FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gao, R Reece, K Sissung, T Reed, E Price, DK Figg, WD AF Gao, Rui Reece, Kelie Sissung, Tristan Reed, Eddie Price, Douglas K. Figg, William D. TI The ERCC1 N118N polymorphism does not change cellular ERCC1 protein expression or platinum sensitivity SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE ERCC1; Silent mutation; Codon bias; DNA repair; Platinum drugs ID LUNG-CANCER PATIENTS; ADVANCED COLORECTAL-CANCER; MESSENGER-RNA EXPRESSION; DNA-REPAIR; COMBINATION CHEMOTHERAPY; EXCISION-REPAIR; OVARIAN-CANCER; CODON-118 POLYMORPHISM; CHO CELLS; SURVIVAL AB Genetic polymorphisms in ERCC1 are thought to contribute to altered sensitivity to platinum-based chemotherapy. Although ERCC1 N118N (500 C > T, rs11615) is the most studied polymorphism, the impact of this polymorphism on platinum-based chemotherapy remains unclear. This is the first study in which the functional impact of ERCC1 N118N on gene expression and platinum sensitivity was explored. The aim of this study is to investigate if the reduced codon usage frequency of AAT, which contains the variant allele of the silent mutation, has functional impact on ERCC1 in a well-controlled biological system. Specifically, the ERCC1 cDNA clone with either the C or T allele was introduced into an ERCC1 deficient cell line, UV20, and assayed for the effect of the two alleles on ERCC1 transcription, translation and platinum sensitivity. Both ERCC1 mRNA and protein expression levels increased upon cisplatin treatment, peaking at 4h post-treatment, however there were no differences between the two alleles (p > 0.05). Cells complemented with ERCC1 showed significantly higher survival proportion than the parental cell line following platinum exposure (p < 0.0001), although no differences were observed between the cells transfected with the wild type or the polymorphic allele. These data suggest that N118N itself is not related to the phenotypic differences in ERCC1 expression or function, but rather this polymorphism may be linked to other causative variants or haplotypes. (C) 2011 Elsevier B.V. All rights reserved. C1 [Gao, Rui; Reece, Kelie; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Sissung, Tristan; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Gao, Rui] Univ Maryland, College Pk, MD 20742 USA. [Reed, Eddie] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU NIH, National Cancer Institute, Bethesda, MD, USA FX This study was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Bethesda, MD, USA. NR 38 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 EI 1873-135X J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 15 PY 2011 VL 708 IS 1-2 BP 21 EP 27 DI 10.1016/j.mrfmmm.2011.01.002 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 747PV UT WOS:000289332800003 PM 21315089 ER PT J AU Magnani, JW Johnson, VM Sullivan, LM Gorodeski, EZ Schnabel, RB Lubitz, SA Levy, D Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Johnson, Victor M. Sullivan, Lisa M. Gorodeski, Eiran Z. Schnabel, Renate B. Lubitz, Steven A. Levy, Daniel Ellinor, Patrick T. Benjamin, Emelia J. TI P Wave Duration and Risk of Longitudinal Atrial Fibrillation in Persons >= 60 Years Old (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FAILURE; INTERVAL; PROFILE; INDEXES; DISEASE; STROKE AB Long-term risk prediction is a priority for the prevention of atrial fibrillation (AF). P wave indices are electrocardiographic measurements describing atrial conduction. The role of P wave indices in the prospective determination of AF and mortality risk has had limited assessment. We quantified by digital caliper the P wave indices of maximum duration and dispersion in 1,550 Framingham Heart Study participants >= 60 years old (58% women) from single-channel electrocardiograms recorded from 1968 through 1971. We examined the association of selected P wave indices and long-term outcomes using Cox proportional hazards regression incorporating age, gender, body mass index, systolic blood pressure, treatment for hypertension, significant murmur, heart failure, and PR interval. Over a median follow-up of 15.8 years (range 0 to 38.7), 359 participants developed AF and 1,525 died. Multivariable-adjusted hazard ratios (HRs) per SD increase in maximum P wave duration were 1.15 (95% confidence interval [CI] 0.90 to 1.47, p = 0.27) for AF and 1.02 (95% CI 0.96 to 1.08, p = 0.18) for mortality. The upper 5% of P wave maximum duration had a multivariable-adjusted HR of 2.51 (95% CI 1.13 to 5.57, p = 0.024) for AF and an HR of 1.11 (95% CI 0.87 to 1.40, p = 0.20) for mortality. We found no significant associations between P wave dispersion with incidence of AF or mortality. In conclusion, maximum P wave duration at the upper fifth percentile was associated with long-term AF risk in an elderly community-based cohort. P wave duration is an electrocardiographic endophenotype for AF. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107: 917-921) C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Magnani, Jared W.; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gorodeski, Eiran Z.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany. [Schnabel, Renate B.] Gutenberg Heart Study Div Prevent Med, Mainz, Germany. [Lubitz, Steven A.; 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. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. EM jmagnani@bu.edu RI Schnabel, Renate/F-6527-2014; OI Gorodeski, Eiran/0000-0003-3756-8831; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association, Dallas, Texas [09FTF2190028]; National Institutes of Health, Bethesda, Maryland [N01-HC 25195, RC1HL101056, 1R01HL102214, 1HL104156, HL092577] FX This research was funded by Award 09FTF2190028 from the American Heart Association, Dallas, Texas to Dr. Magnani and Grants N01-HC 25195, RC1HL101056, and 1R01HL102214 (Dr. Benjamin), 1HL104156 (Dr. Ellinor), and HL092577 (Dr. Ellinor and Dr. Benjamin) from the National Institutes of Health, Bethesda, Maryland. NR 19 TC 60 Z9 64 U1 1 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2011 VL 107 IS 6 BP 917 EP 921 DI 10.1016/j.amjcard.2010.10.075 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 740WO UT WOS:000288825300019 PM 21255761 ER PT J AU Tsao, CW Gona, P Salton, C Danias, PG Blease, S Hoffmann, U Fox, CS Albert, M Levy, D O'Donnell, CJ Manning, WJ Yeon, SB AF Tsao, Connie W. Gona, Philimon Salton, Carol Danias, Peter G. Blease, Susan Hoffmann, Udo Fox, Caroline S. Albert, Mark Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. Yeon, Susan B. TI Subclinical and Clinical Correlates of Left Ventricular Wall Motion Abnormalities in the Community SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY CALCIUM; MAGNETIC-RESONANCE; MYOCARDIAL-INFARCTION; HEART-DISEASE; PROGNOSTIC-SIGNIFICANCE; CARDIOVASCULAR-DISEASE; COMPUTED-TOMOGRAPHY; FOLLOW-UP; POPULATION; ATHEROSCLEROSIS AB The prevalence and clinical correlates of left ventricular (LV) wall motion abnormalities (WMAs), associated with morbidity and mortality, have not been well-characterized in the population. Framingham Heart Study Offspring Cohort participants (n = 1,794, 844 men, age 65 9 years) underwent cine cardiovascular magnetic resonance for evaluation of LV function. A subset (n = 1,009, 460 men) underwent cardiac multidetector computed tomography for analysis of coronary artery calcium. The presence of coronary heart disease and heart failure (CHD-HF) were assessed in relation to the presence of WMAs. WMAs were present in 117 participants (6.5%) and were associated with male gender, elevated hemoglobin Ale, LV mass, LV end-diastolic volume, and lower LV ejection fraction. Of the 1,637 participants without CHD-HF, 68 (4.2%) had WMAs. In this group, WMAs were associated with obesity, hypertension, and Framingham coronary heart disease risk score in the age- and gender-adjusted analyses and were associated with male gender and hypertension on multivariate analysis. Most subjects with WMAs were in the greatest coronary artery calcium groups. The presence of coronary artery calcium greater than the seventy-fifth percentile and Agatston score > 100. were associated with a greater than twofold risk of WMAs in the age- and gender-adjusted analysis but were no longer significant when additionally adjusted for CHD-HF. Previous Q-wave myocardial infarction was present in 29% of the 117 participants with WMAs. In conclusion, in the present longitudinally followed free-living population, 4.2% of the participants without CHD-HF had WMAs. WMAs were associated with the clinical parameters associated with cardiovascular disease risk. Aggressive risk factor modification may be prudent for subjects with WMAs, particularly those free of clinical CHD-HF. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:949-955) C1 [Tsao, Connie W.; Salton, Carol; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA. [Tsao, Connie W.; Salton, Carol; Danias, Peter G.; Manning, Warren J.; Yeon, Susan B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. [Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Gona, Philimon; Blease, Susan; Fox, Caroline S.; Levy, Daniel; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Albert, Mark] Michigan State Univ, Coll Human Med, Grand Rapids, MI USA. [O'Donnell, Christopher J.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. RP Yeon, SB (reprint author), Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA. EM syeon@bidmc.harvard.edu FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-25195]; National Institutes of Health, Bethesda, Maryland [1RO1 HL70279, T32 HL07374] FX The Framingham Heart Study was supported by contract N01-HC-25195 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. The present study was supported in part by grant 1RO1 HL70279 and training grant T32 HL07374 (to C. W. Tsao) from the National Institutes of Health, Bethesda, Maryland. NR 25 TC 5 Z9 5 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2011 VL 107 IS 6 BP 949 EP 955 DI 10.1016/j.amjcard.2010.11.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 740WO UT WOS:000288825300025 PM 21247548 ER PT J AU Zhang, YE AF Zhang, Ying E. TI Stopped in Translation: EMT Control Meets Eukaryotic Elongation SO DEVELOPMENTAL CELL LA English DT Editorial Material ID CELLS; ILEI; DAB2 C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM zhangyin@mail.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU Intramural NIH HHS [ZIA BC010419-11] NR 6 TC 3 Z9 4 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR 15 PY 2011 VL 20 IS 3 BP 289 EP 290 DI 10.1016/j.devcel.2011.02.012 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 739SF UT WOS:000288737600006 PM 21397840 ER PT J AU Gokhale, NA Zaremba, A Shears, SB AF Gokhale, Nikhil A. Zaremba, Angelika Shears, Stephen B. TI Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain SO BIOCHEMICAL JOURNAL LA English DT Article DE cell-signalling; compartmentalization; diphosphoinositol polyphosphates; inositol pyrophosphates ID PLECKSTRIN HOMOLOGY DOMAINS; INOSITOL HEXAKISPHOSPHATE KINASE; DIPHOSPHOINOSITOL POLYPHOSPHATES; PH DOMAINS; PYROPHOSPHATES; CELLS; PHOSPHATE; PROTEIN; IDENTIFICATION; LOCALIZATION AB The inositol pyrophosphates are multifunctional signalling molecules. One of the families of enzymes that synthesize the inositol pyrophosphates are the Vip1/PPIP5Ks (PP-InsP(5) kinases). The kinase domains in Vip1/PPIP5Ks have been mapped to their N-terminus. Each of these proteins also possess a phosphatase-like domain of unknown significance. In the present study, we show that this phosphatase-like domain is not catalytically active. Instead, by using SPR (surface plasmon resonance) to study protein binding to immobilized lipid vesicles, we show that this domain is specialized for binding PtdIns(3,4,5)P(3) (PPIP5K1 K(d) = 96 nM; PPIP5K2 K(d) = 705 nM). Both PtdIns(3,4)P(2) and PtdIns(4,5)P2 are significantly weaker ligands, and no significant binding of PtdIns(3,5)P(2) was detected. We confirm the functional importance of this domain in inositol lipid binding by site-directed mutagenesis. We present evidence that the PtdIns(3,4,5)P(3)-binding domain is an unusual hybrid, in which a partial PH (pleckstrin homology) consensus sequence is spliced into the phosphatase-like domain. Agonist-dependent activation of the PtdIns 3-kinase pathway in NIH 3T3 cells drives translocation of PPIP5K1 from the cytosol to the plasma membrane. We have therefore demonstrated receptor-regulated compartmentalization of inositol pyrophosphate synthesis in mammalian cells. C1 [Gokhale, Nikhil A.; Zaremba, Angelika; Shears, Stephen B.] Natl Inst Environm Hlth Sci, Inositol Signaling Grp, Lab Signal Transduct, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), Natl Inst Environm Hlth Sci, Inositol Signaling Grp, Lab Signal Transduct, NIH,DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM Shears@niehs.nih.gov FU National Institutes of Health/National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Environmental Health Sciences. NR 50 TC 16 Z9 19 U1 0 U2 4 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 MAR 15 PY 2011 VL 434 BP 415 EP 426 DI 10.1042/BJ20101437 PN 3 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 738BI UT WOS:000288613900006 PM 21222653 ER PT J AU Landgren, O Kyle, RA Rajkumar, SV AF Landgren, Ola Kyle, Robert A. Rajkumar, S. Vincent TI From Myeloma Precursor Disease to Multiple Myeloma: New Diagnostic Concepts and Opportunities for Early Intervention SO CLINICAL CANCER RESEARCH LA English DT Article ID UNDETERMINED SIGNIFICANCE MGUS; BENCE-JONES PROTEINURIA; INDEPENDENT RISK-FACTOR; LIGHT-CHAIN RATIO; MONOCLONAL GAMMOPATHY; WALDENSTROMS MACROGLOBULINEMIA; CLINICAL-COURSE; LONG-TERM; PROGRESSION; PREVALENCE AB Since monoclonal gammopathy of undetermined significance (MGUS) was first described more than 30 years ago, the definition of the entity has evolved. Today, 3 distinct clinical MGUS subtypes have been defined: non-immunoglobulin M (IgM; IgG or IgA) MGUS, IgM MGUS, and light chain MGUS. Each clinical MGUS subtype is characterized by unique intermediate stages and progression events. Although we now have strong evidence that multiple myeloma is consistently preceded by a precursor state at the molecular level, there is urgent need to better understand mechanisms that regulate transformation from precursor to full-blown multiple myeloma. In the future, if such knowledge was available, it would allow clinicians to define high-risk and low-risk precursor patients for a more tailored clinical management. Also, it would provide insights on the individual patient's disease biology, which, in turn, can be used for targeted and more individualized treatment strategies. On the basis of current clinical guidelines, patients diagnosed with MGUS and smoldering myeloma should not be treated outside of clinical trials. In the near future, it seems reasonable to believe that high-risk precursor patients will likely become candidates for early treatment strategies. In this review, we discuss novel insights from recent studies and propose future directions of relevance for clinical management and research studies. Clin Cancer Res; 17(6); 1243-52. (C)2011 AACR. C1 [Landgren, Ola] NCI, Ctr Canc Res, NIH, Med Oncol Branch, Bethesda, MD 20892 USA. [Kyle, Robert A.; Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Rochester, MN USA. RP Landgren, O (reprint author), NCI, Ctr Canc Res, NIH, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov OI Rajkumar, S. Vincent/0000-0002-5862-1833 FU NCI of the NIH; NCI [CA 62242, CA 107-476-03] FX This work was supported by the Intramural Research Program of the NCI of the NIH; the grants CA 62242 and CA 107-476-03 from the NCI; and the facilities and resources of the Divisions of Hematology, Biostatistics, Clinical Biochemistry and Immunology, and Epidemiology at the Mayo Clinic, Rochester, Minnesota. NR 53 TC 28 Z9 28 U1 0 U2 5 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 MAR 15 PY 2011 VL 17 IS 6 BP 1243 EP 1252 DI 10.1158/1078-0432.CCR-10-1822 PG 10 WC Oncology SC Oncology GA 735RR UT WOS:000288435300006 PM 21411440 ER PT J AU Rudd, ML Price, JC Fogoros, S Godwin, AK Sgroi, DC Merino, MJ Bell, DW AF Rudd, Meghan L. Price, Jessica C. Fogoros, Sarah Godwin, Andrew K. Sgroi, Dennis C. Merino, Maria J. Bell, Daphne W. TI A Unique Spectrum of Somatic PIK3CA (p110 alpha) Mutations Within Primary Endometrial Carcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CANCER; TUMOR-SUPPRESSOR; POOR-PROGNOSIS; GENE-MUTATIONS; HIGH-FREQUENCY; PATHWAY; DOMAIN; PTEN; CARCINOGENESIS; PHOSPHATASE AB Purpose: The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC). Experimental Design: We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wild type and mutant constructs in U2OS cells and measuring levels of AKT(Ser473) phosphorylation. Results: Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1-7 and half were in exons 9 and 20. The exons 1-7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110 alpha. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93, and Lys111 formed mutation hotspots. The p110 alpha-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKT(Ser473) compared to wild-type p110 alpha. Overall, 62% of exons 1-7 PIK3CA mutants and 64% of exons 9-20 PIK3CA mutants were activating; 72% of exon 1-7 mutations have not previously been reported in endometrial cancer. Conclusions: Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110 alpha; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway. Clin Cancer Res; 17(6); 1331-40. (C)2011 AACR. C1 [Rudd, Meghan L.; Price, Jessica C.; Fogoros, Sarah; Bell, Daphne W.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, NIH, Bethesda, MD 20892 USA. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, 50 South Dr,MSC-8000, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov FU National Human Genome Research Institute/NIH; NIH [R01 CA140323, U01 CA113916, R01-1CA112021-01]; NCI SPORE in breast cancer at Massachusetts General Hospital; Ovarian Cancer Research Fund; Avon Foundation FX The Intramural Program of the National Human Genome Research Institute/NIH (D. W. Bell); NIH R01 CA140323 (A. K. Godwin), U01 CA113916 (A. K. Godwin), NIH R01-1CA112021-01 (D. C. Sgroi), NCI SPORE in breast cancer at Massachusetts General Hospital (D. C. Sgroi), the Ovarian Cancer Research Fund (A. K. Godwin), and the Avon Foundation (D. C. Sgroi). NR 41 TC 99 Z9 99 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 MAR 15 PY 2011 VL 17 IS 6 BP 1331 EP 1340 DI 10.1158/1078-0432.CCR-10-0540 PG 10 WC Oncology SC Oncology GA 735RR UT WOS:000288435300014 PM 21266528 ER PT J AU Yi, JM Dhir, M Van Neste, L Downing, SR Jeschke, J Glockner, SC Calmon, MD Hooker, CM Funes, JM Boshoff, C Smits, KM van Engeland, M Weijenberg, MP Iacobuzio-Donahue, CA Herman, JG Schuebel, KE Baylin, SB Ahuja, N AF Yi, Joo Mi Dhir, Mashaal Van Neste, Leander Downing, Stephanie R. Jeschke, Jana Gloeckner, Sabine C. Calmon, Marilia de Freitas Hooker, Craig M. Funes, Juan M. Boshoff, Chris Smits, Kim M. van Engeland, Manon Weijenberg, Matty P. Iacobuzio-Donahue, Christine A. Herman, James G. Schuebel, Kornel E. Baylin, Stephen B. Ahuja, Nita TI Genomic and Epigenomic Integration Identifies a Prognostic Signature in Colon Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; DNA METHYLATION MARKERS; PROMOTER HYPERMETHYLATION; COLORECTAL CARCINOMAS; TUMOR PROGRESSION; TISSUE INHIBITOR; GENE-EXPRESSION; HUMAN BREAST; STEM-CELLS; INACTIVATION AB Purpose: The importance of genetic and epigenetic alterations maybe in their aggregate role in altering core pathways in tumorigenesis. Experimental Design: Merging genome-wide genomic and epigenomic alterations, we identify key genes and pathways altered in colorectal cancers (CRC). DNA methylation analysis was tested for predicting survival in CRC patients using Cox proportional hazard model. Results: We identified 29 low frequency-mutated genes that are also inactivated by epigenetic mechanisms in CRC. Pathway analysis showed the extracellular matrix (ECM) remodeling pathway is silenced in CRC. Six ECM pathway genes were tested for their prognostic potential in large CRC cohorts (n = 777). DNA methylation of IGFBP3 and EVL predicted for poor survival (IGFBP3: HR = 2.58, 95% CI: 1.37-4.87, P = 0.004; EVL: HR = 2.48, 95% CI: 1.07-5.74, P = 0.034) and simultaneous methylation of multiple genes predicted significantly worse survival (HR = 8.61, 95% CI: 2.16-34.36, P < 0.001 for methylation of IGFBP3, EVL, CD109, and FLNC). DNA methylation of IGFBP3 and EVL was validated as a prognostic marker in an independent contemporary-matched cohort (IGFBP3 HR = 2.06, 95% CI: 1.04-4.09, P - 0.038; EVL HR - 2.23, 95% CI: 1.00-5.0, P - 0.05) and EVL DNA methylation remained significant in a secondary historical validation cohort (HR = 1.41, 95% CI: 1.05-1.89, P = 0.022). Moreover, DNA methylation of selected ECM genes helps to stratify the high-risk stage 2 colon cancers patients who would benefit from adjuvant chemotherapy (HR: 5.85, 95% CI: 2.03-16.83, P = 0.001 for simultaneous methylation of IGFBP3, EVL, and CD109). Conclusions: CRC that have silenced genes in ECM pathway components show worse survival suggesting that our finding provides novel prognostic biomarkers for CRC and reflects the high importance of integrative analyses linking genetic and epigenetic abnormalities with pathway disruption in cancer. Clin Cancer Res; 17(6); 1535-45. (C) 2011 AACR. C1 [Yi, Joo Mi; Hooker, Craig M.; Herman, James G.; Baylin, Stephen B.; Ahuja, Nita] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA. [Dhir, Mashaal; Downing, Stephanie R.; Jeschke, Jana; Gloeckner, Sabine C.; Calmon, Marilia de Freitas; Ahuja, Nita] Johns Hopkins Univ, Dept Surg, Baltimore, MD 21231 USA. [Iacobuzio-Donahue, Christine A.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. [Van Neste, Leander; Funes, Juan M.; Boshoff, Chris] Univ Ghent, Dept Mol Biotechnol, Fac Biosci Engn, B-9000 Ghent, Belgium. [Van Neste, Leander] MDxHealth, Ghent, Belgium. [Funes, Juan M.; Boshoff, Chris] UCL, Canc Res UK Viral Oncol Grp, London, England. [Smits, Kim M.; van Engeland, Manon; Weijenberg, Matty P.] Maastricht Univ Med Ctr, GROW Sch Oncol & Dev Biol, Dept Pathol, Maastricht, Netherlands. [Schuebel, Kornel E.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Yi, Joo Mi] Dongnam Inst Radiol & Res Med Sci DIRAMS, Res Ctr, Pusan, South Korea. RP Ahuja, N (reprint author), Johns Hopkins Univ, Dept Surg & Oncol, Baltimore, MD 21231 USA. EM nahuja@jhmi.edu RI Ahuja, Nita/H-1064-2011; Calmon, Marilia/H-3150-2012; van Engeland, Manon/A-7479-2009 OI van Engeland, Manon/0000-0002-7952-6843 FU National Institute of Environmental Health Sciences [ES011858]; NIH [K23CA127141]; Jeannik M. Littlefield AACR Grant in Metastatic Colon Cancer; Mary Kay Ash Foundation; Susan G. Komen Foundation; American College of Surgeons/Society of University Surgeons Career Development Award FX The study was supported by the National Institute of Environmental Health Sciences (grant number: ES011858), the NIH (grant number: K23CA127141), the Jeannik M. Littlefield AACR Grant in Metastatic Colon Cancer, the Mary Kay Ash Foundation, the Susan G. Komen Foundation, and the American College of Surgeons/Society of University Surgeons Career Development Award. NR 43 TC 62 Z9 64 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2011 VL 17 IS 6 BP 1535 EP 1545 DI 10.1158/1078-0432.CCR-10-2509 PG 11 WC Oncology SC Oncology GA 735RR UT WOS:000288435300033 PM 21278247 ER PT J AU Stathis, A Hotte, SJ Chen, EX Hirte, HW Oza, AM Moretto, P Webster, S Laughlin, A Stayner, LA McGill, S Wang, L Zhang, WJ Espinoza-Delgado, I Holleran, JL Egorin, MJ Siu, LL AF Stathis, Anastasios Hotte, Sebastien J. Chen, Eric X. Hirte, Holger W. Oza, Amit M. Moretto, Patricia Webster, Sheila Laughlin, Anne Stayner, Lee-Anne McGill, Shauna Wang, Lisa Zhang, Wen-jiang Espinoza-Delgado, Igor Holleran, Julianne L. Egorin, Merrill J. Siu, Lillian L. TI Phase I Study of Decitabine in Combination with Vorinostat in Patients with Advanced Solid Tumors and Non-Hodgkin's Lymphomas SO CLINICAL CANCER RESEARCH LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; VALPROIC ACID; MYELODYSPLASTIC SYNDROMES; DNA METHYLTRANSFERASE; 5-AZA-2'-DEOXYCYTIDINE; CANCER; SAHA; PHENYLBUTYRATE; 5-AZACYTIDINE AB Purpose: This phase I study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the combination of decitabine with vorinostat. Patients and Methods: Patients with advanced solid tumors or non-Hodgkin's lymphomas were eligible. Sequential and concurrent schedules were studied. Results: Forty-three patients were studied in 9 different dose levels (6 sequential and 3 concurrent). The maximum tolerated dose (MTD) on the sequential schedule was decitabine 10 mg/m(2)/day on days 1 to 5 and vorinostat 200 mg three times a day on days 6 to 12. The MTD on the concurrent schedule was decitabine 10 mg/m(2)/day on days 1 to 5 with vorinostat 200 mg twice a day on days 3 to 9. However, the sequential schedule of decitabine 10 mg/m(2)/day on days 1 to 5 and vorinostat 200 mg twice a day on days 6 to 12 was more deliverable than both MTDs with fewer delays on repeated dosing and it represents the recommended phase II (RP2D) dose of this combination. Dose-limiting toxicities during the first cycle consisted of myelosuppression, constitutional and gastrointestinal symptoms and occurred in 12 of 42 (29%) patients evaluable for toxicity. The most common grade 3 or higher adverse events were neutropenia (49% of patients), thrombocytopenia (16%), fatigue (16%), lymphopenia (14%), and febrile neutropenia (7%). Disease stabilization for 4 cycles or more was observed in 11 of 38 (29%) evaluable patients. Conclusion: The combination of decitabine with vorinostat is tolerable on both concurrent and sequential schedules in previously treated patients with advanced solid tumors or non-Hodgkin's lymphomas. The sequential schedule was easier to deliver. The combination showed activity with prolonged disease stabilization in different tumor types. Clin Cancer Res; 17(6); 1582-90. (C) 2011 AACR. C1 [Siu, Lillian L.] Univ Toronto, Princess Margaret Hosp, Div Med Oncol & Hematol, Phase Consortium 1, Toronto, ON M5G 2M9, Canada. [Espinoza-Delgado, Igor] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Siu, LL (reprint author), Univ Toronto, Princess Margaret Hosp, Div Med Oncol & Hematol, Phase Consortium 1, 610 Univ Ave,Suite 5-718, Toronto, ON M5G 2M9, Canada. EM lillian.siu@uhn.on.ca FU NCI [U01CA132123, U01CA099168, P30-CA47904] FX Supported by NCI Grants. U01CA132123, U01CA099168, and P30-CA47904 NR 30 TC 52 Z9 56 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2011 VL 17 IS 6 BP 1582 EP 1590 DI 10.1158/1078-0432.CCR-10-1893 PG 9 WC Oncology SC Oncology GA 735RR UT WOS:000288435300038 PM 21278245 ER PT J AU Bhave, VS Donthamsetty, S Latendresse, JR Cunningham, ML Mehendale, HM AF Bhave, Vishakha S. Donthamsetty, Shashikiran Latendresse, John R. Cunningham, Michael L. Mehendale, Harihara M. TI Secretory phospholipase A(2)-mediated progression of hepatotoxicity initiated by acetaminophen is exacerbated in the absence of hepatic COX-2 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Acetaminophen; Cycloxygenase-2; Hepatotoxicity; Prostaglandin E-2; Secretory Phospholipase A(2); TNF-alpha ID ACUTE LIVER-INJURY; NECROSIS-FACTOR-ALPHA; HEPATOCELLULAR REGENERATION; MODEL HEPATOTOXICANTS; MEDIATES PROGRESSION; ACUTE-INFLAMMATION; RECEPTOR-ALPHA; NITRIC-OXIDE; RAT-LIVER; CYCLOOXYGENASE-2 AB We have previously reported that among the other death proteins, hepatic secretory phospholipase A(2) (sPLA(2)) is a leading mediator of progression of liver injury initiated by CCI4 in rats. The aim of our present study was to test the hypothesis that increased hepatic sPLA(2) released after acetaminophen (APAP) challenge mediates progression of liver injury in wild type (WT) and COX-2 knockout (KO) mice. COX-2 WT and KO mice were administered a normally non lethal dose (400 mg/kg) of acetaminophen. The COX-2 1(0 mice suffered 60% mortality compared to 100% survival of the WT mice, suggesting higher susceptibility of COX-2 KO mice to sPLA(2)-mediated progression of acetaminophen hepatotoxicity. Liver injury was significantly higher at later time points in the KO mice compared to the WT mice indicating that the abatement of progression of injury requires the presence of COX-2. This difference in hepatotoxicity was not due to increased bioactivation of acetaminophen as indicated by unchanged cyp2E1 protein and covalently bound C-14-APAP in the livers of KO mice. Hepatic sPLA(2) activity and plasma TNF-alpha were significantly higher after APAP administration in the KO mice. This was accompanied by a corresponding fall in hepatic PGE(2) and lower compensatory liver regeneration and repair (H-3-thymidine incorporation) in the KO mice. These results suggest that hindered compensatory tissue repair and poor resolution of inflammation for want of beneficial prostaglandins render the liver very vulnerable to sPLA(2)-mediated progression of liver injury. These findings are consistent with the destructive role of sPLA(2) in the progression and expansion of tissue injury as a result of continued hydrolytic breakdown of plasma membrane phospholipids of perinecrotic hepatocytes unless mitigated by sufficient co-induction of COX-2. (C) 2011 Published by Elsevier Inc. C1 [Bhave, Vishakha S.; Donthamsetty, Shashikiran; Mehendale, Harihara M.] Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. [Latendresse, John R.] Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR USA. [Cunningham, Michael L.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, 700 Univ Ave,Bienville 259, Monroe, LA 71209 USA. EM mehendale@ulm.edu OI Bhave, Vishakha/0000-0003-0149-579X FU Louisiana Board of Regents; DeGree Endowed Chair in Toxicology Fund; NIH, National Institute of Environmental Health Sciences (NIEHS) FX This work was supported in part by the Louisiana Board of Regents Support Funds, DeGree Endowed Chair in Toxicology, and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS). NR 43 TC 8 Z9 8 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2011 VL 251 IS 3 BP 173 EP 180 DI 10.1016/j.taap.2011.01.013 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 735NC UT WOS:000288421000001 PM 21277885 ER PT J AU Lindley, MC Lorick, SA Spinner, JR Krull, AR Mootrey, GT Ahmed, F Myers, R Bednash, GP Cymet, TC Maeshiro, R Raines, CF Shannon, SC Sondheimer, HM Strikas, RA AF Lindley, Megan C. Lorick, Suchita A. Spinner, Jovonni R. Krull, Andrea R. Mootrey, Gina T. Ahmed, Faruque Myers, Rosa Bednash, Geraldine P. Cymet, Tyler C. Maeshiro, Rika Raines, C. Fay Shannon, Stephen C. Sondheimer, Henry M. Strikas, Raymond A. TI Student Vaccination Requirements of US Health Professional Schools: A Survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNIZATION PRACTICES ACIP; HEPATITIS-B VACCINATION; INFLUENZA VACCINATION; UNITED-STATES; CARE WORKERS; ADVISORY-COMMITTEE; NOSOCOMIAL PERTUSSIS; MEASLES OUTBREAKS; INFECTION-CONTROL; ATTITUDES AB Background: Unvaccinated health care personnel are at increased risk for transmitting vaccine-preventable diseases to their patients. The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel, including students, receive measles, mumps, rubella, hepatitis B, varicella, influenza, and pertussis vaccines. Prematriculation vaccination requirements of health professional schools represent an early opportunity to ensure that health care personnel receive recommended vaccines. Objective: To examine prematriculation vaccination requirements and related policies at selected health professional schools in the United States and compare requirements with current ACIP recommendations. Design: Cross-sectional study using an Internet-based survey. Setting: Medical and baccalaureate nursing schools in the United States and its territories. Participants: Deans of accredited medical schools granting MD (n = 130) and DO (n = 26) degrees and of baccalaureate nursing programs (n = 603). Measurements: Proportion of MD-granting and DO-granting schools and baccalaureate nursing programs that require that entering students receive vaccines recommended by the ACIP for health care personnel. Results: 563 schools (75%) responded. More than 90% of all school types required measles, mumps, rubella, and hepatitis B vaccines for entering students; varicella vaccination also was commonly required. Tetanus, diphtheria, and acellular pertussis vaccination was required by 66%, 70%, and 75% of nursing, MD-granting, and DO-granting schools, respectively. Nursing and DO-granting schools (31% and 45%, respectively) were less likely than MD-granting schools (78%) to offer students influenza vaccines free of charge. Limitations: Estimates were conservative, because schools that reported that they did not require proof of immunity for a given vaccine were considered not to require that vaccine. Estimates also were restricted to schools that train physicians and nurses. Conclusion: The majority of schools now require most ACIP-recommended vaccines for students. Medical and nursing schools should adopt policies on student vaccination and serologic testing that conform to ACIP recommendations and should encourage annual influenza vaccination by offering influenza vaccination to students at no cost. C1 [Lindley, Megan C.; Lorick, Suchita A.; Mootrey, Gina T.; Ahmed, Faruque; Strikas, Raymond A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Spinner, Jovonni R.] NIH, Bethesda, MD 20892 USA. [Krull, Andrea R.] US Dept HHS, Washington, DC 20201 USA. [Myers, Rosa] Off Womens Hlth Reg 3, Philadelphia, PA 19106 USA. [Bednash, Geraldine P.] Coll Nursing, Amer Assoc, Washington, DC 20036 USA. [Cymet, Tyler C.; Shannon, Stephen C.] Coll Osteopath Med, Amer Assoc, Chevy Chase, MD 20815 USA. [Maeshiro, Rika] Assoc Amer Med Coll, Washington, DC 20037 USA. [Raines, C. Fay] Univ Alabama, Coll Nursing, Huntsville, AL 35899 USA. RP Lindley, MC (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop E-52, Atlanta, GA 30333 USA. EM MLindley@cdc.gov NR 61 TC 26 Z9 26 U1 1 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 15 PY 2011 VL 154 IS 6 BP 391 EP + DI 10.7326/0003-4819-154-6-201103150-00004 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 734WA UT WOS:000288370000003 PM 21403075 ER PT J AU Peer, CJ Sissung, TM Figg, WD AF Peer, Cody J. Sissung, Tristan M. Figg, William D. TI CHIP and gp78-mediated ubiquitination of CYP3A4 Implications for the pharmacology of anticancer agents SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE CYP3A4; ubiquitination; gp78; CHIP ID RETICULUM-ASSOCIATED DEGRADATION; MOTILITY FACTOR-RECEPTOR; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; RAT HEPATOCYTES; CYTOCHROMES P450; CANCER-THERAPY; 26S PROTEASOME; HEME; LIVER C1 [Peer, Cody J.; Sissung, Tristan M.; Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Branch, CCR,NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, CCR,NIH, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 29 TC 8 Z9 8 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR 15 PY 2011 VL 11 IS 6 BP 549 EP 551 DI 10.4161/cbt.11.6.14834 PG 3 WC Oncology SC Oncology GA 734XE UT WOS:000288374400001 PM 21270532 ER PT J AU Zou, S Chang, J LaFever, L Tang, WL Johnson, EL Hu, J Wilk, R Krause, HM Drummond-Barbosa, D Irusta, PM AF Zou, Sige Chang, Joy LaFever, Leesa Tang, Wangli Johnson, Erika L. Hu, Jack Wilk, Ronit Krause, Henry M. Drummond-Barbosa, Daniela Irusta, Pablo M. TI Identification of dAven, a Drosophila melanogaster ortholog of the cell cycle regulator Aven Identification of Drosophila Aven SO CELL CYCLE LA English DT Article DE Drosophila melanogaster; Aven; Ataxia telangiectasia mutated; ATM and Rad 3-related; cell cycle; checkpoint ID EARLY EMBRYONIC LETHALITY; DNA-DAMAGE; ATAXIA-TELANGIECTASIA; TELOMERE MAINTENANCE; IONIZING-RADIATION; CHROMOSOMAL FRAGMENTATION; TARGETED DISRUPTION; INDUCED APOPTOSIS; PROTEIN-KINASE; DEATH PATHWAY AB Aven is a regulator of the DNA damage response and G(2)/M cell cycle progression. Overexpression of Aven is associated with poor prognosis in patients with childhood acute lymphoblastic leukemia and acute myeloid leukemia, and altered intracellular Aven distribution is associated with infiltrating ductal carcinoma and papillary carcinoma breast cancer subtypes. Although Aven orthologs have been identified in most vertebrate species, no Aven gene has been reported in invertebrates. Here, we describe a Drosophila melanogaster open reading frame (ORF) that shares sequence and functional similarities with vertebrate Aven genes. The protein encoded by this ORF, which we named dAven, contains several domains that are highly conserved among Aven proteins of fish, amphibian, bird and mammalian origins. In flies, knockdown of dAven by RNA interference (RNAi) resulted in lethality when its expression was reduced either ubiquitously or in fat cells using Gal4 drivers. Animals undergoing moderate dAven knockdown in the fat body had smaller fat cells displaying condensed chromosomes and increased levels of the mitotic marker phosphorylated histone H3 (PHH3), suggesting that dAven was required for normal cell cycle progression in this tissue. Remarkably, expression of dAven in Xenopus egg extracts resulted in G(2)/M arrest that was comparable to that caused by human Aven. Taken together, these results suggest that, like its vertebrate counterparts, dAven plays a role in cell cycle regulation. Drosophila could be an excellent model for studying the function of Aven and identifying cellular factors that influence its activity, revealing information that may be relevant to human disease. C1 [Zou, Sige; Chang, Joy; Irusta, Pablo M.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Chang, Joy; Irusta, Pablo M.] Georgetown Univ, Med Ctr, Dept Human Sci, Washington, DC 20007 USA. [LaFever, Leesa; Drummond-Barbosa, Daniela] Johns Hopkins Bloomberg Sch Publ Hlth, Div Reprod Biol, Dept Biochem & Mol Biol, Baltimore, MD USA. [Tang, Wangli; Johnson, Erika L.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. [Hu, Jack; Wilk, Ronit; Krause, Henry M.] Univ Toronto, Banting & Best Dept Med Res, Dept Mol Genet, Terrence Donelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. RP Irusta, PM (reprint author), NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM pmi2@georgetown.edu FU Fundacion INFANT (PI); National Institute on Aging, NIH; [R01 GM069875] FX This work was supported by Fundacion INFANT (PI), R01 GM069875 (DDB), and Intramural Research Program of the National Institute on Aging, NIH (SZ). LL designed and performed experiments in Figure 4 under the guidance of DDB. The authors would like to thank Sheryl Southard and Mark Van Doren from Johns Hopkins University for their help with some experiments performed during the course of this project. NR 80 TC 5 Z9 5 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2011 VL 10 IS 6 BP 989 EP 998 DI 10.4161/cc.10.6.15080 PG 10 WC Cell Biology SC Cell Biology GA 734UX UT WOS:000288366400027 PM 21368576 ER PT J AU Fiandaca, MS Salegio, EA Yin, DL Richardson, RM Valles, FE Larson, PS Starr, PA Lonser, RR Bankiewicz, KS AF Fiandaca, Massimo S. Salegio, Ernesto Aguilar Yin, Dali Richardson, R. Mark Valles, Francisco E. Larson, Paul S. Starr, Philip A. Lonser, Russell R. Bankiewicz, Krystof S. TI Human/nonhuman primate AC-PC ratio-Considerations for translational brain measurements SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE AC-PC ratio; Human; MRI; Non-human primate; Parkinson's disease; Stereotactic surgery; Translational study ID CONVECTION-ENHANCED DELIVERY; SUBTHALAMIC NUCLEUS STIMULATION; PHASE-I TRIAL; PARKINSONS-DISEASE; GENE-THERAPY; NEUROTROPHIC FACTOR; TECHNICAL APPROACH; OPEN-LABEL; INFUSION; PLACEMENT AB This comparative magnetic resonance imaging (MRI) analysis evaluated the ratio of AC-PC (anterior commissure to posterior commissure) distance measures in selected groups of humans and nonhuman primates (NHPs). An understanding of the basis of this ratio between primate species may allow more accurate translation of NHP stereotactic targeting measurements to upcoming human trials. MRI datasets of adult humans [n = 21], and juvenile and adult NHPs (Macaca fascicularis [n = 40], and Macaca mulatto [n = 32]), were evaluated in a mid-sagittal plane to obtain the AC-PC distance measure for each examined subject. Two trained evaluators, blinded to each other's results, carried out three separate measurements of the AC-PC length for each subject. Each observer carried out measurements of the entire dataset [n = 93] before repeating the measurements two additional times. Previous dataset measures were not available for review at the time of subsequent measures. Inter- and intra-observer variabilities were not statistically significant. Minimal intraspecies variation was found in the AC-PC measurement of our human and NHP groups. We found significant interspecies differences, however, more between humans and NHPs, and less between the NHP groups. Regression analysis confirms the strong linear relationship of AC-PC distance based primarily on species in our study groups. Human/NHP AC-PC ratios varied between 2.1 and 2.3 based on the compared NHP species groups. We conclude that the scale differences in brain measurements between NHPs and humans described in this study allows improved translation of stereotactic targeting coordinates in future human clinical trials, which may lead to improved efficacy and safety. (C) 2010 Elsevier B.V. All rights reserved. C1 [Fiandaca, Massimo S.; Salegio, Ernesto Aguilar; Yin, Dali; Richardson, R. Mark; Valles, Francisco E.; Bankiewicz, Krystof S.] Univ Calif San Francisco, Dept Neurol Surg, Movement Disorders Lab, San Francisco, CA 94103 USA. [Larson, Paul S.; Starr, Philip A.] Univ Calif San Francisco, Dept Neurol Surg, Movement Disorders Clin, San Francisco, CA 94143 USA. [Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Fiandaca, MS (reprint author), Univ Calif San Francisco, Dept Neurol Surg, Movement Disorders Lab, 1855 Folsom St,MCB 226, San Francisco, CA 94103 USA. EM Massimo.Fiandaca@ucsf.edu; Ernest.Aguilar@ucsf.edu; Dali.Yin@ucsf.edu; Francisco.Valles@ucsf.edu; LarsonP@neurosurg.ucsf.edu; StarrP@neurosurg.ucsf.edu; LonserR@ninds.nih.gov; Krystof.Bankiewicz@ucsf.edu RI Richardson, Robert/C-6819-2016 OI Richardson, Robert/0000-0003-2620-7387 FU NIH-NINDS [U54NS045309]; NIH [P01 CA118816] FX This work was supported in part by a NIH-NINDS award (U54NS045309), NIH award (P01 CA118816), and a gift from the Kinetics Foundation. We appreciated the statistical assistance of Fred Derrick, Ph.D., Professor of Economics at Loyola University of Maryland's Sellinger School of Business and Management. We are grateful for the technical assistance of John Bringas, Philip Pivirotto, and Janine Beyer. The authors thank Saif Baig and Francisco Gimenez for their laboratory efforts associated with this study. We also acknowledge the courage and generosity of those who volunteer to become subjects in clinical studies and help to generate much useful data for the benefit of others. NR 43 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 15 PY 2011 VL 196 IS 1 BP 124 EP 130 DI 10.1016/j.jneumeth.2010.12.023 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 736GU UT WOS:000288479800016 PM 21185868 ER PT J AU Sixt, M Parent, CA AF Sixt, Michael Parent, Carole A. TI Cells on the move in Philadelphia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Editorial Material C1 [Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sixt, Michael] IST Austria, A-3900 Klosterneuburg, Austria. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov OI Sixt, Michael/0000-0002-6620-9179 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR 15 PY 2011 VL 22 IS 6 BP 724 EP 724 DI 10.1091/mbc.E10-12-0958 PG 1 WC Cell Biology SC Cell Biology GA 734VN UT WOS:000288368200010 PM 21406587 ER PT J AU Dey, M Velyvis, A Li, JJ Chiu, E Chiovitti, D Kay, LE Sicheri, F Dever, TE AF Dey, Madhusudan Velyvis, Algirdas Li, John J. Chiu, Elaine Chiovitti, David Kay, Lewis E. Sicheri, Frank Dever, Thomas E. TI Requirement for kinase-induced conformational change in eukaryotic initiation factor 2 alpha (eIF2 alpha) restricts phosphorylation of Ser51 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSLATION INITIATION; SUBSTRATE RECOGNITION; CRYSTAL-STRUCTURE; CHEMICAL-SHIFTS; ALPHA-SUBUNIT; PROTEIN; PKR; ELF2-ALPHA; BINDING; EIF2B AB As phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) on Ser51 inhibits protein synthesis, cells restrict this phosphorylation to the antiviral protein kinase PKR and related eIF2 alpha kinases. In the crystal structure of the PKR-eIF2 alpha complex, the C-terminal lobe of the kinase contacts eIF2 alpha on a face remote from Ser51, leaving Ser51 similar to 20 angstrom from the kinase active site. PKR mutations that cripple the eIF2 alpha-binding site impair phosphorylation; here, we identify mutations in eIF2 alpha that restore Ser51 phosphorylation by PKR with a crippled substrate-binding site. These eIF2 alpha mutations either disrupt a hydrophobic network that restricts the position of Ser51 or alter a linkage between the PKR-docking region and the Ser51 loop. We propose that the protected state of Ser51 in free eIF2 alpha prevents promiscuous phosphorylation and the attendant translational regulation by heterologous kinases, whereas docking of eIF2 alpha on PKR induces a conformational change that regulates the degree of Ser51 exposure and thus restricts phosphorylation to the proper kinases. C1 [Velyvis, Algirdas; Li, John J.; Chiu, Elaine; Chiovitti, David; Kay, Lewis E.; Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada. [Dey, Madhusudan; Dever, Thomas E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Dey, Madhusudan] Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. [Velyvis, Algirdas; Kay, Lewis E.] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. [Velyvis, Algirdas; Kay, Lewis E.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A8, Canada. [Li, John J.; Chiu, Elaine; Chiovitti, David; Sicheri, Frank] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Syst Biol, Toronto, ON M5G 1X5, Canada. RP Sicheri, F (reprint author), Univ Toronto, Dept Mol Genet, 100 Coll St, Toronto, ON M5S 1A8, Canada. EM sicheri@lunenfeld.ca; tdever@nih.gov RI Sicheri, Frank/F-8856-2013; OI Dever, Thomas/0000-0001-7120-9678 FU National Institutes of Health, National Institute of Child Health and Human Development; Canadian Cancer Society [19233]; Natural Sciences and Engineering Research Council of Canada; Canadian Institutes of Health Research FX We thank members of the Dever, Sicheri, Kay, and Hinnebusch labs for advice and for discussions. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development (T. E. D.), by grants from the Canadian Cancer Society to F. S. (Grant 19233), and by grants from the Natural Sciences and Engineering Research Council of Canada and from the Canadian Institutes of Health Research to L. E. K. NR 15 TC 11 Z9 11 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 MAR 15 PY 2011 VL 108 IS 11 BP 4316 EP 4321 DI 10.1073/pnas.1014872108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735WI UT WOS:000288450900017 PM 21368187 ER PT J AU Lau, JY Britton, JC Nelson, EE Angold, A Ernst, M Goldwin, M Grillon, C Leibenluft, E Lissek, S Norcross, M Shiffrin, N Pine, DS AF Lau, Jennifer Y. Britton, Jennifer C. Nelson, Eric E. Angold, Adrian Ernst, Monique Goldwin, Michelle Grillon, Christian Leibenluft, Ellen Lissek, Shmuel Norcross, Maxine Shiffrin, Nina Pine, Daniel S. TI Distinct neural signatures of threat learning in adolescents and adults SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amygdala; brain development; discriminative fear conditioning; threat responding; anxiety ID PREFRONTAL CORTEX; FACIAL EXPRESSIONS; AMYGDALA RESPONSE; EMOTIONAL REACTIVITY; COGNITIVE REGULATION; CONDITIONED FEAR; ANXIETY; EXTINCTION; CHILDHOOD; BRAIN AB Most teenage fears subside with age, a change that may reflect brain maturation in the service of refined fear learning. Whereas adults clearly demarcate safe situations from real dangers, attenuating fear to the former but not the latter, adolescents' immaturity in prefrontal cortex function may limit their ability to form clear-cut threat categories, allowing pervasive fears to manifest. Here we developed a discrimination learning paradigm that assesses the ability to categorize threat from safety cues to test these hypotheses on age differences in neurodevelopment. In experiment 1, we first demonstrated the capacity of this paradigm to generate threat/safety discrimination learning in both adolescents and adults. Next, in experiment 2, we used this paradigm to compare the behavioral and neural correlates of threat/safety discrimination learning in adolescents and adults using functional MRI. This second experiment yielded three sets of findings. First, when labeling threats online, adolescents reported less discrimination between threat and safety cues than adults. Second, adolescents were more likely than adults to engage early-maturing subcortical structures during threat/safety discrimination learning. Third, adults' but not adolescents' engagement of late-maturing prefrontal cortex regions correlated positively with fear ratings during threat/safety discrimination learning. These data are consistent with the role of dorsolateral regions during category learning, particularly when differences between stimuli are subtle [Miller EK, Cohen JD (2001) Annu Rev Neurosci 24:167-202]. These findings suggest that maturational differences in subcortical and prefrontal regions between adolescent and adult brains may relate to age-related differences in threat/safety discrimination. C1 [Lau, Jennifer Y.