Jacoby, AM Jacob, RF Walter, MF Bellamine, A Mizuno, Y Malinski, T AF Mason, P. R. Kubant, R. Jacoby, A. M. Jacob, R. F. Walter, M. F. Bellamine, A. Mizuno, Y. Malinski, T. TI Saxagliptin Treatment Reduces sCD40 Levels and Increases Endothelial Nitric Oxide Bioavailability in Obese, Insulin-Resistant Rats. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Mason, P. R.; Mizuno, Y.] Harvard Univ, Sch Med, Boston, MA USA. [Mason, P. R.; Jacob, R. F.; Mizuno, Y.] Elucida Res LLC, Beverly, MA USA. [Kubant, R.; Jacoby, A. M.; Malinski, T.] Ohio Univ, Athens, OH 45701 USA. [Walter, M. F.] NIH, Bethesda, MD 20892 USA. [Bellamine, A.] Bristol Myers Squibb Co, Princeton, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401486 ER PT J AU Maudsley, S Liao, S Yuan, L Lefkowitz, RJ Luttrell, LM Gesty-Palmer, D AF Maudsley, S. Liao, S. Yuan, L. Lefkowitz, R. J. Luttrell, L. M. Gesty-Palmer, D. TI The Unique Efficacy Profile of a beta-Arrestin Pathway-Selective Parathyroid Hormone Receptor Agonist Revealed by Metabolic Pathways Analysis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Maudsley, S.] Natl Inst Hlth, Baltimore, MD USA. [Liao, S.; Yuan, L.; Lefkowitz, R. J.; Gesty-Palmer, D.] Duke Univ, Med Ctr, Durham, NC USA. [Luttrell, L. M.] Med Univ S Carolina, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401141 ER PT J AU Morissette, R Schoenhoff, F Griswold, B Fiori, J Sloper, L Carlson, O Van Eyk, J McDonnell, N AF Morissette, R. Schoenhoff, F. Griswold, B. Fiori, J. Sloper, L. Carlson, O. Van Eyk, J. McDonnell, N. TI Dissecting the Role of the TGF-b Pathway in Genetically Mediated Vascular Disorders. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Morissette, R.; Griswold, B.; Fiori, J.; Sloper, L.; Carlson, O.; McDonnell, N.] NIA, Baltimore, MD 21224 USA. [Schoenhoff, F.; Van Eyk, J.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402146 ER PT J AU Nader, N Ng, SM Lambrou, G Pervanidou, N Wang, YH Chrousos, GP Kino, T AF Nader, N. Ng, S. M. Lambrou, G. Pervanidou, N. Wang, Y. H. Chrousos, G. P. Kino, T. TI AMPK Moderates the Actions of Glucocorticoids on Hepatic Glucose Metabolism In Vivo through P38 MAPK-Mediated GR Phosphorylation. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Nader, N.; Ng, S. M.; Kino, T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Ng, S. M.] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Lambrou, G.; Pervanidou, N.; Chrousos, G. P.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Wang, Y. H.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402029 ER PT J AU Nader, N Bachrach, BE Hurt, DE Gajula, S Pittman, A Lescher, R Kino, T AF Nader, N. Bachrach, B. E. Hurt, D. E. Gajula, S. Pittman, A. Lescher, R. Kino, T. TI A Novel Point Mutation in the Helix 10 of the Human Glucocorticoid Receptor Causes Generalized Glucocorticoid Resistance by Disrupting the Structure of the Ligand-Binding Domain SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Nader, N.; Kino, T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Bachrach, B. E.; Gajula, S.; Pittman, A.; Lescher, R.] Univ Missouri, Childrens Hosp Columbia, Columbia, MO USA. [Hurt, D. E.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401023 ER PT J AU Napora, J Short, RG Muller, D Carlson, O Travison, TG Maggio, M Egan, J Basaria, S AF Napora, Josh Short, Ryan G. Muller, Denis Carlson, Olga Travison, Thomas G. Maggio, Marcello Egan, Josephine Basaria, Shehzad TI High Dose Isoflavones Do Not Improve Metabolic and Inflammatory Parameters in Androgen Deprived Men with Prostate Cancer. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society ID DEPRIVATION THERAPY C1 [Napora, Josh; Short, Ryan G.; Muller, Denis; Carlson, Olga; Egan, Josephine] NIA, Baltimore, MD 21224 USA. [Travison, Thomas G.; Basaria, Shehzad] Boston Univ, Med Ctr, Boston, MA USA. [Maggio, Marcello] Univ Parma, I-43100 Parma, Italy. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403052 ER PT J AU Neary, NM Lopez-Chavez, A Boyce, AM Abel, BS Stratakis, CA Giaccone, G Nieman, LK AF Neary, N. M. Lopez-Chavez, A. Boyce, A. M. Abel, B. S. Stratakis, C. A. Giaccone, G. Nieman, L. K. TI Neuroendocrine ACTH Producing Carcinoma of the Thymus - Experience with 10 Patients. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Neary, N. M.; Boyce, A. M.; Abel, B. S.; Stratakis, C. A.; Nieman, L. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Lopez-Chavez, A.; Giaccone, G.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403672 ER PT J AU Ng, SSM Li, A Keiko, O Kino, T AF Ng, Sinnie Sin Man Li, Andrew Keiko, Ozato Kino, Tomoshige TI Dexamethasone Synergistically Increases Secretion of the Anti-Inflammatory Cytokine Interleukin-10 in Murine Dendritic Cells upon Viral Infection: Potential Implication to Stress-Mediated Modification of Susceptibility to Viiral Infection. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ng, Sinnie Sin Man; Li, Andrew; Keiko, Ozato; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Bethesda, MD USA. [Ng, Sinnie Sin Man] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402118 ER PT J AU Ochsner, SA Watkins, CM Chen, ES Steffen, DL Risek, B Agoulnik, IU Weigel, NL Schrader, WT McKenna, NJ AF Ochsner, Scott A. Watkins, Chris M. Chen, Edward S. Steffen, David L. Risek, Boris Agoulnik, Irina U. Weigel, Nancy L. Schrader, William T. McKenna, Neil J. TI GEMS (Gene Expression MetaSignatures), a Web Resource for Querying Meta-Analysis of Expression Microarray Datasets: Dihydrotestosterone in LNCaP Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ochsner, Scott A.; Watkins, Chris M.; Chen, Edward S.; Steffen, David L.; Agoulnik, Irina U.; Weigel, Nancy L.; McKenna, Neil J.] Baylor Coll Med, Houston, TX 77030 USA. [Risek, Boris; Schrader, William T.] Florida InterNatl Univ, Miami, FL USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403066 ER PT J AU Prodanov, T Raygada, M Sullivan, S Vanderhoof, V Nelson, LM AF Prodanov, T. Raygada, M. Sullivan, S. Vanderhoof, V. Nelson, L. M. TI A Case of Primary Ovarian Insufficiency in a Woman with an FMR1 Full Mutation. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Prodanov, T.; Sullivan, S.; Vanderhoof, V.; Nelson, L. M.] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401374 ER PT J AU Ramachandran, R Gravenstein, KS Melvin, DL Carlson, OD Egan, JM Ferrucci, L Chia, CW AF Ramachandran, R. Gravenstein, K. S. Melvin, D. L. Carlson, O. D. Egan, J. M. Ferrucci, L. Chia, C. W. TI Contributions of Adiposity, Leptin, Adiponectin, and Muscle Mass to Insulin Resistance in the Baltimore Longitudinal Study of Aging (BLSA). SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ramachandran, R.; Gravenstein, K. S.; Melvin, D. L.; Carlson, O. D.; Egan, J. M.; Ferrucci, L.; Chia, C. W.] NIA, Natl Inst Hlth, Baltimore, MD 21224 USA. Medstar Res Inst, Baltimore, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401428 ER PT J AU Ren, R Cidlowski, JA AF Ren, R. Cidlowski, J. A. TI Anti-Apoptotic Actions of Glucocorticoid in Cardiomyocytes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Ren, R.; Cidlowski, J. A.] Natl Inst Environm Hlth Scis, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401026 ER PT J AU Richardson, VM DeVito, MJ AF Richardson, V. M. DeVito, M. J. TI Hepatic Enzyme Inducers Increase Thyroxine (T-4) Catabolism in Human and Rat Hepatocytes. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Soc C1 [Richardson, V. M.] US EPA, Res Triangle Pk, NC 27711 USA. [Richardson, V. M.] Univ N Carolina, Chapel Hill, NC USA. [DeVito, M. J.] NIEHS, NTP, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402082 ER PT J AU Rogers, NH Van der Brug, MP Cookson, MR Sun, Y Smith, RG AF Rogers, N. H. Van der Brug, M. P. Cookson, M. R. Sun, Y. Smith, R. G. TI Hepatic Changes in Metabolic Gene Expression in Old Ghrelin and Ghrelin Receptor Knockout Mice. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Rogers, N. H.; Van der Brug, M. P.; Smith, R. G.] Scripps Florida, Jupiter, FL USA. [Cookson, M. R.] NIA, NIH, Bethesda, MD 20892 USA. [Sun, Y.] Baylor Coll Med, Houston, TX 77030 USA. RI Rogers, nicole/J-4838-2012 NR 1 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402507 ER PT J AU Rone, MB Rammouz, G Blonder, J Prieto, DA Veenstra, T Papadopoulos, V AF Rone, M. B. Rammouz, G. Blonder, J. Prieto, D. A. Veenstra, T. Papadopoulos, V. TI Identification of Hormone-Induced Bioactive Mitochondrial Protein Complexes in MA-10 Leydig Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Rone, M. B.; Papadopoulos, V.] Georgetown Univ, Washington, DC USA. [Rone, M. B.; Rammouz, G.; Papadopoulos, V.] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Blonder, J.; Prieto, D. A.; Veenstra, T.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989403020 ER PT J AU Smith, K Sullivan, SD Vanderhoof, V Sterling, E Abrams, L Ryan, M Nelson, LM AF Smith, K. Sullivan, S. D. Vanderhoof, V. Sterling, E. Abrams, L. Ryan, M. Nelson, L. M. TI A Survey of Young Women with 46,XX Hypergonadotropic Hypogonadism Indicates a Strong Preference for the Term 'Primary Ovarian Insufficiency' as Compared to 'Premature Ovarian Failure.'. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Smith, K.; Sullivan, S. D.; Vanderhoof, V.; Nelson, L. M.] NICHD, NIH, Bethesda, MD USA. [Sterling, E.] Rachels Well Inc, Marietta, GA USA. [Abrams, L.] Natl Fragile X Fdn, Walnut Creek, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401369 ER PT J AU Sullivan, SD Popat, V Davis, M Covington, S Ryan, M Vanderhoof, VH Koziol, DE Troendle, J Nelson, LM AF Sullivan, S. D. Popat, V. Davis, M. Covington, S. Ryan, M. Vanderhoof, V. H. Koziol, D. E. Troendle, J. Nelson, L. M. TI Serum Free Testosterone Levels Are Positively Associated with Perceived Stigma in Young Women with Primary Ovarian Insufficiency. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Sullivan, S. D.; Popat, V.; Covington, S.; Vanderhoof, V. H.; Koziol, D. E.; Troendle, J.; Nelson, L. M.] NICHD, Natl Inst Hlth, Bethesda, MD USA. [Davis, M.] Arizona State Univ, Tempe, AZ USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401367 ER PT J AU Sullivan, SD Baker, V Hegde, A Popat, V Vanderhoof, V Troendle, J Nelson, LM AF Sullivan, S. D. Baker, V. Hegde, A. Popat, V. Vanderhoof, V. Troendle, J. Nelson, L. M. TI The Phenotypes of Women with Spontaneous 46, XX Primary Ovarian Insufficiency (POI) Associated with a Premutation in the Fragile X Mental Retardation (FMR1) Gene (FXPOI) and Women with the Idiopathic Disorder (iPOI) Are Similar. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Sullivan, S. D.; Popat, V.; Vanderhoof, V.; Troendle, J.; Nelson, L. M.] NICHD, NIH, Bethesda, MD USA. [Baker, V.; Hegde, A.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989401366 ER PT J AU Sun, GH Das, B Fu, LZ Shi, YB AF Sun, Guihong Das, Biswajit Fu, Liezhen Shi, Yun-Bo TI Temporal and Spatio-Regulation of Tissue-Specific Thyroid Hormone Response Genes during Intestinal Metamorphosis in Xenopus Laevis. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Sun, Guihong; Das, Biswajit; Fu, Liezhen; Shi, Yun-Bo] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402585 ER PT J AU Tomic, M Kretschmannova, K Kucka, M Nesterova, M Stratakis, CA Stojilkovic, SS AF Tomic, M. Kretschmannova, K. Kucka, M. Nesterova, M. Stratakis, C. A. Stojilkovic, S. S. TI Cyclic Nucleotides and Pacemaking in Anterior Pituitary Cells. SO ENDOCRINE REVIEWS LA English DT Meeting Abstract CT 92nd Meeting and Expo of the Endocrine Society (ENDO 2010) CY JUN 19-22, 2010 CL San Diego, CA SP Endocrine Society C1 [Tomic, M.; Kretschmannova, K.; Kucka, M.; Nesterova, M.; Stratakis, C. A.; Stojilkovic, S. S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2010 VL 31 IS 3 SU 1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652FV UT WOS:000281989402298 ER EF