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Lau, Jennifer Y.; Britton, Jennifer C.; Nelson, Eric E.; Ernst, Monique; Goldwin, Michelle; Grillon, Christian; Leibenluft, Ellen; Lissek, Shmuel; Norcross, Maxine; Shiffrin, Nina; Pine, Daniel S.] NIMH, NIH, Bethesda, MD 20892 USA. [Goldwin, Michelle] Univ Illinois, Dept Psychol, Chicago, IL 60607 USA. [Angold, Adrian] Duke Univ, Sch Med, Ctr Dev Epidemiol, Durham, NC 27710 USA. [Lissek, Shmuel] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA. [Shiffrin, Nina] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. RP Lau, JY (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England. EM jennifer.lau@psy.ox.ac.uk RI Nelson, Eric/B-8980-2008; Britton, Jennifer/J-4501-2013 OI Nelson, Eric/0000-0002-3376-2453; FU National Institute of Mental Health, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 47 TC 52 Z9 52 U1 0 U2 5 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 MAR 15 PY 2011 VL 108 IS 11 BP 4500 EP 4505 DI 10.1073/pnas.1005494108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735WI UT WOS:000288450900048 PM 21368210 ER PT J AU Dowd, KA Pierson, TC AF Dowd, Kimberly A. Pierson, Theodore C. TI Antibody-mediated neutralization of flaviviruses: A reductionist view SO VIROLOGY LA English DT Review DE Flavivirus; Antibody-mediated neutralization; Antibody-dependent enhancement of infection; West Nile virus; Dengue virus; Complement ID WEST-NILE-VIRUS; TICK-BORNE ENCEPHALITIS; DENGUE HEMORRHAGIC-FEVER; HUMANIZED MONOCLONAL-ANTIBODY; PROTEIN DOMAIN-III; DEPENDENT ENHANCEMENT; ENVELOPE PROTEIN; ANTIGENIC STRUCTURE; ANIMAL VIRUSES; STRUCTURAL BASIS AB Flaviviruses are a group of similar to 70 small RNA viruses responsible for significant morbidity and mortality across the globe. Efforts to develop effective vaccines for several clinically important flaviviruses are underway. Antibodies are a significant component of the host's protective response against flavivirus infection with the potential to contribute to immunity via several distinct mechanisms, including an ability to directly neutralize virus infection. Conversely, virus-reactive antibodies have been implicated in the increased risk of severe clinical manifestations following secondary dengue virus infection. In this review, we will discuss recent progress toward understanding the molecular basis of antibody-mediated neutralization of flaviviruses. Neutralization requires engagement of the virion with a stoichiometry that exceeds a required threshold. From this perspective, we will discuss viral and host factors that impact the number of antibody molecules bound to the virus particle and significantly modulate the potency of neutralizing antibodies. (C) 2011 Elsevier Inc. All rights reserved. C1 [Dowd, Kimberly A.; Pierson, Theodore C.] NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Pierson, TC (reprint author), NIAID, Viral Pathogenesis Sect, Viral Dis Lab, NIH, 33 North Dr,Bldg 33,Room 1E19A2, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU National Institute of Allergy and Infectious Disease FX The authors thank Drs. Michael Diamond, Heather Hickman, Thomas Kristie and members of our laboratory for helpful discussions and critical comments on this manuscript. This work was supported by the intramural program of the National Institute of Allergy and Infectious Disease. NR 118 TC 64 Z9 64 U1 1 U2 10 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 MAR 15 PY 2011 VL 411 IS 2 SI SI BP 306 EP 315 DI 10.1016/j.virol.2010.12.020 PG 10 WC Virology SC Virology GA 734OI UT WOS:000288343000015 PM 21255816 ER PT J AU Wang, H O'Reilly, EJ Weisskopf, MG Logroscino, G McCullough, ML Schatzkin, A Kolonel, LN Ascherio, A AF Wang, Hao O'Reilly, Eilis J. Weisskopf, Marc G. Logroscino, Giancarlo McCullough, Marjorie L. Schatzkin, Arthur Kolonel, Laurence N. Ascherio, Alberto TI Vitamin E Intake and Risk of Amyotrophic Lateral Sclerosis: A Pooled Analysis of Data From 5 Prospective Cohort Studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE alpha-tocopherol; amyotrophic lateral sclerosis; antioxidants; cohort studies; diet; vitamin E ID FOOD FREQUENCY QUESTIONNAIRE; SOCIETY CANCER PREVENTION; BASE-LINE CHARACTERISTICS; MOTOR-NEURON DISEASE; OXIDATIVE STRESS; DIETARY-INTAKE; DOUBLE-BLIND; POPULATION; SURVIVAL; HEALTH AB The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses' Health Study (1976-2004), the Health Professionals Follow-up Study (1986-2004), the Cancer Prevention Study II Nutrition Cohort (1992-2004), the Multiethnic Cohort Study (1993-2005), and the National Institutes of Health-AARP Diet and Health Study (1995-2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend = 0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for <= 1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2-4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for >= 5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend = 0.002) but not in men (P-trend = 0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration. C1 [Wang, Hao; O'Reilly, Eilis J.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Weisskopf, Marc G.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Weisskopf, Marc G.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Logroscino, Giancarlo] Univ Bari, Dept Neurol & Psychiat, Sch Med, Bari, Italy. [McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA. [Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP O'Reilly, EJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM eoreilly@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242 FU National Institute of Neurological Disorders and Stroke [R01 NS045893]; National Cancer Institute [P01 CA87969, P01 CA055075] FX This work was supported by grant R01 NS045893 from the National Institute of Neurological Disorders and Stroke and by grants P01 CA87969 and P01 CA055075 from the National Cancer Institute. NR 40 TC 40 Z9 42 U1 1 U2 8 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 MAR 15 PY 2011 VL 173 IS 6 BP 595 EP 602 DI 10.1093/aje/kwq416 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 733PL UT WOS:000288274800001 PM 21335424 ER PT J AU Qiu, CF Frederick, IO Zhang, CL Sorensen, TK Enquobahrie, DA Williams, MA AF Qiu, Chunfang Frederick, Ihunnaya O. Zhang, Cuilin Sorensen, Tanya K. Enquobahrie, Daniel A. Williams, Michelle A. TI Risk of Gestational Diabetes Mellitus in Relation to Maternal Egg and Cholesterol Intake SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cholesterol; diabetes; gestational; eggs ID DIETARY-CHOLESTEROL; GLUCOSE-TOLERANCE; WOMEN; FAT; MEN; ATHEROSCLEROSIS; QUESTIONNAIRE; PREECLAMPSIA; CONSUMPTION; PREGNANCY AB Higher egg and cholesterol intakes are associated with increased risk of type 2 diabetes mellitus. However, their association with gestational diabetes mellitus (GDM) has not been evaluated. The authors assessed such associations in both a prospective cohort study (1996-2008; 3,158 participants) and a case-control study (1998-2002; 185 cases, 411 controls). A food frequency questionnaire was used to assess maternal diet. Multivariable models were used to derive relative risks and 95% confidence intervals. Compared with no egg consumption, adjusted relative risks for GDM were 0.94, 1.01, 1.12, 1.54, and 2.52 for consumption of <= 1, 2-3, 4-6, 7-9, and >= 10 eggs/week, respectively (P for trend = 0.008). Women with high egg consumption (>= 7/week) had a 1.77-fold increased risk compared with women with lower consumption (95% confidence interval (CI): 1.19, 2.63). The relative risk for the highest quartile of cholesterol intake (>= 294 mg/day) versus the lowest (< 151 mg/day) was 2.35 (95% CI: 1.35, 4.09). In the case-control study, the adjusted odds ratio for consuming >= 7 eggs/week versus < 7 eggs/week was 2.65 (95% CI: 1.48, 4.72), and the odds of GDM increased with increasing cholesterol intake (P for trend = 0.021). In conclusion, high egg and cholesterol intakes before and during pregnancy are associated with increased risk of GDM. C1 [Qiu, Chunfang; Frederick, Ihunnaya O.; Sorensen, Tanya K.; Enquobahrie, Daniel A.; Williams, Michelle A.] Swedish Med Ctr, Ctr Perinatal Studies, Seattle, WA 98104 USA. [Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Enquobahrie, Daniel A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Qiu, CF (reprint author), Swedish Med Ctr, Ctr Perinatal Studies, 1124 Columbia St,Suite 750, Seattle, WA 98104 USA. EM Chun-fang.Qiu@Swedish.org FU National Institutes of Health [R01HD-32562, R01HD-355566]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported by awards (R01HD-32562 and R01HD-355566) from the National Institutes of Health. Dr. Cuilin Zhang was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 31 TC 18 Z9 18 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 MAR 15 PY 2011 VL 173 IS 6 BP 649 EP 658 DI 10.1093/aje/kwq425 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 733PL UT WOS:000288274800006 PM 21324948 ER PT J AU Prideaux, B Dartois, V Staab, D Weiner, DM Goh, A Via, LE Barry, CE Stoeckli, M AF Prideaux, Brendan Dartois, Veronique Staab, Dieter Weiner, Danielle M. Goh, Anne Via, Laura E. Barry, Clifton E., III Stoeckli, Markus TI High-Sensitivity MALDI-MRM-MS Imaging of Moxifloxacin Distribution in Tuberculosis-Infected Rabbit Lungs and Granulomatous Lesions SO ANALYTICAL CHEMISTRY LA English DT Article ID BODY TISSUE-SECTIONS; PULMONARY TUBERCULOSIS; BACTERICIDAL ACTIVITY; PENETRATION; ETHAMBUTOL AB MALDI-MSI is a powerful technology for localizing drug and metabolite distributions in biological tissues. To enhance our understanding of tuberculosis (TB) drug efficacy and how efficiently certain drugs reach their site of action, MALDI-MSI was applied to image the distribution of the second-line TB drug moxifloxacin at a range of time points after dosing. The ability to perform multiple monitoring of selected ion transitions in the same experiment enabled extremely sensitive imaging of moxifloxacin within tuberculosis infected rabbit lung biopsies in less than 15 min per tissue section. Homogeneous application of a reference standard during the matrix spraying process enabled the ion suppressing effects of the inhomogeneous lung tissue to be normalized. The drug was observed to accumulate in granulomatous lesions at levels higher than that in the surrounding lung tissue from 1.5 h postdose until the final time point. MALDI-MSI moxifloxacin distribution data were validated by quantitative LC/MS/MS analysis of lung and granuloma extracts from adjacent biopsies taken from the same animals. Drug distribution within the granulomas was observed to be inhomogeneous; and very low levels were observed in the caseum in comparison to the cellular granuloma regions. In this experiment the MALDI-MRM-MSI method was shown to be a rapid and sensitive method for analyzing the distribution of anti-TB compounds and will be applied to distribution studies of additional drugs in the future. C1 [Prideaux, Brendan; Staab, Dieter; Stoeckli, Markus] Novartis Inst BioMed Res, Basel, Switzerland. [Weiner, Danielle M.; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. [Dartois, Veronique; Goh, Anne] Novartis Inst Trop Dis, Biopolis, Singapore. RP Prideaux, B (reprint author), Novartis Inst BioMed Res, Basel, Switzerland. EM brendan.prideaux@novartis.com RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU National Institutes of Health, National Institute of Allergy and Infectious Disease; Bill and Melinda Gates Foundation; Wellcome Trust through the Grand Challenges in Global Health Initiative (PI, Douglas Young, Imperial College); PI, Joanne Flynne, University of Pittsburgh FX The authors acknowledge the contributions of Emmanuel Dayao and Daniel Schimel (National Institute of Allergy and Infectious Disease) for animal handling and biopsy preparation, and Peiting Zeng and Hui Qing Mg (Novartis Institute for Tropical Disease) for analytical and technical support. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease, and grants from the Bill and Melinda Gates Foundation and the Wellcome Trust through the Grand Challenges in Global Health Initiative (PI, Douglas Young, Imperial College) and the TB Drug Accelerator program (PI, Joanne Flynne, University of Pittsburgh). NR 21 TC 116 Z9 116 U1 1 U2 45 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 2011 VL 83 IS 6 BP 2112 EP 2118 DI 10.1021/ac1029049 PG 7 WC Chemistry, Analytical SC Chemistry GA 732KE UT WOS:000288182900034 PM 21332183 ER PT J AU Chan, KC Veenstra, TD Issaq, HJ AF Chan, King C. Veenstra, Timothy D. Issaq, Haleem J. TI Comparison of Fluorescence, Laser-Induced Fluorescence, and Ultraviolet Absorbance Detection for Measuring HPLC Fractionated Protein/Peptide Mixtures SO ANALYTICAL CHEMISTRY LA English DT Article ID CAPILLARY-ELECTROPHORESIS; PEPTIDES; PROTEINS AB Proteomics is the study of all proteins in a biological sample. High-pressure liquid chromatography coupled online with mass spectrometry (HPLC/MS) is currently the method of choice for proteomic analysis. Proteins are extracted, separated at the protein or peptide level (after enzymatic digestion), and fractions are analyzed by HPLC/MS. Detection during off-line fractionation is generally conducted using UV-vis, which is not sensitive enough to distinguish fractions having the largest concentration of proteins/peptides and should not be combined prior to HPLC/MS. To overcome this deficiency, we utilize fluorescence or UV-laser induced fluorescence (UV-LIF) detection for measuring proteins/peptides during the off-line fractionation. Fluorescence detection allows low-abundance proteins/peptides that contain aromatic amino acids to be measured. In this study, peptide/protein samples fractionated using ion-exchange chromatography were detected using UV absorbance, fluorescence, and UV-LIF. The results indicated that fluorescence and UV-LIF were able to detect the lower abundance proteins/peptides to give a more representative chromatogram, allowing the analyst to decide which fractions should be combined prior to HPLC/tandem mass spectrometry (MS/MS) analysis. C1 [Chan, King C.; Veenstra, Timothy D.; Issaq, Haleem J.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM issaqh@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. NR 6 TC 5 Z9 5 U1 0 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 2011 VL 83 IS 6 BP 2394 EP 2396 DI 10.1021/ac1032462 PG 3 WC Chemistry, Analytical SC Chemistry GA 732KE UT WOS:000288182900073 PM 21319742 ER PT J AU Edmonson, MN Zhang, JH Yan, CH Finney, RP Meerzaman, DM Buetow, KH AF Edmonson, Michael N. Zhang, Jinghui Yan, Chunhua Finney, Richard P. Meerzaman, Daoud M. Buetow, Kenneth H. TI Bambino: a variant detector and alignment viewer for next-generation sequencing data in the SAM/BAM format SO BIOINFORMATICS LA English DT Article AB Summary: Bambino is a variant detector and graphical alignment viewer for next-generation sequencing data in the SAM/BAM format, which is capable of pooling data from multiple source files. The variant detector takes advantage of SAM-specific annotations, and produces detailed output suitable for genotyping and identification of somatic mutations. The assembly viewer can display reads in the context of either a user-provided or automatically generated reference sequence, retrieve genome annotation features from a UCSC genome annotation database, display histograms of non-reference allele frequencies, and predict protein-coding changes caused by SNPs. Availability: Bambino is written in platform-independent Java and available from https://cgwb.nci.nih.gov/golden Path/bamview/documentation/index.html, along with documentation and example data. Bambino may be launched online via Java Web Start or downloaded and run locally. Contact: edmonson@nih.gov. C1 [Edmonson, Michael N.; Meerzaman, Daoud M.; Buetow, Kenneth H.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. [Zhang, Jinghui] St Jude Childrens Hosp, Dept Computat Biol, Memphis, TN 38105 USA. [Yan, Chunhua; Finney, Richard P.] NCI, Ctr Bioinformat & Informat Technol, Rockville, MD 20852 USA. RP Edmonson, MN (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. EM edmonson@nih.gov RI Sincan, Murat /A-3794-2010 FU National Institutes of Health [ZIH BC 010470] FX Funding: This work was supported by the National Institutes of Health (ZIH BC 010470). NR 8 TC 32 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 15 PY 2011 VL 27 IS 6 BP 865 EP 866 DI 10.1093/bioinformatics/btr032 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 733QI UT WOS:000288277300019 PM 21278191 ER PT J AU Grillon, C Heller, R Hirschhorn, E Kling, MA Pine, DS Schulkin, J Vythilingam, M AF Grillon, Christian Heller, Randi Hirschhorn, Elizabeth Kling, Mitchel A. Pine, Daniel S. Schulkin, Jay Vythilingam, Meena TI Acute Hydrocortisone Treatment Increases Anxiety but Not Fear in Healthy Volunteers: A Fear-Potentiated Startle Study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Amygdala; anxiety; BNST; corticotropin-releasing hormone (CRH); cortisol; fear; predictability; startle reflex ID CORTICOTROPIN-RELEASING HORMONE; POSTTRAUMATIC-STRESS-DISORDER; CRH MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; PREFRONTAL CORTEX; CONTEXTUAL-FEAR; PANIC DISORDER; CUED FEAR; CORTICOSTERONE; CORTISOL AB Background: The debilitating effects of chronic glucocorticoids excess are well-known, but comparatively little is understood about the role of acute cortisol. Indirect evidence in rodents suggests that acute cortisone could selectively increase some forms of long-duration aversive states, such as "anxiety," but not relatively similar, briefer aversive states, such as "fear." However, no prior experimental studies in humans consider the unique effects of cortisol on anxiety and fear, using well-validated methods for eliciting these two similar but dissociable aversive states. The current study examines these effects, as instantiated with short- and long-duration threats. Methods: Healthy volunteers (n = 18) received placebo or a low (20 mg) or a high (60 mg) dose of hydrocortisone in a double-blind crossover design. Subjects were exposed repeatedly to three 150-sec duration conditions: no shock; predictable shocks, in which shocks were signaled by a short-duration threat cue; and unpredictable shocks. Aversive states were indexed by acoustic startle. Fear was operationally defined as the increase in startle reactivity during the threat cue in the predictable condition (fear-potentiated startle). Anxiety was operationally defined as the increase in baseline startle from the no shock to the two threat conditions (anxiety-potentiated startle). Results: Hydrocortisone affected neither baseline nor short-duration, fear-potentiated startle but increased long-duration anxiety-potentiated startle. Conclusions: These results suggest that hydrocortisone administration in humans selectively increases anxiety but not fear. Possible mechanisms implicated are discussed in light of prior data in rodents. Specifically, hydrocortisone might increase anxiety via sensitization of corticotrophin-releasing hormones in the bed nucleus of the stria terminalis. C1 [Grillon, Christian; Heller, Randi; Hirschhorn, Elizabeth; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Kling, Mitchel A.] Philadelphia Vet Adm Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Schulkin, Jay] Georgetown Univ Sch Med, Dept Neurosci, Washington, DC USA. [Vythilingam, Meena] Off Assistant Secretary Def, Falls Church, VA USA. RP Grillon, C (reprint author), NIMH MAP, 15K North Dr,Bldg 15K,Room 203,MSC 2670, Bethesda, MD 20892 USA. EM Christian.grillon@nih.gov RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 FU National Institute of Mental Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health. NR 53 TC 14 Z9 14 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 MAR 15 PY 2011 VL 69 IS 6 BP 549 EP 555 DI 10.1016/j.biopsych.2010.12.013 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 732NW UT WOS:000288193400009 PM 21277566 ER PT J AU Landgren, AM Landgren, O Gridley, G Dores, GM Linet, MS Morton, LM AF Landgren, Anne M. Landgren, Ola Gridley, Gloria Dores, Grace M. Linet, Martha S. Morton, Lindsay M. TI Autoimmune Disease and Subsequent Risk of Developing Alimentary Tract Cancers Among 4.5 Million US Male Veterans SO CANCER LA English DT Article DE alimentary; gastrointestinal; autoimmune disease; inflammation; cancer ID INFLAMMATORY-BOWEL-DISEASE; COMPLICATING CROHNS-DISEASE; PRIMARY BILIARY-CIRRHOSIS; POPULATION-BASED COHORT; MULTIPLE-SCLEROSIS; CELIAC-DISEASE; PERNICIOUS-ANEMIA; RHEUMATOID-ARTHRITIS; POLYARTERITIS-NODOSA; HELICOBACTER-PYLORI AB BACKGROUND: Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer. METHODS: On the basis of 4,501,578 US male veterans, the authors identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow-up. By using Poisson regression methods, the authors calculated relative risks (RRs) and 95% confidence intervals. RESULTS: A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR, 6.01; 95% confidence interval [Cl], 4.76-7.57); pernicious anemia and stomach cancer (RR, 3.17; 95% Cl, 2.47-4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR, 2.53; 95% Cl, 1.05-6.11; RR, 2.06; 95% Cl, 1.70-2.48; and RR, 2.07; 95% Cl, 1.62-2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter disease), and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR, 1.86-2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis. CONCLUSIONS: These findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm the findings and improve understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis. Cancer 2011;117:1163-71. Published 2010 by the American Cancer Society* C1 [Landgren, Anne M.; Dores, Grace M.; Linet, Martha S.; Morton, Lindsay M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. [Landgren, Anne M.] Mid Sweden Univ, Dept Hlth Sci, Sundsvall, Sweden. [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gridley, Gloria] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Dores, Grace M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK USA. RP Morton, LM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7040,MSC 7238, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 57 TC 51 Z9 53 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 2011 VL 117 IS 6 BP 1163 EP 1171 DI 10.1002/cncr.25524 PG 9 WC Oncology SC Oncology GA 734PZ UT WOS:000288349300008 PM 21381009 ER PT J AU Piszczek, G Lee, JC Tjandra, N Lee, CR Seok, YJ Levine, RL Peterkofsky, A AF Piszczek, Grzegorz Lee, Jennifer C. Tjandra, Nico Lee, Chang-Ro Seok, Yeong-Jae Levine, Rodney L. Peterkofsky, Alan TI Deuteration of Escherichia coli Enzyme I-Ntr alters its stability SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Phosphotransferase system; Deuteration; Conformation; Protein structure ID SUGAR PHOSPHOTRANSFERASE SYSTEM; N-TERMINAL DOMAIN; CONFORMATIONAL STABILITY; PROTEIN IIA(NTR); ALPHA-SYNUCLEIN; PHOSPHOENOLPYRUVATE; FLUORESCENCE; ARGINASE; MASS; NPR AB Enzyme I-Ntr is the first protein in the nitrogen phosphotransferase pathway. Using an array of biochemical and biophysical tools, we characterized the protein, compared its properties to that of EI of the carbohydrate PTS and, in addition, examined the effect of substitution of all nonexchangeable protons by deuterium (perdeuteration) on the properties of EINtr. Notably, we find that the catalytic function (autophosphorylation and phosphotransfer to NPr) remains unperturbed while its stability is modulated by deuteration. In particular, the deuterated form exhibits a reduction of approximately 4 degrees C in thermal stability, enhanced oligomerization propensity, as well as increased sensitivity to proteolysis in vitro. We investigated tertiary, secondary, and local structural changes, both in the absence and presence of PEP, using near- and far-UV circular dichroism and Trp fluorescence spectroscopy. Our data demonstrate that the aromatic residues are particularly sensitive probes for detecting effects of deuteration with an enhanced quantum yield upon PEP binding and apparent decreases in tertiary contacts for Tyr and Trp side chains. Trp mutagenesis studies showed that the region around Trp522 responds to binding of both PEP and NPr. The significance of these results in the context of structural analysis of EINtr are evaluated. Published by Elsevier Inc. C1 [Piszczek, Grzegorz; Lee, Jennifer C.; Tjandra, Nico; Levine, Rodney L.; Peterkofsky, Alan] NHLBI, Bethesda, MD 20892 USA. [Lee, Chang-Ro; Seok, Yeong-Jae] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul 151742, South Korea. RP Peterkofsky, A (reprint author), NIH, Bldg 50,Room 2316, Bethesda, MD 20892 USA. EM peterkofsky@nih.gov RI Lee, Jennifer/E-9658-2015; Levine, Rodney/D-9885-2011 OI Lee, Jennifer/0000-0003-0506-8349; FU National Heart, Lung and Blood Institute; MEST, Korea [NRF 2010-0017384] FX This work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute.; The authors acknowledge helpful discussions with Drs. Edward Korn (NIH), Osnat Herzberg and John Moult (Center for Advanced Research in Biotechnology), expert guidance in the use of the stop-quench instrument by Dr. James Sellers (NIH) as well as the excellent technical assistance of Nancy Wehr (NIH). We thank Dr. David Christianson (University of Pennsylvania) for gifts of hydrogenated and perdeuterated human arginase and Dr. Nelson Cole (NIH) for a gift of alpha-synuclein. YJS was supported by the National Research Foundation Grant (NRF 2010-0017384) funded by MEST, Korea. NR 41 TC 4 Z9 4 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 2011 VL 507 IS 2 BP 332 EP 342 DI 10.1016/j.abb.2010.12.022 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 730TR UT WOS:000288058000017 PM 21185804 ER PT J AU Haspel, N Zanuy, D Nussinov, R Teesalu, T Ruoslahti, E Aleman, C AF Haspel, Nurit Zanuy, David Nussinov, Ruth Teesalu, Tambet Ruoslahti, Erkki Aleman, Carlos TI Binding of a C-End Rule Peptide to the Neuropilin-1 Receptor: A Molecular Modeling Approach SO BIOCHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY; FORCE-FIELD; HEPARIN-BINDING; CELLS SECRETE; TUMOR; ANGIOGENESIS; SIMULATIONS; PROTEINS; DYNAMICS AB Neuropilin-1 (NRP-1) is a receptor that plays an essential role in angiogenesis, vascular permeability, and nervous system development. Previous studies have shown that peptides with an N-terminal Arg, especially peptides with the four-residue consensus sequence R/K/XXR/K, bind to NRP-1 cell surfaces. Peptides containing such consensus sequences promote binding and internalization into cells, while blocking the C-terminal Arg (or Lys) prevents the internalization. In this study, we use molecular dynamics simulations to model the structural properties of the NRP-1 complex with a prototypic CendR peptide, RPAR. Our simulations show that RPAR binds NRP-1 through specific interactions of the RPAR C-terminus: three hydrogen bonds and a salt bridge anchor the ligand in the receptor pocket. The modeling results were used as the starting point for a systematic computational study of new RPAR analogues based on chemical modifications of their natural amino acids. Comparison of the structural properties of the new peptide-receptor complexes with the original organization suggests that some of the analogues can increase the binding affinity while reducing the natural sensitivity of RXXR to endogenous proteases. C1 [Haspel, Nurit] Univ Massachusetts, Dept Comp Sci, Boston, MA 02125 USA. [Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, ETSEIB, Dept Engn Quim, E-08028 Barcelona, Spain. [Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Teesalu, Tambet; Ruoslahti, Erkki] Univ Calif Santa Barbara, Sanford Burnham Med Res Inst UCSB, Ctr Nanomed, Santa Barbara, CA 93106 USA. [Ruoslahti, Erkki] Sanford Burnham Med Res Inst, Canc Res Ctr, La Jolla, CA 92037 USA. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Haspel, N (reprint author), Univ Massachusetts, Dept Comp Sci, Boston, MA 02125 USA. EM nurit.haspel@umb.edu; david.zanuy@upc.edu RI Zanuy, David/G-3930-2014; Teesalu, Tambet/J-1802-2015; Haspel, Nurit/D-1961-2017 OI Zanuy, David/0000-0001-7704-2178; FU National Science Foundation through TeraGrid resources provided by the Texas Advanced Computing Center (TACC) [TG-MCB100025]; Generalitat de Catalunya [2009 SGR 925]; National Cancer Institute, National Institutes of Health (NIH) [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the National Science Foundation through TeraGrid resources provided by the Texas Advanced Computing Center (TACC) under Grant TG-MCB100025 (N. H.). Financial support from Generalitat de Catalunya is gratefully acknowledged (Research Group 2009 SGR 925; XRQTC; ICREA Academia prize for excellence in research to C.A.). This project has been funded in part by the National Cancer Institute, National Institutes of Health (NIH), via Contract HHSN261200800001E. This research was also supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 23 TC 28 Z9 29 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 15 PY 2011 VL 50 IS 10 BP 1755 EP 1762 DI 10.1021/bi101662j PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730AY UT WOS:000287997000020 PM 21247217 ER PT J AU Valdez, JM Scheinberg, P Nunez, O Wu, CO Young, NS Walsh, TJ AF Valdez, Jessica M. Scheinberg, Phillip Nunez, Olga Wu, Colin O. Young, Neal S. Walsh, Thomas J. TI Decreased Infection-Related Mortality and Improved Survival in Severe Aplastic Anemia in the Past Two Decades SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CYCLOPHOSPHAMIDE; COLONY-STIMULATING FACTOR; LIPOSOMAL AMPHOTERICIN-B; ANTI-THYMOCYTE GLOBULIN; ANTITHYMOCYTE GLOBULIN; IMMUNOSUPPRESSIVE THERAPY; ANTIFUNGAL THERAPY; ANTILYMPHOCYTE GLOBULIN; PERSISTENT FEVER AB Background. Persistent neutropenia associated with severe aplastic anemia (SAA) is an important risk factor for development of life-threatening infections. Earlier studies underscored the high mortality associated with invasive fungal infections (IFIs) in SAA. However, little is known about the current patterns of infections and the impact of advances in anti-infective therapy on survival in SAA. Methods. We reviewed the records of 174 patients with SAA admitted to the Hematology Branch at NHLBI from 1989 to 2008 who were unresponsive to initial immunosuppressive therapy (IST) at 6 months. Three patient groups determined by IST protocol and time interval were compared: group 1 (43 patients; December 1989-October 1996), group 2 (51 patients; November 1996-October 2002), and group 3 (80 patients; November 2002-April 2008). Outcome variables included infections, patterns of resistance, survival, and infection-related mortality. Results. During the past 2 decades, infection-related mortality decreased from 37% in group 1 to 11% in group 3 (P<.001), and the frequency of IFIs decreased from 49% in group 1 to 8% in group 3 (P<.001). Overall 5-year survival for all patients (n = 420) increased from 64% in group 1 to 79% in group 3 (P<.001). Among nonresponders (n = 174), it increased from 23% in group 1 to 57% in group 3 (P<.001). In multivariate analysis, younger age, absolute neutrophil count >200 cells/mu L before IST, absence of IFIs, and use of voriconazole were independently predictive of survival. Conclusion. During the past 2 decades, there has been a significant decrease in IFIs, infection-related mortality, and overall mortality in patients with SAA unresponsive to initial IST. C1 [Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med Coll, New York, NY 10065 USA. [Walsh, Thomas J.] New York Presbyterian Hosp, New York, NY USA. [Valdez, Jessica M.] NCI, Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20892 USA. [Valdez, Jessica M.; Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Scheinberg, Phillip; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med Coll, 1300 York Ave,Rm A-421, New York, NY 10065 USA. EM thw2003@med.cornell.edu OI Scheinberg, Phillip/0000-0002-9047-4538 FU National Institutes of Health, National Heart, Lung and Blood Institute; National Cancer Institute; Vestagen FX Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute and National Cancer Institute.; T.J.W. has received a research grant from Vestagen, has served on Advisory Boards of Novartis Therapeutics, and is a consultant for Trius and Novartis. All other authors: no conflicts. NR 26 TC 29 Z9 35 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 MAR 15 PY 2011 VL 52 IS 6 BP 726 EP 735 DI 10.1093/cid/ciq245 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 730FX UT WOS:000288020300006 PM 21367725 ER PT J AU De Ravin, SS Challipalli, M Anderson, V Shea, YR Marciano, B Hilligoss, D Marquesen, M DeCastro, R Liu, YC Sutton, DA Wickes, BL Kammeyer, PL Sigler, L Sullivan, K Kang, EM Malech, HL Holland, SM Zelazny, AM AF De Ravin, Suk See Challipalli, Malliswari Anderson, Victoria Shea, Yvonne R. Marciano, Beatriz Hilligoss, Dianne Marquesen, Martha DeCastro, Rosamma Liu, Yen-chun Sutton, Deanna A. Wickes, Brian L. Kammeyer, Patricia L. Sigler, Lynne Sullivan, Kathleen Kang, Elizabeth M. Malech, Harry L. Holland, Steven M. Zelazny, Adrian M. TI Geosmithia argillacea: An Emerging Cause of Invasive Mycosis in Human Chronic Granulomatous Disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTERNAL TRANSCRIBED SPACER; PAECILOMYCES-VARIOTII; ASPERGILLUS-FUMIGATUS; NEOSARTORYA-UDAGAWAE; CYSTIC-FIBROSIS; INFECTION; PATIENT; OSTEOMYELITIS; PENICILLIUM; NIDULANS AB Background. Chronic granulomatous disease (CGD) is an inherited disorder of the nicotinamide adenine dinucleotide phosphate oxidase that leads to defective production of microbicidal superoxide and other oxidative radicals, resulting in increased susceptibility to invasive infections, especially those due to fungi. Methods. Geosmithia argillacea was identified from cultured isolates by genomic sequencing of the internal transcribed spacer region. Isolates previously identified as Paecilomyces variotii, a filamentous fungus closely resembling G. argillacea, were also examined. Results. We identified G. argillacea as the cause of invasive mycosis in 7 CGD patients. In 5 cases, the fungus had been previously identified morphologically as P. variotii. All patients had pulmonary lesions; 1 had disseminated lesions following inhalational pneumonia. Infections involved the chest wall and contiguous ribs in 2 patients and disseminated to the brain in 1 patient. Four patients with pneumonia underwent surgical intervention. All patients responded poorly to medical treatment, and 3 died. Conclusions. We report the first cases of invasive mycosis caused by G. argillacea in CGD patients. G. argillacea infections in CGD are often refractory and severe with a high fatality rate. Surgical intervention has been effective in some cases. G. argillacea is a previously underappreciated and frequently misidentified pathogen in CGD that should be excluded when P. variotii is identified morphologically. C1 [De Ravin, Suk See] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Anderson, Victoria; Marciano, Beatriz; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Shea, Yvonne R.; Zelazny, Adrian M.] NCI, Microbiol Serv, Dept Lab Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. [Liu, Yen-chun] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Challipalli, Malliswari; Kammeyer, Patricia L.] Loyola Univ, Dept Pediat, Maywood, IL 60153 USA. [Challipalli, Malliswari; Kammeyer, Patricia L.] Loyola Univ, Dept Pathol, Maywood, IL 60153 USA. [Sutton, Deanna A.; Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Sullivan, Kathleen] Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA. [Sigler, Lynne] Univ Alberta Microfungus Collect & Herbarium, Edmonton, AB, Canada. RP De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,5W-3816, Bethesda, MD 20892 USA. EM sderavin@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775; Sullivan, Kathleen/0000-0003-4018-1646 FU National Institutes of Allergy and Infectious Diseases Division of Intramural Research; Clinical Center of the National Institutes of Health; Natural Sciences and Engineering Research Council of Canada (NSERC) FX This work was supported by the National Institutes of Allergy and Infectious Diseases Division of Intramural Research and the Clinical Center of the National Institutes of Health. L. Sigler receives grant support from the Natural Sciences and Engineering Research Council of Canada (NSERC). NR 27 TC 29 Z9 29 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 MAR 15 PY 2011 VL 52 IS 6 BP E136 EP E143 DI 10.1093/cid/ciq250 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 730FX UT WOS:000288020300001 PM 21367720 ER PT J AU Zhang, Z O'Rourke, JR McManus, MT Lewandoski, M Harfe, BD Sun, X AF Zhang, Zhen O'Rourke, Jason R. McManus, Michael T. Lewandoski, Mark Harfe, Brian D. Sun, Xin TI The microRNA-processing enzyme Dicer is dispensable for somite segmentation but essential for limb bud positioning SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Limb; Limb positioning; Somite; Dicer; MicroRNA; Mouse ID MOUSE DEVELOPMENT; VERTEBRATE LIMB; C-ELEGANS; EXPRESSION; ZEBRAFISH; GENES; SOMITOGENESIS; MORPHOGENESIS; INITIATION; MESODERM AB Dicer is an enzyme that processes microRNAs (miRNAs) to their mature forms. As miRNAs were first discovered for their role in the control of developmental timing, we investigated their potential requirement in mouse somitogenesis, an event with precise temporal periodicity. To address the collective role of miRNAs in mesoderm development including somite formation, we used T (Brachyury)-Cre mouse line to inactivate Dicer in most cells of the mesoderm lineage. This Dicer mutant exhibits a reduced anterior-posterior axis. Somite number remains normal in mutant embryos up until the death of the embryos more than two days after Dicer inactivation. Consistent with this, the molecular machineries required for establishing segmentation, including clock and wave front, are not perturbed. However, somite size is reduced and later-formed somites are caudalized, coincident with increased cell death. Outside of the paraxial mesoderm and prior to apparent reduction of the axis in the mutant, the position of the hindlimb bud, a lateral plate mesoderm-derived structure, is posteriorly shifted and the timing of hindlimb bud initiation is delayed accordingly. We observed changes in the expression of genes critical for limb positioning, which include a shifted and delayed downregulation of Hand2 and Tbx3, and shifted and delayed upregulation of Gli3 in the prospective limb bud field. The 3' UTRs of both Hand2 and Tbx3 harbor target sites for a seed sequence-sharing family of miRNAs mir-25/32/92/363/367. As an example of the family we show that mir-363, a miRNA with elevated expression in the prospective limb bud field, is capable of inhibiting Hand2/Tbx3 expression in vitro in a binding site-dependent manner. Together, our findings provide the first demonstration that in mouse embryonic mesoderm, while Dicer is dispensable for somite segmentation, it is essential for proper limb bud positioning. (C) 2011 Elsevier Inc. All rights reserved. C1 [Zhang, Zhen; Sun, Xin] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. [O'Rourke, Jason R.; Harfe, Brian D.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. [McManus, Michael T.] Univ Calif San Francisco, Dept Microbiol & Immunol, Ctr Diabet, San Francisco, CA 94143 USA. [Lewandoski, Mark] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Sun, X (reprint author), Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. EM xsun@wisc.edu RI Zhang, Zhen/D-4804-2012; Zhang, Zhen/F-1840-2013 FU NIH [HD045522, HD045522-05S1]; Burroughs-Wellcome career award [1002361] FX We thank Dr. John Fallon, Dr. Jerome Gros and members of the Sun laboratory for insightful discussions, technical contributions and critical reading of the manuscript. We are grateful to Drs. Rosa Beddington, Susan Cole, Achim Gossler, Stacey Huppert, Raphael Kopan, Gail Martin Yumiko Saga, and Terry Yamaguchi for providing plasmids from which RNA in situ probes were prepared. We thank Amber Lashua for excellent technical assistance. This work was supported by NIH Grants HD045522 and HD045522-05S1 (to X.S.) and a Burroughs-Wellcome career award #1002361 (to X.S.). NR 55 TC 17 Z9 17 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2011 VL 351 IS 2 BP 254 EP 265 DI 10.1016/j.ydbio.2011.01.005 PG 12 WC Developmental Biology SC Developmental Biology GA 730QE UT WOS:000288048300003 PM 21256124 ER PT J AU Thomas, EA Coppola, G Tang, B Kuhn, A Kim, S Geschwind, DH Brown, TB Luthi-Carter, R Ehrlich, ME AF Thomas, Elizabeth A. Coppola, Giovanni Tang, Bin Kuhn, Alexandre Kim, SoongHo Geschwind, Daniel H. Brown, Timothy B. Luthi-Carter, Ruth Ehrlich, Michelle E. TI In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE TRANSGENIC MICE; GENE-EXPRESSION; NEURODEGENERATIVE DISEASES; NEUROLOGICAL SYMPTOMS; NEUROTROPHIC FACTOR; RAT STRIATUM; TARGET GENES; MOUSE MODEL; BRAIN; DYSREGULATION AB Huntington's disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell- autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared with those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support. While genes related to excitotoxicity, dopamine signaling and trophic support were altered in both DE5 and R6/2 mice, which may be either cell autonomous or non-cell autonomous, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell-autonomous mechanisms. Overall, HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt, in the absence of expression in cortical neurons. C1 [Kim, SoongHo; Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Thomas, Elizabeth A.; Tang, Bin] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Coppola, Giovanni; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, Program Neurogenet, Los Angeles, CA 90024 USA. [Coppola, Giovanni; Geschwind, Daniel H.] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. [Kim, SoongHo; Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. [Kuhn, Alexandre] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Brown, Timothy B.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Luthi-Carter, Ruth] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. RP Ehrlich, ME (reprint author), Mt Sinai Sch Med, Dept Neurol, Annenberg 14-44,1 Gustave L Levy Pl, New York, NY 10029 USA. EM michelle.ehrlich@mssm.edu FU National Institutes of Health [NS-059936, NS-045942, NS44169]; Cure Huntington's Disease Initiative award FX This work was supported by the National Institutes of Health (NS-059936 and NS-045942 to M.E.E., NS44169 to E.A.T.) and a Cure Huntington's Disease Initiative award to M.E.E. NR 48 TC 33 Z9 34 U1 1 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 MAR 15 PY 2011 VL 20 IS 6 BP 1049 EP 1060 DI 10.1093/hmg/ddq548 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 726WW UT WOS:000287758600001 PM 21177255 ER PT J AU Wei, H Zhang, ZJ Saha, A Peng, SY Chandra, G Quezado, Z Mukherjee, AB AF Wei, Hui Zhang, Zhongjian Saha, Arjun Peng, Shiyong Chandra, Goutam Quezado, Zenaide Mukherjee, Anil B. TI Disruption of adaptive energy metabolism and elevated ribosomal p-S6K1 levels contribute to INCL pathogenesis: partial rescue by resveratrol SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; SKELETAL-MUSCLE; LIFE-SPAN; MITOCHONDRIAL BIOGENESIS; OXIDATIVE STRESS; SIRT1; ACTIVATION; MICE; PGC-1-ALPHA; DISEASE AB The infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease. Despite our knowledge that palmitoyl-protein thioesterase-1 (PPT1)-deficiency causes INCL, the molecular mechanism(s) of neurodegeneration and the drastically reduced lifespan of these patients remain poorly understood. Consequently, an effective treatment for this disease is currently unavailable. We previously reported that oxidative stress-mediated abnormality in mitochondria activates caspases-9 pathway of apoptosis in INCL fibroblasts and in neurons of Ppt1-knockout (Ppt1-KO) mice, which mimic INCL. Since mitochondria play critical roles in maintaining cellular energy homeostasis, we hypothesized that oxidative stress-mediated disruption of energy metabolism and homeostasis may contribute to INCL pathogenesis. We report here that, in cultured INCL fibroblasts and in the brain tissues of Ppt1-KO mice, the NAD(+)/NADH ratio, the levels of phosphorylated-AMPK (p-AMPK), peroxisome proliferator-activated receptor-g (PPARg) coactivator-1 alpha (PGC-1 alpha) and Silent Information Regulator T1 (SIRT1) are markedly down-regulated. This suggested an abnormality in AMPK/SIRT1/PGC-1 alpha signaling pathway of energy metabolism. Moreover, we found that, in INCL fibroblasts and in the Ppt1-KO mice, phosphorylated-S6K-1 (p-S6K1) levels, which inversely correlate with lifespan, are markedly elevated. Most importantly, resveratrol (RSV), an antioxidant polyphenol, elevated the NAD(+)1/NADH ratio, levels of ATP, p-AMPK, PGC-1 alpha and SIRT1 while decreasing the level of p-S6K1 in both INCL fibroblasts and in Ppt1-KO mice, which showed a modest increase in lifespan. Our results show that disruption of adaptive energy metabolism and increased levels of p-S6K1 are contributing factors in INCL pathogenesis and provide the proof of principle that small molecules such as RSV, which alleviate these abnormalities, may have therapeutic potential. C1 [Quezado, Zenaide] NIH, Dept Anesthesia & Surg Serv, NIH Clin Ctr, Bethesda, MD 20892 USA. [Wei, Hui; Zhang, Zhongjian; Saha, Arjun; Peng, Shiyong; Chandra, Goutam; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NIH, Dept Anesthesia & Surg Serv, NIH Clin Ctr, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov RI Peng, Shiyong/D-6391-2014; Quezado, Zenaide/O-4860-2016 OI Peng, Shiyong/0000-0003-0697-3674; Quezado, Zenaide/0000-0001-9793-4368 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Batten Disease Support and Research Association (BDSRA) FX This research was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and the Batten Disease Support and Research Association (BDSRA). NR 46 TC 25 Z9 25 U1 0 U2 4 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 MAR 15 PY 2011 VL 20 IS 6 BP 1111 EP 1121 DI 10.1093/hmg/ddq555 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 726WW UT WOS:000287758600006 PM 21224254 ER PT J AU Hernandez, DG Nalls, MA Gibbs, JR Arepalli, S van der Brug, M Chong, S Moore, M Longo, DL Cookson, MR Traynor, BJ Singleton, AB AF Hernandez, Dena G. Nalls, Michael A. Gibbs, J. Raphael Arepalli, Sampath van der Brug, Marcel Chong, Sean Moore, Matthew Longo, Dan L. Cookson, Mark R. Traynor, Bryan J. Singleton, Andrew B. TI Distinct DNA methylation changes highly correlated with chronological age in the human brain SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASES AB Methylation at CpG sites is a critical epigenetic modification in mammals. Altered DNA methylation has been suggested to be a central mechanism in development, some disease processes and cellular senescence. Quantifying the extent and identity of epigenetic changes in the aging process is therefore potentially important for understanding longevity and age-related diseases. In the current study, we have examined DNA methylation at > 27 000 CpG sites throughout the human genome, in frontal cortex, temporal cortex, pons and cerebellum from 387 human donors between the ages of 1 and 102 years. We identify CpG loci that show a highly significant, consistent correlation between DNA methylation and chronological age. The majority of these loci are within CpG islands and there is a positive correlation between age and DNA methylation level. Lastly, we show that the CpG sites where the DNA methylation level is significantly associated with age are physically close to genes involved in DNA binding and regulation of transcription. This suggests that specific age-related DNA methylation changes may have quite a broad impact on gene expression in the human brain. C1 [Hernandez, Dena G.; Nalls, Michael A.; Gibbs, J. Raphael; Arepalli, Sampath; Chong, Sean; Moore, Matthew; Cookson, Mark R.; Traynor, Bryan J.; Singleton, Andrew B.] NIA, Neurogenet Lab, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Lymphocyte Cell Biol Unit, Baltimore, MD 21224 USA. [Hernandez, Dena G.; Gibbs, J. Raphael] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hernandez, Dena G.; Gibbs, J. Raphael] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England. [van der Brug, Marcel] Scripps Res Inst, Dept Mol & Integrat Neurosci, Jupiter, FL USA. RP Singleton, AB (reprint author), NIA, Neurogenet Lab, Bldg 35,Room 1A1014,35 Convent Dr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000932-02] FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project Z01 AG000932-02. NR 13 TC 158 Z9 161 U1 1 U2 12 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 MAR 15 PY 2011 VL 20 IS 6 BP 1164 EP 1172 DI 10.1093/hmg/ddq561 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 726WW UT WOS:000287758600011 PM 21216877 ER PT J AU Pichler, I Minelli, C Sanna, S Tanaka, T Schwienbacher, C Naitza, S Porcu, E Pattaro, C Busonero, F Zanon, A Maschio, A Melville, SA Piras, MG Longo, DL Guralnik, J Hernandez, D Bandinelli, S Aigner, E Murphy, AT Wroblewski, V Marroni, F Theurl, I Gnewuch, C Schadt, E Mitterer, M Schlessinger, D Ferrucci, L Witcher, DR Hicks, AA Weiss, G Uda, M Pramstaller, PP AF Pichler, Irene Minelli, Cosetta Sanna, Serena Tanaka, Toshiko Schwienbacher, Christine Naitza, Silvia Porcu, Eleonora Pattaro, Cristian Busonero, Fabio Zanon, Alessandra Maschio, Andrea Melville, Scott A. Piras, Maria Grazia Longo, Dan L. Guralnik, Jack Hernandez, Dena Bandinelli, Stefania Aigner, Elmar Murphy, Anthony T. Wroblewski, Victor Marroni, Fabio Theurl, Igor Gnewuch, Carsten Schadt, Eric Mitterer, Manfred Schlessinger, David Ferrucci, Luigi Witcher, Derrick R. Hicks, Andrew A. Weiss, Guenter Uda, Manuela Pramstaller, Peter P. TI Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSFERRIN RECEPTOR 2; PROTEASE MATRIPTASE-2 TMPRSS6; GENOME-WIDE ASSOCIATION; HEREDITARY HEMOCHROMATOSIS; SERINE-PROTEASE; ISOLATED POPULATION; FERRITIN LEVELS; HEPCIDIN; ANEMIA; HOMEOSTASIS AB The genetic determinants of variation in iron status are actively sought, but remain incompletely understood. Meta-analysis of two genome-wide association (GWA) studies and replication in three independent cohorts was performed to identify genetic loci associated in the general population with serum levels of iron and markers of iron status, including transferrin, ferritin, soluble transferrin receptor (sTfR) and sTfR-ferritin index. We identified and replicated a novel association of a common variant in the type-2 transferrin receptor (TFR2) gene with iron levels, with effect sizes highly consistent across samples. In addition, we identified and replicated an association between the HFE locus and ferritin and confirmed previously reported associations with the TF, TMPRSS6 and HFE genes. The five replicated variants were tested for association with expression levels of the corresponding genes in a publicly available data set of human liver samples, and nominally statistically significant expression differences by genotype were observed for all genes, although only rs3811647 in the TF gene survived the Bonferroni correction for multiple testing. In addition, we measured for the first time the effects of the common variant in TMPRSS6, rs4820268, on hepcidin mRNA in peripheral blood (n = 83 individuals) and on hepcidin levels in urine (n = 529) and observed an association in the same direction, though only borderline significant. These functional findings require confirmation in further studies with larger sample sizes, but they suggest that common variants in TMPRSS6 could modify the hepcidin-iron feedback loop in clinically unaffected individuals, thus making them more susceptible to imbalances of iron homeostasis. C1 [Pichler, Irene; Minelli, Cosetta; Schwienbacher, Christine; Pattaro, Cristian; Zanon, Alessandra; Melville, Scott A.; Marroni, Fabio; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, I-39100 Bolzano, Italy. [Pichler, Irene; Minelli, Cosetta; Schwienbacher, Christine; Pattaro, Cristian; Zanon, Alessandra; Melville, Scott A.; Marroni, Fabio; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, D-23538 Lubeck, Germany. [Sanna, Serena; Naitza, Silvia; Porcu, Eleonora; Busonero, Fabio; Maschio, Andrea; Piras, Maria Grazia; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy. [Tanaka, Toshiko; Longo, Dan L.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Schwienbacher, Christine] Univ Ferrara, Dept Expt & Diagnost Med, I-44121 Ferrara, Italy. [Melville, Scott A.] Boston Univ, Sch Med, Genet Program, Boston, MA 02118 USA. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Hernandez, Dena] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Bandinelli, Stefania] ASF, Geriatr Rehabil Unit, I-50100 Florence, Italy. [Aigner, Elmar] Salzburger Landeskliniken, Zent Lab, A-5020 Salzburg, Austria. [Murphy, Anthony T.; Wroblewski, Victor; Witcher, Derrick R.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46201 USA. [Marroni, Fabio] IGA, Inst Appl Genom, I-33100 Udine, Italy. [Theurl, Igor; Weiss, Guenter] Med Univ Innsbruck, Dept Internal Med Clin Immunol & Infect Dis 1, A-6020 Innsbruck, Austria. [Gnewuch, Carsten] Univ Regensburg, Inst Clin Chem & Lab Med, D-93047 Regensburg, Germany. [Schadt, Eric] Pacific Biosci, Menlo Pk, CA 94025 USA. [Mitterer, Manfred] Franz Tappeiner Hosp, Dept Transfus Med, I-39012 Merano, Italy. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy. RP Pichler, I (reprint author), European Acad Bolzano, Inst Med Genet, Viale Druso 1, I-39100 Bozen Bolzano, Italy. EM irene.pichler@eurac.edu; peter.pramstaller@eurac.edu RI Pramstaller, Peter/C-2357-2008; Naitza, Silvia/D-5620-2017; Hicks, Andrew/E-9518-2017; OI Weiss, Guenter/0000-0003-0709-2158; Hicks, Andrew/0000-0001-6320-0411; Pichler, Irene/0000-0001-8251-0757; Marroni, Fabio/0000-0002-1556-5907; sanna, serena/0000-0002-3768-1749; piras, maria grazia/0000-0001-9004-0900 FU Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano; South Tyrolean Sparkasse Foundation; National Institute on Aging [NO1-AG-1-2109, Z01AG000015-50]; Italian Ministry of Health [ICS110.1/RF97.71]; US National Institute on Aging [263 MD 9164, 263 MD 821336]; Ministry of Health FX The work was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano; the South Tyrolean Sparkasse Foundation for the MICROS study; the National Institute on Aging [NO1-AG-1-2109 to the SardiNIA ('ProgeNIA') team] for the SardiNia study; the Italian Ministry of Health (ICS110.1/RF97.71); the US National Institute on Aging (263 MD 9164, 263 MD 821336) for the InCHIANTI study; the Intramural Research Program of the National Institute on Aging (Z01AG000015-50); and an R&D contract with MedStar Research Institute for the BLSA study. NR 47 TC 32 Z9 32 U1 1 U2 3 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 MAR 15 PY 2011 VL 20 IS 6 BP 1232 EP 1240 DI 10.1093/hmg/ddq552 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 726WW UT WOS:000287758600017 PM 21208937 ER PT J AU Jimenez-Movilla, M Dean, J AF Jimenez-Movilla, Maria Dean, Jurrien TI ZP2 and ZP3 cytoplasmic tails prevent premature interactions and ensure incorporation into the zona pellucida SO JOURNAL OF CELL SCIENCE LA English DT Article DE Cytoplasmic tails; Zona pellucida; Oocytes; Intracellular trafficking; Extracellular matrix; ZP2; ZP3; beta-Tectorin ID SPERM RECEPTOR; MOUSE EGGS; IN-VITRO; FLUORESCENCE COMPLEMENTATION; MONOCLONAL-ANTIBODIES; PROTEIN INTERACTIONS; MASS-SPECTROMETRY; DOMAIN PROTEINS; LIVING CELLS; L-SELECTIN AB The zona pellucida contains three proteins (ZP1, ZP2, ZP3), the precursors of which possess signal peptides, 'zona' domains and short (9-15 residue) cytoplasmic tails downstream of a transmembrane domain. The ectodomains of ZP2 and ZP3 are sufficient to form the insoluble zona matrix and yet each protein traffics through oocytes without oligomerization. ZP2 and ZP3 were fluorescently tagged and molecular interactions were assayed by fluorescent complementation in CHO cells and growing oocytes. ZP2 and ZP3 traffic independently, but colocalize at the plasma membrane. However, protein-protein interactions were observed only after release and incorporation of ZP2 and ZP3 into the extracellular matrix surrounding mouse oocytes. In the absence of their hydrophilic cytoplasmic tails, ZP2 and ZP3 interacted within the cell and did not participate in the zona pellucida. A heterologous GPI-anchored 'zona' domain protein fused with the cytoplasmic tails was integrated into the zona matrix. We conclude that the cytoplasmic tails are sufficient and necessary to prevent intracellular oligomerization while ensuring incorporation of processed ZP2 and ZP3 into the zona pellucida. C1 [Jimenez-Movilla, Maria; Dean, Jurrien] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov RI Jimenez-Movilla, Maria/I-1004-2015 OI Jimenez-Movilla, Maria/0000-0002-1572-8219 FU National Institutes of Health, NIDDK FX For their help and advice, we thank Lyn Gauthier (microinjection of oocytes) and Boris Baibakov (confocal microscopy). This research was supported by the Intramural Research Program of the National Institutes of Health, NIDDK. Deposited in PMC for release after 12 months. NR 71 TC 14 Z9 15 U1 1 U2 4 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 MAR 15 PY 2011 VL 124 IS 6 BP 940 EP 950 DI 10.1242/jcs.079988 PG 11 WC Cell Biology SC Cell Biology GA 730CU UT WOS:000288009900013 PM 21378311 ER PT J AU Saini, RV Wilson, C Finn, MW Wang, TH Krensky, AM Clayberger, C AF Saini, Reena V. Wilson, Christine Finn, Michael W. Wang, Tianhong Krensky, Alan M. Clayberger, Carol TI Granulysin Delivered by Cytotoxic Cells Damages Endoplasmic Reticulum and Activates Caspase-7 in Target Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOCHROME-C RELEASE; 2 DISTINCT PATHWAYS; GRANZYME-B; MEDIATED CYTOTOXICITY; NATURAL-KILLER; CYTOLYTIC LEUKOCYTES; EFFECTOR MOLECULES; INDUCED APOPTOSIS; NK-LYSIN; T-CELLS AB Granulysin is a human cytolytic molecule present in cytotoxic granules with perforin and granzymes. Recombinant 9-kDa granulysin kills a variety of microbes, including bacteria, yeast, fungi, and parasites, and induces apoptosis in tumor cells by causing intracellular calcium overload, mitochondrial damage, and activation of downstream caspases. Reasoning that granulysin delivered by cytotoxic cells may work in concert with other molecules, we crossed granulysin transgenic (GNLY(+/-)) mice onto perforin (perf)-or granzyme B (gzmb)-deficient mice to examine granulysin-mediated killing in a more physiologic whole-cell system. Splenocytes from these animals were activated in vitro with IL-15 to generate cytolytic T cells and NK cells. Cytotoxic cells expressing granulysin require perforin, but not granzyme B, to cause apoptosis of targets. Whereas granzyme B induces mitochondrial damage and activates caspases-3 and -9 in targets, cytotoxic cell-delivered granulysin induces endoplasmic reticulum stress and activates caspase-7 with no effect on mitochondria or caspases-3 and -9. In addition, recombinant granulysin and cell-delivered granulysin activate distinct apoptotic pathways in target cells. These findings suggest that cytotoxic cells have evolved multiple nonredundant cell death pathways, enabling host defense to counteract escape mechanisms employed by pathogens or tumor cells. The Journal of Immunology, 2011, 186: 3497-3504. C1 [Saini, Reena V.; Wilson, Christine; Finn, Michael W.; Wang, Tianhong; Krensky, Alan M.; Clayberger, Carol] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Clayberger, C (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bldg 37,Room 2016,37 Convent Dr, Bethesda, MD 20892 USA. EM claybergerc@mail.nih.gov FU National Institutes of Health, National Cancer Institute; Center for Cancer Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research. NR 43 TC 24 Z9 25 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2011 VL 186 IS 6 BP 3497 EP 3504 DI 10.4049/jimmunol.1003409 PG 8 WC Immunology SC Immunology GA 729BU UT WOS:000287923500025 PM 21296981 ER PT J AU Zwiers, A Fuss, IJ Seegers, D Konijn, T Garcia-Vallejo, JJ Samsom, JN Strober, W Kraal, G Bouma, G AF Zwiers, Antonie Fuss, Ivan J. Seegers, Diana Konijn, Tanja Garcia-Vallejo, Juan J. Samsom, Janneke N. Strober, Warren Kraal, Georg Bouma, Gerd TI A Polymorphism in the Coding Region of Il12b Promotes IL-12p70 and IL-23 Heterodimer Formation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INHERITED INTERLEUKIN-12 DEFICIENCY; ACTIVE CROHNS-DISEASE; EXPERIMENTAL COLITIS; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION; LOCI; GENE; RESPONSES AB IL-12 and IL-23 are heterodimeric cytokines involved in the induction of Th1 and Th17 immune responses. Previous work indicated that a region on chromosome 11 encoding the IL-12p40 subunit regulates strain differences in susceptibility to murine trinitrobenzene sulfonic acid-induced colitis. In addition, this region determines strain differences in LPS-induced IL-12 responses. In this study, we investigated how polymorphisms in the coding region of murine Il12b influence IL-12 and IL-23 heterodimer formation. Transfection studies using constructs containing IL-12p35 linked to IL-12p40 from the colitis-resistant C57BL/6 strain or to the polymorphic p40 variant from the colitis-susceptible SJL/J strain demonstrated that SJL/J-derived p40 constructs synthesized significantly more IL-12p70 than did constructs harboring the C57BL/6-p40 variant. This could not be attributed to differences in synthesis rate or secretion, implicating a greater affinity of SJL/J-derived IL-12p40 for its IL-12p35 subunit. This greater affinity is also associated with increased IL-23 synthesis. In addition, C57BL/6 mice transgenic for the SJL/J 40 variant synthesized significantly more IL-12p70 upon LPS challenge and were more prone to develop colonic inflammation than did C57BL/6 mice transgenic for the C57BL/6-p40 variant. The more efficient binding of the polymorphic Il12b variant to p35 and p19 is most likely due to conformational changes following differential glycosylation as a consequence of the polymorphism. The high synthesis rate of the mature cytokines resulting from this efficient binding can lead to rapid proinflammatory skewing of immune responses and distortion of the homeostatic balance underlying the greater susceptibility for colitis. The Journal of Immunology, 2011, 186: 3572-3580. C1 [Zwiers, Antonie; Seegers, Diana; Bouma, Gerd] Vrije Univ, Med Ctr, Dept Gastroenterol & Hepatol, NL-1007 MB Amsterdam, Netherlands. [Zwiers, Antonie; Konijn, Tanja; Garcia-Vallejo, Juan J.; Kraal, Georg; Bouma, Gerd] Vrije Univ, Med Ctr, Dept Mol Cell Biol & Immunol, NL-1007 MB Amsterdam, Netherlands. [Fuss, Ivan J.; Strober, Warren] NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. [Samsom, Janneke N.] Erasmus Univ, Med Ctr, Dept Pediat Gastroenterol & Nutr, NL-3015 CE Rotterdam, Netherlands. RP Bouma, G (reprint author), Vrije Univ, Med Ctr, Dept Gastroenterol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM g.bouma@vumc.nl RI Garcia-Vallejo, Juan/H-4162-2012; Samsom, Janneke/C-5304-2013; bouma, gerd/E-2520-2013 OI Garcia-Vallejo, Juan/0000-0001-6238-7069; FU Intramural NIH HHS [Z99 AI999999] NR 35 TC 10 Z9 10 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2011 VL 186 IS 6 BP 3572 EP 3580 DI 10.4049/jimmunol.1001330 PG 9 WC Immunology SC Immunology GA 729BU UT WOS:000287923500033 PM 21321105 ER PT J AU Ganesan, A Crum-Cianflone, N Higgins, J Qin, J Rehm, C Metcalf, J Brandt, C Vita, J Decker, CF Sklar, P Bavaro, M Tasker, S Follmann, D Maldarelli, F AF Ganesan, Anuradha Crum-Cianflone, Nancy Higgins, Jeanette Qin, Jing Rehm, Catherine Metcalf, Julia Brandt, Carolyn Vita, Jean Decker, Catherine F. Sklar, Peter Bavaro, Mary Tasker, Sybil Follmann, Dean Maldarelli, Frank TI High Dose Atorvastatin Decreases Cellular Markers of Immune Activation Without Affecting HIV-1 RNA Levels: Results of a Double-blind Randomized Placebo Controlled Clinical Trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COA REDUCTASE INHIBITORS; COENZYME-A REDUCTASE; ANTIRETROVIRAL THERAPY; T-CELLS; HUMAN PLASMA; IN-VIVO; STATINS; VIRUS; INFECTION; REPLICATION AB Background. 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results. Methods. We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4-6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log(10) decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4(+) and CD8(+) T cells was used to measure immune activation. Results. Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (-0.13 log(10) copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4(+) HLA-DR(+) (-2.5%; P = .02), CD8(+) HLA-DR(+) (-5%; P = .006), and CD8(+) HLA-DR(+) CD38(+) T cells (-3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol. Conclusions. Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes. C1 [Ganesan, Anuradha; Vita, Jean; Decker, Catherine F.] Natl Naval Med Ctr, Div Infect Dis, Bethesda, MD 20889 USA. [Ganesan, Anuradha; Crum-Cianflone, Nancy] Uniformed Serv Univ Hlth Sci, Infectious Dis Clin Res Program, Bethesda, MD USA. [Crum-Cianflone, Nancy; Brandt, Carolyn; Bavaro, Mary] USN, San Diego Med Ctr, Div Infect Dis, San Diego, CA USA. [Higgins, Jeanette] Natl Canc Inst Frederick, AIDS Monitoring Lab, Clin Serv Program, Sci Applicat Int Corp Frederick Inc, Bethesda, MD USA. [Metcalf, Julia] NIAID, Biostat Res Branch, Clin Res Branch, Bethesda, MD 20892 USA. [Rehm, Catherine] NIAID, Clin Res Sect, Bethesda, MD 20892 USA. [Sklar, Peter] Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19104 USA. [Sklar, Peter] Merck Res Labs, N Wales, PA USA. [Tasker, Sybil] Pharmaceut Prod Dev Inc, Wilmington, DE USA. [Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. RP Ganesan, A (reprint author), Natl Naval Med Ctr, Div Infect Dis, 8901 Wisconsin Ave,Bldg 5,Room 240, Bethesda, MD 20889 USA. EM anuradha.ganesan@med.navy.mil FU Infectious Disease Clinical Research Program (IDCRP); DoD through the Uniformed Services University of the Health Sciences [IDCRP-015]; National Institute of Allergy and Infectious Diseases, NIH [Y1-AI-5072]; National Cancer Institute, National Institutes of Health [NO1-CO-12400]; National Institute of Allergy and Infectious Diseases FX This work was supported by the Infectious Disease Clinical Research Program (IDCRP), a DoD program executed through the Uniformed Services University of the Health Sciences (grant IDCRP-015); with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, under Inter-Agency Agreement Y1-AI-5072; with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. NO1-CO-12400; and by the National Institute of Allergy and Infectious Diseases. NR 49 TC 80 Z9 80 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2011 VL 203 IS 6 BP 756 EP 764 DI 10.1093/infdis/jiq115 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700003 PM 21325137 ER PT J AU Sandler, NG Wand, H Roque, A Law, M Nason, MC Nixon, DE Pedersen, C Ruxrungtham, K Lewin, SR Emery, S Neaton, JD Brenchley, JM Deeks, SG Sereti, I Douek, DC AF Sandler, Netanya G. Wand, Handan Roque, Annelys Law, Matthew Nason, Martha C. Nixon, Daniel E. Pedersen, Court Ruxrungtham, Kiat Lewin, Sharon R. Emery, Sean Neaton, James D. Brenchley, Jason M. Deeks, Steven G. Sereti, Irini Douek, Daniel C. CA INSIGHT SMART Study Grp TI Plasma Levels of Soluble CD14 Independently Predict Mortality in HIV Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; T-CELL-ACTIVATION; IMMUNE ACTIVATION; MICROBIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; VIRAL LOAD; DISEASE; LIPOPOLYSACCHARIDE; ENDOTOXIN; EXPRESSION AB Methods. This nested case-control study included 74 subjects who died, 120 of whom developed cardiovascular disease and 81 of whom developed AIDS during the Strategies for Management of Anti-Retroviral Therapy (SMART) study with matched control subjects. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), soluble CD14 (sCD14), endotoxin core antibody (EndoCAb), and 16S ribosomal DNA (rDNA) were measured in baseline plasma samples. Results. Subjects with the highest quartile of sCD14 levels had a 6-fold higher risk of death than did those in the lowest quartile (95% confidence interval, 2.2-16.1; P <.001), with minimal change after adjustment for inflammatory markers, CD4(+) T cell count, and HIV RNA level. No other marker was significantly associated with clinical outcomes. I-FABP, LPS, and sCD14 were increased and EndoCAb was decreased in study subjects, compared with healthy volunteers. sCD14 level correlated with levels of IL-6, C-reactive protein, serum amyloid A and D-dimer. Conclusions. sCD14, a marker of monocyte response to LPS, is an independent predictor of mortality in HIV infection. Therapeutic attenuation of innate immune activation may improve survival in patients with HIV infection. C1 [Sandler, Netanya G.; Roque, Annelys; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Nason, Martha C.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Nixon, Daniel E.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. [Neaton, James D.] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Deeks, Steven G.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, HIV AIDS Div, San Francisco, CA USA. [Pedersen, Court] Odense Univ Hosp, Dept Infect Dis, DK-5000 Odense, Denmark. [Ruxrungtham, Kiat] Chulalongkorn Univ, Thai Red Cross AIDS Res Ctr, HIV Netherlands Australia Thailand Res Collaborat, Bangkok, Thailand. [Ruxrungtham, Kiat] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand. [Wand, Handan; Law, Matthew; Emery, Sean] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. [Lewin, Sharon R.] Alfred Hosp, Infect Dis Unit, Melbourne, Vic, Australia. [Lewin, Sharon R.] Monash Univ, Dept Med, Melbourne, Vic 3004, Australia. [Lewin, Sharon R.] Burnet Inst, Ctr Virol, Melbourne, Vic, Australia. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov OI Utay, Netanya/0000-0002-6407-8670; Lewin, Sharon Ruth/0000-0002-0330-8241 FU National Institute of Allergy and Infectious Disease, National Institutes of Health; NIH [AI-76174]; National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand FX This work was supported in part by the intramural program of the National Institute of Allergy and Infectious Disease, National Institutes of Health and NIH grant AI-76174. K. R. is partially supported by the Research Team Strengthening Grant, the National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand. NR 50 TC 447 Z9 450 U1 6 U2 29 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 MAR 15 PY 2011 VL 203 IS 6 BP 780 EP 790 DI 10.1093/infdis/jiq118 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700006 PM 21252259 ER PT J AU Julg, B Moodley, ES Qi, Y Ramduth, D Reddy, S Mncube, Z Gao, XJ Goulder, PJ Detels, R Ndung'u, T Walker, BD Carrington, M AF Julg, Boris Moodley, Eshia S. Qi, Ying Ramduth, Danni Reddy, Shabashini Mncube, Zenele Gao, Xiaojiang Goulder, Philip J. Detels, Roger Ndung'u, Thumbi Walker, Bruce D. Carrington, Mary TI Possession of HLA Class II DRB1*1303 Associates with Reduced Viral Loads in Chronic HIV-1 Clade C and B Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CD4(+) T-CELLS; CHRONIC HEPATITIS-B; HLA-DRB1-ASTERISK-13 ALLELES; AUTOIMMUNE HEPATITIS; DOMINANT INFLUENCE; VIRUS-INFECTION; MEMORY; AIDS; SUSCEPTIBILITY; CARCINOMA AB Methods.In this study we investigated the effect of HLA class II alleles on HIV disease outcome and HIV-specific T cell responses in a cohort of 426 antiretroviral therapy-naive, HIV-1 clade C-infected, predominantly female black South Africans. Results.The HLA class II allele DRB1*1303 was independently associated with lower plasma viral loads in this population (P = .02), an association that was confirmed in a second cohort of 1436 untreated, HIV-1 clade B-infected, male European Americans, suggesting that DRB1*1303-mediated protection is independent of ethnicity, sex, and viral clade. Interestingly, DRB1*1303 carriage was not associated with an increased frequency of interferon (IFN) gamma-positive HIV-specific CD4(+) T cell responses. Conclusions.These data demonstrate the independent effect of an HLA class II allele, DRB1*1303, on HIV disease progression, in the absence of increased IFN-gamma-positive HIV-specific CD4(+) T cell frequencies, suggesting that the protective activity of DRB1*1303 may be mediated via an alternative mechanism. C1 [Qi, Ying; Gao, Xiaojiang; Carrington, Mary] NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Frederick, MD 21702 USA. [Julg, Boris; Moodley, Eshia S.; Ramduth, Danni; Reddy, Shabashini; Mncube, Zenele; Goulder, Philip J.; Ndung'u, Thumbi; Walker, Bruce D.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Julg, Boris; Moodley, Eshia S.; Ramduth, Danni; Reddy, Shabashini; Mncube, Zenele; Goulder, Philip J.; Ndung'u, Thumbi; Walker, Bruce D.] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Julg, Boris; Goulder, Philip J.; Ndung'u, Thumbi; Walker, Bruce D.; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Detels, Roger] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Detels, Roger] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Goulder, Philip J.] Univ Oxford, Dept Pediat, Oxford, England. RP Carrington, M (reprint author), NCI Frederick, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick, Bldg 560,Room 21-89,Miller Dr, Frederick, MD 21702 USA. EM carringm@mail.nih.gov OI Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health [R01-AI067073, R01-AI46995-01, N01-A1 15422]; South African AIDS Vaccine Initiative; Howard Hughes Medical Institute; Mark and Lisa Schwartz Foundation; Bill and Melinda Gates Foundation; South African Department of Science and Technology/National Research Foundation Research Chair Initiative; International AIDS Vaccine Initiative; Doris Duke Charitable Foundation; National Cancer Institute (NCI) [HHSN261200800001E, UO1-AI-35042, 5-MO1-RR-00052 [GCRC], UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041]; Center for Cancer Research; National Institute of Allergy and Infectious Diseases FX This research was funded by the National Institutes of Health (grant numbers R01-AI067073 and R01-AI46995-01 and contract number N01-A1 15422), the South African AIDS Vaccine Initiative, the Howard Hughes Medical Institute International Program, the Mark and Lisa Schwartz Foundation, the Bill and Melinda Gates Foundation, the South African Department of Science and Technology/National Research Foundation Research Chair Initiative, the International AIDS Vaccine Initiative, the Doris Duke Charitable Foundation, the National Cancer Institute (NCI) (contract number HHSN261200800001E), and the Intramural Research Program of the NCI, Center for Cancer Research. The MACS is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the NCI (grant numbers UO1-AI-35042, 5-MO1-RR-00052 [GCRC], UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, and UO1-AI-35041). NR 34 TC 20 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2011 VL 203 IS 6 BP 803 EP 809 DI 10.1093/infdis/jiq122 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700009 PM 21257739 ER PT J AU Castle, PE Rodriguez, AC Burk, RD Herrero, R Wacholder, S Hildesheim, A Morales, J Rydzak, G Schiffman, M AF Castle, Philip E. Cecilia Rodriguez, Ana Burk, Robert D. Herrero, Rolando Wacholder, Sholom Hildesheim, Allan Morales, Jorge Rydzak, Greg Schiffman, Mark CA PEG Grp TI Long-Term Persistence of Prevalently Detected Human Papillomavirus Infections in the Absence of Detectable Cervical Precancer and Cancer SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NATURAL-HISTORY; INTRAEPITHELIAL NEOPLASIA; COSTA-RICA; FOLLOW-UP; WOMEN; RISK; ACQUISITION; GUANACASTE; CLEARANCE; DIAGNOSIS AB Methods. In a large, population-based natural study conducted in Guanacaste, Costa Rica, we studied a subset of 810 initially HPV-positive women with >= 3 years of active follow-up with >= 3 screening visits who had no future evidence of cervical precancer. Cervical specimens were tested for > 40 HPV genotypes using a MY09/11 L1-targeted polymerase chain reaction method. Results. Seventy-two prevalently-detected HPV infections (5%) in 58 women (7%) persisted until the end of the follow-up period (median duration of follow-up, 7 years) without evidence of cervical precancer. At enrollment, women with long-term persistence were more likely to have multiple prevalently-detected HPV infections (P <.001) than were women who cleared their baseline HPV infections during follow-up. In a logistic regression model, women with long-term persistence were more likely than women who cleared infections to have another newly-detected HPV infection detectable at >= 3 visits (odds ratio, 2.6; 95% confidence interval, 1.2-5.6). Conclusions. Women with long-term persistence of HPV infection appear to be generally more susceptible to other HPV infections, especially longer-lasting infections, than are women who cleared their HPV infections. C1 [Castle, Philip E.; Wacholder, Sholom; Hildesheim, Allan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Rydzak, Greg] Informat Management Serv Inc, Silver Spring, MD USA. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. [Cecilia Rodriguez, Ana; Herrero, Rolando; Morales, Jorge] INCIENSA Fdn, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,EPS Rm 5026,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Institutes of Health [N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023, CA78527]; National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX National Institutes of Health (N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023, intramural program, CA78527 to RB). The Guanacaste cohort (design and conduct of the study, sample collection, management, analysis and interpretation of the data) for the enrollment and follow-up phases were supported [in part] by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 24 TC 15 Z9 16 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 MAR 15 PY 2011 VL 203 IS 6 BP 814 EP 822 DI 10.1093/infdis/jiq116 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700011 PM 21343148 ER PT J AU Campos, NG Rodriguez, AC Castle, PE Herrero, R Hildesheim, A Katki, H Kim, JJ Wacholder, S Morales, J Burk, RD Schiffman, M AF Campos, Nicole G. Cecilia Rodriguez, Ana Castle, Philip E. Herrero, Rolando Hildesheim, Allan Katki, Hormuzd Kim, Jane J. Wacholder, Sholom Morales, Jorge Burk, Robert D. Schiffman, Mark TI Persistence of Concurrent Infections with Multiple Human Papillomavirus Types: A Population-based Cohort Study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL NEOPLASIA; DNA DETECTION; RISK; WOMEN AB The presence of more than one human papillomavirus (HPV) genotype may influence the duration of prevalently detected infections. This analysis included 1,646 infections detected at enrollment in 980 women from the Guanacaste, Costa Rica, cohort who were actively followed up every 6-12 months for up to 8 years. We categorized HPV infections as single or multiple types. Persistence of infections was estimated using discrete-time survival analysis. The difference between the duration of single and that of concurrent multiple type-specific prevalent HPV infections was not significant (P=.9; log-rank test). Concurrent, prevalent detection of additional HPV types did not change the likelihood of viral persistence. C1 [Campos, Nicole G.; Kim, Jane J.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Cecilia Rodriguez, Ana; Herrero, Rolando; Morales, Jorge] Fdn Inciensa, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Castle, Philip E.; Hildesheim, Allan; Katki, Hormuzd; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. RP Campos, NG (reprint author), 742 Paradiso Ave, Coral Gables, FL 33146 USA. EM gastin@post.harvard.edu RI Katki, Hormuzd/B-4003-2015; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute, National Institutes of Health [R01 CA93435]; Intramural Research Program FX This work was supported by the National Cancer Institute, National Institutes of Health (grant number R01 CA93435); and the Intramural Research Program. NR 15 TC 14 Z9 14 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 MAR 15 PY 2011 VL 203 IS 6 BP 823 EP 827 DI 10.1093/infdis/jiq131 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700012 PM 21257737 ER PT J AU Perles-Barbacaru, TA Procissi, D Demyanenko, AV Hall, FS Uhl, GR Jacobs, RE AF Perles-Barbacaru, Teodora-Adriana Procissi, Daniel Demyanenko, Andrey V. Hall, F. Scott Uhl, George R. Jacobs, Russell E. TI Quantitative pharmacologic MRI: Mapping the cerebral blood volume response to cocaine in dopamine transporter knockout mice SO NEUROIMAGE LA English DT Article ID FUNCTIONAL MRI; EXTRACELLULAR DOPAMINE; MONOAMINE TRANSPORTERS; NUCLEUS-ACCUMBENS; PLACE PREFERENCE; CONTRAST AGENTS; RAT-BRAIN; SEROTONIN; METABOLISM; REWARD AB The use of pharmacologic MRI (phMRI) in mouse models of brain disorders allows noninvasive in vivo assessment of drug-modulated local cerebral blood volume changes (Delta CBV) as one correlate of neuronal and neurovascular activities. In this report, we employed CBV-weighted phMRI to compare cocaine-modulated neuronal activity in dopamine transporter (DAT) knockout (KO) and wild-type mice. Cocaine acts to block the dopamine, norepinephrine, and serotonin transporters (DAT. NET, and SERT) that clear their respective neurotransmitters from the synapses, helping to terminate cognate neurotransmission. Cocaine consistently reduced CBV, with a similar pattern of regional Delta CBV in brain structures involved in mediating reward in both DAT genotypes. The largest effects (-20% to 30% Delta CBV) were seen in the nucleus accumbens and several cortical regions. Decreasing response amplitudes to cocaine were noted in more posterior components of the cortico-mesolimbic circuit. DAT KO mice had significantly attenuated Delta CBV amplitudes, shortened times to peak response, and reduced response duration in most regions. This study demonstrates that DAT knockout does not abolish the phMRI responses to cocaine, suggesting that adaptations to loss of DAT and/or retained cocaine activity in other monoamine neurotransmitter systems underlie these responses in DAT KO mice. (C) 2010 Elsevier Inc. All rights reserved. C1 [Perles-Barbacaru, Teodora-Adriana; Procissi, Daniel; Demyanenko, Andrey V.; Jacobs, Russell E.] CALTECH, Beckman Inst, Biol Imaging Ctr, Pasadena, CA 91125 USA. [Hall, F. Scott; Uhl, George R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Jacobs, RE (reprint author), CALTECH, Beckman Inst, Biol Imaging Ctr, Caltech M-C 139-74,1200 E Calif Blvd, Pasadena, CA 91125 USA. EM rjacobs@caltech.edu RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU Beckman Institute; NIDA [R01DA18184]; NCRR [U24 RR021760 Mouse BIRN]; National Institute on Drug Abuse FX The author. thank Hargun Sohi and Thomas Ng for their technical assistance, Davit Janvelyan for helping with the AIR software, Guerbet Research (Aulnay-Sous-Bois, France) for providing the P904 contrast agent. This project was funded in part by the Beckman Institute, NIDA R01DA18184, and NCRR U24 RR021760 Mouse BIRN and by funding from the National Institute on Drug Abuse, Intramural Research Program (GRU, FSH). NR 52 TC 11 Z9 12 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR 15 PY 2011 VL 55 IS 2 BP 622 EP 628 DI 10.1016/j.neuroimage.2010.12.048 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 724DL UT WOS:000287556200021 PM 21185387 ER PT J AU Rifkind, JM Nagababu, E Ramasamy, S AF Rifkind, Joseph M. Nagababu, Enika Ramasamy, Somasundaram TI The quaternary hemoglobin conformation regulates the formation of the nitrite-induced bioactive intermediate and the dissociation of nitric oxide from this intermediate SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Nitrite reduction; Nitric oxide; Hemoglobin quaternary conformation ID S-NITROSOHEMOGLOBIN; HYPOXIC CONDITIONS; HEME-PROTEINS; DEOXYHEMOGLOBIN; REDUCTION; NO; METHEMOGLOBIN; VASODILATION; OXYHEMOGLOBIN; METMYOGLOBIN AB Deoxyhemoglobin reduces nitrite to nitric oxide (NO). In order to study the effect of the hemoglobin quaternary conformation on the nitrite reaction, we compared T-state deoxyhemoglobin with R-state deoxyhemoglobin produced by reacting hemoglobin with carboxypeptidase-A prior to deoxygenation. The nitrite reaction with deoxyhemoglobin was followed by chemiluminescence, electron paramagnetic resonance and visible spectroscopy. The initial steps in this reaction involve the binding of nitrite to deoxyhemoglobin followed by the formation of an electron delocalized metastable intermediate that retains potential NO bioactivity. This reaction is shown by visible spectroscopy to occur 5.6 times faster in the R-state than in the T-state. However, the dissociation of NO from the delocalized intermediate is shown to be facilitated by the T-quaternary conformation with a 9.6 fold increase in the rate constant. The preferred NO-release in the T-state, which has a higher affinity for the membrane, can result in the NO diffusing out of the RBC and being released to the vasculature at low partial pressures of oxygen. Published by Elsevier Inc. C1 [Rifkind, Joseph M.; Nagababu, Enika; Ramasamy, Somasundaram] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM rifkindj@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. NR 37 TC 9 Z9 9 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAR 15 PY 2011 VL 24 IS 2 BP 102 EP 109 DI 10.1016/j.niox.2011.01.001 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 727JQ UT WOS:000287795100006 PM 21236353 ER PT J AU Ghosh, P Ghosh, K Tiwari, RC AF Ghosh, Pulak Ghosh, Kaushik Tiwari, Ram C. TI Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints SO STATISTICS IN MEDICINE LA English DT Article DE longitudinal data; dropout; joint model; multiple changepoint; Dirichlet process prior; clustering ID SURVIVAL-DATA; FAILURE; MIXTURES; PROGRESSION; PROFILES AB In longitudinal studies of patients with the human immunodeficiency virus (HIV), objectives of interest often include modeling of individual-level trajectories of HIV ribonucleic acid (RNA) as a function of time. Such models can be used to predict the effects of different treatment regimens or to classify subjects into subgroups with similar trajectories. Empirical evidence, however, suggests that individual trajectories often possess multiple points of rapid change, which may vary from subject to subject. Additionally, some individuals may end up dropping out of the study and the tendency to drop out may be related to the level of the biomarker. Modeling of individual viral RNA profiles is challenging in the presence of these changes, and currently available methods do not address all the issues such as multiple changes, informative dropout, clustering, etc. in a single model. In this article, we propose a new joint model, where a multiple-changepoint model is proposed for the longitudinal viral RNA response and a proportional hazards model for the time of dropout process. Dirichlet process (DP) priors are used to model the distribution of the individual random effects and error distribution. In addition to robustifying the model against possible misspecifications, the DP leads to a natural clustering of subjects with similar trajectories which can be of importance in itself. Sharing of information among subjects with similar trajectories also results in improved parameter estimation. A fully Bayesian approach for model fitting and prediction is implemented using MCMC procedures on the ACTG 398 clinical trial data. The proposed model is seen to give rise to improved estimates of individual trajectories when compared with a parametric approach. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Ghosh, Kaushik] Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Syst, Bangalore 560076, Karnataka, India. [Tiwari, Ram C.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Ghosh, K (reprint author), Univ Nevada, Dept Math Sci, 4505 Maryland Pkwy,Box 454020, Las Vegas, NV 89154 USA. EM kaushik.ghosh@unlv.edu NR 29 TC 1 Z9 1 U1 1 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2011 VL 30 IS 6 BP 611 EP 626 DI 10.1002/sim.4119 PG 16 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 724YJ UT WOS:000287612100002 PM 21337357 ER PT J AU Subramanian, J Simon, R AF Subramanian, Jyothi Simon, Richard TI An evaluation of resampling methods for assessment of survival risk prediction in high-dimensional settings SO STATISTICS IN MEDICINE LA English DT Article DE microarray data analysis; prognostic signatures; survival analysis; resampling methods; prediction accuracy ID NEGATIVE BREAST-CANCER; GENE-EXPRESSION DATA; CELL LUNG-CANCER; MICROARRAY DATA; COX REGRESSION; CLASSIFICATION; VALIDATION; PERFORMANCE; LYMPHOMA; MARKER AB Resampling techniques are often used to provide an initial assessment of accuracy for prognostic prediction models developed using high-dimensional genomic data with binary outcomes. Risk prediction is most important, however, in medical applications and frequently the outcome measure is a right-censored time-to-event variable such as survival. Although several methods have been developed for survival risk prediction with high-dimensional genomic data, there has been little evaluation of the use of resampling techniques for the assessment of such models. Using real and simulated datasets, we compared several resampling techniques for their ability to estimate the accuracy of risk prediction models. Our study showed that accuracy estimates for popular resampling methods, such as sample splitting and leave-one-out cross validation (Loo CV), have a higher mean square error than for other methods. Moreover, the large variability of the split-sample and Loo CV may make the point estimates of accuracy obtained using these methods unreliable and hence should be interpreted carefully. A k-fold cross-validation with k = 5 or 10 was seen to provide a good balance between bias and variability for a wide range of data settings and should be more widely adopted in practice. Published in 2010 by John Wiley & Sons, Ltd. C1 [Subramanian, Jyothi; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@mail.nih.gov NR 36 TC 17 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2011 VL 30 IS 6 BP 642 EP 653 DI 10.1002/sim.4106 PG 12 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 724YJ UT WOS:000287612100004 PM 21337359 ER PT J AU Meinhold, CL de Gonzalez, AB Bowman, ED Brenner, AV Jones, RT Lacey, JV Loffredo, CA Perlmutter, D Schonfeld, SJ Trivers, GE Harris, CC AF Meinhold, Cari L. de Gonzalez, Amy Berrington Bowman, Elise D. Brenner, Alina V. Jones, Raymond T. Lacey, James V., Jr. Loffredo, Christopher A. Perlmutter, Donna Schonfeld, Sara J. Trivers, Glenwood E. Harris, Curtis C. TI Reproductive and hormonal factors and the risk of nonsmall cell lung cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung neoplasms; reproductive factors; menstrual factors; exogenous hormones; case-control study ID ESTROGEN-RECEPTOR-ALPHA; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; CHINESE-WOMEN; PROSPECTIVE COHORT; FAMILY-HISTORY; SMOKING; ADENOCARCINOMA; DISEASE; HEALTH AB Although exposure to estrogen may directly influence or modify the association between cigarette smoking and lung cancer risk, results from epidemiologic studies examining the association between reproductive and hormonal factors and risk of lung cancer among women have been inconsistent. Between 1998 and 2008, 430 women diagnosed with nonsmall cell lung cancer, 316 hospital controls and 295 population controls were recruited into the multi-center Maryland Lung Cancer Study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) according to reproductive and hormonal exposures adjusting for age, smoking, passive smoking, education and household income. Results were similar for hospital and population based controls, so the control groups were combined. Reduced risks of lung cancer were observed among women with greater parity (>= 5 vs. 1-2 births: OR = 0.50, 95% CI = 0.32, 0.78, p-trend = 0.002) and later ages at last birth (>= 30 vs. <25 years old: OR = 0.68, 95% CI = 0.48, 0.98, p-trend = 0.04). After mutual adjustment parity, but not age at last birth, remained significantly inversely associated with risk (p-trend = 0.01). No associations were found for nonsmall cell lung cancer risk with age at menarche, age at first birth, menopausal status, oral contraceptive use or menopausal hormone use, including use of oral estrogens. Compatible with findings from recent epidemiologic studies, we observed a reduction in the risk of nonsmall cell lung cancer with increasing number of births. Other reproductive and hormonal exposures, including menopausal hormone therapy use, were not associated with risk. C1 [Meinhold, Cari L.; de Gonzalez, Amy Berrington; Brenner, Alina V.; Schonfeld, Sara J.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Bowman, Elise D.; Trivers, Glenwood E.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Rockville, MD 20852 USA. [Jones, Raymond T.; Perlmutter, Donna] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Lacey, James V., Jr.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA. [Loffredo, Christopher A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Genet & Epidemiol Program, Washington, DC USA. RP Meinhold, CL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 7051,6120 Execut Blvd, Rockville, MD 20852 USA. EM meinholdc@mail.nih.gov RI Kitahara, Cari/R-8267-2016 FU National Institutes of Health/National Cancer Institute FX Grant sponsor: Intramural Research Program of the National Institutes of Health/National Cancer Institute NR 41 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 2011 VL 128 IS 6 BP 1404 EP 1413 DI 10.1002/ijc.25434 PG 10 WC Oncology SC Oncology GA 718XB UT WOS:000287158700016 PM 20473922 ER PT J AU Bates, SE AF Bates, Susan E. TI Multiple Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article C1 NCI, CCR Focus, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, CCR Focus, Bethesda, MD 20892 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2011 VL 17 IS 6 BP 1224 EP 1224 DI 10.1158/1078-0432.CCR-11-0294 PG 1 WC Oncology SC Oncology GA 735RR UT WOS:000288435300003 PM 21411437 ER PT J AU Locatis, C Berner, ES Hammack, G Smith, S Maisiak, R Ackerman, M AF Locatis, Craig Berner, Eta S. Hammack, Glenn Smith, Steve Maisiak, Richard Ackerman, Michael TI Communication and proximity effects on outcomes attributable to sense of presence in distance bioinformatics education SO BMC MEDICAL EDUCATION LA English DT Article ID IMPACT AB Background: Online learning is increasingly popular in medical education and sense of presence has been posited as a factor contributing to its success. Communication media influences on sense of presence and learning outcomes were explored in this study. Test performance and ratings of instruction and technology, factors influenced by sense of presence, are compared under four conditions involving different media and degrees of student physical presence: 1) videoconference co-located, 2) webcast co-located, 3) videoconference dispersed, and 4) webcast dispersed. Methods: Eighty one first to forth year medical students heard a lecture on telemedicine and were asked to collaboratively search a telemedicine website under conditions where the lecture was delivered by videoconference or one way streaming (webcast) and where students were either co-located or dispersed. In the videoconference conditions, co-located students could use the technology to interact with the instructor and could interact with each other face to face, while the dispersed students could use the technology to interact with both the instructor and each other. In the webcast conditions, all students could use chat to communicate with the instructor or each other, although the co-located students also could interact orally. After hearing the lecture, students collaboratively searched a telemedicine website, took a test on lecture-website content and rated the instruction and the technology they used. Test scores on lecture and website content and ratings of instruction and technology for the four conditions were compared with analysis of variance and chi-square tests. Results: There were no significant differences in overall measures, although there were on selected ratings of instruction. Students in both webcast conditions indicated they were encouraged more to follow up on their own and felt instruction was more interactive than co-located videoconferencing students. Dispersed videoconferencing students indicated the highest levels of interaction and there was evidence they interacted more. Conclusion: Results do not strongly support proximity as a sense of presence factor affecting performance and attitudes, but do suggest communication medium may affect interactivity. C1 [Locatis, Craig; Ackerman, Michael] Natl Lib Med, Off High Performance Comp & Commun, Bethesda, MD 20894 USA. [Berner, Eta S.] Univ Alabama Birmingham, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. [Hammack, Glenn] NuPhysicia LLC, Houston, TX 77027 USA. [Smith, Steve] Univ Alabama Birmingham, Med Student Serv, Birmingham, AL USA. [Maisiak, Richard] Maisiak Associates, Scottsdale, AZ 85254 USA. RP Locatis, C (reprint author), Natl Lib Med, Off High Performance Comp & Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM locatis@nlm.nih.gov OI Berner, Eta/0000-0003-4319-2949 FU National Library of Medicine [HHSN276200700281P, 467-MZ-501661]; National Institutes of Health FX This study was funded by National Library of Medicine contracts HHSN276200700281P and 467-MZ-501661 to the University of Alabama at Birmingham and as part of the National Institutes of Health Intramural Research Program. The authors appreciate the assistance of Ms. Marcie Battles in carrying out this study. NR 28 TC 1 Z9 1 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD MAR 14 PY 2011 VL 11 AR 10 DI 10.1186/1472-6920-11-10 PG 7 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA 742KV UT WOS:000288943000001 PM 21401942 ER PT J AU Dagdug, L Berezhkovskii, AM Makhnovskii, YA Zitserman, VY Bezrukov, SM AF Dagdug, Leonardo Berezhkovskii, Alexander M. Makhnovskii, Yurii A. Zitserman, Vladimir Yu. Bezrukov, Sergey M. TI Communication: Turnover behavior of effective mobility in a tube with periodic entropy potential SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE-TRANSPORT; DIFFUSION; CHANNEL AB Using Brownian dynamics simulations, we study the effective mobility and diffusion coefficient of a point particle in a tube formed from identical compartments of varying diameter, as functions of the driving force applied along the tube axis. Our primary focus is on how the driving force dependences of these transport coefficients are modified by the changes in the compartment shape. In addition to monotonically increasing or decreasing behavior of the effective mobility in periodic entropy potentials reported earlier, we now show that the effective mobility can even be nonmonotonic in the driving force. (C) 2011 American Institute of Physics. [doi:10.1063/1.3561680] C1 [Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Zitserman, Vladimir Yu.] Russian Acad Sci, Joint Inst High Temp, Moscow 125412, Russia. [Makhnovskii, Yurii A.] Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. [Dagdug, Leonardo; Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X FU National Institutes of Health (NIH); Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Russian foundation for Basic Research [10-03-00393] FX This study was supported by the Intramural Research Program of the National Institutes of Health (NIH), Center for Information Technology and Eunice Kennedy Shriver National Institute of Child Health and Human Development. Yu.A.M. and V.Yu.Z. thank the Russian foundation for Basic Research for support (Grant No. 10-03-00393). NR 25 TC 25 Z9 26 U1 1 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 14 PY 2011 VL 134 IS 10 AR 101102 DI 10.1063/1.3561680 PG 3 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 735EE UT WOS:000288395400002 PM 21405148 ER PT J AU Rosansky, SJ Eggers, P Jackson, K Glassock, R Clark, WF AF Rosansky, Steven J. Eggers, Paul Jackson, Kirby Glassock, Richard Clark, William F. TI Early Start of Hemodialysis May Be Harmful SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RESIDUAL RENAL-FUNCTION; DIALYSIS INITIATION; KIDNEY-DISEASE; SURVIVAL; MORTALITY; COMORBIDITY; NUTRITION; OUTCOMES; IMPACT AB Background: A dramatic increase in the "early start" of dialysis with an estimated glomerular filtration rate (eGFR) at least 10 mL/min/1.73 m(2) has occurred in the United States since at least 1996. Several recent studies have reported a comorbidity-adjusted survival disadvantage of early start of dialysis. The current study examines a relatively "healthy" dialysis cohort to minimize confounding issues and determine whether early initiation of hemodialysis is associated with a survival benefit or harm. Methods: We examined demographics, year of dialysis initiation, primary etiology of renal failure, and body mass index, hemoglobin, and serum albumin levels in 81 176 nondiabetic, 20- to 64-year-old, in-center incident hemodialysis patients with no reported comorbidity besides hypertension. We compared survival, using a piecewise proportional hazards model to estimate covariate-adjusted mortality hazard ratios (HRs) for eGFR at the time of initiation of dialysis. We also performed time-dependent adjusted analysis stratified by initial serum albumin levels lower than 2.5 g/dL, 2.5 to 3.49 g/dL, and 3.5 g/dL or higher (the "healthiest" group [HG]). Results: Unadjusted 1-year mortality by eGFR ranged from 6.8% in the reference group (eGFR < 5.0 mL/min/1.73m(2)) to 20.1% in the highest eGFR group ( >= 15.0 mL/min/1.73 m(2)). Compared with the reference group, the HR for the HG was 1.27 (eGFR, 5.0-9.9 mL/min/1.73m(2)), 1.53 (eGFR, 10.0-14.9 mL/min/1.73 m(2)), and 2.18 (eGFR >= 15.0 mL/ min/1.73 m(2)) and ranged from 1.50 to 3.53 mL/min/1.73 m(2) in the first year of dialysis for the early-start group. Conclusion: The increased HR during hemodialysis associated with early start in the healthiest group of patients undergoing dialysis indicates that early start of dialysis may be harmful. C1 [Rosansky, Steven J.] Wm Jennings Bryan Dorn Vet Hosp, Dorn Res Inst, Columbia, SC 29206 USA. [Rosansky, Steven J.; Jackson, Kirby] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Eggers, Paul] NIDDKD, Bethesda, MD 20892 USA. [Glassock, Richard] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Clark, William F.] London Hlth Sci Ctr, Div Nephrol, London, ON, Canada. RP Rosansky, SJ (reprint author), Wm Jennings Bryan Dorn Vet Hosp, Dorn Res Inst, 526 N Trenholm Rd, Columbia, SC 29206 USA. EM sjrcra@yahoo.com NR 24 TC 86 Z9 90 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2011 VL 171 IS 5 BP 396 EP 403 DI 10.1001/archinternmed.2010.415 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 734IW UT WOS:000288328800006 PM 21059968 ER PT J AU Rosansky, SJ Eggers, P Jackson, K Glassock, R Clark, WF AF Rosansky, Steven J. Eggers, Paul Jackson, Kirby Glassock, Richard Clark, William F. TI Survivor Bias in Early- vs Late-Start Hemodialysis Studies Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Rosansky, Steven J.] Wm Jennings Bryan Dorn Vet Hosp, Dorn Res Inst, Columbia, SC 29206 USA. [Rosansky, Steven J.; Jackson, Kirby] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. [Eggers, Paul] NIDDK, Bethesda, MD USA. [Glassock, Richard] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Clark, William F.] London Hlth Sci Ctr, Div Nephrol, London, ON, Canada. RP Rosansky, SJ (reprint author), Wm Jennings Bryan Dorn Vet Hosp, Dorn Res Inst, 526 N Trenholm Rd, Columbia, SC 29206 USA. EM sjrcra@yahoo.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2011 VL 171 IS 5 BP 478 EP 478 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 734IW UT WOS:000288328800031 ER PT J AU Bulua, AC Simon, A Maddipati, R Pelletier, M Park, H Kim, KY Sack, MN Kastner, DL Siegel, RM AF Bulua, Ariel C. Simon, Anna Maddipati, Ravikanth Pelletier, Martin Park, Heiyoung Kim, Kye-Young Sack, Michael N. Kastner, Daniel L. Siegel, Richard M. TI Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; NITRIC-OXIDE SYNTHASE; INNATE IMMUNE-RESPONSES; NF-KAPPA-B; OXIDATIVE STRESS; NADPH OXIDASE; INFLAMMASOME ACTIVATION; INDEPENDENT ACTIVATION; ENDOPLASMIC-RETICULUM; NALP3 INFLAMMASOME AB Reactive oxygen species (ROS) have an established role in inflammation and host defense, as they kill intracellular bacteria and have been shown to activate the NLRP3 inflammasome. Here, we find that ROS generated by mitochondrial respiration are important for normal lipopolysaccharide (LPS)-driven production of several proinflammatory cytokines and for the enhanced responsiveness to LPS seen in cells from patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder caused by missense mutations in the type 1 TNF receptor (TNFR1). We find elevated baseline ROS in both mouse embryonic fibroblasts and human immune cells harboring TRAPS-associated TNFR1 mutations. A variety of antioxidants dampen LPS-induced MAPK phosphorylation and inflammatory cytokine production. However, gp91(phox) and p22(phox) reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits are dispensable for inflammatory cytokine production, indicating that NADPH oxidases are not the source of proinflammatory ROS. TNFR1 mutant cells exhibit altered mitochondrial function with enhanced oxidative capacity and mitochondria! ROS generation, and pharmacological blockade of mitochondria! ROS efficiently reduces inflammatory cytokine production after LPS stimulation in cells from TRAPS patients and healthy controls. These findings suggest that mitochondria! ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases. C1 [Bulua, Ariel C.; Maddipati, Ravikanth; Pelletier, Martin; Park, Heiyoung; Siegel, Richard M.] NHLBI, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Simon, Anna; Kastner, Daniel L.] NHLBI, Inflammatory Biol Sect, Clin Invest Lab, NIAMSD,NIH, Bethesda, MD 20892 USA. [Kim, Kye-Young; Sack, Michael N.] NHLBI, Lab Mitochondrial Biol Cardiometabol Syndromes, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Bulua, Ariel C.] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA. RP Siegel, RM (reprint author), NHLBI, Immunoregulat Sect, Autoimmun Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Simon, Anna/D-3757-2009 OI Simon, Anna/0000-0002-6141-7921 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health; Foundation for the National Institutes of Health; Foundation for the Pfizer Inc. FX This research was supported by intramural research funding from National Institute of Arthritis and Musculoskeletal and Skin Diseases. A.C. Bulua was supported by the National Institutes of Health Clinical Research Training Program, a public-private partnership between the Foundation for the National Institutes of Health and Pfizer Inc. NR 64 TC 309 Z9 314 U1 4 U2 22 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 14 PY 2011 VL 208 IS 3 BP 519 EP 533 DI 10.1084/jem.20102049 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 735ZW UT WOS:000288460300010 PM 21282379 ER PT J AU Linas, BS Minkoff, H Cohen, MH Karim, R Cohan, D Wright, RL Young, M Watts, DH Golub, ET AF Linas, Beth S. Minkoff, Howard Cohen, Mardge H. Karim, Roksana Cohan, Deborah Wright, Rodney L. Young, Mary Watts, D. Heather Golub, Elizabeth T. TI Relative time to pregnancy among HIV-infected and uninfected women in the Women's Interagency HIV Study, 2002-2009 SO AIDS LA English DT Article DE HIV; parity; pregnancy; time to pregnancy; women ID POSITIVE WOMEN; COHORT AB Objectives: To determine the incidence rate of, and the relative time to pregnancy by HIV status in US women between 2002 and 2009. Design: The Women's Interagency HIV Study (WIHS) is an ongoing, multicenter prospective cohort study of the natural and treated history of HIV infection and related outcomes among women with and without HIV. Methods: Eligible participants were 45 years of age or less; sexually active with male partner(s) or reported a pregnancy outcome within the past year; and never reported hysterectomy, tubal ligation, or oopherectomy. Poisson regression was conducted to compare pregnancy incidence rates over time by HIV status. Relative time to pregnancy was ascertained via Kaplan-Meier plots and generalized gamma survival analysis. Results: Adjusting for age, number of male sex partners, contraception, parity, exchanging sex, and alcohol use, HIV infection was associated with a 40% reduction in the incidence rate of pregnancy [incidence rate ratio = 0.60, 95% confidence interval (CI) 0.46-0.78]. The time for HIV-infected women to become pregnant was 73% longer relative to HIV-uninfected women (relative time = 1.73, 95% CI 1.35-2.36). In addition to HIV infection, decreased parity and older age were independent predictors of lower pregnancy incidence. Conclusions: Despite the beneficial effects of modern antiretroviral therapy on survival and prevention of maternal-to-child transmission, our findings suggest that pregnancy incidence remains lower among HIV-infected women. Whether this lower incidence is due to behavioral differences or reduced biologic fertility remains an area worthy of further study. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Linas, Beth S.; Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, New York, NY USA. [Minkoff, Howard] SUNY Downstate, New York, NY USA. [Cohen, Mardge H.] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Univ, Chicago, IL 60612 USA. [Karim, Roksana] Univ So Calif, Ctr Hlth Profess, Los Angeles, CA USA. [Cohan, Deborah] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Wright, Rodney L.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Women, New York, NY USA. [Wright, Rodney L.] Montefiore Med Ctr, New York, NY USA. [Young, Mary] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Linas, BS (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 Wolfe St E6532, Baltimore, MD 21205 USA. EM blinas@jhsph.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 10 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2011 VL 25 IS 5 BP 707 EP 711 DI 10.1097/QAD.0b013e3283445811 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 729PT UT WOS:000287963600021 PM 21297418 ER PT J AU Chang, J Lindsay, RJ Kulkarni, S Lifson, JD Carrington, M Altfeld, M AF Chang, Judy Lindsay, Robert J. Kulkarni, Smita Lifson, Jeffrey D. Carrington, Mary Altfeld, Marcus TI Polymorphisms in interferon regulatory factor 7 reduce interferon-alpha responses of plasmacytoid dendritic cells to HIV-1 SO AIDS LA English DT Article ID SIV INFECTION; IMMUNE ACTIVATION; VIRUS-INFECTIONS; NATURAL HOSTS; TLR7 AB Recognition of HIV-1 ssRNA by Toll-like receptor 7 induces the production of the pro-inflammatory cytokines that may contribute to the systemic immune activation associated with HIV-1 disease progression. Here, we describe a novel association between polymorphisms in interferon regulatory factor 7 (IRF7), a master regulator of interferon-alpha (IFN-alpha), and the ability of plasmacytoid dendritic cells to produce IFN-alpha in response to HIV-1. IRF7 polymorphisms may, therefore, affect the ability of individuals to respond to HIV-1 and modulate HIV-1 disease progression. C1 [Chang, Judy; Lindsay, Robert J.; Carrington, Mary; Altfeld, Marcus] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Kulkarni, Smita; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21701 USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Navy Yard, MA 02129 USA. EM maltfeld@partners.org FU Doris Duke Charitable Foundation; Phillip T. and Susan M. Ragon Foundation; Bill and Melinda Gates Foundation; National Health and Medical Research Council of Australia [519578]; Ragon Fellowship; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; [RO1 216753] FX The authors thank the Brigham and Women's Hospital PhenoGenetic Project for providing DNA samples from healthy individuals that were used in the replication effort of this study. These studies were supported by RO1 216753 and the Doris Duke Charitable Foundation. They also thank the Phillip T. and Susan M. Ragon Foundation and the Bill and Melinda Gates Foundation for their support. J.J.C. is supported by a fellowship awarded from the National Health and Medical Research Council of Australia (519578) and a Ragon Fellowship and M. A. is a Doris Duke Distinguished Clinical Scientist. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 14 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2011 VL 25 IS 5 BP 715 EP 717 DI 10.1097/QAD.0b013e328343c186 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 729PT UT WOS:000287963600023 PM 21297422 ER PT J AU Sansing, HA Sarkeshik, A Yates, JR Patel, V Gutkind, JS Yamada, KM Berrier, AL AF Sansing, Hope A. Sarkeshik, Ali Yates, John R. Patel, Vyomesh Gutkind, J. Silvio Yamada, Kenneth M. Berrier, Allison L. TI Integrin alpha beta 1, alpha(v)beta, alpha(6)beta effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Integrin; Cytoplasmic effectors; Oral carcinoma; Tumor invasion; Cell spreading; Proliferation; Cisplatin; Chemoresistance; Matrigel ID NECK-CANCER; HEAD; CISPLATIN; ADHESION; GROWTH; CELLS; CHEMOSENSITIVITY; RESISTANCE; APOPTOSIS AB Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomics screen of proteins recruited to clustered integrin alpha beta 1, alpha(v)beta or alpha(6)beta receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen land laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin. (C) 2011 Elsevier Inc. All rights reserved. C1 [Sansing, Hope A.; Berrier, Allison L.] Louisiana State Univ, Sch Dent, Hlth Sci Ctr, Dept Oral & Craniofacial Biol, New Orleans, LA 70119 USA. [Sarkeshik, Ali; Yates, John R.] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Berrier, AL (reprint author), Louisiana State Univ, Sch Dent, Hlth Sci Ctr, Dept Oral & Craniofacial Biol, 1100 Florida Ave,Clin Bldg,Room 8301, New Orleans, LA 70119 USA. EM allison.berrier@gmail.com RI Gutkind, J. Silvio/A-1053-2009 FU NCMHD/NIDCR/NIH; NIDCR; LSUHSC-NO School of Dentistry; Yates Laboratory (NIH) [P41 RR011823] FX The authors thank the Katrina Visiting Faculty Program sponsored by the NCMHD/NIDCR/NIH, the NIDCR intramural research program and LSUHSC-NO School of Dentistry for support, and the Yates Laboratory (NIH Grant P41 RR011823) for the proteomics. The expertise provided by Hynda Kleinman and Deborah Philp in invasion assays and Becky Worthy lake in microscopy are greatly appreciated. The authors also thank the Department of Oral and Craniofacial Biology for their core facilities. NR 30 TC 19 Z9 21 U1 0 U2 5 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 MAR 11 PY 2011 VL 406 IS 2 BP 171 EP 176 DI 10.1016/j.bbrc.2011.01.109 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 738CF UT WOS:000288616200003 PM 21291860 ER PT J AU Chattopadhyay, MK Fernandez, C Sharma, D McPhie, P Masison, DC AF Chattopadhyay, Manas K. Fernandez, Cristina Sharma, Deepak McPhie, Peter Masison, Daniel C. TI Yeast ornithine decarboxylase and antizyme form a 1:1 complex in vitro: Purification and characterization of the inhibitory complex SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Affinity constants; Antizyme-ODC complex; Circular dichroism; Protein-protein interaction; Surface plasmon resonance ID STATIC LIGHT-SCATTERING; SACCHAROMYCES-CEREVISIAE; REQUIRES INTERACTION; PROTEIN INHIBITOR; DEGRADATION; POLYAMINES; PROTEASOME; EXPRESSION; INSIGHTS; BINDING AB Saccharomyces cerevisiae antizyme (AZ) resembles mammalian AZ in its mode of synthesis by translational frameshifting and its ability to inhibit and facilitate the degradation of ornithine decarboxylase (ODC). Despite many studies on the interaction of AZ and ODC, the ODC:AZ complex has not been purified from any source and thus clear information about the stoichiometry of the complex is still lacking. In this study we have studied the yeast antizyme protein and the ODC:AZ complex. The far UV CD spectrum of the full-length antizyme shows that the yeast protein consists of 51% beta-sheet, 19% alpha-helix, and 24% coils. Surface plasmon resonance analyses show that the association constant (K(A)) between yeast AZ and yeast ODC is 6 x 10(7) (M(-1)). Using purified His-tagged AZ as a binding partner, we have purified the ODC:AZ inhibitory complex. The isolated complex has no ODC activity. The molecular weight of the complex is 90 kDa, which indicates a one to one stoichiometric binding of AZ and ODC in vitro. Comparison of the circular dichroism (CD) spectra of the two individual proteins and of the ODC:AZ complex shows a change in the secondary structure in the complex. Published by Elsevier Inc. C1 [Chattopadhyay, Manas K.; Fernandez, Cristina; Sharma, Deepak; McPhie, Peter; Masison, Daniel C.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Chattopadhyay, MK (reprint author), NIDDK, Lab Biochem & Genet, NIH, 8 Ctr Dr,Bldg 8,Room 219, Bethesda, MD 20892 USA. EM manasc@intra.niddk.nih.gov RI Fernandez, Cristina/G-2269-2015 OI Fernandez, Cristina/0000-0003-3792-4015 FU NIH (National Institute of Diabetes, Digestive and Kidney Diseases) FX This research was supported by the Intramural Research Program of the NIH (National Institute of Diabetes, Digestive and Kidney Diseases). The authors would like to thank Dr. Herbert Tabor and Dr. Allen P. Minton for supporting this research and critical reviewing of the manuscript. We would also like to thank Dr. Begona Monterroso for helping in dynamic light scattering experiment of ODC-AZ complex. NR 31 TC 2 Z9 4 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 11 PY 2011 VL 406 IS 2 BP 177 EP 182 DI 10.1016/j.bbrc.2011.01.113 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 738CF UT WOS:000288616200004 PM 21295540 ER PT J AU Xu, KY Zhu, WZ Chen, L DeFilippi, C Zhang, J Xiao, RP AF Xu, Kai Y. Zhu, Weizhong Chen, Ling DeFilippi, Christopher Zhang, Jin Xiao, Rui-Ping TI Mechanistic distinction between activation and inhibition of (Na++K+)-ATPase-mediated Ca2+ influx in cardiomyocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE (Na++K+)-ATPase; Na+/Ca+-exchanger; Ca2+ influx; Allosteric activator; Digitalis drugs ID NA+/CA2+ EXCHANGE; ALPHA-SUBUNIT; ARRHYTHMIAS; OVERLOAD; INOTROPY; CHANNEL AB (Na++K+)-ATPase (NKA) mediates positive inotropy in the heart. Extensive studies have demonstrated that the reverse-mode NA(+)/Ca2+-exchanger (NCX) plays a critical role in increasing intracellular Ca2+ concentration through the inhibition of NKA-induced positive inotropy by cardiac glycosides. Little is known about the nature of the NCX functional mode in the activation of NKA-induced positive inotropy. Here, we examined the effect of an NKA activator SSA412 antibody on Ca-45 influx in isolated rat myocytes and found that KB-R7943, a NCX reverse-mode inhibitor, fails to inhibit the activation of NKA-induced Ca-45 influx, suggesting that the Ca2+ influx via the reverse-mode NCX does not mediate this process. Nifedipine, an L-type Ca2+ channel (LTCC) inhibitor, completely blocks the activation of NKA-induced Ca-45 influx, suggesting that the LTCC is responsible for the moderate increase in intracellular Ca2+. In contrast, the inhibition of NKA by ouabain induces 4.7-fold Ca-45 influx compared with the condition of activation of NKA. Moreover, approximately 70% of ouabain-induced Ca-45 influx was obstructed by KB-R7943 and only 30% was impeded by nifedipine, indicating that both the LTCC and the NCX contribute to the rise in intracellular Ca2+ and that the NCX reverse-mode is the major source for the Ca-45 influx induced by the inhibition of NKA. This study provides direct evidence to demonstrate that the activation of NKA-induced Ca2+ increase is independent of the reverse-mode NCX and pinpoints a mechanistic distinction between the activation and inhibition of the NKA-mediated Ca2+ influx path ways in cardiomyocytes. (C) 2011 Elsevier Inc. All rights reserved. C1 [Xu, Kai Y.] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Zhu, Weizhong; Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Chen, Ling; DeFilippi, Christopher] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Zhang, Jin] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. RP Xu, KY (reprint author), 10 S Pine St,MSTF-434E, Baltimore, MD 21201 USA. EM kxu002@umaryland.edu FU NIH [HL-52175] FX We thank Mr. B. Ziman for isolating rat myocytes. The work was supported by the NIH Grant HL-52175 (KY. Xu) and the NIH Intramural Research Grant (R.-P. Xiao). NR 15 TC 5 Z9 7 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 11 PY 2011 VL 406 IS 2 BP 200 EP 203 DI 10.1016/j.bbrc.2011.02.013 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 738CF UT WOS:000288616200008 PM 21303662 ER PT J AU Kottke, T Sander, K Weizel, L Schneider, EH Seifert, R Stark, H AF Kottke, Tim Sander, Kerstin Weizel, Lilia Schneider, Erich H. Seifert, Roland Stark, Holger TI Receptor-specific functional efficacies of alkyl imidazoles as dual histamine H-3/H-4 receptor ligands SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Histamine receptor; Inflammation; Agonist; Inverse agonist; GTP gamma S binding; Imidazole ID HIGH CONSTITUTIVE ACTIVITY; H-3 RECEPTOR; MOLECULAR-CLONING; HOMOLOGY MODEL; 1ST POTENT; ANTAGONISTS; PHARMACOLOGY; DERIVATIVES; BINDING; SEARCH AB Histamine H-3 and H-4 receptors are highly related G protein-coupled receptors. Preclinical and clinical data strongly suggest the potential therapeutic application of selectively acting histamine H-4 receptor ligands to inflammatory conditions but also hint at a certain interference of the two receptors in diseases attended with itch and pain. The aim of this investigation was to identify dual acting ligands as pharmacological tools. Receptor binding profiles of omega-(1H-imidazol-4-yl)alkyl derivatives structurally defined as amides, carbamates, esters, ethers, ketones and ureas were evaluated with respect to their potencies at histamine H-3 and H-4 receptors. A two-step screening method based on in vitro radioligand binding studies and functional [S-35]GTP gamma S binding experiments was performed. The examined series of imidazole-containing compounds displayed both, selective histamine H-4 receptor and dual acting histamine H-3/H-4 receptor ligands. Slight structural modifications caused major differences in selectivity profiles and on functional properties at the human histamine H-4 receptor. N-(3-(1H-Imidazol-4-yl)propyl)-2-cyclohexylacetamide 11 was identified as most potent and selective human histamine H-4 receptor ligand in this series (K-i = 45 nM). Amide- and ether-containing structures consistently exhibited partial agonist efficacies, whereas ureas, ketones, esters and carbamates mainly acted as antagonists and inverse agonists. We identified novel dual acting histamine H-3/H-4 receptor ligands with varying efficacies at the histamine H-4 receptor subtype, whereas histamine H-3 receptor antagonism was kept constant, e.g. 3-(1H-imidazol-4-yl)propyl (cyclohexylmethyl)carbamate 19 or 4-(3-(3-phenylpropylthio)propyl)-1H-imidazole 30. These compounds state valuable pharmacological tools in studies of diseases, in which histamine H-3 and H-4 receptor signalling contributes to pathophysiological conditions. (C) 2011 Elsevier B.V. All rights reserved. C1 [Kottke, Tim; Sander, Kerstin; Weizel, Lilia; Stark, Holger] Goethe Univ Frankfurt, Inst Pharmaceut Chem, ZAFES NeFF OSF CMP, D-60438 Frankfurt, Germany. [Schneider, Erich H.] NIAID, NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. [Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-3000 Hannover, Germany. RP Stark, H (reprint author), Goethe Univ Frankfurt, Inst Pharmaceut Chem, ZAFES NeFF OSF CMP, Max von Laue Str 9, D-60438 Frankfurt, Germany. EM h.stark@pharmchem.uni-frankfurt.de RI Stark, Holger/A-4235-2009; Schneider, Erich/B-9051-2016; Fachbereich14, Dekanat/C-8553-2015 OI Stark, Holger/0000-0003-0642-0180; Schneider, Erich/0000-0002-7905-4276; FU ESF COST Action [BM0806]; Hessia LOEWE Program for NeFF and OSF FX We greatly thank Prof. Dr. Dr. h. c. Jean-Charles Schwartz (Bioprojet, Saint-Gregoire, France) for providing HEK-293 cells stably expressing the recombinant human histamine H3 receptor gene. The authors acknowledge the support of ESF COST Action BM0806 'Recent advances in histamine receptor H4R research', and the Hessia LOEWE Program for NeFF and OSF. NR 40 TC 26 Z9 26 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 11 PY 2011 VL 654 IS 3 BP 200 EP 208 DI 10.1016/j.ejphar.2010.12.033 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 731YS UT WOS:000288147300002 PM 21237145 ER PT J AU Smith, MA Wright, G Wu, JA Tailor, P Ozato, K Chen, XH Wei, S Piskurich, JF Ting, JPY Wright, KL AF Smith, Matthew A. Wright, Gabriela Wu, Jian Tailor, Prafullakumar Ozato, Keiko Chen, Xianghong Wei, Sheng Piskurich, Janet F. Ting, Jenny P. -Y. Wright, Kenneth L. TI Positive Regulatory Domain I (PRDM1) and IRF8/PU.1 Counter-regulate MHC Class II Transactivator (CIITA) Expression during Dendritic Cell Maturation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL REPRESSOR BLIMP-1; IFN-GAMMA; B-LYMPHOCYTES; MICE LACKING; DEVELOPMENTAL REGULATION; RECEPTOR EXPRESSION; BINDING-PROTEIN; DOWN-REGULATION; PROMOTER-III; GENES AB Dendritic cells (DCs) are key mediators of immune function through robust and tightly regulated presentation of antigen in the context of the MHC Class II. MHC Class II expression is controlled by the transactivator CIITA. CIITA expression in conventional DCs is uniquely dependent on an uncharacterized myeloid cell-specific promoter, CIITApI. We now identify in vivo the promoter structure and factors regulating CIITApI. In immature DCs transcription requires binding of PU.1, IRF8, NF kappa B, and Sp1 to the promoter. PU.1 binds independently at one site and in a required heterodimer with IRF8 at a composite element. DCs from IRF8-null mice have an unoccupied CIITApI promoter that can be rescued by reconstitution with IRF8 in vitro. Furthermore, mutation of either PU.1 site or the IFR8 site inhibits transcriptional activation. In vivo footprinting and chromatin immunoprecipitation reveals that DC maturation induces complete disassociation of the bound activators paralleled by recruitment of PRDM1/Blimp-1 to the promoter. PRDM1 is a transcriptional repressor with essential roles in B cells, T cells, NK cells, and DCs. We show that PRDM1 co-repressors, G9a and HDAC2, are recruited to CIITApI, leading to a loss of histone acetylation and acquisition of histone H3K9 dimethylation and heterochromatin protein 1 gamma (HP1 gamma). PRDM1 binding also blocks IRF8-mediated activation dependent on the PU.1/IRF composite element. Together these findings reveal the mechanisms regulating CIITA and, thus, antigen presentation in DCs, demonstrating that PRDM1 and IRF8/PU.1 counter-regulate expression. The activity of PRDM1 in silencing all three cell type-specific CIITA promoters places it as a central regulator of antigen presentation. C1 [Smith, Matthew A.; Wright, Gabriela; Wu, Jian; Chen, Xianghong; Wei, Sheng; Wright, Kenneth L.] Univ S Florida, Dept Mol Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Smith, Matthew A.; Wright, Gabriela; Wu, Jian; Chen, Xianghong; Wei, Sheng; Wright, Kenneth L.] Univ S Florida, Dept Oncol Sci, Tampa, FL 33612 USA. [Tailor, Prafullakumar; Ozato, Keiko] NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. [Piskurich, Janet F.] Texas Tech Univ Hlth Sci Ctr, Dept Med Educ, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Ting, Jenny P. -Y.] Univ N Carolina, Dept Immunol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Wright, KL (reprint author), Univ S Florida, Dept Mol Med, H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr,MRC 4 E, Tampa, FL 33612 USA. EM ken.wright@moffitt.org FU National Institutes of Health [CA114504, CA080990, AI029564] FX This work was supported, in whole or in part, by National Institutes of Health Grants CA114504 and CA080990 (to K. L. W.) and AI029564. NR 68 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 MAR 11 PY 2011 VL 286 IS 10 BP 7893 EP 7904 DI 10.1074/jbc.M110.165431 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300020 PM 21216962 ER PT J AU Xiong, YB Qiu, F Piao, WJ Song, C Wahl, LM Medvedev, AE AF Xiong, Yanbao Qiu, Fu Piao, Wenji Song, Chang Wahl, Larry M. Medvedev, Andrei E. TI Endotoxin Tolerance Impairs IL-1 Receptor-Associated Kinase (IRAK) 4 and TGF-beta-activated Kinase 1 Activation, K63-linked Polyubiquitination and Assembly of IRAK1, TNF Receptor-associated Factor 6, and I kappa B Kinase gamma and Increases A20 Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOLL-LIKE-RECEPTOR; TUMOR-NECROSIS-FACTOR; INTESTINAL EPITHELIAL-CELLS; SIGNALING PATHWAY; NEGATIVE REGULATOR; INNATE IMMUNITY; LYS63-LINKED POLYUBIQUITINATION; COMPLEX-FORMATION; GENE-EXPRESSION; DOWN-REGULATION AB Endotoxin tolerance reprograms Toll-like receptor 4 responses by impairing LPS-elicited production of pro-inflammatory cytokines without inhibiting expression of anti-inflammatory or anti-microbial mediators. In septic patients, Toll-like receptor tolerance is thought to underlie decreased pro-inflammatory cytokine expression in response to LPS and increased incidence of microbial infections. The impact of endotoxin tolerance on recruitment, post-translational modifications and signalosome assembly of IL-1 receptor-associated kinase (IRAK) 4, IRAK1, TNF receptor-associated factor (TRAF) 6, TGF-beta-activated kinase (TAK) 1, and I kappa B kinase (IKK) gamma is largely unknown. We report that endotoxin tolerization of THP1 cells and human monocytes impairs LPS-mediated receptor recruitment and activation of IRAK4, ablates K63-linked polyubiquitination of IRAK1 and TRAF6, compromises assembly of IRAK1-TRAF6 and IRAK1-IKK gamma platforms, and inhibits TAK1 activation. Deficiencies in these signaling events in LPS-tolerant cells coincided with increased expression of A20, an essential deubiquitination enzyme, and sustained A20-IRAK1 associations. Overexpression of A20 inhibited LPS-induced activation of NF-kappa B and ablated NF-kappa B reporter activation driven by ectopic expression of MyD88, IRAK1, IRAK2, TRAF6, and TAK1/TAB1, while not affecting the responses induced by IKK beta and p65. A20 shRNA knockdown abolished LPS tolerization of THP1 cells, mechanistically linking A20 and endotoxin tolerance. Thus, deficient LPS-induced activation of IRAK4 and TAK1, K63-linked polyubiquitination of IRAK1 and TRAF6, and disrupted IRAK1-TRAF6 and IRAK1-IKK gamma assembly associated with increased A20 expression and A20-IRAK1 interactions are new determinants of endotoxin tolerance. C1 [Xiong, Yanbao; Qiu, Fu; Piao, Wenji; Song, Chang; Medvedev, Andrei E.] Univ Maryland, Dept Microbiol & Immunol, Sch Med, Baltimore, MD 21201 USA. [Wahl, Larry M.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Medvedev, AE (reprint author), Univ Maryland, Dept Microbiol & Immunol, Sch Med, 685 W Baltimore St,HSF-1 Bldg,Rm 380, Baltimore, MD 21201 USA. EM amedvedev@som.umaryland.edu FU National Institutes of Health [AI-059524] FX This work was supported, in whole or in part, by National Institutes of Health Grant AI-059524 (to A. E. M.). NR 75 TC 41 Z9 42 U1 3 U2 6 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 MAR 11 PY 2011 VL 286 IS 10 BP 7905 EP 7916 DI 10.1074/jbc.M110.182873 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300021 PM 21220427 ER PT J AU Comstock, CES Augello, MA Schiewer, MJ Karch, J Burd, CJ Ertel, A Knudsen, ES Jessen, WJ Aronow, BJ Knudsen, KE AF Comstock, Clay E. S. Augello, Michael A. Schiewer, Matthew J. Karch, Jason Burd, Craig J. Ertel, Adam Knudsen, Erik S. Jessen, Walter J. Aronow, Bruce J. Knudsen, Karen E. TI Cyclin D1 Is a Selective Modifier of Androgen-dependent Signaling and Androgen Receptor Function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROSTATE-CANCER CELLS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; HISTONE MODIFICATIONS; RESPONSIVE GENES; KINASE-ACTIVITY; CDK INHIBITORS; CO-REPRESSOR; ACTIVATION AB D-type cyclins regulate cellular outcomes in part through cyclin-dependent, kinase-independent mechanisms that modify transcription factor action, and recent in vivo studies showed that cyclin D1 associates with a large number of transcriptional regulators in cells of the retina and breast. Given the frequency of cyclin D1 alterations in cancer, it is imperative to delineate the molecular mechanisms by which cyclin D1 controls key transcription factor networks in human disease. Prostate cancer was used as a paradigm because this tumor type is reliant at all stages of the disease on androgen receptor (AR) signaling, and cyclin D1 has been shown to negatively modulate AR-dependent expression of prostate-specific antigen (KLK3/PSA). Strategies were employed to control cyclin D1 expression under conditions of hormone depletion, and the effect of cyclin D1 on subsequent androgen-dependent gene expression was determined using unbiased gene expression profiling. Modulating cyclin D1 conferred widespread effects on androgen signaling and revealed cyclin D1 to be a selective effector of hormone action. A subset of androgen-induced target genes, known to be directly regulated by AR, was strongly suppressed by cyclin D1. Analyses of AR occupancy at target gene regulatory loci of clinical relevance demonstrated that cyclin D1 limits AR residence after hormone stimulation. Together, these findings reveal a new function for cyclin D1 in controlling hormone-dependent transcriptional outcomes and demonstrate a pervasive role for cyclin D1 in regulating transcription factor dynamics. C1 [Comstock, Clay E. S.; Augello, Michael A.; Schiewer, Matthew J.; Ertel, Adam; Knudsen, Erik S.; Knudsen, Karen E.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Comstock, Clay E. S.; Augello, Michael A.; Schiewer, Matthew J.; Ertel, Adam; Knudsen, Erik S.; Knudsen, Karen E.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. [Knudsen, Karen E.] Thomas Jefferson Univ, Dept Urol, Philadelphia, PA 19107 USA. [Knudsen, Karen E.] Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Karch, Jason] Univ Cincinnati, Dept Cell & Canc Biol, Cincinnati, OH 45221 USA. [Burd, Craig J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Jessen, Walter J.] Covance Biomarker Ctr Excellence, Greenfield, IN 46140 USA. [Aronow, Bruce J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Knudsen, KE (reprint author), 233 S 10th St,BLSB 1008A, Philadelphia, PA 19107 USA. EM Karen.Knudsen@kimmelcancercenter.org RI Aronow, Bruce/F-8438-2012; OI Comstock, Clay/0000-0001-5867-1489; Jessen, Walter/0000-0003-3840-4337; Burd, Craig/0000-0002-6899-6751 FU National Institutes of Health [CA099996]; Department of Defense [PC094507, PC094195, PC094596] FX This work was supported, in whole or in part, by National Institutes of Health Grant CA099996 (to K. E. K.). This work was also supported by Department of Defense New Investigator Award PC094507 (to C. E. S. C.) and Department of Defense Predoctoral Fellowships PC094195 (to M. J. S.) and PC094596 (to M. A. A.). NR 92 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2011 VL 286 IS 10 BP 8117 EP 8127 DI 10.1074/jbc.M110.170720 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300042 PM 21212260 ER PT J AU Kubota, T Matsuoka, M Xu, SX Otsuki, N Takeda, M Kato, A Ozato, K AF Kubota, Toru Matsuoka, Mayumi Xu, Songxiao Otsuki, Noriyuki Takeda, Makoto Kato, Atsushi Ozato, Keiko TI PIASy Inhibits Virus-induced and Interferon-stimulated Transcription through Distinct Mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; STAT1-MEDIATED GENE ACTIVATION; TOLL-LIKE RECEPTORS; NEGATIVE REGULATION; SIGNALING PATHWAYS; INNATE IMMUNITY; RIG-I; NUCLEAR-BODIES; RNA HELICASE; SUMO AB The protein inhibitor of activated STAT (PIAS) family proteins regulates innate immune responses by controlling transcription induced by Toll-like receptor, RIG-I-like receptor signaling, and JAK/STAT pathways. Here, we show that PIASy negatively regulates type I interferon (IFN) transcription. Virus infection led to enhanced type I IFN induction in PIASy null cells, and conversely PIASy overexpression reduced IFN transcription. A mutation in the LXXLL motif of the SAP domain abolished inhibition of IFN-stimulated gene expression but did not affect virus or Toll-like receptor/RIG-I-like receptor-stimulated IFN transcription, indicating that PIASy employs distinct mechanisms to inhibit virus-induced and IFN-stimulated transcription. SUMO E3 activity was not required for PIASy inhibition of IFN transcription; however, PIASy relied on the SUMO modification mechanism to inhibit IFN transcription, because the activity of the SUMO-interacting motif was required for inhibition, and knockdown of SUMO E2 enzyme UBC9 decreased inhibitory activity of PIASy. Our results demonstrate that PIASy negatively regulates both IFN transcription and IFN-stimulated gene expression through multiple mechanisms utilizing the function of different domains. C1 [Kubota, Toru; Otsuki, Noriyuki; Takeda, Makoto; Kato, Atsushi] Natl Inst Infect Dis, Dept Virol 3, Tokyo 2080011, Japan. [Matsuoka, Mayumi] Natl Inst Infect Dis, Dept Bacterial Pathogenesis & Infect Control, Tokyo 2080011, Japan. [Xu, Songxiao; Ozato, Keiko] NICHD, Lab Mol Growth Regulat, Genom Differentiat Program, NIH, Bethesda, MD 20892 USA. RP Kubota, T (reprint author), Natl Inst Infect Dis, Dept Virol 3, Tokyo 2080011, Japan. EM kubota@nih.go.jp FU NICHD; NIH; Ministry of Education, Culture, Sports, Science, and Technology of Japan [22590424] FX This work was supported, in whole or in part, by National Institutes of Health grant from the Intramural Research Program of NICHD and Trans NIH Bio-defense Program. This work was also supported by Grant-in-aid 22590424 for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 54 TC 12 Z9 12 U1 3 U2 6 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 MAR 11 PY 2011 VL 286 IS 10 BP 8165 EP 8175 DI 10.1074/jbc.M110.195255 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300047 PM 21199872 ER PT J AU McGlinchey, RP Shewmaker, F Hu, KN McPhie, P Tycko, R Wickner, RB AF McGlinchey, Ryan P. Shewmaker, Frank Hu, Kan-nian McPhie, Peter Tycko, Robert Wickner, Reed B. TI Repeat Domains of Melanosome Matrix Protein Pmel17 Orthologs Form Amyloid Fibrils at the Acidic Melanosomal pH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; BETA-SHEET STRUCTURE; PINK-EYED DILUTION; SECONDARY-STRUCTURE; EXPERIMENTAL CONSTRAINTS; MURINE MELANOMA; POLAR ZIPPERS; PRION; PARALLEL AB Most amyloids are pathological, but fragments of Pmel17 form a functional amyloid in vertebrate melanosomes essential for melanin synthesis and deposition. We previously reported that only at the mildly acidic pH (4-5.5) typical of melanosomes, the repeat domain (RPT) of human Pmel17 can form amyloid in vitro. Combined with the known presence of RPT in the melanosome filaments and the requirement of this domain for filament formation, we proposed that RPT may be the core of the amyloid formed in vivo. Although most of Pmel17 is highly conserved across a broad range of vertebrates, the RPT domains vary dramatically, with no apparent homology in some cases. Here, we report that the RPT domains of mouse and zebrafish, as well as a small splice variant of human Pmel17, all form amyloid specifically at mildly acid pH (pH similar to 5.0). Protease digestion, mass per unit length measurements, and solid-state NMR experiments suggest that amyloid of the mouse RPT has an in-register parallel beta-sheet architecture with two RPT molecules per layer, similar to amyloid of the A beta peptide. Although there is no sequence conservation between human and zebrafish RPT, amyloid formation at acid pH is conserved. C1 [McGlinchey, Ryan P.; Shewmaker, Frank; McPhie, Peter; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Hu, Kan-nian; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr,MSC0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov FU National Institutes of Health NIDDK FX This work was supported, in whole or in part, by National Institutes of Health NIDDK Intramural Program. NR 55 TC 18 Z9 20 U1 0 U2 6 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 MAR 11 PY 2011 VL 286 IS 10 BP 8385 EP 8393 DI 10.1074/jbc.M110.197152 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300067 PM 21148556 ER PT J AU Fukuda, Y Aguilar-Bryan, L Vaxillaire, M Dechaume, A Wang, Y Dean, M Moitra, K Bryan, J Schuetz, JD AF Fukuda, Yu Aguilar-Bryan, Lydia Vaxillaire, Martine Dechaume, Aurelie Wang, Yao Dean, Michael Moitra, Karobi Bryan, Joseph Schuetz, John D. TI Conserved Intramolecular Disulfide Bond Is Critical to Trafficking and Fate of ATP-binding Cassette (ABC) Transporters ABCB6 and Sulfonylurea Receptor 1 (SUR1)/ABCC8 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID QUALITY-CONTROL; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; PLASMA-MEMBRANE; CYSTIC-FIBROSIS; N-GLYCOSYLATION; PROTEIN; CHANNELS; OLIGOSACCHARIDES; IDENTIFICATION AB The ATP-binding cassette (ABC) transporter ABCB6 is a mitochondrial porphyrin transporter that activates porphyrin biosynthesis. ABCB6 lacks a canonical mitochondrial targeting sequence but reportedly traffics to other cellular compartments such as the plasma membrane. How ABCB6 reaches these destinations is unknown. In this study, we show that endogenous ABCB6 is glycosylated in multiple cell types, indicating trafficking through the endoplasmic reticulum (ER), and has only one atypical site for glycosylation (NXC) in its amino terminus. ABCB6 remained glycosylated when the highly conserved cysteine (Cys-8) was substituted with serine to make a consensus site, NXS. However, this substitution blocked ER exit and produced ABCB6 degradation, which was mostly reversed by the proteasomal inhibitor MG132. The amino terminus of ABCB6 has an additional highly conserved ER luminal cysteine (Cys-26). When Cys-26 was mutated alone or in combination with Cys-8, it also resulted in instability and ER retention. Further analysis revealed that these two cysteines form a disulfide bond. We discovered that other ABC transporters with an amino terminus in the ER had similarly configured conserved cysteines. This analysis led to the discovery of a disease-causing mutation in the sulfonylurea receptor 1 (SUR1)/ABCC8 from a patient with hyperinsulinemic hypoglycemia. The mutant allele only contains a mutation in a conserved amino-terminal cysteine, producing SUR1 that fails to reach the cell surface. These results suggest that for ABC transporters the propensity to form a disulfide bond in the ER defines a unique checkpoint that determines whether a protein is ER-retained. C1 [Fukuda, Yu; Wang, Yao; Schuetz, John D.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Fukuda, Yu] Univ Tennessee, Hlth Sci Ctr, Coll Grad Hlth Sci, Interdisciplinary Program, Memphis, TN 38163 USA. [Aguilar-Bryan, Lydia; Bryan, Joseph] Pacific NW Res Inst, Seattle, WA 98122 USA. [Vaxillaire, Martine; Dechaume, Aurelie] CNRS, Inst Biol, UMR Unit 8090, F-59019 Lille, France. [Vaxillaire, Martine; Dechaume, Aurelie] Inst Pasteur, F-59019 Lille, France. [Dean, Michael; Moitra, Karobi] NCI, Expt Immunol Lab, NIH, Frederick, MD 21702 USA. RP Schuetz, JD (reprint author), St Jude Childrens Hosp, Dept Pharmaceut Sci, MS 313,262 Danny Thomas Pl, Memphis, TN 38105 USA. EM John.Schuetz@stjude.org RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU National Institutes of Health [ES058571, P30 CA21745, CA21865]; American Lebanese Syrian Associated Charities; Thrasher Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants ES058571, P30 CA21745, and CA21865. This work was also supported by the American Lebanese Syrian Associated Charities and by a grant from the Thrasher Foundation (to L. A.-B.). NR 41 TC 17 Z9 18 U1 1 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 MAR 11 PY 2011 VL 286 IS 10 BP 8481 EP 8492 DI 10.1074/jbc.M110.174516 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300076 PM 21199866 ER PT J AU Neutzner, A Neutzner, M Benischke, AS Ryu, SW Frank, S Youle, RJ Karbowski, M AF Neutzner, Albert Neutzner, Melanie Benischke, Anne-Sophie Ryu, Seung-Wook Frank, Stephan Youle, Richard J. Karbowski, Mariusz TI A Systematic Search for Endoplasmic Reticulum (ER) Membrane-associated RING Finger Proteins Identifies Nixin/ZNRF4 as a Regulator of Calnexin Stability and ER Homeostasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; QUALITY-CONTROL; UBIQUITIN; LIGASE; DEGRADATION; PROTEOMICS; MEDIATORS; PATHWAYS; TOPOLOGY; DATABASE AB To identify novel regulators of endoplasmic reticulum (ER)-linked protein degradation and ER function, we determined the entire inventory of membrane-spanning RING finger E3 ubiquitin ligases localized to the ER. We identified 24 ER membrane-anchored ubiquitin ligases and found Nixin/ZNRF4 to be central for the regulation of calnexin turnover. Ectopic expression of wild type Nixin induced a dramatic down-regulation of the ER-localized chaperone calnexin that was prevented by inactivation of the Nixin RING domain. Importantly, Nixin physically interacts with calnexin in a glycosylation-independent manner, induces calnexin ubiquitination, and p97-dependent degradation, indicating an ER-associated degradation-like mechanism of calnexin turnover. C1 [Neutzner, Albert; Ryu, Seung-Wook; Youle, Richard J.; Karbowski, Mariusz] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Neutzner, Albert; Neutzner, Melanie; Benischke, Anne-Sophie] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland. [Neutzner, Albert; Neutzner, Melanie; Benischke, Anne-Sophie] Univ Basel Hosp, Univ Eye Clin, CH-4031 Basel, Switzerland. [Neutzner, Melanie; Frank, Stephan] Univ Basel, Inst Pathol, Dept Neuropathol, CH-4031 Basel, Switzerland. [Ryu, Seung-Wook] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Taejon 305701, South Korea. [Karbowski, Mariusz] Univ Maryland, Sch Med, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. [Karbowski, Mariusz] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. RP Neutzner, A (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM albert.neutzner@unibas.ch; mkarbowski@umaryland.edu OI Neutzner, Albert/0000-0001-9254-5558 FU National Institutes of Health from NIGMS [RO1 GM083131] FX This work was supported, in whole or in part, by National Institutes of Health Grant RO1 GM083131 from NIGMS (to M. K.). NR 38 TC 25 Z9 27 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2011 VL 286 IS 10 BP 8633 EP 8643 DI 10.1074/jbc.M110.197459 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DQ UT WOS:000288013300089 PM 21205830 ER PT J AU Parker, R Sereti, I AF Parker, Raphaelle Sereti, Irini TI The power of 1 in HIV therapeutics SO BLOOD LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; LYMPHOMA C1 [Parker, Raphaelle; Sereti, Irini] NIAID, Bethesda, MD 20892 USA. RP Parker, R (reprint author), NIAID, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 8 TC 2 Z9 2 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 MAR 10 PY 2011 VL 117 IS 10 BP 2746 EP 2747 DI 10.1182/blood-2011-01-324921 PG 3 WC Hematology SC Hematology GA 732SJ UT WOS:000288209600002 PM 21393496 ER PT J AU Niemela, JE Lu, LH Fleisher, TA Davis, J Caminha, I Natter, M Beer, LA Dowdell, KC Pittaluga, S Raffeld, M Rao, VK Oliveira, JB AF Niemela, Julie E. Lu, Lianghao Fleisher, Thomas A. Davis, Joie Caminha, Iusta Natter, Marc Beer, Laurel A. Dowdell, Kennichi C. Pittaluga, Stefania Raffeld, Mark Rao, V. Koneti Oliveira, Joao B. TI Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis SO BLOOD LA English DT Article ID LYMPHOPROLIFERATIVE SYNDROME; FAS MUTATIONS; ONCOGENIC RAS; CELL-CYCLE; LYMPHOCYTE; ACTIVATION; APOPTOSIS; LEUKEMIA; DISEASE; PATIENT AB Somatic gain-of-function mutations in members of the RAS subfamily of small guanosine triphosphatases are found in > 30% of all human cancers. We recently described a syndrome of chronic nonmalignant lymphadenopathy, splenomegaly, and autoimmunity associated with a mutation in NRAS affecting hematopoietic cells, and initially we classified the disease as a variant of the autoimmune lymphoproliferative syndrome. Here, we demonstrate that somatic mutations in the related KRAS gene can also be associated with a nonmalignant syndrome of autoimmunity and breakdown of leukocyte homeostasis. The activating KRAS mutation impaired cytokine withdrawal-induced T-cell apoptosis through the suppression of the proapoptotic protein BCL-2 interacting mediator of cell death and facilitated proliferation through p27(kip1) down-regulation. These defects could be corrected in vitro by mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1 or phosphatidyl inositol-3 kinase inhibition. We suggest the use of the term RAS-associated autoimmune leukoproliferative disease to differentiate this disorder from autoimmune lymphoproliferative syndrome. (Blood. 2010; 117(10): 2883-2886) C1 [Niemela, Julie E.; Lu, Lianghao; Fleisher, Thomas A.; Caminha, Iusta; Beer, Laurel A.; Oliveira, Joao B.] NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. [Davis, Joie; Dowdell, Kennichi C.; Rao, V. Koneti] NIAID, ALPS Unit, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Natter, Marc] Tufts Univ, Sch Med, Div Pediat Rheumatol, Boston, MA 02111 USA. [Pittaluga, Stefania; Raffeld, Mark] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Oliveira, JB (reprint author), NIH, Dept Lab Med, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA. EM oliveirajb@cc.nih.gov OI Oliveira, Joao/0000-0001-9388-8173; Niemela, Julie/0000-0003-4197-3792 FU National Institutes of Health Clinical Center FX This work was supported by the Intramural Research Program of the National Institutes of Health Clinical Center. NR 26 TC 37 Z9 39 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 MAR 10 PY 2011 VL 117 IS 10 BP 2883 EP 2886 DI 10.1182/blood-2010-07-295501 PG 4 WC Hematology SC Hematology GA 732SJ UT WOS:000288209600024 PM 21079152 ER PT J AU Lim, JK Murphy, PM AF Lim, Jean K. Murphy, Philip M. TI Chemokine control of West Nile virus infection SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Leukocyte trafficking; Flavivirus; Chemoattractant; Encephalitis ID CRYPTOCOCCUS-NEOFORMANS INFECTION; CENTRAL-NERVOUS-SYSTEM; T-CELL TRAFFICKING; MYCOBACTERIUM-TUBERCULOSIS; INFLAMMATORY MONOCYTES; DISEASE PROGRESSION; BONE-MARROW; ENCEPHALITIS; RECRUITMENT; RISK AB West Nile virus (WNV) is a re-emerging pathogen responsible for fatal outbreaks of meningoencephalitis in humans. Recent research using a mouse model of infection has indicated that specific chemokines and chemokine receptors help mediate the host response to WNV acting by at least three mechanisms: control of early neutrophil recruitment to the infection site (Cxcr2), control of monocytosis in blood (Ccr2) and control of leukocyte movement from blood to brain (Cxcr4, Cxcr3, Cxcl10 and possibly Ccr5). CCR5 also appears to be important in human infection, since individuals genetically deficient in this receptor have increased risk of symptomatic disease once infected. These findings provide detailed insight into non-redundant chemokine roles in organ-specific leukocyte recruitment during infection, and emphasize the importance of the balance between pathogen control and immunopathology in determining overall clinical outcome. Published by Elsevier Inc. C1 [Lim, Jean K.] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. [Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), 9000 Rockville Pike,Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The authors would like to thank Engin Erdogan for assistance with figure preparation. This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 31 TC 23 Z9 24 U1 0 U2 8 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 MAR 10 PY 2011 VL 317 IS 5 SI SI BP 569 EP 574 DI 10.1016/j.yexcr.2011.01.009 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 735KU UT WOS:000288414000003 PM 21376172 ER PT J AU Yoshimura, T Oppenheim, JJ AF Yoshimura, Teizo Oppenheim, Joost J. TI Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); Two multifunctional receptors with unusual properties SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE Chemokine receptor; G-protein-coupled receptor; Inflammation; Leukocyte trafficking ID PLASMACYTOID DENDRITIC CELLS; MESSENGER-RNA EXPRESSION; PROTEIN-COUPLED RECEPTOR; RESOLVIN E1; IN-VIVO; LEUKOCYTE POPULATIONS; CHEMERIN RECEPTOR; ACTIVATION; CHEMR23; INFLAMMATION AB Chemokine-like receptor 1 (CMKLR1), also known as ChemR23, and chemokine (C-C motif) receptor-like 2 (CCRL2) are 7-transmembrane receptors that were cloned in the late 1990s based on their homology to known G-protein-coupled receptors. They were previously orphan receptors without any known biological roles; however, recent studies identified ligands for these receptors and their functions have begun to be unveiled. The plasma protein-derived chemoattractant chemerin is a ligand for CMKLR1 and activation of CMKLR1 with chemerin induces the migration of macrophages and dendritic cells (DCs) in vitro, suggesting a proinflammatory role. However, in vivo studies using CMKLR-deficient mice suggest an anti-inflammatory role for this receptor, possibly due to the recruitment of tolerogenic plasmacytoid DCs. Chemerin/CMKLR1 interaction also promotes adipogenesis and angiogenesis. The anti-inflammatory lipid mediator, resolving E1, is another CMKLR1 ligand and it inhibits leukocyte infiltration and proinflammatory gene expression. These divergent results suggest that CMKLR1 is a multifunctional receptor. The chemokine CCL5 and CCL19 are reported to bind to CCRL2. Like Duffy antigen for chemokine receptor (DARC), D6 and CCX-CKR, CCRL2 does not signal, but it constitutively recycles, potentially reducing local concentration of CCL5 and CCL19 and subsequent immune responses. Surprisingly, chemerin, a ligand for CMKLR1, is a ligand for CCRL2. CCRL2 binds chemerin and increases local chemerin concentration to efficiently present it to CMKLR1 on nearby cells, providing a link between CCRL2 and CMKLR1. Although these findings suggest an anti-inflammatory role, a recent study using CCRL2-deficient mice indicates a proinflammatory role; thus, CCRL2 may also be multifunctional. Further studies using CMKLR1- or CCRL2-deficient mice are needed to further define the role of these receptors in immune responses and other cellular processes. (C) 2010 Elsevier Inc. All rights reserved. C1 [Yoshimura, Teizo; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Yoshimura, T (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Bldg 559,Rm 2, Frederick, MD 21702 USA. EM yoshimut@mail.nih.gov; oppenhej@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 BC009369-18, Z01 BC009369-17] NR 62 TC 49 Z9 55 U1 0 U2 13 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 MAR 10 PY 2011 VL 317 IS 5 SI SI BP 674 EP 684 DI 10.1016/j.yexcr.2010.10.023 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 735KU UT WOS:000288414000013 PM 21056554 ER PT J AU Nabel, GJ Wei, CJ Ledgerwood, JE AF Nabel, Gary J. Wei, Chih-Jen Ledgerwood, Julie E. TI Vaccinate for the next H2N2 pandemic now SO NATURE LA English DT Editorial Material ID INFLUENZA-VIRUSES C1 [Nabel, Gary J.; Wei, Chih-Jen; Ledgerwood, Julie E.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 10 TC 39 Z9 40 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 10 PY 2011 VL 471 IS 7337 BP 157 EP 158 DI 10.1038/471157a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732FK UT WOS:000288170200013 PM 21390107 ER PT J AU DePaolo, RW Abadie, V Tang, F Fehlner-Peach, H Hall, JA Wang, W Marietta, EV Kasarda, DD Waldmann, TA Murray, JA Semrad, C Kupfer, SS Belkaid, Y Guandalini, S Jabri, B AF DePaolo, R. W. Abadie, V. Tang, F. Fehlner-Peach, H. Hall, J. A. Wang, W. Marietta, E. V. Kasarda, D. D. Waldmann, T. A. Murray, J. A. Semrad, C. Kupfer, S. S. Belkaid, Y. Guandalini, S. Jabri, B. TI Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens SO NATURE LA English DT Article ID REGULATORY T-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; CELIAC-DISEASE; BOWEL-DISEASE; GLUTEN SENSITIVITY; TRANSGENIC MICE; ORAL TOLERANCE; TGF-BETA; CLASS-I; DIFFERENTIATION AB Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens(1,2). A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte antigen (HLA) HLA-DQ2 or HLA-DQ8 molecules develop inflammatory T-cell and antibody responses against dietary gluten, a protein present in wheat(3). The mechanisms underlying this dysregulated mucosal immune response to a soluble antigen have not been identified. Retinoic acid, a metabolite of vitamin A, has been shown to have a critical role in the induction of intestinal regulatory responses(4-6). Here we find in mice that in conjunction with IL-15, a cytokine greatly upregulated in the gut of coeliac disease patients(3,7), retinoic acid rapidly activates dendritic cells to induce JNK (also known as MAPK8) phosphorylation and release the proinflammatory cytokines IL-12p70 and IL-23. As a result, in a stressed intestinal environment, retinoic acid acted as an adjuvant that promoted rather than prevented inflammatory cellular and humoral responses to fed antigen. Altogether, these findings reveal an unexpected role for retinoic acid and IL-15 in the abrogation of tolerance to dietary antigens. C1 [DePaolo, R. W.; Abadie, V.; Tang, F.; Fehlner-Peach, H.; Wang, W.; Semrad, C.; Kupfer, S. S.; Jabri, B.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Hall, J. A.; Belkaid, Y.] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Hall, J. A.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Marietta, E. V.] Mayo Clin, Dept Dermatol, Coll Med, Rochester, MN 55905 USA. [Marietta, E. V.] Mayo Clin, Dept Immunol, Coll Med, Rochester, MN 55905 USA. [Kasarda, D. D.] ARS, USDA, Western Reg Res Ctr, Albany, CA 94710 USA. [Waldmann, T. A.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Murray, J. A.] Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Coll Med, Rochester, MN 55905 USA. [Guandalini, S.; Jabri, B.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Jabri, B.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Jabri, B (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM bjabri@bsd.uchicago.edu RI Guandalini, Stefano/G-8084-2011; OI DePaolo, William/0000-0002-3880-4544; murray, joseph/0000-0003-1941-9090 FU Digestive Disease Research Core Center at the University of Chicago [DK42086, R01 DK67180, R01DK71003]; Crohn's and Colitis Foundation; University of Chicago Celiac Disease Center FX We thank coeliac disease patients and their family members as well as the University of Chicago Celiac Disease Center for supporting our research. We thank B. Sally, L. M. Sollid and M. Musch for critical reading of the manuscript. We thank C. Ciszewski, B. Uzunparmak, and N. Grandison for their help with the collection and analysis of human biopsies. We thank M. Constantinides for technical assistance with mice breeding. We also thank the University of Chicago flow cytometry facility for technical assistance. Dd-IL-15 transgenic mice were a gift from M. Caligiuri. RAR alpha-deficient mice were provided by P. Chambon and C. Benoist. This work was supported by the Digestive Disease Research Core Center at the University of Chicago (DK42086), R01 DK67180 (for B.J.), R01DK71003 (for J.A.M.), and the Crohn's and Colitis Foundation (for V.A.). NR 37 TC 183 Z9 186 U1 3 U2 40 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 10 PY 2011 VL 471 IS 7337 BP 220 EP U110 DI 10.1038/nature09849 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732FK UT WOS:000288170200038 PM 21307853 ER PT J AU Mullighan, CG Zhang, JH Kasper, LH Lerach, S Payne-Turner, D Phillips, LA Heatley, SL Holmfeldt, L Collins-Underwood, JR Ma, J Buetow, KH Pui, CH Baker, SD Brindle, PK Downing, JR AF Mullighan, Charles G. Zhang, Jinghui Kasper, Lawryn H. Lerach, Stephanie Payne-Turner, Debbie Phillips, Letha A. Heatley, Sue L. Holmfeldt, Linda Collins-Underwood, J. Racquel Ma, Jing Buetow, Kenneth H. Pui, Ching-Hon Baker, Sharyn D. Brindle, Paul K. Downing, James R. TI CREBBP mutations in relapsed acute lymphoblastic leukaemia SO NATURE LA English DT Article ID RUBINSTEIN-TAYBI SYNDROME; GENETIC ALTERATIONS; BINDING PROTEIN; GENOMIC ANALYSIS; P300; CBP; CANCER; REVEALS; CELLS; COACTIVATOR AB Relapsed acute lymphoblastic leukaemia (ALL) is a leading cause of death due to disease in young people, but the biological determinants of treatment failure remain poorly understood. Recent genome-wide profiling of structural DNA alterations in ALL have identified multiple submicroscopic somatic mutations targeting key cellular pathways(1,2), and have demonstrated substantial evolution in genetic alterations from diagnosis to relapse(3). However, DNA sequence mutations in ALL have not been analysed in detail. To identify novel mutations in relapsed ALL, we resequenced 300 genes in matched diagnosis and relapse samples from 23 patients with ALL. This identified 52 somatic non-synonymous mutations in 32 genes, many of which were novel, including the transcriptional coactivators CREBBP and NCOR1, the transcription factors ERG, SPI1, TCF4 and TCF7L2, components of the Ras signalling pathway, histone genes, genes involved in histone modification (CREBBP and CTCF), and genes previously shown(1,2) to be targets of recurring DNA copy number alteration in ALL. Analysis of an extended cohort of 71 diagnosis-relapse cases and 270 acute leukaemia cases that did not relapse found that 18.3% of relapse cases had sequence or deletion mutations of CREBBP, which encodes the transcriptional coactivator and histone acetyltransferase CREB-binding protein (CREBBP, also known as CBP)(4). The mutations were either present at diagnosis or acquired at relapse, and resulted in truncated alleles or deleterious substitutions in conserved residues of the histone acetyltransferase domain. Functionally, the mutations impaired histone acetylation and transcriptional regulation of CREBBP targets, including glucocorticoid responsive genes. Several mutations acquired at relapse were detected in subclones at diagnosis, suggesting that the mutations may confer resistance to therapy. These results extend the landscape of genetic alterations in leukaemia, and identify mutations targeting transcriptional and epigenetic regulation as a mechanism of resistance in ALL. C1 [Mullighan, Charles G.; Payne-Turner, Debbie; Phillips, Letha A.; Heatley, Sue L.; Holmfeldt, Linda; Collins-Underwood, J. Racquel; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Zhang, Jinghui] St Jude Childrens Hosp, Dept Computat Biol, Memphis, TN 38105 USA. [Kasper, Lawryn H.; Lerach, Stephanie; Brindle, Paul K.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. [Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Buetow, Kenneth H.] NCI, Ctr Bioinformat, Rockville, MD 20892 USA. [Buetow, Kenneth H.] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. [Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Baker, Sharyn D.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. RP Mullighan, CG (reprint author), St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. EM charles.mullighan@stjude.org OI Holmfeldt, Linda/0000-0003-4140-3423; Mullighan, Charles/0000-0002-1871-1850 FU ALSAC of St Jude and Cancer Center [P30 CA021765, DE018183] FX We thank T. Jeevan, S. Orwick and A. Gibson for technical assistance, B. Schulman for assistance with structural modelling, and B. Woolf and J. Hartigan of Beckman Coulter Genomics for assistance with sequencing. We thank the Tissue Resources Facility of St Jude Children's Research Hospital for providing samples, and the following St Jude core facilities: Vector Development and Production, Flow Cytometry and Cell Sorting, Cell and Tissue Imaging, the Animal Resource Center, and the DNA sequencing and Macromolecular Synthesis laboratories of the Hartwell Center for Bioinformatics and Biotechnology. This study was supported by ALSAC of St Jude and Cancer Center support grant P30 CA021765, and grant number DE018183 (P.K.B.). C.G.M. is a Pew Scholar in the Biomedical Sciences. NR 42 TC 230 Z9 234 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 10 PY 2011 VL 471 IS 7337 BP 235 EP U127 DI 10.1038/nature09727 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732FK UT WOS:000288170200041 PM 21390130 ER PT J AU Opsenica, I Burnett, JC Gussio, R Opsenica, D Todorovic, N Lanteri, CA Sciotti, RJ Gettayacamin, M Basilico, N Taramelli, D Nuss, JE Wanner, L Panchal, RG Solaja, BA Bavari, S AF Opsenica, Igor Burnett, James C. Gussio, Rick Opsenica, Dejan Todorovic, Nina Lanteri, Charlotte A. Sciotti, Richard J. Gettayacamin, Montip Basilico, Nicoletta Taramelli, Donatella Nuss, Jonathan E. Wanner, Laura Panchal, Rekha G. Solaja, Bogdan A. Bavari, Sina TI A Chemotype That Inhibits Three Unrelated Pathogenic Targets: The Botulinum Neurotoxin Serotype A Light Chain, P. falciparum Malaria, and the Ebola Filovirus SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IN-VITRO; ANTIMALARIAL-DRUGS; PROTEOLYTIC ACTIVITY; VIRUS; CHLOROQUINE; TOXIN; 4-AMINOQUINOLINE; METALLOPROTEASE; PHARMACOPHORE; MECHANISMS AB A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinolinebased antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting beta-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities. C1 [Burnett, James C.] SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Natl Canc Inst Frederick, Frederick, MD 21702 USA. [Opsenica, Igor; Solaja, Bogdan A.] Univ Belgrade, Fac Chem, Belgrade 11158, Serbia. [Gussio, Rick] Natl Canc Inst Frederick, Dev Therapeut Program, Frederick, MD 21702 USA. [Opsenica, Dejan; Todorovic, Nina] Inst Chem Technol & Met, Belgrade, Serbia. [Lanteri, Charlotte A.; Sciotti, Richard J.] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. [Gettayacamin, Montip] Armed Forces Res Inst Med Sci, Dept Vet Med, Bangkok 10400, Thailand. [Basilico, Nicoletta; Taramelli, Donatella] Univ Milan, Dipartimento Sanita Pubbl Microbiol Virol, I-20133 Milan, Italy. [Nuss, Jonathan E.; Wanner, Laura; Panchal, Rekha G.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Burnett, JC (reprint author), SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Natl Canc Inst Frederick, POB B, Frederick, MD 21702 USA. EM burnettjames@mail.nih.gov; bsolaja@chem.bg.ac.rs; sina.bavari@us.army.mil RI Sciotti, Richard/A-9069-2011; Opsenica, Igor/P-5308-2016; OI Opsenica, Igor/0000-0003-4942-4042; Solaja, Bogdan/0000-0002-9975-2725 FU NATO's Public Diplomacy Division [SfP983638]; Defense Threat Reduction Agency [3.10084_09_RD_B, Y3CM 100505]; Ministry of Science and Technological Development of Serbia [172008]; Serbian Academy of Sciences and Arts; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported by: (1) NATO's Public Diplomacy Division in the framework of "Science for Peace" project SfP983638, (2) Defense Threat Reduction Agency project 3.10084_09_RD_B (and also Agreement Y3CM 100505 (MR-MC and NCI, National Institutes of Health), and (3) the Ministry of Science and Technological Development of Serbia (grant: no. 172008) and the Serbian Academy of Sciences and Arts. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the U.S. Army, The contents of this manuscript have been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army, Department of Defense, or National Institutes of Health. For J. C.B., in accordance with SAIC-Frederick, Inc. contractual requirements, the following statement must be included: this project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. NR 74 TC 23 Z9 25 U1 0 U2 13 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 MAR 10 PY 2011 VL 54 IS 5 BP 1157 EP 1169 DI 10.1021/jm100938u PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 727WJ UT WOS:000287833300004 PM 21265542 ER PT J AU Nakagawa-Goto, K Wu, PC Lai, CY Hamel, E Zhu, H Zhang, LY Kozaka, T Ohkoshi, E Goto, M Bastow, KF Lee, KH AF Nakagawa-Goto, Kyoko Wu, Pei-Chi Lai, Chin-Yu Hamel, Ernest Zhu, Hao Zhang, Liying Kozaka, Takashi Ohkoshi, Emika Goto, Masuo Bastow, Kenneth F. Lee, Kuo-Hsiung TI Antitumor Agents. 284. New Desmosdumotin B Analogues with Bicyclic B-Ring as Cytotoxic and Antitubulin Agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC AGENTS; ANTICANCER AGENTS; COLCHICINE; TUBULIN; COMBRETASTATIN; DERIVATIVES; MECHANISM; BINDING; PROTEIN AB We previously reported that the biological activity of analogues of desmosdumotin B (1) was dramatically changed depending on the B-ring system. A naphthalene B-ring analogue 3 exerted potent in vitro activity against a diverse panel of human tumor cell lines with GI(50) values of 0.8-2.1 mu M. In contrast, 1 analogues with a phenyl B-ring showed unique selective activity against P-glycoprotein (P-gp) over-expressing multidrug resistant cell line. We have now prepared and evaluated, 1 analogues with bicyclic or tricyclic aromatic B-ring systems as in vitro inhibitors of human cancer cell line proliferation. Among all synthesized derivatives, 21 with a benzo[b]thiophenyl B-ring was highly active, with GI(50) values of 0.06-0.16 mu M, and this activity was not influenced by overexpression of P-gp. Furthermore, 21 inhibited tubulin assembly in vitro with an IC(50) value of 2.0 mu M and colchicine binding by 7896 as well as cellular microtubule polymerization and spindle formation. C1 [Nakagawa-Goto, Kyoko; Wu, Pei-Chi; Lai, Chin-Yu; Kozaka, Takashi; Ohkoshi, Emika; Lee, Kuo-Hsiung] Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Hamel, Ernest] Natl Canc Inst Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Zhu, Hao; Zhang, Liying] Univ N Carolina, Lab Mol Modeling, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Goto, Masuo] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan. RP Nakagawa-Goto, K (reprint author), Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM goto@email.unc.edu; Ken_Bastow@unc.edu; khlee@unc.edu RI Zhang, Liying/A-3163-2014; GOTO, Kyoko/D-8389-2015 OI GOTO, Kyoko/0000-0002-1642-6538 FU National Cancer Institute, NIH [CA-17625]; University Research Council FX This study was supported by Grant CA-17625 from the National Cancer Institute, NIH, awarded to K.-H.L., and by a grant from the University Research Council, awarded to K.N.-G. We thank Dr. Mitch Eddy (NIEHS/NIH) for providing a fluorescence microscope. NR 24 TC 13 Z9 13 U1 2 U2 9 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 MAR 10 PY 2011 VL 54 IS 5 BP 1244 EP 1255 DI 10.1021/jm1011947 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 727WJ UT WOS:000287833300012 PM 21284385 ER PT J AU Petralia, RS Wang, YX Hua, F Yi, Z Zhou, A Ge, L Stephenson, FA Wenthold, RJ AF Petralia, R. S. Wang, Y. X. Hua, F. Yi, Z. Zhou, A. Ge, L. Stephenson, F. A. Wenthold, R. J. TI ORGANIZATION OF NMDA RECEPTORS AT EXTRASYNAPTIC LOCATIONS (vol 167, pg 68, 2010) SO NEUROSCIENCE LA English DT Correction C1 [Petralia, R. S.; Wang, Y. X.; Hua, F.; Yi, Z.; Zhou, A.; Ge, L.; Wenthold, R. J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD USA. [Stephenson, F. A.] Univ London, Sch Pharm, London WC1N 1AX, England. RP Petralia, RS (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD USA. EM petralia@nidcd.nih.gov NR 1 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 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAR 10 PY 2011 VL 176 BP 472 EP 472 DI 10.1016/j.neuroscience.2010.12.020 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 726MT UT WOS:000287727100040 ER PT J AU Lorieau, JL Louis, JM Bax, A AF Lorieau, Justin L. Louis, John M. Bax, Ad TI Helical Hairpin Structure of Influenza Hemagglutinin Fusion Peptide Stabilized by Charge-Dipole Interactions between the N-Terminal Amino Group and the Second Helix SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID O HYDROGEN-BOND; VIRUS HEMAGGLUTININ; LIPID-BILAYERS; NMR-SPECTROSCOPY; SIDE-CHAIN; CONFORMATIONAL-CHANGE; SECONDARY STRUCTURE; MEMBRANE-PROTEINS; ALPHA-HELIX; DYNAMICS AB The fusion domain of the influenza coat protein hemagglutinin HA2, bound to dodecyl phosphocholine micelles, was recently shown to adopt a structure consisting of two antiparallel alpha-helices, packed in an exceptionally tight hairpin configuration. Four interhelical H(alpha) to C=O aliphatic H-bonds were identified as factors stabilizing this fold. Here, we report evidence for an additional stabilizing force: a strong charge-dipole interaction between the N-terminal Gly(1) amino group and the dipole moment of helix 2. pH titration of the amino-terminal (15)N resonance, using a methylene-TROSY-based 3D NMR experiment, and observation of Gly(1) (13)C' show a strongly elevated pK = 8.8, considerably higher than expected for an N-terminal amino group in a lipophilic environment Chemical shifts of three C-terminal carbonyl carbons of helix 2 titrate with the protonation state of Gly(1)-N, indicative of a dose proximity between the N-terminal amino group and the axis of helix 2, providing an optimal charge-dipole stabilization of the antiparallel hairpin fold, pK values of the side-chain carboxylate groups of Glu(11) and Asp(19) are higher by about 1 and 0.5 unit, respectively, than commonly seen for solvent-exposed side chains in water-soluble proteins, indicative of dielectric constants of epsilon = similar to 30 (Glu(11)) and similar to 60 (Asp(19)), placing these groups in the headgroup region of the phospholipid micelle. C1 [Lorieau, Justin L.; Louis, John M.; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov FU NIDDK, NIH; Office of the Director, NIH FX This work was supported by the Intramural Research Program of the NIDDK, NIH, and by the Intramural Antiviral Target Program of the Office of the Director, NIH. We thank Dennis A. Torchia for useful discussions. NR 47 TC 21 Z9 22 U1 1 U2 14 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 MAR 9 PY 2011 VL 133 IS 9 BP 2824 EP 2827 DI 10.1021/ja1099775 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 749HN UT WOS:000289455200009 PM 21319795 ER PT J AU Park, D Don, AS Massamiri, T Karwa, A Warner, B MacDonald, J Hemenway, C Naik, A Kuan, KT Dilda, PJ Wong, JWH Camphausen, K Chinen, L Dyszlewski, M Hogg, PJ AF Park, Danielle Don, Anthony S. Massamiri, Tania Karwa, Amol Warner, Beth MacDonald, Jan Hemenway, Christine Naik, Arati Kuan, Kah-Tiong Dilda, Pierre J. Wong, Jason W. H. Camphausen, Kevin Chinen, Lori Dyszlewski, Mary Hogg, Philip J. TI Noninvasive Imaging of Cell Death Using an Hsp90 Ligand SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR CHAPERONE; INDUCED APOPTOSIS; ANNEXIN-V; PATHOGENESIS; STAUROSPORINE; ACTIVATION; DISEASE; PROTEIN AB Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous add, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma membrane integrity. The compound is retained in the cytosol predominantly by covalent reaction with the 90 kDa heat shock protein (Hsp90), the most abundant molecular chaperone of the eukaryotic cytoplasm. The organoarsenical was tagged with either optical or radioisotope reporting groups to image cell death in cultured cells and in murine tumors ex vivo and in situ. Tumor cell death in mice was noninvasively imaged by SPECT/CT using an (111)In-tagged compound. This versatile compound should enable the imaging of cell death in most experimental settings. C1 [Park, Danielle; Don, Anthony S.; Dilda, Pierre J.; Wong, Jason W. H.; Hogg, Philip J.] Univ New S Wales, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia. [Park, Danielle; Don, Anthony S.; Dilda, Pierre J.; Wong, Jason W. H.; Hogg, Philip J.] Univ New S Wales, POW Clin Sch, Sydney, NSW 2052, Australia. [Massamiri, Tania; Karwa, Amol; Warner, Beth; MacDonald, Jan; Hemenway, Christine; Naik, Arati; Kuan, Kah-Tiong; Chinen, Lori; Dyszlewski, Mary] Covidien Imaging Solut, Hazelwood, MO 63042 USA. [Camphausen, Kevin] NCI, Imaging & Mol Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Hogg, PJ (reprint author), Univ New S Wales, Lowy Canc Res Ctr, Sydney, NSW 2052, Australia. EM p.hogg@unsw.edu.au RI Wong, Jason/A-9466-2008; OI Wong, Jason/0000-0003-2953-7728; Hogg, Philip/0000-0001-6486-2863 FU National Health and Medical Research Council of Australia; New South Wales Cancer Council; American Society of Therapeutic Radiation Oncology FX We thank Mark Raftery and Gavin Mackenzie for assistance with mass spectrometry and microscopy, respectively. This study was supported by grants from the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, and a fellowship (K.C.) from the American Society of Therapeutic Radiation Oncology. NR 35 TC 26 Z9 26 U1 2 U2 12 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 MAR 9 PY 2011 VL 133 IS 9 BP 2832 EP 2835 DI 10.1021/ja110226y PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 749HN UT WOS:000289455200011 PM 21322555 ER PT J AU Miura, K Zhou, H Diouf, A Tullo, G Moretz, SE Aebig, JA Fay, MP Millera, LH Doumbo, OK Sagara, I Dicko, A Long, CA Ellis, RD AF Miura, Kazutoyo Zhou, Hong Diouf, Ababacar Tullo, Gregory Moretz, Samuel E. Aebig, Joan A. Fay, Michael P. Millera, Louis H. Doumbo, Ogobara K. Sagara, Issaka Dicko, Alassane Long, Carole A. Ellis, Ruth D. TI Immunological responses against Plasmodium falciparum Apical Membrane Antigen 1 vaccines vary depending on the population immunized SO VACCINE LA English DT Article DE Apical Membrane Antigen 1; Phase 1 trial; Phase 2 trial; Humoral immunity; ELISA; Growth inhibition assay ID RANDOMIZED CONTROLLED-TRIAL; BLOOD-STAGE ANTIGENS; MALARIA VACCINE; IMMUNOGENICITY TRIAL; INHIBITORY-ACTIVITY; CLINICAL MALARIA; NAIVE ADULTS; ANTIBODIES; PROTECTION; CHILDREN AB Clinical development of malaria vaccines progresses from trials in malaria naive adults to malaria exposed adults followed by malaria exposed children. It is not well known whether immune responses in non-target populations are predictive of those in target populations, particularly in African children. Therefore humoral responses in three different populations (U.S. adults, Malian adults and Malian children) were compared in this study. They were immunized with 80 mu g of Apical Membrane Antigen 1 (AMA1)/alhydrogel on days 0 and 28. Sera were collected on days 0 and 42; antibody levels were determined by ELISA and the functionality of antibodies was evaluated by Growth Inhibition Assay. After immunization, there was no significant difference in antibody levels between the Malian children and the Malian adults, but U.S. adults showed lower antibody levels. Vaccination did not significantly change growth-inhibitory activity in Malian adults, but inhibition increased significantly in both U.S. adults and Malian children. Vaccine-induced inhibitory activity was reversed by pre-incubation with AMA1 protein, but pre-existing infection-induced inhibition was not. This study shows that humoral responses elicited by the AMA1 vaccine varied depending on the population, most likely reflecting different levels of previous malaria exposure. Thus predicting immune responses from non-target populations is not desirable. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Miura, Kazutoyo; Aebig, Joan A.; Millera, Louis H.; Ellis, Ruth D.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. [Zhou, Hong; Diouf, Ababacar; Tullo, Gregory; Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20817 USA. [Doumbo, Ogobara K.; Sagara, Issaka; Dicko, Alassane] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. RP Miura, K (reprint author), 12735 Twinbrook Pkwy,Twinbrook 3,Room 3W-13, Rockville, MD 20852 USA. EM kmiura@niaid.nih.gov; ellisru@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 FU National Institute of Allergy and Infectious Diseases/NIH; PATH/Malaria Vaccine Initiative FX We are very grateful to all volunteers who participated in the clinical trials. We also thank John Treanor, Amagana Dolo, Dapa Diallo, Gregory Mullen and Allan Saul for their contributions to the human trials. This study was supported by the intramural program of the National Institute of Allergy and Infectious Diseases/NIH and the GIA Reference Center was supported by the PATH/Malaria Vaccine Initiative. NR 41 TC 8 Z9 8 U1 0 U2 0 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 MAR 9 PY 2011 VL 29 IS 12 BP 2255 EP 2261 DI 10.1016/j.vaccine.2011.01.043 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 742HP UT WOS:000288932500007 PM 21277408 ER PT J AU Lu, G Hall, TMT AF Lu, Gang Hall, Traci M. Tanaka TI Alternate Modes of Cognate RNA Recognition by Human PUMILIO Proteins SO STRUCTURE LA English DT Article ID ELEGANS PUF PROTEIN; BINDING-SPECIFICITY; TRANSLATIONAL REGULATOR; WIDE IDENTIFICATION; HOMOLOGY DOMAIN; MESSENGER-RNAS; SOFTWARE; TARGETS; SYSTEM; FAMILY AB Human PUMILIO1 (PUM1) and PUMILIO2 (PUM2) are members of the PUMILIO/FBF (PUF) family that regulate specific target mRNAs posttranscriptionally. Recent studies have identified mRNA targets associated with human PUM1 and PUM2. Here, we explore the structural basis of natural target RNA recognition by human PUF proteins through crystal structures of the RNA-binding domains of PUM1 and PUM2 in complex with four cognate RNA sequences, including sequences from p38 alpha and erk2 MAP kinase mRNAs. We observe three distinct modes of RNA binding around the fifth RNA base, two of which are different from the prototypical 1 repeat:1 RNA base binding mode previously identified with model RNA sequences. RNA-binding affinities of PUM1 and PUM2 are not affected dramatically by the different binding modes in vitro. However, these modes of binding create structurally variable recognition surfaces that suggest a mechanism in vivo for recruitment of downstream effector proteins defined by the PUF:RNA complex. C1 [Lu, Gang; Hall, Traci M. Tanaka] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hall, TMT (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM hall4@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences FX We are grateful to Drs. L. Pedersen and J. Krahn of the National Institute of Environmental Health Sciences for crystallographic and data collection support. We also thank our colleagues for fruitful discussion on the experiments and the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 36 TC 26 Z9 27 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAR 9 PY 2011 VL 19 IS 3 BP 361 EP 367 DI 10.1016/j.str.2010.12.019 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 739CG UT WOS:000288689400010 PM 21397187 ER PT J AU Iser, WB Wilson, MA Wood, WH Becker, K Wolkow, CA AF Iser, Wendy B. Wilson, Mark A. Wood, William H., III Becker, Kevin Wolkow, Catherine A. TI Co-Regulation of the DAF-16 Target Gene, cyp-35B1/dod-13, by HSF-1 in C. elegans Dauer Larvae and daf-2 Insulin Pathway Mutants SO PLOS ONE LA English DT Article ID HEAT-SHOCK FACTOR; NEMATODE CAENORHABDITIS-ELEGANS; LIFE-SPAN; TRANSCRIPTION FACTOR; INTERACTING GENES; NERVOUS-SYSTEM; FAMILY-MEMBER; FAT-BODY; LONGEVITY; RECEPTOR AB Insulin/IGF-I-like signaling (IIS) has both cell autonomous and non-autonomous functions. In some cases, targets through which IIS regulates cell-autonomous functions, such as cell growth and metabolism, have been identified. In contrast, targets for many non-autonomous IIS functions, such as C. elegans dauer morphogenesis, remain elusive. Here, we report the use of genomic and genetic approaches to identify potential non-autonomous targets of C. elegans IIS. First, we used transcriptional microarrays to identify target genes regulated non-autonomously by IIS in the intestine or in neurons. C. elegans IIS controls expression of a number of stress response genes, which were differentially regulated by tissue-restricted IIS. In particular, expression of sod-3, a MnSOD enzyme, was not regulated by tissue-restricted IIS on the microarrays, while expression of hsp-16 genes was rescued back to wildtype by tissue restricted IIS. One IIS target regulated non-autonomously by age-1 was cyp-35B1/dod-13, encoding a cytochrome P450. Genetic analysis of the cyp-35B1 promoter showed both DAF-16 and HSF-1 are direct regulators. Based on these findings, we propose that hsf-1 may participate in the pathways mediating non-autonomous activities of age-1 in C. elegans. C1 [Iser, Wendy B.; Wilson, Mark A.; Wolkow, Catherine A.] NIA Intramural Res Program, Invertebrate Mol Genet Unit, Lab Neurosci, Res Resources Branch,NIH Biomed Res Ctr, Baltimore, MD USA. [Wood, William H., III; Becker, Kevin] NIA Intramural Res Program, Gene Express & Genom Unit, Res Resources Branch, NIH Biomed Res Ctr, Baltimore, MD USA. RP Iser, WB (reprint author), NIA Intramural Res Program, Invertebrate Mol Genet Unit, Lab Neurosci, Res Resources Branch,NIH Biomed Res Ctr, Baltimore, MD USA. EM wolkowca@mail.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU NIA [AG000320]; Ellison Medical Foundation FX This work was carried out with funding from the NIA Intramural Research Program (AG000320) and from an Ellison Medical Foundation New Scholar in Aging award (www.ellisonfoundation.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 7 Z9 21 U1 0 U2 5 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 MAR 9 PY 2011 VL 6 IS 3 AR e17369 DI 10.1371/journal.pone.0017369 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732FR UT WOS:000288170900012 PM 21408062 ER PT J AU Kim, H White, CD Sacks, DB AF Kim, Hugh White, Colin D. Sacks, David B. TI IQGAP1 in microbial pathogenesis: Targeting the actin cytoskeleton SO FEBS LETTERS LA English DT Review DE EPEC; IQGAP1; Microbial pathogenesis; Salmonella ID ENTEROPATHOGENIC ESCHERICHIA-COLI; EPITHELIAL-CELLS; PLASMA-MEMBRANE; III SECRETION; PHOSPHATIDYLINOSITOL 3-KINASE; LISTERIA-MONOCYTOGENES; MICROTUBULE DYNAMICS; CAPTURE MICROTUBULES; SIGNAL-TRANSDUCTION; BACTERIAL INVASION AB Microbial pathogens cause widespread morbidity and mortality. Central to the pathogens' virulence is manipulation of the host cell's cytoskeleton, which facilitates microbial invasion, multiplication, and avoidance of the innate immune response. IQGAP1 is a ubiquitously expressed scaffold protein that integrates diverse signaling cascades. Research has shown that IQGAP1 binds to and modulates the activity of multiple proteins that participate in bacterial invasion. Here, we review data that support a role for IQGAP1 in infectious disease via its ability to regulate the actin cytoskeleton. In addition, we explore other mechanisms by which IQGAP1 may be exploited by microbial pathogens. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [White, Colin D.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Kim, Hugh; White, Colin D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kim, Hugh] Brigham & Womens Hosp, Dept Translat Med, Boston, MA 02115 USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, 10 Ctr Dr, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 FU Canadian Institutes of Health Research; National Institutes of Health FX The authors thank all members of the Sacks laboratory for insightful discussions. This work was supported by the Canadian Institutes of Health Research (to H.K.) and the National Institutes of Health (to D.B.S.). NR 85 TC 20 Z9 20 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 9 PY 2011 VL 585 IS 5 BP 723 EP 729 DI 10.1016/j.febslet.2011.01.041 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 729OS UT WOS:000287960900002 PM 21295032 ER PT J AU Martinowich, K Schloesser, RJ Jimenez, DV Weinberger, DR Lu, B AF Martinowich, Keri Schloesser, Robert J. Jimenez, Dennisse V. Weinberger, Daniel R. Lu, Bai TI Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior SO MOLECULAR BRAIN LA English DT Article ID CULTURED HIPPOCAMPAL-NEURONS; RAT VISUAL-CORTEX; SLOW-WAVE SLEEP; CORTICAL INTERNEURONS; MESSENGER-RNA; RECEPTOR TRKB; GABAERGIC INTERNEURONS; SYNAPTIC HOMEOSTASIS; BDNF TRANSCRIPTION; GENE-EXPRESSION AB Background: Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF) in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis. Results: We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark) phase. Conclusion: Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior. C1 [Martinowich, Keri; Weinberger, Daniel R.; Lu, Bai] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Martinowich, Keri; Schloesser, Robert J.; Jimenez, Dennisse V.] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Lu, Bai] GlaxoSmithKline, Shanghai, Peoples R China. RP Lu, B (reprint author), NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. EM bai.b.lu@gsk.com RI Martinowich, Keri/F-9841-2012; OI Martinowich, Keri/0000-0002-5237-0789 FU National Institute of Mental Health (NIMH); NARSAD FX Funding was provided by the Intramural Program of the National Institute of Mental Health (NIMH). KM and RJS are recipients of NARSAD Young Investigator Awards. NR 58 TC 28 Z9 28 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-6606 J9 MOL BRAIN JI Mol. Brain PD MAR 9 PY 2011 VL 4 AR 11 DI 10.1186/1756-6606-4-11 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 007WG UT WOS:000308918500001 PM 21388527 ER PT J AU Liao, JCC Lam, R Brazda, V Duan, SL Ravichandran, M Ma, J Xiao, T Tempel, W Zuo, XB Wang, YX Chirgadze, NY Arrowsmith, CH AF Liao, Jack C. C. Lam, Robert Brazda, Vaclav Duan, Shili Ravichandran, Mani Ma, Justin Xiao, Ting Tempel, Wolfram Zuo, Xiaobing Wang, Yun-Xing Chirgadze, Nickolay Y. Arrowsmith, Cheryl H. TI Interferon-Inducible Protein 16: Insight into the Interaction with Tumor Suppressor p53 SO STRUCTURE LA English DT Article ID STRANDED-DNA-BINDING; C-TERMINAL DOMAIN; CELLULAR SENESCENCE; NEGATIVE REGULATOR; SSDNA RECOGNITION; CYTOPLASMIC DNA; OB-FOLD; SEQUENCE; FAMILY; ACTIVATION AB IFI16 is a member of the interferon-inducible HIN-200 family of nuclear proteins. It has been implicated in transcriptional regulation by modulating protein-protein interactions with p53 tumor suppressor protein and other transcription factors. However, the mechanisms of interaction remain unknown. Here, we report the crystal structures of both HIN-A and HIN-B domains of IFI16 determined at 2.0 and 2.35 angstrom resolution, respectively. Each HIN domain comprises a pair of tightly packed OB-fold subdomains that appear to act as a single unit. We show that both HIN domains of IFI16 are capable of enhancing p53-DNA complex formation and transcriptional activation via distinctive means. HIN-A domain binds to the basic C terminus of p53, whereas the HIN-B domain binds to the core DNA-binding region of p53. Both interactions are compatible with the DNA-bound state of p53 and together contribute to the effect of full-length IFI16 on p53-DNA complex formation and transcriptional activation. C1 [Liao, Jack C. C.; Lam, Robert; Duan, Shili; Ma, Justin; Chirgadze, Nickolay Y.; Arrowsmith, Cheryl H.] Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C4, Canada. [Liao, Jack C. C.; Duan, Shili; Ma, Justin; Arrowsmith, Cheryl H.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. [Lam, Robert; Ravichandran, Mani; Xiao, Ting; Tempel, Wolfram; Arrowsmith, Cheryl H.] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L5, Canada. [Brazda, Vaclav] Acad Sci Czech Republic, Inst Biophys, Vvi, CS-61265 Brno, Czech Republic. [Zuo, Xiaobing; Wang, Yun-Xing] Natl Canc Inst Frederick, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. [Chirgadze, Nickolay Y.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON M5S 1A8, Canada. RP Arrowsmith, CH (reprint author), Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C4, Canada. EM carrow@uhnres.utoronto.ca RI Zuo, Xiaobing/F-1469-2010; Brazda, Vaclav/F-9582-2011; Hsing-Yen, Su/G-9552-2014 FU Canadian Cancer Society; US National Institute of Health Protein Structure Initiative through the Northeast Structural Genomics Consortium [P50-GM62413-0, GM67965]; Canadian Institute of Health Research (CIHR); Terry Fox Foundation; ASCR [M200040904, AV0Z50040507, AV0Z50040702]; GACR [301/10/1211]; 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 We thank the Benchimol laboratory for the H1299 cells and p21-Luc reporter plasmid. We also thank Yi Sheng and Rob Laister for critical revision of the manuscript. This work was supported by grants from Canadian Cancer Society (to C.H.A.), the Ontario Ministry of Health and Long Term Care, the US National Institute of Health Protein Structure Initiative (P50-GM62413-01 and GM67965) through the Northeast Structural Genomics Consortium, a Canadian Institute of Health Research (CIHR) Canada Graduate Scholarship (2005-2008), and Terry Fox Foundation Studentship (2008-2010) (to J.C.C.L.). V.B. is supported by the ASCR (Grants M200040904, AV0Z50040507, and AV0Z50040702) and by the GACR (301/10/1211). The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the CIHR, 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. C.H.A. holds a Canada Research Chair in Structural Proteomics. NR 52 TC 38 Z9 40 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAR 9 PY 2011 VL 19 IS 3 BP 418 EP 429 DI 10.1016/j.str.2010.12.015 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 739CG UT WOS:000288689400016 PM 21397192 ER PT J AU Tazi, L Imamichi, H Hirschfeld, S Metcalf, JA Orsega, S Perez-Losada, M Posada, D Lane, HC Crandall, KA AF Tazi, Loubna Imamichi, Hiromi Hirschfeld, Steven Metcalf, Julia A. Orsega, Susan Perez-Losada, Marcos Posada, David Lane, H. Clifford Crandall, Keith A. TI HIV-1 infected monozygotic twins: a tale of two outcomes SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; AMINO-ACID SITES; HIV-1 ENV GENE; MAXIMUM-LIKELIHOOD; POSITIVE SELECTION; IMMUNE-RESPONSES; IDENTICAL-TWINS; POPULATION; EVOLUTION AB Background: Replicate experiments are often difficult to find in evolutionary biology, as this field is inherently an historical science. However, viruses, bacteria and phages provide opportunities to study evolution in both natural and experimental contexts, due to their accelerated rates of evolution and short generation times. Here we investigate HIV-1 evolution by using a natural model represented by monozygotic twins infected synchronically at birth with an HIV-1 population from a shared blood transfusion source. We explore the evolutionary processes and population dynamics that shape viral diversity of HIV in these monozygotic twins. Results: Despite the identical host genetic backdrop of monozygotic twins and the identical source and timing of the HIV-1 inoculation, the resulting HIV populations differed in genetic diversity, growth rate, recombination rate, and selection pressure between the two infected twins. Conclusions: Our study shows that the outcome of evolution is strikingly different between these two "replicates" of viral evolution. Given the identical starting points at infection, our results support the impact of random epigenetic selection in early infection dynamics. Our data also emphasize the need for a better understanding of the impact of host-virus interactions in viral evolution. C1 [Tazi, Loubna] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Brownsville, TX USA. [Imamichi, Hiromi] NCI, Lab Mol Retrovirol, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Imamichi, Hiromi; Lane, H. Clifford] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Hirschfeld, Steven] NICHHD, NIH, Bethesda, MD 20892 USA. [Metcalf, Julia A.; Orsega, Susan] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Perez-Losada, Marcos] Univ Porto, CIBIO, Ctr Invest Biodiversidade & Recursos Genet, Vairao, Portugal. [Posada, David] Univ Vigo, Dept Biochem Genet & Immunol, Vigo 36310, Spain. [Crandall, Keith A.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA. RP Tazi, L (reprint author), Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Brownsville Reg Campus, Brownsville, TX USA. EM Loubna.Tazi@uth.tmc.edu RI Hirschfeld, Steven/E-2987-2016; Perez-Losada, Marcos/I-4407-2013; Posada, David/C-4502-2008 OI Hirschfeld, Steven/0000-0003-0627-7249; Perez-Losada, Marcos/0000-0002-2585-4657; Crandall, Keith/0000-0002-0836-3389; Posada, David/0000-0003-1407-3406 FU NIH [R01-GM66276]; Brigham Young University; Spanish Ministry of Science and Education [BIO2007-61411]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases FX The authors would like to thank study participants for their help in completing this study. This work was supported by NIH grant R01-GM66276 (KAC, DP) and Brigham Young University, and by the Spanish Ministry of Science and Education grant number BIO2007-61411 to DP. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 55 TC 5 Z9 5 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD MAR 8 PY 2011 VL 11 AR 62 DI 10.1186/1471-2148-11-62 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 748TC UT WOS:000289413900002 PM 21385447 ER PT J AU Naiche, LA Holder, N Lewandoski, M AF Naiche, L. A. Holder, Nakisha Lewandoski, Mark TI FGF4 and FGF8 comprise the wavefront activity that controls somitogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetic redundancy; Spry; T-Cre; axis extension; paraxial mesoderm ID SEGMENTATION CLOCK; MOUSE EMBRYO; RETINOIC ACID; MESODERM FORMATION; WNT/BETA-CATENIN; LIMB DEVELOPMENT; EXPRESSION; SOMITE; AXIS; ACTIVATION AB Somites form along the embryonic axis by sequential segmentation from the presomitic mesoderm (PSM) and differentiate into the segmented vertebral column as well as other unsegmented tissues. Somites are thought to form via the intersection of two activities known as the clock and the wavefront. Previous work has suggested that fibroblast growth factor (FGF) activity may be the wavefront signal, which maintains the PSM in an undifferentiated state. However, it is unclear which (if any) of the FGFs expressed in the PSM comprise this activity, as removal of any one gene is insufficient to disrupt early somitogenesis. Here we show that when both Fgf4 and Fgf8 are deleted in the PSM, expression of most PSM genes is absent, including cycling genes, WNT pathway genes, and markers of undifferentiated PSM. Significantly, markers of nascent somite cell fate expand throughout the PSM, demonstrating the premature differentiation of this entire tissue, a highly unusual phenotype indicative of the loss of wavefront activity. When WNT signaling is restored in mutants, PSM progenitor markers are partially restored but premature differentiation of the PSM still occurs, demonstrating that FGF signaling operates independently of WNT signaling. This study provides genetic evidence that FGFs are the wavefront signal and identifies the specific FGF ligands that encode this activity. Furthermore, these data show that FGF action maintains WNT signaling, and that both signaling pathways are required in parallel to maintain PSM progenitor tissue. C1 [Naiche, L. A.; Holder, Nakisha; Lewandoski, Mark] NCI, Genet Vertebrate Dev Sect, Frederick, MD 21701 USA. RP Lewandoski, M (reprint author), NCI, Genet Vertebrate Dev Sect, Frederick, MD 21701 USA. EM lewandom@mail.nih.gov FU Center for Cancer Research of the National Institutes of Health through the National Cancer Institute FX We thank C. Elder and E. Truffer for expert technical assistance and A. Liu for cell death/proliferation studies. We thank M. Fivash and the Histopathology laboratory (NCI-Frederick) for technical assistance. We also thank A. Boulet and M. Capecchi for sharing prepublication data and T. Yamaguchi, M. Perry, S. Mackem, M. Kuehn, J. Gibson- Brown, and all members of the Lewandoski laboratory for insightful comments on the manuscript. This work was supported by the Center for Cancer Research of the Intramural Research Program of the National Institutes of Health through the National Cancer Institute. NR 47 TC 63 Z9 63 U1 0 U2 10 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 MAR 8 PY 2011 VL 108 IS 10 BP 4018 EP 4023 DI 10.1073/pnas.1007417108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731PA UT WOS:000288120400040 PM 21368122 ER PT J AU Kawai, Y Hamazaki, Y Fujita, H Fujita, A Sato, T Furuse, M Fujimoto, T Jetten, AM Agata, Y Minato, N AF Kawai, Yohei Hamazaki, Yoko Fujita, Harumi Fujita, Akikazu Sato, Takehito Furuse, Mikio Fujimoto, Toyoshi Jetten, Anton M. Agata, Yasutoshi Minato, Nagahiro TI Claudin-4 induction by E-protein activity in later stages of CD4/8 double-positive thymocytes to increase positive selection efficiency SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thymus; repertoire; costimulation ID TIGHT JUNCTION STRANDS; T-CELLS; ROR-GAMMA; SURVIVAL; OCCLUDIN; E47 AB Claudins (Clds) are crucial constituents of tight- junction strands in epithelial cells and have a central role in barrier functions. We show that Cld4 is unexpectedly expressed in normal thymic lymphocytes independently of tight junctions. The Cld4 expression was mostly confined to a portion of the CD4/CD8 double-positive (DP) cells. The proportion of Cld4+ DP cells was markedly increased in MHC-I(-/-)II(-/-)mice but decreased in Ror gamma(-/-)mice, and Cld4(+) DP cells contained higher levels of the rearranged Tcra transcripts involving the most distal Va and Ja segments than Cld4-DP cells. The Cld4 expression levels were reduced in E47-deficient mice in a gene dose-dependent manner, and ChIP analysis indicated that E2A and HEB were bound to the E-box sites of the putative Cldn4 promoter region. Functionally, Cld4 showed a potent T-cell receptor costimulatory activity by coligation with CD3. The Cld4 was distributed diffusely on the cell surface and associated with CD4/lck independently of CD3 in the resting thymocytes. However, Cld4 was strongly recruited to the immunological synapse on specific T-cell receptor engagement through antigen-presenting cells. In the fetal thymic organ culture, knockdown of Cldn4 resulted in the reduced generation of CD4/CD8 single-positive cells from the DP cells. These results suggest that Cld4 is induced by E-protein activity in the later stages of DP cells to increase the efficiency of positive selection, uncovering a hitherto unrecognized function of a Cld family protein. C1 [Hamazaki, Yoko; Agata, Yasutoshi; Minato, Nagahiro] Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan. [Kawai, Yohei; Fujita, Harumi; Minato, Nagahiro] Kyoto Univ, Grad Sch Biostudies, Dept Immunol & Cell Biol, Kyoto 6068501, Japan. [Fujita, Akikazu; Fujimoto, Toyoshi] Nagoya Univ, Grad Sch Med, Dept Anat & Mol Cell Biol, Nagoya, Aichi 4668550, Japan. [Sato, Takehito] Tokai Univ, Sch Med, Dept Immunol, Kanagawa 2591193, Japan. [Furuse, Mikio] Kobe Univ, Grad Sch Med, Div Cell Biol, Kobe, Hyogo 6500017, Japan. [Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Hamazaki, Y (reprint author), Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan. EM hamazaki@imm.med.kyoto-u.ac.jp OI Jetten, Anton/0000-0003-0954-4445 FU Ministry of Education, Culture, Science, Sports, and Technology of the Japanese Government FX We thank Drs. Y. Tanaka, Y. Kato, and M. Hayashi for the generation of the anti- Cld4 monoclonal antibody, Mr. K. Wakae for the ChIP assay, Dr. M. Itoh for the anti- ZO- 1 antibody, Dr. Y. Horiguchi for a CCPE plasmid, Dr. K. Moriwaki for Cldn plasmids, Dr. T. Kitamura for the retroviral vector, Dr. D. L. Wiest for the Scid. adh cell line, and Dr. C. Murre for the E47-/- mice. This work was supported by grants from the Ministry of Education, Culture, Science, Sports, and Technology of the Japanese Government (to Y. H. and N. M.). NR 21 TC 14 Z9 14 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 MAR 8 PY 2011 VL 108 IS 10 BP 4075 EP 4080 DI 10.1073/pnas.1014178108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731PA UT WOS:000288120400050 PM 21325057 ER PT J AU Kubler-Kielb, J Vinogradov, E Lagergard, T Ginzberg, A King, JD Preston, A Maskell, DJ Pozsgay, V Keith, JM Robbins, JB Schneerson, R AF Kubler-Kielb, Joanna Vinogradov, Evgeny Lagergard, Teresa Ginzberg, Ariel King, Jerry D. Preston, Andrew Maskell, Duncan J. Pozsgay, Vince Keith, Jerry M. Robbins, John B. Schneerson, Rachel TI Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hydroxylamine; Gram-negative ID SHIGELLA-DYSENTERIAE TYPE-1; O-SPECIFIC POLYSACCHARIDE; LIPOPOLYSACCHARIDE; IMMUNOGENICITY; MICE; LIPOOLIGOSACCHARIDE; INFECTION; CHILDREN; EFFICACY AB Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity. C1 [Kubler-Kielb, Joanna; Ginzberg, Ariel; Pozsgay, Vince; Keith, Jerry M.; Robbins, John B.; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Vinogradov, Evgeny] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. [Lagergard, Teresa] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Microbiol & Immunol, S-40530 Gothenburg, Sweden. [King, Jerry D.; Maskell, Duncan J.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England. [Preston, Andrew] Univ Bristol, Dept Vet Clin Med, Langford BS40 5DU, North Somerset, England. RP Kubler-Kielb, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov; robbinsjo@nichd.nih.gov OI Vinogradov, Evgeny/0000-0002-5364-1376 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX We thank Chris Mocca and Chunyan Guo (National Institute of Child Health and Human Development) for technical assistance. This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 37 TC 16 Z9 16 U1 1 U2 7 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 MAR 8 PY 2011 VL 108 IS 10 BP 4087 EP 4092 DI 10.1073/pnas.1100782108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731PA UT WOS:000288120400052 PM 21367691 ER PT J AU Hashimoto-Torii, K Kawasawa, YI Kuhn, A Rakic, P AF Hashimoto-Torii, Kazue Kawasawa, Yuka Imamura Kuhn, Alexandre Rakic, Pasko TI Combined transcriptome analysis of fetal human and mouse cerebral cortex exposed to alcohol SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cross-species; human fetus; neuronal subtypes; microarray; Notch ID NEURAL STEM-CELLS; CORTICAL-NEURONS; DEVELOPING NEOCORTEX; SPECTRUM DISORDERS; PRENATAL EXPOSURE; HUMAN BRAIN; ETHANOL; MIGRATION; GROWTH; PROLIFERATION AB Fetal exposure to environmental insults increases the susceptibility to late-onset neuropsychiatric disorders. Alcohol is listed as one of such prenatal environmental risk factors and known to exert devastating teratogenetic effects on the developing brain, leading to complex neurological and psychiatric symptoms observed in fetal alcohol spectrum disorder (FASD). Here, we performed a coordinated transcriptome analysis of human and mouse fetal cerebral cortices exposed to ethanol in vitro and in vivo, respectively. Up-and down-regulated genes conserved in the human and mouse models and the biological annotation of their expression profiles included many genes/terms related to neural development, such as cell proliferation, neuronal migration and differentiation, providing a reliable connection between the two species. Our data indicate that use of the combined rodent and human model systems provides an effective strategy to reveal and analyze gene expression changes inflicted by various physical and chemical environmental exposures during prenatal development. It also can potentially provide insight into the pathogenesis of environmentally caused brain disorders in humans. C1 [Hashimoto-Torii, Kazue; Kawasawa, Yuka Imamura; Rakic, Pasko] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA. [Hashimoto-Torii, Kazue; Kawasawa, Yuka Imamura; Rakic, Pasko] Yale Univ, Sch Med, Kavli Inst Neurosci, New Haven, CT 06510 USA. [Kuhn, Alexandre] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hashimoto-Torii, K (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06510 USA. EM Kazue.Hashimoto-Torii@yale.edu; pasko.rakic@yale.edu FU Kavli Institute for Neuroscience at Yale; National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke [NS038296-09]; NIH/National Institute on Alcohol Abuse and Alcoholism [K99AA018387] FX We thank Drs. B. Poulos for human tissue acquisition, M. Torii and N. Sestan for their valuable comments, N. Iijima for technical advice, and A. Nakai for provision of antibodies. We also thank S. Ellis for technical assistance. This work was supported by the Kavli Institute for Neuroscience at Yale (K.H.-T. and P.R.), National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke NS038296-09 (to P.R.) and NIH/National Institute on Alcohol Abuse and Alcoholism K99AA018387 (to K.H.-T.). NR 56 TC 26 Z9 26 U1 2 U2 12 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 MAR 8 PY 2011 VL 108 IS 10 BP 4212 EP 4217 DI 10.1073/pnas.1100903108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731PA UT WOS:000288120400073 PM 21368140 ER PT J AU Higo, T Mars, RB Boorman, ED Buch, ER Rushworth, MFS AF Higo, Takayasu Mars, Rogier B. Boorman, Erie D. Buch, Ethan R. Rushworth, Matthew F. S. TI Distributed and causal influence of frontal operculum in task control SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE top-down control; prefrontal cortex; bottom-up signal; category-selective regions; inhibition ID PRIMARY MOTOR CORTEX; PREFRONTAL CORTEX; ATTENTIONAL CONTROL; WORKING-MEMORY; BRAIN NETWORKS; CONNECTIONS; MODULATION; SELECTION; MONKEY; COMMON AB It has been suggested that the frontal operculum (fO) is a key node in a network for exerting control over cognitive processes. How it exerts this influence, however, has been unclear. Here, using the complementary approaches of functional MRI and transcranial magnetic stimulation, we have shown that the fO regulates increases and decreases of activity in multiple occipitotemporal cortical areas when task performance depended on directing attention to different classes of stimuli held in memory. Only one region, the fO, was significantly more active when subjects selectively attended to a single stimulus so that it determined task performance. The stimuli that guided task performance could belong to three categories-houses, body parts, and faces-associated with three occipitotemporal regions. On each trial, the pattern of functional correlation between the fO and the three occipitotemporal regions became either positive or negative, depending on which stimulus was to be attended and which ignored. Activation of the fO preceded both activity increases and decreases in the occipitotemporal cortex. The causal dependency of the distributed occipitotemporal pattern of activity increases and decreases on the fO was demonstrated by showing that transcranial magnetic stimulation-mediated interference of the fO diminished top-down selective attentional modulation in the occipitotemporal cortex, but it did not alter bottom-up activation of the same areas to the same stimuli when they were presented in isolation. The fO's prominence in cognitive control may stem from a role in regulating the level of activity of representations in posterior brain areas that are relevant or irrelevant, respectively, for response selection. C1 [Higo, Takayasu; Mars, Rogier B.; Boorman, Erie D.; Buch, Ethan R.; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Higo, Takayasu; Mars, Rogier B.; Boorman, Erie D.; Buch, Ethan R.; Rushworth, Matthew F. S.] Univ Oxford, John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. [Buch, Ethan R.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sec, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Higo, T (reprint author), RIKEN, Brain Sci Inst, Lab Cognit Brain Mapping, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. EM higo@brain.riken.jp; matthew.rushworth@psy.ox.ac.uk RI Buch, Ethan/G-1981-2011 FU Human Frontier Science Program; Medical Research Council FX We thank MaryAnn Noonan, Vanessa Johnen, Steven Knight, and Jan Scholz. This work was supported by the Human Frontier Science Program (T.H.) and the Medical Research Council (M.F.S.R. and R.B.M.). NR 33 TC 46 Z9 46 U1 3 U2 9 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 MAR 8 PY 2011 VL 108 IS 10 BP 4230 EP 4235 DI 10.1073/pnas.1013361108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731PA UT WOS:000288120400076 PM 21368109 ER PT J AU Wang, QJ Hanada, K Feldman, SA Zhao, YB Inozume, T Yang, JC AF Wang, Qiong J. Hanada, Ken-ichi Feldman, Steven A. Zhao, Yangbing Inozume, Takashi Yang, James C. TI Development of a genetically-modified novel T-cell receptor for adoptive cell transfer against renal cell carcinoma SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T-cell receptor; Renal cell carcinoma; Genetic modification; Complementarity determining; Adoptive cell transfer ID CANCER REGRESSION; METASTATIC MELANOMA; LYMPHOCYTES; ANTIGEN; TCR; TUMOR; THERAPY; IDENTIFICATION; SINGLE; LINES AB A novel alpha/beta T-cell clone with broad reactivity against human clear cell renal cell carcinomas (RCC) was generated from a patient with renal cancer. The T-cell receptor (TCR) from this clone recognizes soluble TNF-related apoptosis inducing ligand bound to death receptor 4, a complex found on the surface of nearly all RCC. In this study, we modified this novel TCR by introducing amino acid (M) substitutions in its complementarity determining region 2 (CDR2) and CDR3 regions of both chains, to increase its activity. We demonstrated that tumor recognition by PBL, retrovirally-transduced with these TCRs, was decreased or unchanged by substitutions in the TCR beta chain, and in the CDR2 alpha region. Yet some AA substitutions in the CDR3 alpha region at positions 109 and 112 could augment tumor recognition. Specifically, substituting phenylalanine for tyrosine at AA109 (109Y-F) and alanine or lysine for serine at AA112 (1125-K or 112 S-A) augmented tumor recognition. Increased benefit was seen on combining both AA substitutions and a retrovirus encoding the modified TCR 109Y-F/112S-K conferred the best tumor recognition to transduced PBL This modified TCR retained the recognition pattern of parental clone HC/2G-1 against RCC lines, other tumors and normal tissues. These results document that CDR3 alpha plays an important role in the interaction of the HC/2G-1 TCR and its novel ligand. A phase clinical trial, adoptively transferring autologous PBL transduced with this modified TCR has just begun in patients with metastatic RCC. Published by Elsevier B.V. C1 [Wang, Qiong J.; Hanada, Ken-ichi; Feldman, Steven A.; Inozume, Takashi; Yang, James C.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Zhao, Yangbing] Univ Penn, Abramson Canc Res Inst, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA. RP Wang, QJ (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10-CRC,Room 3W-3840, Bethesda, MD 20892 USA. EM qiongwang@mail.nih.gov; James_Yang@nih.gov RI Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 FU NIH, National Cancer Institute, Center for Cancer Research FX The authors thank Drs. Steven A Rosenberg, Paul Robbins, and Richard Morgan for the thoughtful discussions and technical support. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 24 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 7 PY 2011 VL 366 IS 1-2 BP 43 EP 51 DI 10.1016/j.jim.2011.01.002 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 749FY UT WOS:000289450600006 PM 21255579 ER PT J AU Zhao, R Wang, TZ Kong, D Zhang, L Meng, HX Jiang, Y Wu, YQ Yu, ZX Jin, XM AF Zhao, Ran Wang, Tian-Zhen Kong, Dan Zhang, Lei Meng, Hong-Xue Jiang, Yang Wu, Yi-Qi Yu, Zu-Xi Jin, Xiao-Ming TI Hepatoma cell line HepG2.2.15 demonstrates distinct biological features compared with parental HepG2 SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE HepG2.2.15; HepG2; Hepatitis B virus; Biological feature; Tumor ID VIRUS-X-PROTEIN; HEPATOCELLULAR-CARCINOMA; ERM PROTEINS; TRANSACTIVATION; EXPRESSION; HBX; PROLIFERATION; APOPTOSIS; CANCER; TISSUE AB AIM: To investigate the biological features of hepatitis B virus (HBV)-transfected HepG2.2.15 cells. METHODS: The cell ultrastructure, cell cycle and apoptosis, and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy, flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay. Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice, and the pathological analysis of tumor formation was performed. Two cytoskeletal proteins were detected by Western blotting. RESULTS: Compared with HepG2 cells, HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope. HepG2.2.15 cells proliferated and migrated slowly in vitro, and hardly formed tumor and lung metastasis in nude mice. Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase, and apoptosis was minor in both cell lines. Furthermore, the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION: HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection. (c) 2011 Baishideng. All rights reserved. C1 [Zhao, Ran; Wang, Tian-Zhen; Zhang, Lei; Meng, Hong-Xue; Jiang, Yang; Wu, Yi-Qi; Jin, Xiao-Ming] Harbin Med Coll, Dept Pathol, Harbin 150081, Heilongjiang Pr, Peoples R China. [Kong, Dan] Kanazawa Univ, Canc Res Inst, Kakuma, Kanazawa 9201192, Japan. [Yu, Zu-Xi] NHLBI, NIH, Bethesda, MD 20892 USA. RP Jin, XM (reprint author), Harbin Med Coll, Dept Pathol, 194 Xuefu Rd, Harbin 150081, Heilongjiang Pr, Peoples R China. EM jinxm55@yahoo.com.cn FU Graduate Innovation Foundation of Harbin Medical University [HCXB2010010]; Heilongjiang Science and Technology Department [ZJY04-0102] FX Supported by Graduate Innovation Foundation of Harbin Medical University No. HCXB2010010 and Key Technology Project of Heilongjiang Science and Technology Department, No. ZJY04-0102 NR 24 TC 13 Z9 13 U1 1 U2 6 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD MAR 7 PY 2011 VL 17 IS 9 BP 1152 EP 1159 DI 10.3748/wjg.v17.i9.1152 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 741QI UT WOS:000288878200008 PM 21448419 ER PT J AU Monga, V Meena, CL Rajput, S Pawar, C Sharma, SS Lu, XP Gershengorn, MC Jain, R AF Monga, Vikramdeep Meena, Chhuttan L. Rajput, Satyendra Pawar, Chandrashekhar Sharma, Shyam S. Lu, Xinping Gershengorn, Marvin C. Jain, Rahul TI Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin-Releasing Hormone (TRH) Analogues SO CHEMMEDCHEM LA English DT Article DE CNS; peptides; pharmacology; receptors; thyrotropin-releasing hormone ID CENTRAL-NERVOUS-SYSTEM; INDUCED SEIZURES; REGIOSPECIFIC ALKYLATION; NEURONS; SUBTYPE; HISTIDINE; BIOLOGY; CLONING; CONDUCTANCE; ANESTHETICS AB As part of our search for selective and CNS-active thyrotropinreleasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRHR1 and TRH-R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRHR1 and TRH-R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21a (R=CH3) exhibited binding affinities (K-i values) of 0.17 mu m for TRH-R1 and 0.016 mu m for TRH-R2; it is 10-fold less potent than TRH in binding to TRH-R1 and equipotent with TRH in binding to TRH-R2. Compound 21a, the most selective agonist, activated TRH-R2 with a potency (EC50 value) of 0.0021 mu m, but activated TRH-R1 at EC50 = 0.05 mu m, and exhibited 24-fold selectivity for TRH-R2 over TRH-R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate-induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21a, b and 22a, b decreased sleeping time by nearly 50% more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ-induced seizures, but failed to provide any protection in MES-induced seizures at 10 mu mol kg(-1). The results of this study provide evidence that TRH analogues that show selectivity for TRH-R2 over TRH-R1 possess potent CNS activity. C1 [Monga, Vikramdeep; Meena, Chhuttan L.; Jain, Rahul] Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sas Nagar 160062, Punjab, India. [Rajput, Satyendra; Pawar, Chandrashekhar; Sharma, Shyam S.] Natl Inst Pharmaceut Educ & Res, Dept Pharmacol & Toxicol, Sas Nagar 160062, Punjab, India. [Lu, Xinping; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Jain, R (reprint author), Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sector 67, Sas Nagar 160062, Punjab, India. EM rahuljain@niper.ac.in FU Council of Scientific and Industrial Research, New Delhi [01(1861)/03/EMR-II]; Department of Science and Technology, New Delhi [SR/FTP/CS-79/2005]; University Grant Commission FX This work is supported by the Council of Scientific and Industrial Research, New Delhi (Grant No. 01(1861)/03/EMR-II). V.M. thanks the Department of Science and Technology, New Delhi (Grant No. SR/FTP/CS-79/2005), for the award of a young scientist fellowship. C. L. M. thanks the University Grant Commission for the award of a senior research fellowship. NR 54 TC 8 Z9 8 U1 1 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD MAR 7 PY 2011 VL 6 IS 3 BP 531 EP 543 DI 10.1002/cmdc.201000481 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737WG UT WOS:000288599600017 PM 21302359 ER PT J AU Dixit, VD Yang, H Sayeed, KS Stote, KS Rumpler, WV Baer, DJ Longo, DL Mattson, MP Taub, DD AF Dixit, Vishwa Deep Yang, Hyunwon Sayeed, Khaleel S. Stote, Kim S. Rumpler, William V. Baer, David J. Longo, Dan L. Mattson, Mark P. Taub, Dennis D. TI Controlled meal frequency without caloric restriction alters peripheral blood mononuclear cell cytokine production SO JOURNAL OF INFLAMMATION-LONDON LA English DT Article ID T-CELLS; DIETARY RESTRICTION; NONHUMAN-PRIMATES; OXIDATIVE STRESS; CONTROLLED-TRIAL; IMMUNE-SYSTEM; NORMAL-WEIGHT; RATS; AGE; INFLAMMATION AB Background: Intermittent fasting (IF) improves healthy lifespan in animals by a mechanism involving reduced oxidative damage and increased resistance to stress. However, no studies have evaluated the impact of controlled meal frequency on immune responses in human subjects. Objective: A study was conducted to establish the effects of controlled diets with different meal frequencies, but similar daily energy intakes, on cytokine production in healthy male and female subjects. Design: In a crossover study design with an intervening washout period, healthy normal weight middle-age male and female subjects (n = 15) were maintained for 2 months on controlled on-site one meal per day (OMD) or three meals per day (TMD) isocaloric diets. Serum samples and peripheral blood mononuclear cells (PBMCs) culture supernatants from subjects were analyzed for the presence of inflammatory markers using a multiplex assay. Results: There were no significant differences in the inflammatory markers in the serum of subjects on the OMD or TMD diets. There was an increase in the capacity of PBMCs to produce cytokines in subjects during the first month on the OMD or TMD diets. Lower levels of TNF-alpha, IL-17, MCP-1 and MIP-1 beta were produced by PBMCs from subjects on the OMD versus TMD diet. Conclusions: PBMCs of subjects on controlled diets exhibit hypersensitivities to cellular stimulation suggesting that stress associated with altered eating behavior might affect cytokine production by immune cells upon stimulation. Moreover, stimulated PBMCs derived from healthy individuals on a reduced meal frequency diet respond with a reduced capability to produce cytokines. C1 [Dixit, Vishwa Deep; Yang, Hyunwon; Longo, Dan L.; Taub, Dennis D.] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Sayeed, Khaleel S.; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Stote, Kim S.; Rumpler, William V.; Baer, David J.] ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. [Dixit, Vishwa Deep] Pennington Biomed Res Ctr, Lab Neuroendocrine Immunol, Baton Rouge, LA 70808 USA. RP Taub, DD (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging, NIH; US Department of Agriculture FX We would like to thank the staff at Beltsville Human Nutrition Research Center, USDA for excellent technical assistance during sample preparation and collection of blood samples. This research was supported in part by the Intramural Program of the National Institute on Aging, NIH and the US Department of Agriculture. NR 45 TC 6 Z9 6 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-9255 J9 J INFLAMM-LOND JI J. Inflamm.-Lond. PD MAR 7 PY 2011 VL 8 AR 6 DI 10.1186/1476-9255-8-6 PG 13 WC Immunology SC Immunology GA 734MJ UT WOS:000288337900001 PM 21385360 ER PT J AU Senchenko, VN Krasnov, GS Dmitriev, AA Kudryavtseva, AV Anedchenko, EA Braga, EA Pronina, IV Kondratieva, TT Ivanov, SV Zabarovsky, ER Lerman, MI AF Senchenko, Vera N. Krasnov, George S. Dmitriev, Alexey A. Kudryavtseva, Anna V. Anedchenko, Ekaterina A. Braga, Eleonora A. Pronina, Irina V. Kondratieva, Tatiana T. Ivanov, Sergey V. Zabarovsky, Eugene R. Lerman, Michael I. TI Differential Expression of CHL1 Gene during Development of Major Human Cancers SO PLOS ONE LA English DT Article ID CELL-ADHESION MOLECULE; TUMOR-SUPPRESSOR; CHROMOSOME 3P21.3; BREAST-CANCER; EPITHELIAL MALIGNANCIES; CALL GENE; L1; METASTASIS; INVASION; PATTERNS AB Background: CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis. Methodology/Principal Findings: We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (> 40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (> 40% of cases) - in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P < 0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression. Conclusions/Significance: Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer. C1 [Senchenko, Vera N.; Krasnov, George S.; Dmitriev, Alexey A.; Kudryavtseva, Anna V.; Anedchenko, Ekaterina A.; Zabarovsky, Eugene R.] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Struct & Funct Genom, Moscow, Russia. [Braga, Eleonora A.; Pronina, Irina V.] Russian State Genet Ctr GosNIIgenetika, Lab Mol Diag, Moscow, Russia. [Kondratieva, Tatiana T.] Russian Acad Med Sci, Blokhin Canc Res Ctr, Moscow, Russia. [Ivanov, Sergey V.] NYU, Langone Med Ctr, Dept Cardiothorac Surg, New York, NY USA. [Zabarovsky, Eugene R.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden. [Lerman, Michael I.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Senchenko, VN (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Struct & Funct Genom, Moscow, Russia. EM eugzab@ki.se RI Dmitriev, Alexey/D-6109-2011; Senchenko, Vera/C-8992-2014; Kudryavtseva, Anna/C-9032-2014; Krasnov, George/E-6529-2014; Braga, Eleonora/P-5574-2016; OI Dmitriev, Alexey/0000-0002-6827-9584; Senchenko, Vera/0000-0002-3119-515X; Kudryavtseva, Anna/0000-0002-3722-8207; Ivanov, Sergey/0000-0001-9770-7237; Krasnov, George/0000-0002-6493-8378 FU Russian Foundation for Basic Research [08-04-01577, 10-04-01213]; Russian Ministry of Education and Science [02.740.11.5227, 16.740.11.0173]; Swedish Cancer Society; Swedish Research Council; Swedish Institute; Karolinska Institute; National Cancer Institute, Center for Cancer Research; NCI FX This work was supported by grants 08-04-01577 and 10-04-01213 from the Russian Foundation for Basic Research; State Contracts 02.740.11.5227 and 16.740.11.0173 with the Russian Ministry of Education and Science; grants from the Swedish Cancer Society, the Swedish Research Council, the Swedish Institute and Karolinska Institute and National Cancer Institute, Center for Cancer Research, Intramural Research Program of NCI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 34 Z9 35 U1 1 U2 7 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 MAR 7 PY 2011 VL 6 IS 3 AR e15612 DI 10.1371/journal.pone.0015612 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 731IP UT WOS:000288099800003 PM 21408220 ER PT J AU Nomura, W Narumi, T Ohashi, N Serizawa, Y Lewin, NE Blumberg, PM Furuta, T Tamamura, H AF Nomura, Wataru Narumi, Tetsuo Ohashi, Nami Serizawa, Yuki Lewin, Nancy E. Blumberg, Peter M. Furuta, Toshiaki Tamamura, Hirokazu TI Synthetic Caged DAG-lactones for Photochemically Controlled Activation of Protein Kinase C SO CHEMBIOCHEM LA English DT Article DE cage compounds; diacylglycerol; drug design; enzymes; proteins ID CONFORMATIONALLY CONSTRAINED ANALOGS; PHOTOLABILE PROTECTING GROUP; EXCITED-STATE PROPERTIES; DIACYLGLYCEROL DAG; (COUMARIN-4-YL)METHYL DERIVATIVES; FLUORESCENCE ENHANCEMENT; DEACTIVATION BEHAVIOR; CYCLIC-NUCLEOTIDES; PHORBOL ESTERS; BINDING-SITE C1 [Nomura, Wataru; Narumi, Tetsuo; Ohashi, Nami; Serizawa, Yuki; Furuta, Toshiaki; Tamamura, Hirokazu] Tokyo Med & Dent Univ, Dept Med Chem, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan. [Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Furuta, Toshiaki] Toho Univ, Fac Sci, Chiba 2748510, Japan. RP Tamamura, H (reprint author), Tokyo Med & Dent Univ, Dept Med Chem, Inst Biomat & Bioengn, Chiyoda Ku, 2-3-10 Kandasurugadai, Tokyo 1010062, Japan. EM tamamura.mr@tmd.ac.jp RI Nomura, Wataru/F-5812-2015; Furuta, Toshiaki/F-1363-2011; OI Furuta, Toshiaki/0000-0001-8532-1775; Nomura, Wataru/0000-0001-8348-7544 FU Naito Foundation for Science; NIH, Center for Cancer Research, National Cancer Institute; Japan Society for Promotion of Science FX The authors thank Professor Kazunari Akiyoshi (Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University) for assistance with the laser microscopy. This study was supported in part by the Naito Foundation for Science (to W.N.) and in part by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. N.O. is supported by the Japan Society for Promotion of Science. NR 45 TC 10 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD MAR 7 PY 2011 VL 12 IS 4 BP 535 EP 539 DI 10.1002/cbic.201000670 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 731BG UT WOS:000288080700005 PM 22238145 ER PT J AU Metcalf, CJE Munayco, CV Chowell, G Grenfell, BT Bjornstad, ON AF Metcalf, C. J. E. Munayco, C. V. Chowell, G. Grenfell, B. T. Bjornstad, O. N. TI Rubella metapopulation dynamics and importance of spatial coupling to the risk of congenital rubella syndrome in Peru SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE rubella; epidemiology; metapopulation; congenital rubella syndrome ID CRITICAL COMMUNITY SIZE; QUANTITATIVE INVESTIGATIONS; CHILDHOOD INFECTIONS; MEASLES; VACCINATION; TRANSMISSION; EPIDEMICS; OUTBREAKS; MODEL; DISEASES AB Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Consequently, understanding the age-structured dynamics of this infection has considerable public health value. Vaccination short of the threshold for local elimination of transmission will increase the average age of infection. Accordingly, the classic concern for this infection is the potential for vaccination to increase incidence in individuals of childbearing age. A neglected aspect of rubella dynamics is how age incidence patterns may be moulded by the spatial dynamics inherent to epidemic metapopulations. Here, we use a uniquely detailed dataset from Peru to explore the implications of this for the burden of CRS. Our results show that the risk of CRS may be particularly severe in small remote regions, a prediction at odds with expectations in the endemic situation, and with implications for the outcome of vaccination. This outcome results directly from the metapopulation context: specifically, extinction-re-colonization dynamics are crucial because they allow for significant leakage of susceptible individuals into the older age classes during inter-epidemic periods with the potential to increase CRS risk by as much as fivefold. C1 [Metcalf, C. J. E.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. [Munayco, C. V.] Direcc Gen Epidemiol, Lima, Peru. [Chowell, G.; Grenfell, B. T.; Bjornstad, O. N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Chowell, G.] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85287 USA. [Bjornstad, O. N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Eno Hall, Princeton, NJ 08544 USA. EM cmetcalf@princeton.edu RI Bjornstad, Ottar/I-4518-2012; Munayco, Cesar/G-9990-2013; Chowell, Gerardo/F-5038-2012 OI Munayco, Cesar/0000-0001-7872-8913; Chowell, Gerardo/0000-0003-2194-2251 FU Bill and Melinda Gates Foundation [NIH R01 GM083983-01]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We thank the people of Direccion General de Epidemiologia and the national network of epidemiology for all their hard work in conducting surveillance activities and providing the rubella data used in this study; and Susan Reef for comments and discussion on the manuscript. This work was funded by the Bill and Melinda Gates Foundation and grant NIH R01 GM083983-01 (C.J.E.M., B.T.G., O.N.B), and the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health (B.T.G., O.N.B.). NR 36 TC 22 Z9 22 U1 0 U2 5 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD MAR 6 PY 2011 VL 8 IS 56 BP 369 EP 376 DI 10.1098/rsif.2010.0320 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 710IS UT WOS:000286505600006 PM 20659931 ER PT J AU Feldmann, H Geisbert, TW AF Feldmann, Heinz Geisbert, Thomas W. TI Ebola haemorrhagic fever SO LANCET LA English DT Article ID PROTECTS NONHUMAN-PRIMATES; VIRUS-INFECTED PATIENTS; MARBURG VIRUSES; GUINEA-PIGS; POSTEXPOSURE PROTECTION; ENDOTHELIAL-CELLS; DENDRITIC CELLS; FILOVIRUS INFECTIONS; PERSISTENT INFECTION; RNA INTERFERENCE AB Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock. C1 [Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. [Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Geisbert, Thomas W.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. [Geisbert, Thomas W.] Galveston Natl Lab, Galveston, TX USA. RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov FU Canadian Institutes of Health Research (CIHR); Division of Intramural Research (DIR); National Institutes of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); Public Health Agency of Canada (PHAC); Defense Threat Reduction Agency FX We thank many colleagues in the field for helpful discussions; and the Canadian Institutes of Health Research (CIHR), the intramural (Division of Intramural Research (DIR)), and extramural divisions of the National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and the Public Health Agency of Canada (PHAC), and the Defense Threat Reduction Agency for financial support of our work over the past decade. NR 139 TC 440 Z9 489 U1 52 U2 504 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 5 PY 2011 VL 377 IS 9768 BP 849 EP 862 DI 10.1016/S0140-6736(10)60667-8 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 738GO UT WOS:000288628500033 PM 21084112 ER PT J AU Zeng, XK Hou, SX AF Zeng, Xiankun Hou, Steven X. TI Kidney Stem Cells Found in Adult Zebrafish SO CELL STEM CELL LA English DT Editorial Material ID DROSOPHILA MALPIGHIAN TUBULES AB Recently in Nature, Davidson and coworkers (Diep et al., 2011) identified nephron progenitors/stem cells located at the point of fusion with the pronephric tubules in adult zebrafish. Clumps of progenitors give rise to functional nephrons after serial transplantation, demonstrating the ability of tissue stem cells to regenerate damaged kidney structures. C1 [Zeng, Xiankun; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Hou, SX (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM hous@mail.nih.gov NR 9 TC 1 Z9 2 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 4 PY 2011 VL 8 IS 3 BP 247 EP 249 DI 10.1016/j.stem.2011.02.008 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 735HI UT WOS:000288404400005 PM 21362564 ER PT J AU Caretti, G Palacios, D Sartorelli, V Puri, PL AF Caretti, Giuseppina Palacios, Daniela Sartorelli, Vittorio Puri, Pier Lorenzo TI Phosphoryl-EZH-ion SO CELL STEM CELL LA English DT Review ID EMBRYONIC STEM-CELLS; SUPPRESSES METHYLATION; SKELETAL-MUSCLE; GENE-EXPRESSION; PROTEIN EZH2; POLYCOMB; DIFFERENTIATION; CHROMATIN; KINASES; ATLAS AB Polycomb group (PcG) proteins regulate gene expression in embryonic and adult stem cells, but the mechanisms responsible for PcG gene targeting and regulation remain largely unknown. Recent evidence shows that EZH2, the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), is a nuclear phosphoprotein linking cell-cycle-intrinsic or extracellular signals to specific epigenetic signatures. C1 [Sartorelli, Vittorio] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. [Caretti, Giuseppina] Univ Milan, Dept Biomol Sci & Biotechnol, I-20133 Milan, Italy. [Palacios, Daniela; Puri, Pier Lorenzo] IRCCS Fdn Santa Lucia, DTI, I-00143 Rome, Italy. [Palacios, Daniela; Puri, Pier Lorenzo] European Brain Res Inst, I-00143 Rome, Italy. [Puri, Pier Lorenzo] Sanford Burnham Inst Med Res, La Jolla, CA 92037 USA. RP Sartorelli, V (reprint author), NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. EM sartorev@mail.nih.gov; plpuri@dti.telethon.it RI Palacios, Daniela/K-4698-2016; OI Palacios, Daniela/0000-0002-2207-2369; Puri, Pier Lorenzo/0000-0003-4964-0095 FU National Institute of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [R01 AR053779]; AIRC [MFAG 5386]; Fondazione Telethon FX P.L.P. is an Associate Telethon Scientist of the Dulbecco Telethon Institute (DTI) and Associate Investigator of Sanford Children's Health Research Center. This work has been supported by R01 AR053779 from the National Institute of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (PLP) and by the Intramural Program of the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health (V.S.). G.C. is supported by AIRC MFAG 5386. We thank Dr. D. Pasini and Dr. J.G. Ryall for critical reading of the manuscript. NR 24 TC 16 Z9 16 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 4 PY 2011 VL 8 IS 3 BP 262 EP 265 DI 10.1016/j.stem.2011.02.012 PG 4 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 735HI UT WOS:000288404400008 PM 21362566 ER PT J AU Najm, FJ Chenoweth, JG Anderson, PD Nadeau, JH Redline, RW McKay, RDG Tesar, PJ AF Najm, Fadi J. Chenoweth, Josh G. Anderson, Philip D. Nadeau, Joseph H. Redline, Raymond W. McKay, Ronald D. G. Tesar, Paul J. TI Isolation of Epiblast Stem Cells from Preimplantation Mouse Embryos SO CELL STEM CELL LA English DT Article ID SELF-RENEWAL; BLASTOCYST INJECTION; GROUND-STATE; ES CELLS; PLURIPOTENCY; DERIVATION; LINES; FATE AB Pluripotent stem cells provide a platform to interrogate control elements that function to generate all cell types of the body. Despite their utility for modeling development and disease, the relationship of mouse and human pluripotent stem cell states to one another remains largely undefined. We have shown that mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) are distinct, pluripotent states isolated from pre- and post-implantation embryos respectively. Human ES cells are different than mouse ES cells and share defining features with EpiSCs, yet are derived from pre-implantation human embryos. Here we show that EpiSCs can be routinely derived from pre-implantation mouse embryos. The preimplantation-derived EpiSCs exhibit molecular features and functional properties consistent with bona fide EpiSCs. These results provide a simple method for isolating EpiSCs and offer direct insight into the intrinsic and extrinsic mechanisms that regulate the acquisition of distinct pluripotent states. C1 [Najm, Fadi J.; Anderson, Philip D.; Nadeau, Joseph H.; Tesar, Paul J.] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. [Najm, Fadi J.; Anderson, Philip D.; Nadeau, Joseph H.; Tesar, Paul J.] Case Western Reserve Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Cleveland, OH 44106 USA. [Redline, Raymond W.] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA. [Chenoweth, Josh G.; McKay, Ronald D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tesar, PJ (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. EM paul.tesar@case.edu RI Tesar, Paul/C-9848-2014 OI Tesar, Paul/0000-0003-1532-3155 FU Case Western Reserve University School of Medicine; Center for Stem Cell and Regenerative Medicine; Athymic Animal and Radiation Resources Core facilities of the Case Comprehensive Cancer Center [P30 CA43703]; NIH/NINDS FX This research was supported by funding from the Case Western Reserve University School of Medicine, the Center for Stem Cell and Regenerative Medicine, the Athymic Animal and Radiation Resources Core facilities of the Case Comprehensive Cancer Center (P30 CA43703), and the NIH/NINDS intramural research program. P.J.T. is a Robertson Investigator of the New York Stem Cell Foundation and a Mt. Sinai Health Care Foundation Scholar. We are grateful to Leslie Cooperman as well as members of the P. Scacheri laboratory for technical assistance and provision of reagents and Irene Tsung for graphical abstract artwork. NR 34 TC 85 Z9 87 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 4 PY 2011 VL 8 IS 3 BP 318 EP 325 DI 10.1016/j.stem.2011.01.016 PG 8 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 735HI UT WOS:000288404400013 PM 21362571 ER PT J AU Karaca, E Tozluoglu, M Nussinov, R Haliloglu, T AF Karaca, Ezgi Tozluoglu, Melda Nussinov, Ruth Haliloglu, Turkan TI Alternative Allosteric Mechanisms Can Regulate the Substrate and E2 in SUMO Conjugation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Ubc9-RanGAP1; molecular dynamics; allostery; sumoylation cascade; E3-RanBP2 ID UBIQUITIN-LIKE PROTEINS; MOLECULAR-DYNAMICS; E3 LIGASE; SUMOYLATION; UBC9; COMPLEX; BINDING; RANGAP1; SYSTEM; IDENTIFICATION AB Sumoylation is the covalent attachment of small ubiquitin-like modifier (SUMO) to a target protein. Similar to other ubiquitin-like pathways, three enzyme types are involved that act in succession: an activating enzyme (E1), a conjugating enzyme (E2), and a ligase (E3). To date, unlike other ubiquitin-like mechanisms, sumoylation of the target RanGAP1 (Target(RanGAP1)) does not absolutely require the E3 of the system, RanBP2 (E3(RanBP2)), since the presence of E2 (E2(Ubc9)) is enough to sumoylate Target(RanGAP1). However, in the presence of E3, sumoylation is more efficient. To understand the role of the target specificity of E3(RanBP2) and E2(Ubc9), we carried out molecular dynamics simulations for the structure of E2(Ubc9)-SUMO-Target(RanGAP1) with and without the E3(RanBP2) ligase. Analysis of the dynamics of E2(Ubc9)-SUMO-Target(RanGAP1) in the absence and presence of E3(RanBP2) revealed that two different allosteric sites regulate the ligase activity: in the presence of E3(RanBP2), the E2(Ubc9)'s loop 2; (ii) in the absence of E3(RanBP2), the Leu65-Arg70 region of SUMO. These results provide a first insight into the question of how E3(RanBP2) can act as an intrinsic E3 for E2(Ubc9) and why, in its absence, the activity of E2(Ubc9)-SUMO-Target(RanGAP1) could still be maintained, albeit at lower efficiency. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Karaca, Ezgi; Tozluoglu, Melda; Haliloglu, Turkan] Bogazici Univ, Polymer Res Ctr, TR-34342 Bebek, Turkey. [Karaca, Ezgi; Tozluoglu, Melda; Haliloglu, Turkan] Bogazici Univ, Dept Chem Engn, TR-34342 Bebek, Turkey. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, POB B,Bldg 469,Room 149, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov; turkan@prc.boun.edu.tr FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; NIH; Betil Fund; TUBA (Turkish Academy of Sciences); DPT [2009K120520]; TUBITAK [107T382] FX This project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. R.L. acknowledges support from the NIH extramural program. T. H. acknowledges support from the Betil Fund, TUBA (Turkish Academy of Sciences), DPT (2009K120520), and TUBITAK project (TUBITAK, 107T382). The authors thank Bulent Balta for helpful discussions and Seren Soner for technical support. NR 44 TC 7 Z9 7 U1 0 U2 2 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 MAR 4 PY 2011 VL 406 IS 4 BP 620 EP 630 DI 10.1016/j.jmb.2010.12.044 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 734US UT WOS:000288365800009 PM 21216249 ER PT J AU Rosas, SR Kagan, JM Schouten, JT Slack, PA Trochim, WMK AF Rosas, Scott R. Kagan, Jonathan M. Schouten, Jeffrey T. Slack, Perry A. Trochim, William M. K. TI Evaluating Research and Impact: A Bibliometric Analysis of Research by the NIH/NIAID HIV/AIDS Clinical Trials Networks SO PLOS ONE LA English DT Article ID AIDS LITERATURE; LATIN-AMERICA; CITATION; METRICS; AFRICA; OUTPUT AB Evaluative bibliometrics uses advanced techniques to assess the impact of scholarly work in the context of other scientific work and usually compares the relative scientific contributions of research groups or institutions. Using publications from the National Institute of Allergy and Infectious Diseases (NIAID) HIV/AIDS extramural clinical trials networks, we assessed the presence, performance, and impact of papers published in 2006-2008. Through this approach, we sought to expand traditional bibliometric analyses beyond citation counts to include normative comparisons across journals and fields, visualization of co-authorship across the networks, and assess the inclusion of publications in reviews and syntheses. Specifically, we examined the research output of the networks in terms of the a) presence of papers in the scientific journal hierarchy ranked on the basis of journal influence measures, b) performance of publications on traditional bibliometric measures, and c) impact of publications in comparisons with similar publications worldwide, adjusted for journals and fields. We also examined collaboration and interdisciplinarity across the initiative, through network analysis and modeling of co-authorship patterns. Finally, we explored the uptake of network produced publications in research reviews and syntheses. Overall, the results suggest the networks are producing highly recognized work, engaging in extensive interdisciplinary collaborations, and having an impact across several areas of HIV-related science. The strengths and limitations of the approach for evaluation and monitoring research initiatives are discussed. C1 [Rosas, Scott R.; Slack, Perry A.] Concept Syst Inc, Ithaca, NY USA. [Kagan, Jonathan M.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Schouten, Jeffrey T.] Fred Hutchinson Canc Res Ctr, HIV AIDS Network Coordinat Project, Seattle, WA 98104 USA. [Trochim, William M. K.] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. RP Rosas, SR (reprint author), Concept Syst Inc, Ithaca, NY USA. EM srosas@conceptsystems.com FU National Institute of Allergy & Infectious Diseases (NIAID) [N01-AI-50022]; National Center for Research Resources (NCRR) [UL1-RR-024996]; NIAID [U01 AI068614, U01AI068636, U01AI068619, U01AI068632, U01AI068641, U01AI068633]; NCRR are components of the National Institutes of Health, Department of Health and Human Services, United States Government FX This work was supported, in part, by Contract No. N01-AI-50022, "HIV Clinical Research Support'' from the National Institute of Allergy & Infectious Diseases (NIAID), in part by Grant No. UL1-RR-024996, from the National Center for Research Resources (NCRR) and in part by grants U01 AI068614, U01AI068636, U01AI068619, U01AI068632, U01AI068641, and U01AI068633 (NIAID). NIAID and NCRR are components of the National Institutes of Health, Department of Health and Human Services, United States Government. No additional external funding was received for this study. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SRR and PAS are employed by Concept Systems, Inc and WMKT is a co-owner of the company. All three served as consultants to NIAID and contributed to the study design, analysis, and manuscript preparation. NR 46 TC 25 Z9 26 U1 2 U2 40 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 MAR 4 PY 2011 VL 6 IS 3 AR e17428 DI 10.1371/journal.pone.0017428 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 730HX UT WOS:000288025500013 PM 21394198 ER PT J AU Lisboa, FA Warren, J Sulkowski, G Aparicio, M David, G Zudaire, E Dveksler, GS AF Lisboa, Felipe A. Warren, James Sulkowski, Gisela Aparicio, Marta David, Guido Zudaire, Enrique Dveksler, Gabriela S. TI Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; HERPES-SIMPLEX-VIRUS; ALTERNATIVE ACTIVATION; TROPHOBLAST CELLS; GROWTH-FACTOR; EXPRESSION; ANGIOGENESIS; MONOCYTES; MUTANTS; BINDING AB Pregnancy-specific beta 1 glycoproteins (PSGs) are the most abundant fetal proteins in the maternal bloodstream in late pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 postfertilization. There are 11 human PSG genes, which encode a family of proteins exhibiting significant conservation at the amino acid level. We and others have proposed that PSGs have an immune modulatory function. In addition, we recently postulated that they are proangiogenic due to their ability to induce the secretion of VEGF-A and the formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs remain unknown. Therefore, we conducted these studies to identify the receptor for PSG1, the highest expressed member of the family. We show that removal of cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of cells or competition with heparin completely inhibited binding of PSG1. In addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on their surface, and binding was restored upon transfection with all four syndecans and glypican-1. Importantly, the presence of GAGs on the surface of endothelial cells was required for the ability of PSG1 to induce tube formation. This finding indicates that the PSG1-GAG interaction mediates at least some of the PSG1 proposed functions. C1 [Lisboa, Felipe A.; Warren, James; Sulkowski, Gisela; Dveksler, Gabriela S.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Aparicio, Marta; Zudaire, Enrique] NCI, Angiogenesis Core Facil, Radiat Oncol Branch, NIH,Adv Technol Ctr, Bethesda, MD 20892 USA. [David, Guido] Katholieke Univ Leuven, Dept Mol & Dev Genet, Vlaams Inst Biotechnol, B-3000 Louvain, Belgium. RP Dveksler, GS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, Rm B3096,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM gdveksler@usuhs.mil FU National Institutes of Health [R01HD035832] FX This work was supported, in whole or in part, by National Institutes of Health Grant R01HD035832 (to G. S. D.). NR 50 TC 21 Z9 22 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 4 PY 2011 VL 286 IS 9 BP 7577 EP 7586 DI 10.1074/jbc.M110.161810 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726PH UT WOS:000287737300071 PM 21193412 ER PT J AU Qiu, Y Stavreva, DA Luo, Y Indrawan, A Chang, MR Hager, GL AF Qiu, Yi Stavreva, Diana A. Luo, Yi Indrawan, Anindya Chang, Myron Hager, Gordon L. TI Dynamic Interaction of HDAC1 with a Glucocorticoid Receptor-regulated Gene Is Modulated by the Activity State of the Promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVING CELLS; CHROMATIN DYNAMICS; TRANSCRIPTION; TRAFFICKING; INHIBITION; EXCHANGE; ALPHA AB Although histone deacetylases (HDACs) are normally considered as co-repressors, HDAC1 has been identified as a coactivator for the glucocorticoid receptor (GR) (Qiu, Y., Zhao, Y., Becker, M., John, S., Parekh, B. S., Huang, S., Hendarwanto, A., Martinez, E. D., Chen, Y., Lu, H., Adkins, N. L., Stavreva, D. A., Wiench, M., Georgel, P. T., Schiltz, R. L., and Hager, G. L. (2006) Mol. Cell 22, 669-679). Furthermore, HDAC1 is acetylated, and its acetylation level is linked to the transcription state of a GR-induced promoter (mouse mammary tumor virus). GR is also known to interact dynamically with regulatory elements in living cells (McNally, J. G., Muller, W. G., Walker, D., Wolford, R., and Hager, G. L. (2000) Science 287, 1262-1265). However, HDAC1 dynamics have never been studied. We demonstrate here that HDAC1 also exchanges rapidly with promoter chromatin, and its exchange rate is significantly modulated during the development of promoter activity. Prior to induction, HDAC1 mobility was retarded compared with the exchange rate for GR. HDAC1 mobility then increased substantially, coordinately with the peak of promoter activity. At later time points, promoter activity was severely repressed, and HDAC1 mobility returned to the rate of exchange observed for the uninduced promoter. Thus, alterations of the exchange rates of HDAC1 at the promoter are correlated with the activity state of the promoter. These findings provide direct evidence for the functional role of highly mobile transcription factor complexes in transcription regulation. C1 [Qiu, Yi; Luo, Yi] Univ Florida, Shands Canc Ctr, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. [Chang, Myron] Univ Florida, Dept Epidemiol & Hlth Policy Res, Div Biostat, Gainesville, FL 32610 USA. [Stavreva, Diana A.; Indrawan, Anindya; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), Univ Florida, Shands Canc Ctr, Dept Anat & Cell Biol, Rm 356,2033 Mowry Rd, Gainesville, FL 32610 USA. EM qiuy@ufl.edu; hagerg@exchange.nih.gov FU National Institutes of Health [R01 HL095674-01]; Bankhead-Coley Research Foundation FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program and Grant R01 HL095674-01 (to Y. Q.). This work was also supported by the Bankhead-Coley Research Foundation (to Y. Q.). NR 27 TC 14 Z9 14 U1 1 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 MAR 4 PY 2011 VL 286 IS 9 BP 7641 EP 7647 DI 10.1074/jbc.M110.185488 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726PH UT WOS:000287737300077 PM 21127047 ER PT J AU Liao, MJ Zhang, Y Kang, JH Dufau, ML AF Liao, Mingjuan Zhang, Ying Kang, Jung-Hoon Dufau, Maria L. TI Coactivator Function of Positive Cofactor 4 ( PC4) in Sp1-directed Luteinizing Hormone Receptor (LHR) Gene Transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTONE DEACETYLASE 1; SP1 SITES; REGULATE TRANSCRIPTION; PROLACTIN RECEPTOR; P53 FUNCTION; DNA-BINDING; PROMOTER; ACTIVATION; PROTEIN; EXPRESSION AB The LHR has an essential role in sexual development and reproductive function, and its transcription is subjected to several modes of regulation. In this study, we investigated PC4 coactivator function in the control of LHR transcription. Knockdown of PC4 by siRNA inhibited the LHR basal promoter activity and trichostatin A (TSA)-induced gene transcriptional activation and expression in MCF-7 cells. While overexpression of PC4 alone had no effect on the LHR gene, it significantly enhanced Sp1-but not Sp3-mediated LHR transcriptional activity. PC4 directly interacts with Sp1 at the LHR promoter, and this interaction is negatively regulated by PC4 phosphorylation. The coactivator domain (22-91 aa) of PC4 and DNA binding domain of Sp1 are essential for PC4/Sp1 interaction. ChIP assay revealed significant occupancy of PC4 at the LHR promoter that increased upon TSA treatment. Disruption of PC4 expression significantly reduced TSA-induced recruitment of TFIIB and RNAP II, at the promoter. PC4 functions are beyond TSA-induced phosphatase release, PI3K-mediated Sp1 phosphorylation, and HDAC1/2/mSin3A co-repressor release indicating its role as linker coactivator of Sp1 and the transcriptional machinery. These findings demonstrated a critical aspect of LHR modulation whereby PC4 acts as a coactivator of Sp1 to contribute to the human of LHR transcription. C1 [Liao, Mingjuan; Zhang, Ying; Kang, Jung-Hoon; Dufau, Maria L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Endocrinol Sect, Program Dev Endocrinol & Genet, NIH, Bldg 49,Rm 6A-36, Bethesda, MD 20892 USA. EM dufaum@mail.nih.gov FU National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program through the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 42 TC 7 Z9 7 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 MAR 4 PY 2011 VL 286 IS 9 BP 7681 EP 7691 DI 10.1074/jbc.M110.188532 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726PH UT WOS:000287737300081 PM 21193408 ER PT J AU Pape, KA Taylor, JJ Maul, RW Gearhart, PJ Jenkins, MK AF Pape, Kathryn A. Taylor, Justin J. Maul, Robert W. Gearhart, Patricia J. Jenkins, Marc K. TI Different B Cell Populations Mediate Early and Late Memory During an Endogenous Immune Response SO SCIENCE LA English DT Article ID INDUCED CYTIDINE DEAMINASE; SUBSETS; RECOMBINATION; HYPERMUTATION; EXPRESSION; ANTIGENS; AID AB Memory B cells formed in response to microbial antigens provide immunity to later infections; however, the inability to detect rare endogenous antigen-specific cells limits current understanding of this process. Using an antigen-based technique to enrich these cells, we found that immunization with a model protein generated B memory cells that expressed isotype-switched immunoglobulins (swIg) or retained IgM. The more numerous IgM(+) cells were longer lived than the swIg(+) cells. However, swIg(+) memory cells dominated the secondary response because of the capacity to become activated in the presence of neutralizing serum immunoglobulin. Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves. C1 [Pape, Kathryn A.; Taylor, Justin J.; Jenkins, Marc K.] Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA. [Maul, Robert W.; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Jenkins, MK (reprint author), Univ Minnesota, Sch Med, Ctr Immunol, Dept Microbiol, Minneapolis, MN 55455 USA. EM jenki002@umn.edu RI Jenkins, Marc/G-1063-2012; OI Jenkins, Marc/0000-0001-8009-7655; Maul, Robert/0000-0002-6958-8514 FU NIH [R01 AI036914, R37 AI027998, F32 AI091033, T32 CA009138]; NIH, National Institute on Aging FX We thank J. Walter and R. Speier for expert technical assistance and all members of the Jenkins lab for helpful discussions. This work was supported by grants from the NIH (R01 AI036914 and R37 AI027998 to M.K.J., F32 AI091033 and T32 CA009138 to J.T.), and the Intramural Research Program of the NIH, National Institute on Aging (R.W.M. and P.J.G.). NR 26 TC 158 Z9 160 U1 3 U2 17 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 MAR 4 PY 2011 VL 331 IS 6021 BP 1203 EP 1207 DI 10.1126/science.1201730 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 729SN UT WOS:000287971200045 PM 21310965 ER PT J AU Oury, F Sumara, G Sumara, O Ferron, M Chang, HX Smith, CE Hermo, L Suarez, S Roth, BL Ducy, P Karsenty, G AF Oury, Franck Sumara, Grzegorz Sumara, Olga Ferron, Mathieu Chang, Haixin Smith, Charles E. Hermo, Louis Suarez, Susan Roth, Bryan L. Ducy, Patricia Karsenty, Gerard TI Endocrine Regulation of Male Fertility by the Skeleton SO CELL LA English DT Article ID MOUSE LEYDIG-CELLS; PROTEIN-COUPLED RECEPTOR; RAT SEMINIFEROUS TUBULES; RNA HELICASE GRTH/DDX25; BONE MASS; METABOLIC SYNDROME; ENERGY-METABOLISM; GENETIC-CONTROL; EXPRESSION; SERUM AB Interactions between bone and the reproductive system have until now been thought to be limited to the regulation of bone remodeling by the gonads. We now show that, in males, bone acts as a regulator of fertility. Using coculture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, though they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G protein-coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes that is required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin and provides the first evidence that the skeleton is an endocrine regulator of reproduction. C1 [Oury, Franck; Sumara, Grzegorz; Sumara, Olga; Ferron, Mathieu; Karsenty, Gerard] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. [Ducy, Patricia] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Chang, Haixin; Suarez, Susan] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. [Smith, Charles E.; Hermo, Louis] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol Med Chem & Nat Prod, Sch Med, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Med, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Pharmacol Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. RP Karsenty, G (reprint author), Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. EM gk2172@columbia.edu RI Ferron, Mathieu/M-7794-2013; Roth, Bryan/F-3928-2010 FU NIH; Fond de la recherche en sante du Quebec; HFSP FX We thank Drs. Behringer and Ko for generously providing the Amh-mis-Cre and Cyp17-iCre mice; Dr. Hampson for generously providing us Gprc6a antibody; Dr. A. F. Parlow for measurements of LH in serum (National Hormone and Peptide Program); Drs. Przedborski and Jackson-Lewis for gracious help with stereological analysis; Drs. Mark, Yadav, Yoshizawa, Allen, and Setola for critical experimental advice; and G. Ren for mouse genotyping. This work was supported by grants from the NIH (G. K.), Fond de la recherche en sante du Quebec (M. F.), and HFSP (G. S. and F. O.). NR 52 TC 217 Z9 229 U1 5 U2 48 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 4 PY 2011 VL 144 IS 5 BP 796 EP 809 DI 10.1016/j.cell.2011.02.004 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 730CE UT WOS:000288007100017 PM 21333348 ER PT J AU Liu, YP Bubolz, AH Mendoza, S Zhang, DX Gutterman, DD AF Liu, Yanping Bubolz, Aaron H. Mendoza, Suelhem Zhang, David X. Gutterman, David D. TI H2O2 Is the Transferrable Factor Mediating Flow-Induced Dilation in Human Coronary Arterioles SO CIRCULATION RESEARCH LA English DT Article DE coronary arterioles; shear stress; reactive oxygen species ID CA2+-ACTIVATED K+ CHANNELS; ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION; VASCULAR SMOOTH-MUSCLE; HYDROGEN-PEROXIDE; NITRIC-OXIDE; ARTERY ENDOTHELIUM; IN-VIVO; MECHANISMS; CELLS; ACTIVATION AB Rationale: Endothelial derived hydrogen peroxide (H2O2) is a necessary component of the pathway regulating flow-mediated dilation (FMD) in human coronary arterioles (HCAs). However, H2O2 has never been shown to be the endothelium-dependent transferrable hyperpolarization factor (EDHF) in response to shear stress. Objective: We examined the hypothesis that H2O2 serves as the EDHF in HCAs to shear stress. Methods and Results: Two HCAs were cannulated in series (a donor intact vessel upstream and endothelium-denuded detector vessel downstream). Diameter changes to flow were examined in the absence and presence of polyethylene glycol catalase (PEG-CAT). The open state probability of large conductance Ca2+-activated K+ (BKCa) channels in smooth muscle cells downstream from the perfusate from an endothelium-intact arteriole was examined by patch clamping. In some experiments, a cyanogen bromide-activated resin column bound with CAT was used to remove H2O2 from the donor vessel. When flow proceeds from donor to detector, both vessels dilate (donor: 68 +/- 7%; detector: 45 +/- 11%). With flow in the opposite direction, only the donor vessel dilates. PEG-CAT contacting only the detector vessel blocked FMD in that vessel (6 +/- 4%) but not in donor vessel (61 +/- 13%). Paxilline inhibited dilation of endothelium-denuded HCAs to H2O2. Effluent from donor vessels elicited K+ channel opening in an iberiotoxin-or PEG-CAT-sensitive fashion in cell-attached patches but had little effect on channel opening on inside-out patches. Vasodilation of detector vessels was diminished when exposed to effluent from CAT-column. Conclusions: Flow induced endothelial production of H2O2, which acts as the transferrable EDHF activating BKCa channels on the smooth muscle cells. (Circ Res. 2011; 108: 566-573.) C1 [Gutterman, David D.] Med Coll Wisconsin, Res Off, Dept Internal Med, Milwaukee, WI 53226 USA. [Liu, Yanping] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Bubolz, Aaron H.; Mendoza, Suelhem; Zhang, David X.; Gutterman, David D.] Zablocki Vet Adm Med Ctr, Milwaukee, WI 53295 USA. RP Gutterman, DD (reprint author), Med Coll Wisconsin, Res Off, Dept Internal Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM dgutterm@mcw.edu FU NIH [R01 HL080704, R01 HL094971]; Veterans Administration FX This work was supported by NIH grants R01 HL080704 and R01 HL094971 (to D. D. G.) and a Veterans Administration Merit Award to D.D.G. NR 40 TC 73 Z9 75 U1 0 U2 4 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 MAR 4 PY 2011 VL 108 IS 5 BP 566 EP U64 DI 10.1161/CIRCRESAHA.110.237636 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 729PW UT WOS:000287963900010 PM 21233456 ER PT J AU Allende, ML Bektas, M Lee, BG Bonifacino, E Kang, JM Tuymetova, G Chen, WP Saba, JD Proia, RL AF Allende, Maria L. Bektas, Meryem Lee, Bridgin G. Bonifacino, Eliana Kang, Jiman Tuymetova, Galina Chen, WeiPing Saba, Julie D. Proia, Richard L. TI Sphingosine-1-phosphate Lyase Deficiency Produces a Pro-inflammatory Response While Impairing Neutrophil Trafficking SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; VASCULAR S1P GRADIENT; DOUBLE-NULL MICE; P-SELECTIN; IN-VIVO; BIOACTIVE SPHINGOLIPIDS; LEUKOCYTE RECRUITMENT; LYMPHOCYTE EGRESS; ENDOTHELIAL-CELLS; KINASE 1 AB Sphingosine-1-phosphate (S1P) lyase catalyzes the degradation of S1P, a potent signaling lysosphingolipid. Mice with an inactive S1P lyase gene are impaired in the capacity to degrade S1P, resulting in highly elevated S1P levels. These S1P lyase-deficient mice have low numbers of lymphocytes and high numbers of neutrophils in their blood. We found that the S1P lyase-deficient mice exhibited features of an inflammatory response including elevated levels of pro-inflammatory cytokines and an increased expression of genes in liver associated with an acute-phase response. However, the recruitment of their neutrophils into inflamed tissues was impaired and their neutrophils were defective in migration to chemotactic stimulus. The IL-23/IL-17/granulocyte-colony stimulating factor (G-CSF) cytokine-controlled loop regulating neutrophil homeostasis, which is dependent on neutrophil trafficking to tissues, was disturbed in S1P lyase-deficient mice. Deletion of the S1P4 receptor partially decreased the neutrophilia and inflammation in S1P lyase-deficient mice, implicating S1P receptor signaling in the phenotype. Thus, a genetic block in S1P degradation elicits a pro-inflammatory response but impairs neutrophil migration from blood into tissues. C1 [Allende, Maria L.; Bektas, Meryem; Lee, Bridgin G.; Bonifacino, Eliana; Kang, Jiman; Tuymetova, Galina; Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Chen, WeiPing] NIDDK, Microarray Core Lab, NIH, Bethesda, MD 20892 USA. [Saba, Julie D.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU National Institutes of Health, NIDDK [CA77528]; National Institutes of Health [C06 RR018823] FX This research was supported, in whole or in part, by the Intramural Research Program of the National Institutes of Health, NIDDK by Public Health Service Grant CA77528 (to J.D.S.) and National Institutes of Health Grant C06 RR018823 (to the Medical University of South Carolina Lipomics Core). NR 73 TC 63 Z9 64 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 MAR 4 PY 2011 VL 286 IS 9 BP 7348 EP 7358 DI 10.1074/jbc.M110.171819 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726PH UT WOS:000287737300051 PM 21173151 ER PT J AU Schelbert, EB Testa, SM Meier, CG Ceyrolles, WJ Levenson, JE Blair, AJ Kellman, P Jones, BL Ludwig, DR Schwartzman, D Shroff, SG Wong, TC AF Schelbert, Erik B. Testa, Stephen M. Meier, Christopher G. Ceyrolles, William J. Levenson, Joshua E. Blair, Alexander J. Kellman, Peter Jones, Bobby L. Ludwig, Daniel R. Schwartzman, David Shroff, Sanjeev G. Wong, Timothy C. TI Myocardial extravascular extracellular volume fraction measurement by gadolinium cardiovascular magnetic resonance in humans: slow infusion versus bolus SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; MYOCYTE CELL LOSS; AGING RAT-HEART; DILATED CARDIOMYOPATHY; INVERSION-RECOVERY; GADOPENTETATE DIMEGLUMINE; PARTITION-COEFFICIENT; CONTRAST AGENTS; GD-DTPA; FIBROSIS AB Background: Myocardial extravascular extracellular volume fraction (Ve) measures quantify diffuse fibrosis not readily detectable by conventional late gadolinium (Gd) enhancement (LGE). Ve measurement requires steady state equilibrium between plasma and interstitial Gd contrast. While a constant infusion produces steady state, it is unclear whether a simple bolus can do the same. Given the relatively slow clearance of Gd, we hypothesized that a bolus technique accurately measures Ve, thus facilitating integration of myocardial fibrosis quantification into cardiovascular magnetic resonance (CMR) workflow routines. Assuming equivalence between techniques, we further hypothesized that Ve measures would be reproducible across scans. Methods: In 10 volunteers (ages 20-81, median 33 yr, 3 females), we compared serial Ve measures from a single short axis slice from two scans: first, during a constant infusion, and second, 12-50 min after a bolus (0.2 mmol/kg gadoteridol) on another day. Steady state during infusion was defined when serial blood and myocardial T1 data varied < 5%. We measured T1 on a 1.5 T Siemens scanner using a single-shot modified Look Locker inversion recovery sequence (MOLLI) with balanced SSFP. To shorten breath hold times, T1 values were measured with a shorter sampling scheme that was validated with spin echo relaxometry (TR = 15 sec) in CuSO4-Agar phantoms. Serial infusion vs. bolus Ve measures (n = 205) from the 10 subjects were compared with generalized estimating equations (GEE) with exchangeable correlation matrices. LGE images were also acquired 12-30 minutes after the bolus. Results: No subject exhibited LGE near the short axis slices where Ve was measured. The Ve range was 19.3-29.2% and 18.4-29.1% by constant infusion and bolus, respectively. In GEE models, serial Ve measures by constant infusion and bolus did not differ significantly (difference = 0.1%, p = 0.38). For both techniques, Ve was strongly related to age (p < 0.01 for both) in GEE models, even after adjusting for heart rate. Both techniques identically sorted older individuals with higher mean Ve values. Conclusion: Myocardial Ve can be measured reliably and accurately 12-50 minutes after a simple bolus. Ve measures are also reproducible across CMR scans. Ve estimation can be integrated into CMR workflow easily, which may simplify research applications involving the quantification of myocardial fibrosis. C1 [Schelbert, Erik B.; Testa, Stephen M.; Meier, Christopher G.; Ceyrolles, William J.; Levenson, Joshua E.; Ludwig, Daniel R.; Schwartzman, David; Shroff, Sanjeev G.; Wong, Timothy C.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Schelbert, Erik B.; Wong, Timothy C.] UPMC, Cardiovasc Magnet Resonance Ctr, Pittsburgh, PA USA. [Schelbert, Erik B.; Schwartzman, David; Wong, Timothy C.] UPMC, Cardiovasc Inst, Pittsburgh, PA USA. [Blair, Alexander J.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Kellman, Peter] NHLBI, Bethesda, MD 20892 USA. [Jones, Bobby L.] Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Shroff, Sanjeev G.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Schelbert, EB (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. EM schelberteb@upmc.edu OI Wong, Timothy/0000-0002-1045-2698; Schelbert, Erik/0000-0003-0356-4437 FU Pittsburgh Foundation; American Heart Association Scientist Development [09SDG2180083]; Atlantic Philanthropies, Inc; John A. Hartford Foundation; Association of Specialty Professors; American Heart Association; National Center for Research Resources (NCRR) [5UL1 RR024153-04]; National Institutes of Health (NIH); Howard Hughes Medical Institute [52005865] FX Funding bodies had no role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication. Dr Schelbert is supported by a Pittsburgh Foundation grant and an American Heart Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award; funding provided by: Atlantic Philanthropies, Inc, the John A. Hartford Foundation, the Association of Specialty Professors, and the American Heart Association. Contributions from Dr. Jones were made possible by Grant Number 5UL1 RR024153-04 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Mr. Blair received Howard Hughes Medical Institute support from grant number 52005865. NR 44 TC 88 Z9 90 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD MAR 4 PY 2011 VL 13 AR 16 DI 10.1186/1532-429X-13-16 PG 14 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 736NX UT WOS:000288502500001 PM 21375743 ER PT J AU Niu, LG Termini, JM Kanagavelu, SK Gupta, S Rolland, MM Kulkarni, V Pavlakis, GN Felber, BK Mullins, JI Fischl, MA Stone, GW AF Niu, Liguo Termini, James M. Kanagavelu, Saravana K. Gupta, Sachin Rolland, Morgane M. Kulkarni, Viraj Pavlakis, George N. Felber, Barbara K. Mullins, James I. Fischl, Margaret A. Stone, Geoffrey W. TI Preclinical evaluation of HIV-1 therapeutic ex vivo dendritic cell vaccines expressing consensus Gag antigens and conserved Gag epitopes SO VACCINE LA English DT Article DE Dendritic cell; Therapeutic vaccination; HIV; RNA ID CD8(+) T-CELLS; 1-INFECTED INDIVIDUALS; IMMUNE DYSFUNCTION; UP-REGULATION; INFECTION; RESPONSES; CD4(+); DYSREGULATION; REPLICATION; SUPPRESSION AB Background: Dendritic cell (DC) therapy is a promising technology for the treatment of HIV infected individuals. HIV-1 Gag- and Nef RNA-loaded DC have previously been shown to induce immune responses ex vivo following coculture with autologous lymphocytes. However, polyfunctionality and memory responses following coculture have not been evaluated. In addition, little is known regarding whether specific HIV-1 proteome components, such as highly conserved regions of the HIV-1, could enhance clinical responses following DC therapy. Methodology and principal findings: To determine the breadth of the immune responses to antigen loaded DC, we analyzed polyfunctional T cell response ex vivo to Gag RNA loaded DC. Blood samples were used to generate monocyte derived DC, which were then matured and cocultured with autologous lymphocytes. We found that cytokine-matured DC loaded with Gag RNA was able to induce Gag-specific IFN-gamma and IL-2 responses after a 12-day coculture. We characterized these responses by polyfunctional intracellular cytokine staining and evaluation of T cell memory phenotypes. Central memory CD8+T cells were induced ex vivo after DC coculture from each of 3 patients, and the effector memory pool was increased by DC coculture from 2 patients. We also observed a decrease in the terminal effector and intermediate CD8+ T cell pool and an increase in the naive/other population. There was a reduction in terminal effector and intermediate CD4+ T cells, and a corresponding increase in naive/other CD4+ T cells. Finally, we evaluated conserved regions of Gag as a novel DC therapy immunogen and found that a conserved element (CE) p24 Gag antigen elicited IFN-gamma and IL-2 responses comparable to those induced by a full-length Gag antigen. Conclusions: We showed that RNA-loaded DC therapy induced a polyfunctional T cell response ex vivo, supporting the use of such DC-therapy for HIV infection. However, the central and effector memory phenotypes of T cells did not appear to be enhanced during coculture with Gag RNA-loaded DC. Furthermore, comparable antigen-specific responses were induced in HIV infected individuals using full-length Gag or only conserved elements of the Gag p24 protein. This indicates that immune responses can be focused onto the conserved elements of Gag in the absence of other Gag components. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Niu, Liguo; Termini, James M.; Kanagavelu, Saravana K.; Gupta, Sachin; Stone, Geoffrey W.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Fischl, Margaret A.] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Rolland, Morgane M.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Rolland, Morgane M.; Mullins, James I.] Univ Washington, Dept Med, Seattle, WA USA. [Kulkarni, Viraj; Pavlakis, George N.; Felber, Barbara K.] NCI, Frederick, MD 21701 USA. RP Stone, GW (reprint author), Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, 1580 NW 10th Ave, Miami, FL 33136 USA. EM gstone@med.miami.edu FU University of Miami Developmental Center for AIDS Research [1P30AI073961]; University of Miami FX This work was supported by the University of Miami Developmental Center for AIDS Research (1P30AI073961) and startup funds provided by the University of Miami. We wish to acknowledge the assistance of Daniel Kavanagh and Eli Gilboa for study design and training and Juan Casuso for patient recruitment. We also wish to acknowledge the NIH AIDS Research and Reference Reagent Program for Gag and Nef peptide pools. NR 33 TC 17 Z9 17 U1 0 U2 5 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 MAR 3 PY 2011 VL 29 IS 11 BP 2110 EP 2119 DI 10.1016/j.vaccine.2010.12.131 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 739PU UT WOS:000288731000019 PM 21241732 ER PT J AU Melillo, G AF Melillo, Giovanni TI Hypoxia: jump-starting inflammation SO BLOOD LA English DT Editorial Material ID ACTIVATION C1 Saic Frederick Inc Nci Frederick, Frederick, MD 21702 USA. RP Melillo, G (reprint author), Saic Frederick Inc Nci Frederick, Frederick, MD 21702 USA. NR 11 TC 8 Z9 9 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 MAR 3 PY 2011 VL 117 IS 9 BP 2561 EP 2562 DI 10.1182/blood-2010-12-324913 PG 3 WC Hematology SC Hematology GA 732RR UT WOS:000288207400004 PM 21372159 ER PT J AU Sloand, EM Melenhorst, JJ Tucker, ZCG Pfannes, L Brenchley, JM Yong, A Visconte, V Wu, C Gostick, E Scheinberg, P Olnes, MJ Douek, DC Price, DA Barrett, AJ Young, NS AF Sloand, Elaine M. Melenhorst, J. Joseph Tucker, Zachary C. G. Pfannes, Loretta Brenchley, Jason M. Yong, Agnes Visconte, Valeria Wu, Colin Gostick, Emma Scheinberg, Phillip Olnes, Matthew J. Douek, Daniel C. Price, David A. Barrett, A. John Young, Neal S. TI T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; GENE WT1 PRODUCT; APLASTIC-ANEMIA; NECROSIS-FACTOR; INTERFERON-GAMMA; PROGENITOR CELLS; CD34(+) CELLS; SYNDROME MDS; BONE-MARROW AB Clinical observations and laboratory evidence link bone marrow failure in myelodysplastic syndrome (MDS) to a T cell-mediated immune process that is responsive to immunosuppressive treatment (IST) in some patients. Previously, we showed that trisomy 8 MDS patients had clonally expanded CD8(+) T-cell populations that recognized aneuploid hematopoietic progenitor cells (HPC). Furthermore, microarray analyses showed that Wilms tumor 1 (WT1) gene was overexpressed by trisomy 8 hematopoietic progenitor (CD34(+)) cells compared with CD34(+) cells from healthy donors. Here, we show that WT1 mRNA expression is up-regulated in the bone marrow mononuclear cells of MDS patients with trisomy 8 relative to healthy controls and nontrisomy 8 MDS; WT1 protein levels were also significantly elevated. In addition, using a combination of physical and functional assays to detect the presence and reactivity of specific T cells, respectively, we demonstrate that IST-responsive MDS patients exhibit significant CD4(+) and CD8(+) T-cell responses directed against WT1. Finally, WT1-specific CD8(+) T cells were present within expanded T-cell receptor V beta subfamilies and inhibited hematopoiesis when added to autologous patient bone marrow cells in culture. Thus, our results suggest that WT1 is one of the antigens that triggers T cell-mediated myelosuppression in MDS. (Blood. 2011; 117(9): 2691-2699) C1 [Sloand, Elaine M.; Melenhorst, J. Joseph; Tucker, Zachary C. G.; Pfannes, Loretta; Yong, Agnes; Visconte, Valeria; Scheinberg, Phillip; Olnes, Matthew J.; Barrett, A. John; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Wu, Colin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Gostick, Emma] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales. [Douek, Daniel C.; Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Melenhorst, JJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM melenhoj@nhlbi.nih.gov RI Scheinberg, Phillip/H-5251-2012; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Scheinberg, Phillip/0000-0002-9047-4538 FU Medical Research Council [G0501963] NR 56 TC 42 Z9 44 U1 1 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 MAR 3 PY 2011 VL 117 IS 9 BP 2691 EP 2699 DI 10.1182/blood-2010-04-277921 PG 9 WC Hematology SC Hematology GA 732RR UT WOS:000288207400021 PM 21097671 ER PT J AU Felker, GM Lee, KL Bull, DA Redfield, MM Stevenson, LW Goldsmith, SR LeWinter, MM Deswal, A Rouleau, JL Ofili, EO Anstrom, KJ Hernandez, AF McNulty, SE Velazquez, EJ Kfoury, AG Chen, HH Givertz, MM Semigran, MJ Bart, BA Mascette, AM Braunwald, E O'Connor, CM AF Felker, G. Michael Lee, Kerry L. Bull, David A. Redfield, Margaret M. Stevenson, Lynne W. Goldsmith, Steven R. LeWinter, Martin M. Deswal, Anita Rouleau, Jean L. Ofili, Elizabeth O. Anstrom, Kevin J. Hernandez, Adrian F. McNulty, Steven E. Velazquez, Eric J. Kfoury, Abdallah G. Chen, Horng H. Givertz, Michael M. Semigran, Marc J. Bart, Bradley A. Mascette, Alice M. Braunwald, Eugene O'Connor, Christopher M. CA NHLBI Heart Failure Clinical Res N TI Diuretic Strategies in Patients with Acute Decompensated Heart Failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTINUOUS-INFUSION; LOOP DIURETICS; INTRAVENOUS DIURETICS; RENAL-FUNCTION; ESCAPE TRIAL; FUROSEMIDE; OUTCOMES; DIURESIS; REGISTRY; DYSPNEA AB BACKGROUND Loop diuretics are an essential component of therapy for patients with acute decompensated heart failure, but there are few prospective data to guide their use. METHODS In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and at either a low dose (equivalent to the patient's previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients' global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours, and the change in the serum creatinine level from baseline to 72 hours. RESULTS In the comparison of bolus with continuous infusion, there was no significant difference in patients' global assessment of symptoms (mean AUC, 4236 +/- 1440 and 4373 +/- 1404, respectively; P = 0.47) or in the mean change in the creatinine level (0.05 +/- 0.3 mg per deciliter [4.4 +/- 26.5 mu mol per liter] and 0.07 +/- 0.3 mg per deciliter [6.2 +/- 26.5 mu mol per liter], respectively; P = 0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients' global assessment of symptoms in the high-dose group (mean AUC, 4430 +/- 1401 vs. 4171 +/- 1436; P = 0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08 +/- 0.3 mg per deciliter [7.1 +/- 26.5 mu mol per liter] with the high-dose strategy and 0.04 +/- 0.3 mg per deciliter [3.5 +/- 26.5 mu mol per liter] with the low-dose strategy, P = 0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function. CONCLUSIONS Among patients with acute decompensated heart failure, there were no significant differences in patients' global assessment of symptoms or in the change in renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at a high dose as compared with a low dose. C1 [Felker, G. Michael; Lee, Kerry L.; Anstrom, Kevin J.; Hernandez, Adrian F.; McNulty, Steven E.; Velazquez, Eric J.] Duke Clin Res Inst, Durham, NC 27705 USA. [Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Bull, David A.; Kfoury, Abdallah G.] Univ Utah, Salt Lake City, UT USA. [Redfield, Margaret M.; Chen, Horng H.] Mayo Clin, Rochester, MN USA. [Stevenson, Lynne W.; Givertz, Michael M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldsmith, Steven R.; Bart, Bradley A.] Univ Minnesota, Minneapolis, MN USA. [LeWinter, Martin M.] Univ Vermont, Burlington, VT 05405 USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Deswal, Anita] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Rouleau, Jean L.] Univ Montreal, Montreal, PQ, Canada. [Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Ofili, Elizabeth O.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Mascette, Alice M.] NHLBI, Bethesda, MD 20892 USA. RP Felker, GM (reprint author), Duke Clin Res Inst, 2400 Pratt St,Rm 0311 Terrace Level, Durham, NC 27705 USA. EM michael.felker@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU National Heart, Lung, and Blood Institute [HL084861, HL084875, HL084877, HL084889, HL084890, HL084891, HL084899, HL084904, HL084907, HL084931]; Amgen; Cytokinetics; Corthera; Otsuka; Novartis; Roche Diagnostics; Medtronic; Johnson Johnson; Pfizer; Boehringer Ingelheim; XDx; Scios; Anexon; Nile Therapeutics; GE Healthcare; Forest Pharmaceuticals; Novella Clinical; Medpace; Roche; Actelion Pharmaceuticals; Trevena; Martek Biosciences FX The Heart Failure Clinical Research Network is supported by grants (HL084861, HL084875, HL084877, HL084889, HL084890, HL084891, HL084899, HL084904, HL084907, and HL084931) from the National Heart, Lung, and Blood Institute.; Dr. Felker reports receiving consulting fees from Amgen, Cytokinetics, Corthera, Otsuka, Novartis, and Roche Diagnostics and grant support from Amgen, Cytokinetics, Otsuka, and Roche Diagnostics; Dr. LeWinter, receiving consulting fees from Novartis, grant support from Medtronic, and lecture fees from Medtronic and Novartis; Dr. Anstrom, receiving consulting fees from Johnson & Johnson and Pfizer; Dr. Hernandez, receiving consulting fees from Amgen and grant support from Johnson & Johnson and serving on a clinical end points committee for Corthera; Dr. Velazquez, receiving consulting fees from Novartis and Boehringer Ingelheim, grant support from Johnson & Johnson, and lecture fees from Novartis; Dr. Kfoury, receiving grant support from Novartis and XDx; Dr. Chen, receiving grant support from Scios, Anexon, and Nile Therapeutics, being named as a coinventor on patents for chimeric natriuretic peptides, and receiving royalties from Nile Therapeutics; and Dr. O'Connor, receiving consulting fees from Merck, GE Healthcare, Forest Pharmaceuticals, Medtronic, Novella Clinical, Medpace, Roche, Actelion Pharmaceuticals, Amgen, Trevena, and Martek Biosciences and grant support from Johnson & Johnson. No other potential conflict of interest relevant to this article was reported. NR 26 TC 418 Z9 438 U1 2 U2 27 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 MAR 3 PY 2011 VL 364 IS 9 BP 797 EP 805 DI 10.1056/NEJMoa1005419 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 729DJ UT WOS:000287928400005 PM 21366472 ER PT J AU Gerstein, HC Miller, ME Genuth, S Ismail-Beigi, F Buse, JB Goff, DC Probstfield, JL Cushman, WC Ginsberg, HN Bigger, JT Grimm, RH Byington, RP Rosenberg, YD Friedewald, WT AF Gerstein, Hertzel C. Miller, Michael E. Genuth, Saul Ismail-Beigi, Faramarz Buse, John B. Goff, David C., Jr. Probstfield, Jeffrey L. Cushman, William C. Ginsberg, Henry N. Bigger, J. Thomas Grimm, Richard H., Jr. Byington, Robert P. Rosenberg, Yves D. Friedewald, William T. CA ACCORD Study Grp TI Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GLYCEMIA TREATMENT STRATEGIES; TYPE-2 DIABETES-MELLITUS; ACCORD TRIAL; FOLLOW-UP; RISK; MORTALITY; COHORT; WOMEN AB BACKGROUND Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. METHODS We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. RESULTS Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P = 0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. CONCLUSIONS As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. C1 [Gerstein, Hertzel C.] McMaster Univ, Dept Med, Hamilton, ON L8N 3Z5, Canada. [Gerstein, Hertzel C.] Hamilton Hlth Sci, Hamilton, ON, Canada. [Miller, Michael E.; Goff, David C., Jr.; Byington, Robert P.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Genuth, Saul; Ismail-Beigi, Faramarz] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Buse, John B.] Univ N Carolina, Chapel Hill, NC USA. [Probstfield, Jeffrey L.] Univ Washington, Seattle, WA 98195 USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Ginsberg, Henry N.; Bigger, J. Thomas; Friedewald, William T.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Grimm, Richard H., Jr.] Univ Minnesota, Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. [Rosenberg, Yves D.] NHLBI, Bethesda, MD 20892 USA. RP Gerstein, HC (reprint author), McMaster Univ, Dept Med, HSC 3V38,1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM gerstein@mcmaster.ca RI Friedewald, William/C-8034-2011; Gerstein, Hertzel/B-1235-2013 OI Gerstein, Hertzel/0000-0001-8072-2836 FU National Heart, Lung, and Blood Institute [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, Y1-HC-9035, Y1-HC-1010]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Aging; National Eye Institute; General Clinical Research Centers; Centers for Disease Control and Prevention; Massachusetts Institute of Technology; Novo Nordisk; Amylin; Becton Dickinson; Eli Lilly; Hoffmann-La Roche (now Genentech); Glyco-Mark; Wyeth; Daiichi Sankyo; Bristol-Myers Squibb; Bayhill Therapeutics; LipoScience; MannKind; Veritas; MicroIslet; GlaxoSmithKline; Abbott; Exsulin; Medtronic; Tolerex; Osiris; Halozyme; Hoffmann-La Roche; InterKrin; Merck; Dexcom; Sanofi-Aventis; Johnson Johnson; Fujisawa; American Academy of Family Practice Foundation; Takeda; King; Daiichi-Sankyo; Gilead; Theravance; Pharmacopeia; Sciele; Solvay; Regeneron/Sanofi-Aventis; Roche; Isis/Genzyme; Novartis; Pfizer FX Supported by the National Heart, Lung, and Blood Institute (contracts N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA#Y1-HC-9035, and IAA#Y1-HC-1010), and partially supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute and by General Clinical Research Centers at many sites; substudies within the ACCORD trial on cost-effectiveness and health-related quality of life were supported by the Centers for Disease Control and Prevention. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi-Aventis, and Schering-Plough.; Dr. Bigger reports receiving consulting fees and travel support from Merck and Roche and patent fees and royalties from the Massachusetts Institute of Technology for risk-stratification software; Dr. Buse, receiving consulting fees from Novo Nordisk, Amylin, Becton Dickinson, Eli Lilly, Hoffmann-La Roche (now Genentech), Glyco-Mark, Wyeth, Daiichi Sankyo, Bristol-Myers Squibb, Bayhill Therapeutics, LipoScience, MannKind, Veritas, MicroIslet, GlaxoSmithKline, Abbott, Exsulin, and GI Dynamics and grant support from Amylin, Novo Nordisk, Medtronic, Eli Lilly, Novartis, Tolerex, Osiris, Halozyme, Pfizer, Hoffmann-La Roche, InterKrin, Merck, Sanofi-Aventis, Dexcom, Johnson & Johnson, Bristol-Myers Squibb, Fujisawa, and the American Academy of Family Practice Foundation, holding stock in Insulet, and providing expert testimony for Novo Nordisk; Dr. Cushman, receiving consulting fees from Novartis, Takeda, Sanofi-Aventis, Bristol-Myers Squibb, King, Daiichi-Sankyo, Gilead, Theravance, Pharmacopeia, and Sciele and institutional grant support to the Memphis Veterans Affairs Medical Center from Novartis, GlaxoSmithKline, and Merck; Dr. Genuth, receiving consulting fees from Merck and Daiichi Sankyo and holding stock in Novartis and Johnson & Johnson; Dr. Gerstein, receiving consulting fees from Sanofi-Aventis, GlaxoSmithKline, Eli Lilly, Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, Roche, Medtronic, Merck, Bayer, Bioavail, and Janssen-Ortho, institutional grant support to McMaster University from Sanofi-Aventis, GlaxoSmithKline, Novo Nordisk, Merck, Pronova, Roche, Eli Lilly, and Boehringer Ingelheim, and lecture fees from Sanofi-Aventis, GlaxoSmithKline, Solvay, Boehringer Ingelheim, Servier, Bayer, Eli Lilly, Novo Nordisk, and Takeda; Dr. Ginsberg, being a member of the board of Merck and Schering-Plough and the global advisory board of Bristol-Myers Squibb/AstraZeneca and receiving consulting fees from GlaxoSmithKline, Merck, Bristol-Myers Squibb, AstraZeneca, Regeneron/Sanofi-Aventis, Abbott, Roche, Isis/Genzyme, Novartis, and Pfizer, institutional grant support to the Columbia University College of Physicians and Surgeons from Merck, Roche, Isis/Genzyme, and AstraZeneca, and payment from Pfizer for development of an educational presentation; Dr. Goff, being a member of the data and safety monitoring board for Takeda and receiving institutional grant support to the Wake Forest University School of Medicine from Merck; Dr. Grimm, being a member of the board of Pfizer, receiving consulting fees from Pfizer, Merck, and Novartis, personal and institutional grants to the University of Minnesota from Pfizer, Merck, and Novartis, lecture fees from Pfizer, Merck, Novartis, Forest, Schering-Plough, and Takeda, and travel support from Takeda and Roche, and attending the AstraZeneca symposium at the Cleveland Clinic and investigator meetings for Merck, Novartis, and Pfizer; Dr. Ismail-Beigi, receiving consulting fees from Eli Lilly; Dr. Miller, receiving consulting fees from Roche; and Dr. Probstfield, receiving institutional grant support to the University of Washington School of Medicine from SanofiAventis, Boehringer Ingelheim, and Abbott. No other potential conflict of interest relevant to this article was reported. NR 15 TC 405 Z9 413 U1 3 U2 34 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 MAR 3 PY 2011 VL 364 IS 9 BP 818 EP 828 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 729DJ UT WOS:000287928400007 ER PT J AU Zarin, DA Tse, T Williams, RJ Califf, RM Ide, NC AF Zarin, Deborah A. Tse, Tony Williams, Rebecca J. Califf, Robert M. Ide, Nicholas C. TI The ClinicalTrials.gov Results Database - Update and Key Issues SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIALS; CLINICAL-RESEARCH; GLOBALIZATION; BIAS AB BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data. C1 [Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.; Ide, Nicholas C.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA. [Califf, Robert M.] Duke Univ, Duke Translat Med Inst, Durham, NC USA. RP Zarin, DA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM dzarin@mail.nih.gov FU Intramural NIH HHS [ZIA LM008926-03, Z99 LM999999] NR 29 TC 203 Z9 206 U1 1 U2 20 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 MAR 3 PY 2011 VL 364 IS 9 BP 852 EP 860 DI 10.1056/NEJMsa1012065 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 729DJ UT WOS:000287928400010 PM 21366476 ER PT J AU Kemp, TJ Hildesheim, A Safaeian, M Dauner, JG Pan, YJ Porras, C Schiller, JT Lowy, DR Herrero, R Pinto, LA AF Kemp, Troy J. Hildesheim, Allan Safaeian, Mahboobeh Dauner, Joseph G. Pan, Yuanji Porras, Carolina Schiller, John T. Lowy, Douglas R. Herrero, Rolando Pinto, Ligia A. TI HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection SO VACCINE LA English DT Article DE Human papillomavirus; Antibody; Vaccine ID VIRUS-LIKE PARTICLES; YOUNG-WOMEN; INFECTION; TRIAL; EFFICACY; IMMUNIZATION; RESPONSES; TYPE-18; HPV-18 AB Human papillomavirus (HPV) L1 VLP-based vaccines are protective against HPV vaccine-related types; however, the correlates of protection have not been defined. We observed that vaccination with Cervarix (TM) induced cross-neutralizing antibodies for HPV types for which evidence of vaccine efficacy has been demonstrated (HPV31/45) but not for other types (HPV52/58). In addition, HPV31/45 cross-neutralizing titers showed a significant increase with number of doses (HPV31, p < 0.001; HPV45, p < 0.001) and correlated with HPV16/18 neutralizing titers, respectively. These findings raise the possibility that cross-neutralizing antibodies are effectors of cross-protection observed for the HPV16/18 vaccine.(C) 2011 Elsevier Ltd. All rights reserved. C1 [Kemp, Troy J.; Dauner, Joseph G.; Pan, Yuanji; Pinto, Ligia A.] NCI Frederick, HPV Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Hildesheim, Allan; Safaeian, Mahboobeh] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Porras, Carolina; Herrero, Rolando] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Schiller, John T.; Lowy, Douglas R.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pinto, LA (reprint author), NCI Frederick, HPV Immunol Lab, SAIC Frederick Inc, Bldg 469,Room 205, Frederick, MD 21702 USA. EM pintol@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NCI; Ministry of Health of Costa Rica; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health Office for Research on Women's Health (ORWH) FX The Costa Rica HPV Vaccine Trial is a long-standing collaboration between investigators in Costa Rica and the NCI. The trial is sponsored by the NCI, and conducted with support from the Ministry of Health of Costa Rica. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Other funding sources for this project were from the NCI Intramural Research Program and the National Institutes of Health Office for Research on Women's Health (ORWH). Vaccine was provided for our trial by GlaxoSmithKline Biologicals (GSK Bio, Rixensart, Belgium), under a Clinical Trials Agreement with the NCI. GSK Bio also provided support for aspects of the trial associated with regulatory submission needs of the company under grant FDA BB-IND 7920. Laboratory testing was performed at the NCI-sponsored SAIC-Frederick, Inc. HPV Immunology Laboratory in Frederick, MD. The NCI and Costa Rica investigators are responsible for the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation of the manuscript. The NCI and Costa Rica investigators make final editorial decisions on this and subsequent publications; GSK Bio has the right to review and comment. NR 13 TC 78 Z9 80 U1 0 U2 0 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 MAR 3 PY 2011 VL 29 IS 11 BP 2011 EP 2014 DI 10.1016/j.vaccine.2011.01.001 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 739PU UT WOS:000288731000004 PM 21241731 ER PT J AU Liu, JH Chung, HJ Vogt, M Jin, YT Malide, D He, LS Dundr, M Levens, D AF Liu, Juhong Chung, Hye-Jung Vogt, Matthew Jin, Yetao Malide, Daniela He, Liusheng Dundr, Miroslav Levens, David TI JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress SO EMBO JOURNAL LA English DT Article DE apoptosis; FBP; JTV1; p53; USP29 ID TRANSFER-RNA SYNTHETASE; ELEMENT-BINDING PROTEIN-1; LEUKEMIA NUCLEAR-BODIES; DEUBIQUITINATING ENZYMES; PARKINSONS-DISEASE; MYC EXPRESSION; UBIQUITINATION; DYNAMICS; PATHWAY; COMPLEX AB c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress. The EMBO Journal (2011) 30, 846-858. doi: 10.1038/emboj.2011.11; Published online 1 February 2011 C1 [Liu, Juhong; Jin, Yetao] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Liu, Juhong; Chung, Hye-Jung; Vogt, Matthew; He, Liusheng; Levens, David] NCI, Gene Regulat Sect, Pathol Lab, Bethesda, MD 20892 USA. [Malide, Daniela] NHLBI, Light Microscopy Core Facil, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [He, Liusheng] St Jude Childrens Hosp, Dept Tumor Cell Biol, Flow Cytometry Shared Facil, Memphis, TN 38105 USA. [Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Dept Cell Biol & Anat, N Chicago, IL USA. RP Liu, JH (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 1C11, Bethesda, MD 20892 USA. EM juhong.liu@fda.hhs.gov; levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU NCI; NIH, NCI, CCR FX We thank Dr Barbara Taylor of NCI Flow Core Facility for cell sorting. We thank Dr Xin W Wang for providing p53 and Hdm2 expression vectors. We thank Dr Lixin Zhang for help with FACS analysis. We thank Dr Ashutosh Rao of the Food and Drug Administration for help with confocal microscopy. HCT-116 p53+/+ and p53-/- cells were kind gifts from Dr Bert Vogelstein. We thank Drs Mark Cookson, John Brady and Dinah Singer for their helpful suggestions for the experiments and comments on this manuscript. We thank one of the reviewers for suggesting that the JTV1-mediated p53 stabilization may be oxidative stress specific. This work was supported in part by 2006 NCI Director's Intramural Innovation Award to Juhong Liu. This work was supported by Research Program of the NIH, NCI, CCR. NR 43 TC 48 Z9 49 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 2 PY 2011 VL 30 IS 5 BP 846 EP 858 DI 10.1038/emboj.2011.11 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746IP UT WOS:000289239000006 PM 21285945 ER PT J AU Srinivasan, M Mehta, P Yu, Y Prugar, E Koonin, EV Karzai, AW Sternglanz, R AF Srinivasan, Madhusudhan Mehta, Preeti Yu, Yao Prugar, Evelyn Koonin, Eugene V. Karzai, A. Wali Sternglanz, Rolf TI The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A SO EMBO JOURNAL LA English DT Article DE Kae1; KEOPS-EKC complex; Sua5; t6A; tRNA ID SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; TELOMERE REPLICATION; IN-VITRO; GENE; ANTICODON; DNA; N-(PURIN-6-YLCARBAMOYL)THREONINE; GLUTAREDOXIN; PID261/BUD32 AB The highly conserved Kinase, Endopeptidase and Other Proteins of small Size (KEOPS)/Endopeptidase-like and Kinase associated to transcribed Chromatin (EKC) protein complex has been implicated in transcription, telomere maintenance and chromosome segregation, but its exact function remains unknown. The complex consists of five proteins, Kinase-Associated Endopeptidase (Kae1), a highly conserved protein present in bacteria, archaea and eukaryotes, a kinase (Bud32) and three additional small polypeptides. We showed that the complex is required for a universal tRNA modification, threonyl carbamoyl adenosine (t6A), found in all tRNAs that pair with ANN codons in mRNA. We also showed that the bacterial ortholog of Kae1, YgjD, is required for t6A modification of Escherichia coli tRNAs. The ATPase activity of Kae1 and the kinase activity of Bud32 are required for the modification. The yeast protein Sua5 has been reported previously to be required for t6A synthesis. Using yeast extracts, we established an in vitro system for the synthesis of t6A that requires Sua5, Kae1, threonine, bicarbonate and ATP. It remains to be determined whether all reported defects of KEOPS/EKC mutants can be attributed to the lack of t6A, or whether the complex has multiple functions. The EMBO Journal (2011) 30, 873-881. doi: 10.1038/emboj.2010.343; Published online 24 December 2010 C1 [Srinivasan, Madhusudhan; Mehta, Preeti; Yu, Yao; Prugar, Evelyn; Karzai, A. Wali; Sternglanz, Rolf] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Sternglanz, R (reprint author), SUNY Stony Brook, Dept Biochem & Cell Biol, Life Sci Bldg, Stony Brook, NY 11794 USA. EM rolf@life.bio.sunysb.edu FU NIH [NCRR 1 S10 RR023680-1, R01 GM065319, R01 GM055641, P01 GM088297] FX We thank V de Crecy-Lagard and E Phizicky for valuable information, M Hampsey, P Hieter, D Libri, V Lundblad and T Palmer for reagents, R Haltiwanger for advice, and R Rieger and T Koller of the Stony Brook University Proteomics Center for the mass spectroscopy. The Proteomics Center is supported by an NIH shared instrumentation grant, NCRR 1 S10 RR023680-1. The research was supported NIH grants R01 GM065319 to AWK and R01 GM055641 and P01 GM088297 to RS. NR 33 TC 59 Z9 67 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 2 PY 2011 VL 30 IS 5 BP 873 EP 881 DI 10.1038/emboj.2010.343 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746IP UT WOS:000289239000008 PM 21183954 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI The Unique Alzheimer's beta-Amyloid Triangular Fibril Has a Cavity along the Fibril Axis under Physiological Conditions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID PARTICLE MESH EWALD; MOLECULAR-DYNAMICS; POTENTIAL FUNCTIONS; LIQUID WATER; PROTEIN; DISEASE; POLYMORPHISM; CONSTRAINTS; OLIGOMERS; PEPTIDES AB Elucidating the structure of A beta(1-40) fibrils is of interest in Alzheimer's disease research because it is required for designing therapeutics that target A beta(1-40) fibril formation at an early stage of the disease. M35 is a crucial residue because of its potential oxidation and its strong interactions across beta-strands and across beta-sheets in A beta fibrils. Experimentally, data for the three-fold symmetry structure of the A beta(9-40) fibril suggest formation of tight hydrophobic core through M35 interactions across the fibril axis and strong I31-V39 interactions between different cross-beta units. Herein, on the basis of experimental data, we probe conformers with three-fold symmetry of the full-length A beta(1-40). Our all-atom molecular dynamics simulations in explicit solvent of conformers based on the ssNMR data reproduced experimental observations of M35-M35 and I31-V39 distances. Our interpretation of the experimental data suggests that the observed similar to 5-7 angstrom M35-M35 distance in the fibril three-fold symmetry structure is likely to relate to M35 interactions along the fibril axis, rather than across the fibril axis, since our measured M35-M35 distances across the fibril axis are consistently above 15 angstrom. Consequently, we revealed that the unique A beta(1-40) triangular structure has a large cavity along the fibril axis and that the N-termini can assist in the stabilization of the fibril by interacting with the U-turn domains or with the C-termini domains. Our findings, together with the recent cyroEM characterization of the hollow core in A beta(1-42) fibrils, point to the relevance of a cavity in A beta(1-40/1-42) oligorners which should be considered when targeting oligomer toxicity. C1 [Ma, Buyong; 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, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank Rob Tycko for providing the atomic coordinates of the model obtained in his laboratory. 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). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 29 TC 36 Z9 36 U1 3 U2 22 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 MAR 2 PY 2011 VL 133 IS 8 BP 2742 EP 2748 DI 10.1021/ja1100273 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 733VJ UT WOS:000288291300060 PM 21299220 ER PT J AU Song, WJ Seshadri, M Ashraf, U Mdluli, T Monda, P Keil, M Azevedo, M Kirschner, LS Stratakis, CA Hussain, MA AF Song, Woo-Jin Seshadri, Madhav Ashraf, Uzair Mdluli, Thembi Monda, Prosenjit Keil, Meg Azevedo, Monalisa Kirschner, Lawrence S. Stratakis, Constantine A. Hussain, Mehboob A. TI Snapin Mediates Incretin Action and Augments Glucose-Dependent Insulin Secretion SO CELL METABOLISM LA English DT Article ID PROTEIN-KINASE-A; BETA-CELL PROLIFERATION; CARNEY COMPLEX; DIABETES-MELLITUS; BINDING-PROTEIN; SNARE COMPLEX; PHOSPHORYLATION; EXOCYTOSIS; DYSFUNCTION; INDIVIDUALS AB Impaired insulin secretion contributes to the pathogenesis of type 2 diabetes mellitus (T2DM). Treatment with the incretin hormone glucagon-like peptide-1 (GLP-1) potentiates insulin secretion and improves metabolic control in humans with T2DM. GLP-1 receptor-mediated signaling leading to insulin secretion occurs via cyclic AMP stimulated protein kinase A (PKA)- as well as guanine nucleotide exchange factor-mediated pathways. However, how these two pathways integrate and coordinate insulin secretion remains poorly understood. Here we show that these incretin-stimulated pathways converge at the level of snapin, and that PKA-dependent phosphorylation of snapin increases interaction among insulin secretory vesicle-associated proteins, thereby potentiating glucose-stimulated insulin secretion (GSIS). In diabetic islets with impaired GSIS, snapin phosphorylation is reduced, and expression of a snapin mutant, which mimics site-specific phosphorylation, restores GSIS. Thus, snapin is a critical node in GSIS regulation and provides a potential therapeutic target to improve beta cell function in T2DM. C1 [Song, Woo-Jin; Seshadri, Madhav; Ashraf, Uzair; Mdluli, Thembi; Monda, Prosenjit; Hussain, Mehboob A.] Johns Hopkins Univ, Div Metab, Dept Pediat, Baltimore, MD 21287 USA. [Song, Woo-Jin; Seshadri, Madhav; Ashraf, Uzair; Mdluli, Thembi; Monda, Prosenjit; Hussain, Mehboob A.] Johns Hopkins Univ, Div Metab, Dept Pediat, Baltimore, MD 21287 USA. [Song, Woo-Jin; Seshadri, Madhav; Ashraf, Uzair; Mdluli, Thembi; Monda, Prosenjit; Hussain, Mehboob A.] Johns Hopkins Univ, Div Metab, Dept Biol Chem, Baltimore, MD 21287 USA. [Keil, Meg; Azevedo, Monalisa; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol Genet, NIH, Bethesda, MD 20892 USA. [Kirschner, Lawrence S.] Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. RP Hussain, MA (reprint author), Johns Hopkins Univ, Div Metab, Dept Pediat, Baltimore, MD 21287 USA. EM mhussai4@jhmi.edu RI song, woojin/G-3357-2013 FU NCI NIH HHS [R01 CA112268-05, R01 CA112268]; NIDDK NIH HHS [R24 DK084949, P30 DK079637, R01 DK081472-03, R01 DK081472-01A1, R24 DK084949-01, P60 DK079637, R01 DK081472, R01 DK081472-02, P60 DK079637-05, RC4 DK090816] NR 43 TC 53 Z9 54 U1 0 U2 9 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 MAR 2 PY 2011 VL 13 IS 3 BP 308 EP 319 DI 10.1016/j.cmet.2011.02.002 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 731ZQ UT WOS:000288150200011 PM 21356520 ER PT J AU Fornito, A Zalesky, A Bassett, DS Meunier, D Ellison-Wright, I Yucel, M Wood, SJ Shaw, K O'Connor, J Nertney, D Mowry, BJ Pantelis, C Bullmore, ET AF Fornito, Alex Zalesky, Andrew Bassett, Danielle S. Meunier, David Ellison-Wright, Ian Yuecel, Murat Wood, Stephen J. Shaw, Karen O'Connor, Jennifer Nertney, Deborah Mowry, Bryan J. Pantelis, Christos Bullmore, Edward T. TI Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GRAPH-THEORETICAL ANALYSIS; SURFACE-BASED ANALYSIS; SMALL-WORLD NETWORKS; HUMAN BRAIN; INTELLECTUAL-PERFORMANCE; WIRING OPTIMIZATION; GLOBAL OPTIMIZATION; COMPLEX NETWORKS; CEREBRAL-CORTEX; DEFAULT MODE AB The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization. C1 [Fornito, Alex; Bassett, Danielle S.; Meunier, David; Ellison-Wright, Ian; Bullmore, Edward T.] Univ Cambridge, Brain Mapping Unit, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Bullmore, Edward T.] Addenbrookes Hosp, GSK Clin Unit Cambridge, Cambridge CB2 0QQ, England. [Mowry, Bryan J.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia. [Nertney, Deborah; Mowry, Bryan J.] Univ Queensland, Queensland Ctr Mental Hlth Res, Wacol, Qld 4076, Australia. [Fornito, Alex; Zalesky, Andrew; Yuecel, Murat; Wood, Stephen J.; Shaw, Karen; O'Connor, Jennifer; Pantelis, Christos] Univ Melbourne & Melbourne Hlth, Dept Psychiat, Melbourne Neuropsychiat Ctr, Carlton, Vic 3053, Australia. [Bassett, Danielle S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Ellison-Wright, Ian] Avon & Wiltshire Mental Hlth Partnership NHS Trus, Salisbury SP2 7EP, Wilts, England. [Wood, Stephen J.] Univ Birmingham, Sch Psychol, Edgbaston B15 2TT, England. RP Fornito, A (reprint author), Univ Melbourne & Melbourne Hlth, Dept Psychiat, Melbourne Neuropsychiat Ctr, Levels 2 & 3,161 Barry St, Carlton, Vic 3053, Australia. EM fornitoa@unimelb.edu.au RI Meunier, David/F-2466-2011; Wood, Stephen/M-8652-2014; Pantelis, Christos/H-7722-2014; Bullmore, Edward/C-1706-2012; Alex, Fornito/N-8214-2013; OI Wood, Stephen/0000-0003-4186-5919; Pantelis, Christos/0000-0002-9565-0238; Bullmore, Edward/0000-0002-8955-8283; Alex, Fornito/0000-0001-9134-480X; ZALESKY, ANDREW/0000-0003-2298-9908; Yucel, Murat/0000-0002-4705-452X FU National Health and Medical Research Council (NHMRC) [454797]; Ian Potter Foundation; Australian Research Council [0986320]; National Institutes of Health/Cambridge Graduate Training program FX This work was supported by a National Health and Medical Research Council (NHMRC) Project Grant and the Ian Potter Foundation. A.F. was supported by an NHMRC CJ Martin Fellowship (ID: 454797). A.Z. is supported by the Australian Research Council, Discovery Project 0986320. M.Y. and S.J.W. were supported by an NHMRC Clinical Career Development Award. D.S.B. was supported by the National Institutes of Health/Cambridge Graduate Training program. We thank Drs. Sophie Achard and Sarah Medland for helpful advice. NR 73 TC 126 Z9 130 U1 5 U2 16 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 MAR 2 PY 2011 VL 31 IS 9 BP 3261 EP 3270 DI 10.1523/JNEUROSCI.4858-10.2011 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 730SS UT WOS:000288055200015 PM 21368038 ER PT J AU Romberg, C Mattson, MP Mughal, MR Bussey, TJ Saksida, LM AF Romberg, Carola Mattson, Mark P. Mughal, Mohamed R. Bussey, Timothy J. Saksida, Lisa M. TI Impaired Attention in the 3xTgAD Mouse Model of Alzheimer's Disease: Rescue by Donepezil (Aricept) SO JOURNAL OF NEUROSCIENCE LA English DT Article ID REACTION-TIME-TASK; VISUAL SELECTIVE ATTENTION; MILD COGNITIVE IMPAIRMENT; TRIPLE-TRANSGENIC MODEL; SHORT-TERM-MEMORY; FRONTOTEMPORAL DEMENTIA; VASCULAR DEMENTIA; BASAL FOREBRAIN; CHOLINERGIC MODULATION; PERSEVERATIVE BEHAVIOR AB Several mouse models of Alzheimer's disease (AD) with abundant beta-amyloid and/or aberrantly phosphorylated tau develop memory impairments. However, multiple non-mnemonic cognitive domains such as attention and executive control are also compromised early in AD individuals. Currently, it is unclear whether mutations in the beta-amyloid precursor protein (APP) and tau are sufficient to cause similar, AD-like attention deficits in mouse models of the disease. To address this question, we tested 3xTgAD mice (which express APPswe, PS1M146V, and tauP301L mutations) and wild-type control mice on a newly developed touchscreen-based 5-choice serial reaction time test of attention and response control. The 3xTgAD mice attended less accurately to short, spatially unpredictable stimuli when the attentional demand of the task was high, and also showed a general tendency to make more perseverative responses than wild-type mice. The attentional impairment of 3xTgAD mice was comparable to that of AD patients in two aspects: first, although 3xTgAD mice initially responded as accurately as wild-type mice, they subsequently failed to sustain their attention over the duration of the task; second, the ability to sustain attention was enhanced by the cholinesterase inhibitor donepezil (Aricept). These findings demonstrate that familial AD mutations not only affect memory, but also cause significant impairments in attention, a cognitive domain supported by the prefrontal cortex and its afferents. Because attention deficits are likely to affect memory encoding and other cognitive abilities, our findings have important consequences for the assessment of disease mechanisms and therapeutics in animal models of AD. C1 [Romberg, Carola; Bussey, Timothy J.; Saksida, Lisa M.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Bussey, Timothy J.; Saksida, Lisa M.] Univ Cambridge, Wellcome Trust, Cambridge CB2 3EB, England. [Bussey, Timothy J.; Saksida, Lisa M.] Univ Cambridge, Med Res Council Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. [Mattson, Mark P.; Mughal, Mohamed R.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Romberg, C (reprint author), Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. EM carola.romberg@gmail.com RI Mattson, Mark/F-6038-2012; Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016 OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041 FU Alzheimer's Research Trust; Wellcome Trust; Medical Research Council; National Institute on Aging, National Institutes of Health FX This research was supported by the Alzheimer's Research Trust, the Wellcome Trust, the Medical Research Council, and the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 72 TC 55 Z9 55 U1 1 U2 23 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 MAR 2 PY 2011 VL 31 IS 9 BP 3500 EP 3507 DI 10.1523/JNEUROSCI.5242-10.2011 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 730SS UT WOS:000288055200039 PM 21368062 ER PT J AU Mai, J Trump, S Ali, R Schiltz, RL Hager, G Hanke, T Lehmann, I Attinger, S AF Mai, Juliane Trump, Saskia Ali, Rizwan Schiltz, R. Louis Hager, Gordon Hanke, Thomas Lehmann, Irina Attinger, Sabine TI Are Assumptions about the Model Type Necessary in Reaction-Diffusion Modeling? A FRAP Application SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE PHOTOBLEACHING RECOVERY; ARYL-HYDROCARBON RECEPTOR; INTERACTIONS IN-VIVO; LIVING CELLS; CORRELATION SPECTROSCOPY; ANOMALOUS SUBDIFFUSION; PROTEIN DYNAMICS; GENE-REGULATION; BINDING; CHROMATIN AB At present, fluorescence recovery after photobleaching (FRAP) data are interpreted using various types of reaction-diffusion (RD) models: the model type is usually fixed first, and corresponding model parameters are inferred subsequently. In this article, we describe what we believe to be a novel approach for RD modeling without using any assumptions of model type or parameters. To the best of our knowledge, this is the first attempt to address both model-type and parameter uncertainties in inverting FRAP data. We start from the most general RD model, which accounts for a flexible number of molecular fractions, all mobile, with different diffusion coefficients. The maximal number of possible binding partners is identified and optimal parameter sets for these models are determined in a global search of the parameter-space using the Simulated Annealing strategy. The numerical performance of the described techniques was assessed using artificial and experimental FRAP data. Our general RD model outperformed the standard RD models used previously in modeling FRAP measurements and showed that intracellular molecular mobility can only be described adequately by allowing for multiple RD processes. Therefore, it is important to search not only for the optimal parameter set but also for the optimal model type. C1 [Mai, Juliane; Attinger, Sabine] UFZ Helmholtz Ctr Environm Res, Dept Computat Hydrosyst, Leipzig, Germany. [Trump, Saskia; Lehmann, Irina] UFZ Helmholtz Ctr Environm Res, Dept Environm Immunol, Leipzig, Germany. [Ali, Rizwan; Hanke, Thomas] Tech Univ Dresden, Max Bergmann Ctr Biomat, D-8027 Dresden, Germany. [Ali, Rizwan; Hanke, Thomas] Tech Univ Dresden, Inst Mat Sci, D-8027 Dresden, Germany. [Schiltz, R. Louis; Hager, Gordon] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Attinger, Sabine] Univ Jena, Inst Geosci, Jena, Germany. RP Mai, J (reprint author), UFZ Helmholtz Ctr Environm Res, Dept Computat Hydrosyst, Leipzig, Germany. EM juliane.mai@ufz.de FU Helmholtz Alliance on Systems Biology FX This project was supported by the Helmholtz Alliance on Systems Biology. We are deeply indebted to Jim McNally (National Cancer Institute/National Institutes of Health, Bethesda, Maryland) for critical comments and helpful discussion to improve the initial conditions. NR 46 TC 8 Z9 8 U1 0 U2 6 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 MAR 2 PY 2011 VL 100 IS 5 BP 1178 EP 1188 DI 10.1016/j.bpj.2011.01.041 PG 11 WC Biophysics SC Biophysics GA 730QP UT WOS:000288049400005 PM 21354390 ER PT J AU Gladwin, MT Kato, GJ Weiner, D Onyekwere, OC Dampier, C Hsu, L Hagar, RW Howard, T Nuss, R Okam, MM Tremonti, CK Berman, B Villella, A Krishnamurti, L Lanzkron, S Castro, O Gordeuk, VR Coles, WA Peters-Lawrence, M Nichols, J Hall, MK Hildesheim, M Blackwelder, WC Baldassarre, J Casella, JF AF Gladwin, Mark T. Kato, Gregory J. Weiner, Debra Onyekwere, Onyinye C. Dampier, Carlton Hsu, Lewis Hagar, R. Ward Howard, Thomas Nuss, Rachelle Okam, Maureen M. Tremonti, Carole K. Berman, Brian Villella, Anthony Krishnamurti, Lakshmanan Lanzkron, Sophie Castro, Oswaldo Gordeuk, Victor R. Coles, Wynona A. Peters-Lawrence, Marlene Nichols, James Hall, Mary K. Hildesheim, Mariana Blackwelder, William C. Baldassarre, James Casella, James F. CA DeNOVO Investigators TI Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain Crisis A Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Context Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC). Objective To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care. Design, Setting, and Participants Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008. Intervention Inhaled nitric oxide gas vs inhaled nitrogen placebo. Main Outcome Measures The primary end point was the time to resolution of painful crisis, defined by (1) freedom from parenteral opioid use for 5 hours; (2) pain relief as assessed by visual analog pain scale scores of 6 cm or lower (on 0-10 scale); (3) ability to walk; and (4) patient's and family's decision, with physician consensus, that the remaining pain could be managed at home. Results There was no significant change in the primary end point between the nitric oxide and placebo groups, with a median time to resolution of crisis of 73.0 hours (95% confidence interval [CI], 46.0-91.0) and 65.5 hours (95% CI, 48.1-84.0), respectively (P=.87). There were no significant differences in secondary outcome measures, including length of hospitalization, visual analog pain scale scores, cumulative opioid usage, and rate of acute chest syndrome. Inhaled nitric oxide was well tolerated, with no increase in serious adverse events. Increases in venous methemoglobin concentration confirmed adherence and randomization but did not exceed 5% in any study participant. Significant increases in plasma nitrate occurred in the treatment group, but there were no observed increases in plasma or whole blood nitrite. Conclusion Among patients with SCD hospitalized with VOC, the use of inhaled nitric oxide compared with placebo did not improve time to crisis resolution. C1 [Gladwin, Mark T.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Vasc Med Inst, Pittsburgh, PA 15213 USA. [Kato, Gregory J.; Coles, Wynona A.; Peters-Lawrence, Marlene; Nichols, James; Hildesheim, Mariana] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Hall, Mary K.; Blackwelder, William C.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Weiner, Debra] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Emergency Med, Boston, MA USA. [Okam, Maureen M.; Tremonti, Carole K.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. [Onyekwere, Onyinye C.; Castro, Oswaldo; Gordeuk, Victor R.] Howard Univ Hosp, Washington, DC USA. [Dampier, Carlton] Emory Univ, Sch Med, Atlanta, GA USA. [Dampier, Carlton] Childrens Healthcare Atlanta, Atlanta, GA USA. [Hagar, R. Ward] Childrens Hosp Oakland, Oakland, CA USA. [Hsu, Lewis] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Howard, Thomas] Univ Alabama, Birmingham, AL USA. [Nuss, Rachelle] Univ Colorado, Hlth Sci Ctr, Pediat Branch, Colorado Sickle Cell Treatment & Res Ctr, Denver, CO USA. [Berman, Brian; Villella, Anthony] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. [Lanzkron, Sophie] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Hematol & Oncol, Baltimore, MD 21205 USA. [Casella, James F.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Hematol, Baltimore, MD 21205 USA. [Baldassarre, James] Dept Clin Res, Clinton, NJ USA. RP Gladwin, MT (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Vasc Med Inst, 3459 5th Ave,628 NW, Pittsburgh, PA 15213 USA. EM gladwinmt@upmc.edu RI Krishnamurti, Lakshmanan/F-7637-2011; Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU US government; Institute of Transfusion Medicine; Hemophilia Center of Western Pennsylvania; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH [R01HL098032, RO1HL096973, RC1DK085852, P30AR058910]; NIH; Ikaria/INO Therapeutics; Division of Intramural Research of the NIH; Food and Drug Administration; Novartis Pharmaceuticals; Eli Lilly; Icagen/McNeil; NIH/NHLBI; Anthera Pharmaceuticals; Icagen; BioMarin Pharmaceuticals; NIH [U54HL070585, U10HL083705, R21HD049244, N01HB07159]; NHLBI [HB-06-06]; Cytrex Corporation [188]; Ikaria; Intramural Research Division of the NHLBI, NIH, US Department of Health and Human Services (DHHS); Vascular Medicine Institute; Institute for Transfusion Medicine; NCRR, NIH [UL1RR025005]; NIH Roadmap for Medical Research; Biomarin; TRF Pharma; Emmaus Pharmaceuticals FX All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gladwin reported having received research support in the form of a collaborative research and development agreement between the US government and Ikaria/INO Therapeutics and being listed as a co-inventor on a US patent for the use of nitrite salts for cardiovascular indications. Dr Gladwin reported receiving grant support from the Institute of Transfusion Medicine and the Hemophilia Center of Western Pennsylvania and federal funding from the National Heart, Lung, and Blood Institute (NHLBI); National Institute of Diabetes and Digestive and Kidney Diseases; and National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH (R01HL098032, RO1HL096973, RC1DK085852, P30AR058910). Dr Kato reported having received research grant support from a cooperative research and development agreement between the NIH and Ikaria/INO Therapeutics and from the Division of Intramural Research of the NIH. Dr Weiner reported having received research support from the Food and Drug Administration Orphan Product Development Grant Program. Dr Onyekwere reported having received research support from Novartis Pharmaceuticals, Eli Lilly, Icagen/McNeil, NIH/NHLBI, and Anthera Pharmaceuticals. Dr Dampier reported having received research grant support during the period of this study from Icagen, BioMarin Pharmaceuticals, and the NIH (U54HL070585, U10HL083705, R21HD049244, N01HB07159). Dr Dampier reported having had consulting relationships with Anthera Pharmaceuticals, GlycoMimetics, and Wyeth Pharmaceuticals. Dr Krishnamurti reported having received research support from the NHLBI (HB-06-06). Dr Gordeuk reported having received research support from Biomarin, TRF Pharma, and Emmaus Pharmaceuticals. Dr Baldassarre reported being an employee of Ikaria. Dr Casella reported having received research support from the NIH, NHLBI, National Institute of Neurological Disorders and Stroke, National Center for Research Resources (NCRR), Maternal and Child Health Bureau, and Maryland Department of Health and Mental Hygiene. Dr Casella reported receiving past research support from Cytrex Corporation for the investigation of a drug (poloxamer 188) for use in vaso-occlusive crisis. The results of these studies have been reported. No ongoing relationship exists. No other conflicts were reported.; This project was collaboratively supported and funded by Ikaria and the Intramural Research Division of the NHLBI, NIH, US Department of Health and Human Services (DHHS). The data and safety monitoring board was assembled and supported by the Intramural Research Division of the NHLBI, NIH, US DHHS. Statistical analysis was supported and independently conducted by the investigators using funds from the Vascular Medicine Institute, Hemophilia Center of Western Pennsylvania, and the Institute for Transfusion Medicine (M.T.G.). This study also received support from grant UL1RR025005 to JHU from the NCRR, a component of the NIH and the NIH Roadmap for Medical Research. NR 46 TC 60 Z9 63 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 2 PY 2011 VL 305 IS 9 BP 893 EP 902 DI 10.1001/jama.2011.235 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 728DP UT WOS:000287854700022 PM 21364138 ER PT J AU Persson, C Jia, YB Pettersson, H Dillner, J Nyren, O Ye, WM AF Persson, Christina Jia, Yanbin Pettersson, Helena Dillner, Joakim Nyren, Olof Ye, Weimin TI H. pylori Seropositivity before Age 40 and Subsequent Risk of Stomach Cancer: A Glimpse of the True Relationship? SO PLOS ONE LA English DT Article ID HELICOBACTER-PYLORI; GASTRIC-CANCER; ATROPHIC GASTRITIS; INFECTION; EPIDEMIOLOGY; ADENOCARCINOMAS; COMPLETENESS; METAANALYSIS; IMMUNOBLOT; CARCINOMA AB Stomach carcinogenesis involves mucosal and luminal changes that favor spontaneous disappearance of Helicobacter pylori. Therefore, the association between the infection and cancer risk might typically be underestimated. As acquisition of the infection almost invariably occurs before adulthood, the serostatus at age 16-40 should best reflect the lifetime occurrence of the infection. We therefore conducted a case-control study nested within a historic cohort of about 400,000 individuals who donated sera before age 40 to either of two large Swedish Biobanks between 1968 and 2006, and whose records were linked to complete nationwide registers. For each stomach adenocarcinoma case occurring at least 5 years after serum donation 2 controls were selected matched on age, sex and year of donation and biobank. Serum immunoglobulin G antibodies against H. pylori cell-surface antigens (Hp-CSAs) were measured with an enzyme-linked immunosorbent assay and antibodies against CagA with an immunoblot assay. Conditional logistic regression models were used to estimate odds ratios (ORs) for stomach adenocarcinoma among H. pylori infected relative to uninfected. We confirmed 59 incident cases of stomach adenocarcinoma (41 non-cardia tumors) during follow-up. ORs for non-cardia stomach adenocarcinoma among subjects with Hp-CSA antibodies (regardless of CagA serostatus), antibodies against CagA (regardless of Hp-CSA serostatus), and antibodies to both, relative to those who were seronegative to both, were 17.1 (95% confidence interval [CI] 4.0-72.9), 10.9 (95% CI 3.2-36.9), and 48.5 (95% CI 5.8-407.4), respectively. H. pylori infection is a much stronger risk factor for non-cardia stomach adenocarcinoma than initially realized. However, further studies are needed to answer whether it is a necessary cause, as the possibility of misclassification of H. pylori status could not be ruled out in our study. C1 [Persson, Christina; Jia, Yanbin; Dillner, Joakim; Nyren, Olof; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Pettersson, Helena] Swedish Inst Infect Dis Control, Solna, Sweden. [Dillner, Joakim] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. RP Persson, C (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. EM Weimin.Ye@ki.se FU Martin Rind Stiftelse; Swedish Research Council [K2009-69X-15372-05-2] FX This study was supported by a grant from Martin Rind Stiftelse and partly by a grant from the Swedish Research Council (K2009-69X-15372-05-2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 5 Z9 6 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 MAR 2 PY 2011 VL 6 IS 3 AR e17404 DI 10.1371/journal.pone.0017404 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 729FF UT WOS:000287933300021 PM 21399687 ER PT J AU Vitiello, B AF Vitiello, B. TI Prevention and treatment of child and adolescent depression: challenges and opportunities SO EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES LA English DT Article DE depression; treatment; prevention; children ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SEROTONIN REUPTAKE INHIBITORS; ROUTINE SPECIALIST CARE; COST-EFFECTIVENESS; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; RESISTANT DEPRESSION; MENTAL-DISORDERS; SUICIDE ATTEMPTS AB Objective. To examine the current theoretical rationale and empirical evidence for preventing and treating major depressive disorder in childhood and adolescence. Methods. Selective review of recent controlled investigations on the efficacy and safety of preventive and treatment interventions. Results. Even more than in adults, pediatric clinical trials in depression are dominated by symptomatic improvement with non-specific clinical contact (on average, 50% 'placebo response'). The additional benefit of specific psychotherapeutic or pharmacological treatment is on average modest. Antidepressant medication is effective in speeding up improvement, but more than a third of patients do not reach full remission even after prolonged treatment. The advantage of routinely combining medication with cognitive-behavioral therapy (CBT) is unclear. Depressed suicidal adolescents can benefit from CBT and medications. CBT can protect high-risk youths from developing a depressive episode. Conclusions. Effective interventions to prevent and treat depression in youth exist, but their therapeutic benefit appears to be, on average, small, possibly due to the clinical heterogeneity subsumed under the current diagnostic construct of depressive disorder. More specifically, targeted interventions tailored to individual clinical and biological characteristics may result in greater effectiveness and overall efficiency. C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Room 7147,Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 48 TC 9 Z9 9 U1 4 U2 20 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2045-7960 J9 EPIDEMIOL PSYCH SCI JI Epidemiol. Psychiatr. Sci. PD MAR PY 2011 VL 20 IS 1 BP 37 EP 43 DI 10.1017/S2045796011000102 PG 7 WC Psychiatry SC Psychiatry GA 861VE UT WOS:000298046800008 PM 21657114 ER PT J AU Blanck, HM Thompson, OM Nebeling, L Yaroch, AL AF Blanck, Heidi M. Thompson, Olivia M. Nebeling, Linda Yaroch, Amy L. TI Improving Fruit and Vegetable Consumption: Use of Farm-to-Consumer Venues Among US Adults SO PREVENTING CHRONIC DISEASE LA English DT Article AB Improvements to the food environment including new store development and more farm-to-consumer approaches (ie, farmers' markets, roadside stands, pick-your-own produce farms, or community-supported agriculture programs) may aid Americans in making healthier dietary choices. We analyzed data from a subset of respondents (N = 1,994) in the National Cancer Institute's Food Attitudes and Behaviors Survey, a mail survey of US adults. We determined associations between primary grocery shoppers' region and sociodemographic characteristics and frequency of purchasing fruits and vegetables in the summer from farm-to-consumer venues. A little more than one-quarter (27%) of grocery shoppers reported a frequency of at least weekly use of farm-to-consumer approaches. Older adults and respondents who live in the Northeast were most likely to shop farm-to-consumer venues at least weekly, and no differences were found by sex, race/ethnicity, education, or annual household income. These findings suggest that farm-to-consumer venues are used by many Americans and could be expanded to increase access to fruits and vegetables. C1 [Yaroch, Amy L.] Ctr Human Nutr, Omaha, NE USA. [Nebeling, Linda] NCI, Rockville, MD USA. [Thompson, Olivia M.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Hlth Promot Social & Behav Hlth, Omaha, NE USA. RP Blanck, HM (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, 4770 Buford Hwy NE,Mailstop K-26, Atlanta, GA 30341 USA. EM hblanck@cdc.gov NR 12 TC 9 Z9 10 U1 0 U2 25 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD MAR PY 2011 VL 8 IS 2 AR A49 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874OM UT WOS:000298967900019 PM 21324263 ER PT J AU Fuller, T Thomassen, HA Mulembakani, PM Johnston, SC Lloyd-Smith, JO Kisalu, NK Lutete, TK Blumberg, S Fair, JN Wolfe, ND Shongo, RL Formenty, P Meyer, H Wright, LL Muyembe, JJ Buermann, W Saatchi, SS Okitolonda, E Hensley, L Smith, TB Rimoin, AW AF Fuller, Trevon Thomassen, Henri A. Mulembakani, Prime M. Johnston, Sara C. Lloyd-Smith, James O. Kisalu, Neville K. Lutete, Timothee K. Blumberg, Seth Fair, Joseph N. Wolfe, Nathan D. Shongo, Robert L. Formenty, Pierre Meyer, Hermann Wright, Linda L. Muyembe, Jean-Jacques Buermann, Wolfgang Saatchi, Sassan S. Okitolonda, Emile Hensley, Lisa Smith, Thomas B. Rimoin, Anne W. TI Using Remote Sensing to Map the Risk of Human Monkeypox Virus in the Congo Basin SO ECOHEALTH LA English DT Article DE monkeypox; orthopoxvirus; smallpox vaccination; epidemiology; active surveillance; human transmission ID ECOLOGICAL NICHE; SPECIES DISTRIBUTIONS; DISTRIBUTION MODELS; TRANSMISSION; POPULATION; AFRICA; MAXENT; ZAIRE AB Although the incidence of human monkeypox has greatly increased in Central Africa over the last decade, resources for surveillance remain extremely limited. We conducted a geospatial analysis using existing data to better inform future surveillance efforts. Using active surveillance data collected between 2005 and 2007, we identified locations in Sankuru district, Democratic Republic of Congo (DRC) where there have been one or more cases of human monkeypox. To assess what taxa constitute the main reservoirs of monkeypox, we tested whether human cases were associated with (i) rope squirrels (Funisciurus sp.), which were implicated in monkeypox outbreaks elsewhere in the DRC in the 1980s, or (ii) terrestrial rodents in the genera Cricetomys and Graphiurus, which are believed to be monkeypox reservoirs in West Africa. Results suggest that the best predictors of human monkeypox cases are proximity to dense forests and associated habitat preferred by rope squirrels. The risk of contracting monkeypox is significantly greater near sites predicted to be habitable for squirrels (OR = 1.32; 95% CI 1.08-1.63). We recommend that semi-deciduous rainforests with oil-palm, the rope squirrel's main food source, be prioritized for monitoring. C1 [Lloyd-Smith, James O.; Blumberg, Seth; Rimoin, Anne W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Fuller, Trevon; Thomassen, Henri A.; Buermann, Wolfgang; Saatchi, Sassan S.; Smith, Thomas B.] Univ Calif Los Angeles, Inst Environm, Ctr Trop Res, Los Angeles, CA 90095 USA. [Mulembakani, Prime M.; Lutete, Timothee K.; Okitolonda, Emile] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Johnston, Sara C.; Hensley, Lisa] USA, Med Res Inst Infect Dis, Frederick, MD USA. [Lloyd-Smith, James O.; Blumberg, Seth; Smith, Thomas B.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA. [Kisalu, Neville K.] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90024 USA. [Fair, Joseph N.; Wolfe, Nathan D.] Global Viral Forecasting Initiat, San Francisco, CA USA. [Shongo, Robert L.] Minist Hlth, Kinshasa, Zaire. [Formenty, Pierre] WHO, Dept Global Alert & Response, CH-1211 Geneva, Switzerland. [Meyer, Hermann] Bundeswehr Inst Microbiol, Munich, Germany. [Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Muyembe, Jean-Jacques] Natl Inst Biomed Res, Kinshasa, Zaire. [Buermann, Wolfgang] Univ Calif Los Angeles, Dept Atmospher & Ocean Sci, Los Angeles, CA USA. [Saatchi, Sassan S.] CALTECH, Jet Prop Lab, Radar Sci & Engn Sect, Radar Sci Tech Grp, Pasadena, CA USA. [Rimoin, Anne W.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. RP Rimoin, AW (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM arimoin@ucla.edu RI Lloyd-Smith, James/K-4080-2012; Valle, Ruben/A-7512-2013 OI Lloyd-Smith, James/0000-0001-7941-502X; FU Faucett Family Foundation; National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, MD, USA; National Science Foundation-National Institutes of Health [EF-0430146]; RAPIDD of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; National Institute of Allergy and Infectious Diseases [EID-1R01AI074059-01] FX This work was made possible by the generous support of the Faucett Family Foundation. We respectfully thank the DRC Ministry of Health and local health workers who were responsible for specimen collection and case investigation. Additional support for this study was provided by the National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, MD, USA, by the joint National Science Foundation-National Institutes of Health Ecology of Infectious Diseases Program (grant number EF-0430146), by the RAPIDD program of the Science and Technology Directorate, Department of Homeland Security, by the Fogarty International Center, National Institutes of Health, and by the National Institute of Allergy and Infectious Diseases (grant number EID-1R01AI074059-01). We thank two anonymous reviewers for comments that improved the manuscript. NR 40 TC 14 Z9 15 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1612-9202 J9 ECOHEALTH JI EcoHealth PD MAR PY 2011 VL 8 IS 1 BP 14 EP 25 DI 10.1007/s10393-010-0355-5 PG 12 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 862PI UT WOS:000298105300002 PM 21069425 ER PT J AU Kuntzen, T Neumann-Haefelin, C Lennon, N Talal, AH Carlson, J Brumme, C Timm, J Schmidt, J Wunsch, K Berical, A Berlin, AM Adams, S Young, SK Reyor, LL Kleyman, M McMahon, CM Birch, C zur Wiesch, JS Ledlie, T Michael, K Kodira, C Roberts, AD Schneidewind, A Lauer, GM Kim, AY Rosen, HR Bihl, F Cerny, A Spengler, U Brander, C Galagan, JE Nusbaum, C Walker, BD Lake-Bakaar, GV Daar, ES Jacobson, IM Gomperts, ED Edlin, BR Donfield, SM Chung, RT Marion, T Birren, BW Marincola, F Thimme, R Carrington, M Heckerman, D Henn, MR Allen, TM AF Kuntzen, T. Neumann-Haefelin, C. Lennon, N. Talal, A. H. Carlson, J. Brumme, C. Timm, J. Schmidt, J. Wunsch, K. Berical, A. Berlin, A. M. Adams, S. Young, S. K. Reyor, L. L. Kleyman, M. McMahon, C. M. Birch, C. zur Wiesch, J. Schulze Ledlie, T. Michael, K. Kodira, C. Roberts, A. D. Schneidewind, A. Lauer, G. M. Kim, A. Y. Rosen, H. R. Bihl, F. Cerny, A. Spengler, U. Brander, C. Galagan, J. E. Nusbaum, C. Walker, B. D. Lake-Bakaar, G. V. Daar, E. S. Jacobson, I. M. Gomperts, E. D. Edlin, B. R. Donfield, S. M. Chung, R. T. Marion, T. Birren, B. W. Marincola, F. Thimme, R. Carrington, M. Heckerman, D. Henn, M. R. Allen, T. M. TI POPULATIONAL ANALYSIS REVEALS A LINK BETWEEN COMPLEX VIRAL ESCAPE FROM CD8+T-CELL RESPONSES AND PROTECTION IN HCV INFECTION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Kuntzen, T.; Berical, A.; Reyor, L. L.; Kleyman, M.; McMahon, C. M.; Birch, C.; Schneidewind, A.; Lauer, G. M.; Kim, A. Y.; Walker, B. D.; Carrington, M.; Allen, T. M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Kuntzen, T.] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland. [Neumann-Haefelin, C.; Schmidt, J.; Wunsch, K.; Thimme, R.] Univ Freiburg, Freiburg, Germany. [Lennon, N.; Berlin, A. M.; Young, S. K.; Michael, K.; Kodira, C.; Roberts, A. D.; Nusbaum, C.; Birren, B. W.; Henn, M. R.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Talal, A. H.; Lake-Bakaar, G. V.; Jacobson, I. M.; Edlin, B. R.] Weill Cornell Med Coll, New York, NY USA. [Carlson, J.; Heckerman, D.] Microsoft Res, Redmond, WA USA. [Brumme, C.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Timm, J.; Ledlie, T.] Univ Essen Gesamthsch, Essen, Germany. [Adams, S.; Marincola, F.] NIH, Bethesda, MD 20892 USA. [zur Wiesch, J. Schulze] Univ Hamburg Eppendorf, Hamburg, Germany. [Rosen, H. R.] Univ Cologne, Denver, CO USA. [Bihl, F.] Univ Geneva, Geneva, Switzerland. [Cerny, A.] Clin Moncucco, Lugano, Switzerland. [Spengler, U.] Univ Bonn, D-5300 Bonn, Germany. [Brander, C.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Daar, E. S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Gomperts, E. D.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Donfield, S. M.] Rho Inc, Chapel Hill, NC USA. [Chung, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marion, T.] Univ Tennessee, Memphis, TN USA. EM christoph.neumann-haefelin@uniklinik-freiburg.de RI Neumann-Haefelin, Christoph/E-5550-2011 NR 0 TC 0 Z9 0 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 3 BP S2 EP S2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625600004 ER PT J AU Maass, T Sfakianakis, I Westphal, H Galle, PR Teufel, A AF Maass, T. Sfakianakis, I. Westphal, H. Galle, P. R. Teufel, A. TI DKK2 DELETION RESULTS IN ENHANCED LIVER CANCER DEVELOPMENT SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Maass, T.; Sfakianakis, I.; Galle, P. R.; Teufel, A.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Westphal, H.] NICHD, LMGD, NIH, Bethesda, MD USA. EM teufel@uni-mainz.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 256 BP S105 EP S106 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625600257 ER PT J AU Naggie, S Osinusi, A Katsounas, A Lempicki, R Herrmann, E Shivakumar, B Thompson, A Clark, P Patel, K Muir, A Mchutchison, J Goldstein, D Schlaak, J Masur, H Polis, M Kottilil, S AF Naggie, S. Osinusi, A. Katsounas, A. Lempicki, R. Herrmann, E. Shivakumar, B. Thompson, A. Clark, P. Patel, K. Muir, A. Mchutchison, J. Goldstein, D. Schlaak, J. Masur, H. Polis, M. Kottilil, S. TI DYSREGULATION OF HOST INNATE IMMUNITY IN HCV GENOTYPE 1 INFECTED IL28B CT/TT HAPLOTYPE PATIENTS WITH DEPRESSED VIRAL KINETICS AND THERAPEUTIC RESPONSE SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Naggie, S.; Clark, P.; Patel, K.; Muir, A.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Osinusi, A.; Polis, M.; Kottilil, S.] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Osinusi, A.; Katsounas, A.; Lempicki, R.; Shivakumar, B.] SAIC Frederick Inc, Frederick, MD USA. [Herrmann, E.] Goethe Univ Frankfurt, IBMM, Frankfurt, Germany. [Thompson, A.] St Vincents Hosp, Melbourne, Vic, Australia. [Mchutchison, J.] Gilead Sci Inc, Foster City, CA 94404 USA. [Goldstein, D.] Duke Ctr Human Genome Variat, Durham, NC USA. [Schlaak, J.] Univ Hosp Essen, Essen, Germany. [Masur, H.] NIH, CCMD, Bethesda, MD 20892 USA. EM susanna.naggie@duke.edu RI Lempicki, Richard/E-1844-2012; Clark, Paul/A-1480-2012 OI Lempicki, Richard/0000-0002-7059-409X; Clark, Paul/0000-0002-1821-4969 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 1334 BP S526 EP S527 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625603018 ER PT J AU O'Brien, TR Morgan, TR Pfeiffer, RM Chung, RT Lok, AS Shiffman, ML Dotrang, M Sninsky, JJ Bonkovsky, HL AF O'Brien, T. R. Morgan, T. R. Pfeiffer, R. M. Chung, R. T. Lok, A. S. Shiffman, M. L. Dotrang, M. Sninsky, J. J. Bonkovsky, H. L. CA HALT-C Trial Grp TI IL28B GENETIC ATTRIBUTABLE RISK IN HEPATITIS C-ASSOCIATED HEPATOCELLULAR CARCINOMA AND DECOMPENSATED LIVER DISEASE SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [O'Brien, T. R.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Morgan, T. R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, T. R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Chung, R. T.] Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. [Chung, R. T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lok, A. S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Shiffman, M. L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Dotrang, M.] CSC, Rockville, MD USA. [Sninsky, J. J.] Celera Corp, Alameda, CA USA. [Bonkovsky, H. L.] Univ Connecticut, Dept Med, Ctr Hlth, Farmington, CT 06032 USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Bonkovsky, H. L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. EM timothy.morgan@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 1336 BP S527 EP S528 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625603020 ER PT J AU Parvez, MK Emerson, SU Purcell, RH AF Parvez, M. K. Emerson, S. U. Purcell, R. H. TI PACKAGING OF HEPATITIS E VIRUS (HEV) GENOMIC RNA IN TRANS-COMPLEMENTED CAPSID PROTEIN AND PRODUCTION OF INFECTIOUS VIRIONS SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Parvez, M. K.; Emerson, S. U.; Purcell, R. H.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Parvez, M. K.] King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh, Saudi Arabia. EM khalid_parvez@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 43 BP S20 EP S20 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625600044 ER PT J AU Trehanpati, N Kotillil, S Murphy, AA Zhang, X Saha, B Sarin, SK AF Trehanpati, N. Kotillil, S. Murphy, A. A. Zhang, X. Saha, B. Sarin, S. K. TI ROLE OF INTRAHEPATIC INNATE IMMUNE ACTIVATION IN CHRONIC HEPATITIS C: THE ROLE OF NK, NKT AND DENDRITIC CELLS AND THE IMPACT OF IMMUNE SUPPRESSION SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Trehanpati, N.; Saha, B.; Sarin, S. K.] Inst Liver & Biliiary Sci, New Delhi, India. [Kotillil, S.; Murphy, A. A.; Zhang, X.] NIAID, NIH, Bethesda, MD 20892 USA. EM trehanpati@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 312 BP S126 EP S126 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625600313 ER PT J AU Welzel, TM Graubard, BI Zeuzem, S El-Serag, HB Davila, JA McGlynn, KA AF Welzel, T. M. Graubard, B. I. Zeuzem, S. El-Serag, H. B. Davila, J. A. McGlynn, K. A. TI METABOLIC SYNDROME INCREASES THE RISK OF PRIMARY LIVER CANCER IN THE UNITED STATES SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Welzel, T. M.; Zeuzem, S.] Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. [Graubard, B. I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [El-Serag, H. B.] Baylor Coll Med, Gastroenterol & Hepatol Sect, Houston, TX 77030 USA. [Davila, J. A.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [McGlynn, K. A.] NCI, HREB, Div Canc Epidemiol & Genet, Rockville, MD USA. EM tania.welzel@kgu.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 1022 BP S405 EP S406 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625602161 ER PT J AU Weng, HL Radaeva, S Liu, Y Li, Q Shen, H Mullenbach, R Zimmer, V Lammert, F Mertens, P Zakhari, S Dooley, S Gao, B AF Weng, H. -L. Radaeva, S. Liu, Y. Li, Q. Shen, H. Muellenbach, R. Zimmer, V. Lammert, F. Mertens, P. Zakhari, S. Dooley, S. Gao, B. TI IFN-G INHIBITS HEPATIC PROGENITOR CELL ACTIVATION IN CHRONIC LIVER DAMAGE SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the-Study-of-the-Liver (EASL) CY 2011 CL Berlin, GERMANY SP European Assoc Study Liver (EASL) C1 [Weng, H. -L.; Liu, Y.; Li, Q.; Shen, H.; Muellenbach, R.; Dooley, S.] Univ Heidelberg, Med Clin 2, Fac Med Mannheim, D-6800 Mannheim, Germany. [Radaeva, S.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, WA USA. [Radaeva, S.; Zakhari, S.] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, WA USA. [Muellenbach, R.; Zimmer, V.; Lammert, F.] Univ Saarland, Saarland Univ Hosp, Dept Med 2, D-6650 Homburg, Germany. [Mertens, P.] Otto von Guericke Univ, Dept Hypertens & Nephrol, Magdeburg, Germany. EM honglei.weng@medma.uni-heidelberg.de NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2011 VL 54 SU 1 MA 120 BP S53 EP S53 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 856GC UT WOS:000297625600121 ER PT J AU Mital, J Hackstadt, T AF Mital, Jeffrey Hackstadt, Ted TI Diverse Requirements for Src-Family Tyrosine Kinases Distinguish Chlamydial Species SO MBIO LA English DT Article ID TRACHOMATIS TARP; MICROTUBULE NETWORK; MEMBRANE-PROTEINS; GAMMA-INTERFERON; TISSUE TROPISM; HOST-CELLS; PHOSPHORYLATION; INFECTION; INCLUSION; ACTIN AB Chlamydiae are well known for their species specificity and tissue tropism, and yet the individual species and strains show remarkable genomic synteny and share an intracellular developmental cycle unique in the microbial world. Only a relatively few chlamydial genes have been linked to specific disease or tissue tropism. Here we show that chlamydial species associated with human infections, Chlamydia trachomatis and C. pneumoniae, exhibit unique requirements for Src-family kinases throughout their developmental cycle. Utilization of Src-family kinases by C. trachomatis includes tyrosine phosphorylation of the secreted effector Tarp during the entry process, a functional role in microtubule-dependent trafficking to the microtubule organizing center, and a requirement for Src-family kinases for successful initiation of development. Nonhuman chlamydial species C. caviae and C. muridarum show none of these requirements and, instead, appear to be growth restricted by the activities of Src-family kinases. Depletion of Src-family kinases triggers a more rapid development of C. caviae with up to an 800% increase in infectious progeny production. Collectively, the results suggest that human chlamydial species have evolved requirements for tyrosine phosphorylation by Src-family kinases that are not seen in other chlamydial species. The requirement for Src-family kinases thus represents a fundamental distinction between chlamydial species that would not be readily apparent in genomic comparisons and may provide insights into chlamydial disease association and species specificity. IMPORTANCE Chlamydiae are well known for their species specificity and tissue tropism as well as their association with unique diseases. A paradox in the field relates to the remarkable genomic synteny shown among chlamydiae and the very few chlamydial genes linked to specific diseases. We have found that different chlamydial species exhibit unique requirements for Src-family kinases. These differing requirements for Src-family kinases would not be apparent in genomic comparisons and appear to be a previously unrecognized distinction that may provide insights to guide research in chlamydial pathogenesis. C1 [Mital, Jeffrey; Hackstadt, Ted] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Host Parasite Interact Sect,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU NIAID/NIH FX This work was supported by the Intramural Research Program of the NIAID/NIH. NR 55 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2011 VL 2 IS 2 AR e00031-11 DI 10.1128/mBio.00031-11 PG 8 WC Microbiology SC Microbiology GA 845SV UT WOS:000296843700005 ER PT J AU Zhu, LA Tangrea, MA Mukherjee, S Emmert-Buck, MR AF Zhu, Liang Tangrea, Michael A. Mukherjee, Sumana Emmert-Buck, Michael R. TI Layered electrophoretic transfer - A method for pre-analytic processing of histological sections SO PROTEOMICS LA English DT Article DE 2-D protein separation; LET; Technology; Tissue protein mapping ID LASER CAPTURE MICRODISSECTION; MASS-SPECTROMETRY; QUANTUM DOTS; MOLECULAR ANALYSIS; CLINICAL-SAMPLES; PEPTIDE ARRAYS; TISSUE; PROTEINS AB Current technologies for measuring protein expression across a tissue section are based on MS or in situ detection such as immunohistochemistry. However, due to the inherent molecular complexity of tissue samples and the large dynamic range of protein expression in cells, current approaches are often unable to measure moderate- and low-abundant proteins. In addition, they do not provide information on the physico-chemical properties of the proteins studied. To address these problems, we are developing a new pre-analytic methodology termed layered electrophoretic transfer (LET) that selectively separates and processes proteins from an intact tissue section without compromising important two-dimensional histological information. LET offers two potential advantages over standard techniques: (i) A reduced complexity of the tissue proteome for subsequent analysis; (ii) An opportunity to assess the biochemical status of proteins as they exist in situ. As an initial proof-of-concept, we demonstrate here that the protein content from a mixture of molecular weight standards, human tissue lysates, and tissue sections can be successfully transferred and separated using LET, and further demonstrate that the method can be coupled with immunoblotting or MS for downstream measurements. LET technology represents a new pre-analytic tool for interrogating the proteome in tissue sections while preserving valuable spatial information. C1 [Zhu, Liang; Tangrea, Michael A.; Mukherjee, Sumana; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov RI Zhu, Liang/G-1389-2010 FU National Cancer Institute, NIH FX This work was supported by the Center for Cancer Research in the intramural program of the National Cancer Institute, NIH. NR 20 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD MAR PY 2011 VL 11 IS 5 BP 883 EP 889 DI 10.1002/pmic.201000476 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 731VK UT WOS:000288137300005 PM 21280224 ER PT J AU Goldsmith, J Caffo, B Crainiceanu, C Reich, D Du, Y Hendrix, C AF Goldsmith, Jeff Caffo, Brian Crainiceanu, Ciprian Reich, Daniel Du, Yong Hendrix, Craig TI NONLINEAR TUBE-FITTING FOR THE ANALYSIS OF ANATOMICAL AND FUNCTIONAL STRUCTURES SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Medical imaging; support estimation; SPECT; DTI; principal curves; nonlinear curve estimation ID DIFFUSION-TENSOR; CORTICOSPINAL TRACT; MULTIPLE-SCLEROSIS; PRINCIPAL CURVES; VIRTUAL ENDOSCOPY; HUMAN COLON; TRACKING; IMAGES; CENTERLINE; SURFACES AB We are concerned with the estimation of the exterior surface and interior summaries of tube-shaped anatomical structures. This interest is motivated by two distinct scientific goals, one dealing with the distribution of HIV microbicide in the colon and the other with measuring degradation in white-matter tracts in the brain. Our problem is posed as the estimation of the support of a distribution in three dimensions from a sample from that distribution, possibly measured with error. We propose a novel tube-fitting algorithm to construct such estimators. Further, we conduct a simulation study to aid in the choice of a key parameter of the algorithm, and we test our algorithm with validation study tailored to the motivating data sets. Finally, we apply the tube-fitting algorithm to a colon image produced by single photon emission computed tomography (SPECT) and to a white-matter tract image produced using diffusion tensor imaging (DTI). C1 [Goldsmith, Jeff; Caffo, Brian; Crainiceanu, Ciprian] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Reich, Daniel] Ctr Clin, Bethesda, MD 20892 USA. [Du, Yong] Johns Hopkins Med Inst, Div Med Imaging Phys, Baltimore, MD 21287 USA. [Hendrix, Craig] Johns Hopkins Univ, Baltimore, MD 21287 USA. RP Goldsmith, J (reprint author), Johns Hopkins Univ, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM jgoldsmi@jhsph.edu; bcaffo@jhsph.edu; ccrainic@jhsph.edu; daniel.reich@nih.gov; ydu2@jhmi.edu; cwhendrix@jhmi.edu RI Reich, Daniel/E-5701-2010; Hendrix, Craig/G-4182-2014 OI Reich, Daniel/0000-0002-2628-4334; Hendrix, Craig/0000-0002-5696-8665 FU Centers for Disease Control and Prevention [200-2001-08015]; National Institute of Allergy and Infectious Diseases [U19 AI060614, U19AI082637]; National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1 RR 025005]; NIH Roadmap for Medical Research; National Institute of Neurological Disorders and Stroke [R01NS060910]; National Multiple Sclerosis Society FX Supported in part by the Centers for Disease Control and Prevention (Contract No. 200-2001-08015), the National Institute of Allergy and Infectious Diseases Integrated Preclinical/Clinical Program (U19 AI060614 and U19AI082637) and the National Center for Research Resources (NCRR, Grant number UL1 RR 025005), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of CDC or NIH.; Supported by Award Number R01NS060910 from the National Institute of Neurological Disorders and Stroke. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.; The authors would like to acknowledge the National Multiple Sclerosis Society for funding the acquisition of the DTI data. NR 44 TC 5 Z9 5 U1 1 U2 4 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD MAR PY 2011 VL 5 IS 1 BP 337 EP 363 DI 10.1214/10-AOAS384 PG 27 WC Statistics & Probability SC Mathematics GA 827TQ UT WOS:000295451800025 PM 21709824 ER PT J AU Graham, RF Hoskins, JD Cortijo, MP Barbee, GA Folio, LR Lutz, CC AF Graham, Ross F. Hoskins, Jason D. Cortijo, Michael P. Barbee, George A. Folio, Les R. Lutz, Clifford C. TI A Casualty Tracking System Modeled After Air Traffic Control Methodology Employed in a Combat Support Hospital in Iraq SO MILITARY MEDICINE LA English DT Editorial Material C1 [Graham, Ross F.; Hoskins, Jason D.] Uniformed Serv Univ Hlth Sci, Sch Med, Bethesda, MD 20814 USA. [Cortijo, Michael P.] USA, Emergency Med Technician Sect, Dept Emergency Med, Winn Army Community Hosp,CSH 47, Ft Stewart, GA 31314 USA. [Barbee, George A.] USA, Womack Army Med Ctr, MCXC DOEM, CSH 47, Ft Bragg, NC 28310 USA. [Folio, Les R.] NIH, Bethesda, MD 20892 USA. [Lutz, Clifford C.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. RP Graham, RF (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. OI Barbee, George/0000-0002-9509-952X NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 2011 VL 176 IS 3 BP 244 EP 245 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 825BN UT WOS:000295246000002 PM 21456347 ER PT J AU Florin, DA Davies, SJ Olsen, C Lawyer, P Lipnick, R Schultz, G Rowton, E Wilkerson, R Keep, L AF Florin, David A. Davies, Stephen J. Olsen, Cara Lawyer, Phillip Lipnick, Robert Schultz, George Rowton, Edgar Wilkerson, Richard Keep, Lisa TI Morphometric and Molecular Analyses of the Sand Fly Species Lutzomyia shannoni (Diptera: Psychodidae: Phlebotominae) Collected From Seven Different Geographical Areas in the Southeastern United States SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Lutzomyia shannoni; canonical discriminant analysis; principal component analysis; internal transcribed spacer 2; cytochrome c oxidase subunit I ID ITS2 RDNA SEQUENCES; PHYLOGENETIC-RELATIONSHIPS; MITOCHONDRIAL PSEUDOGENES; GENETIC-VARIABILITY; MADAGASCAR DIPTERA; OSSABAW ISLAND; FLIES DIPTERA; AEDES-AEGYPTI; NUCLEAR-DNA; N. SP AB A morphometric and molecular study of adult male and female Lutzomyia shannoni (Dyar 1929) collected at seven different locations within the southeastern United States was conducted to assess the degree of divergence between the grouped specimens from each location. The collection locations were as follows: Fort Bragg, NC; Fort Campbell, KY; Fort Rucker, AL; Ossabaw Island, GA; Patuxent National Wildlife Research Refuge, MD; Suwannee National Wildlife Refuge, FL; and Baton Rouge, LA. Forty males and forty females from each location were analyzed morphometrically from 54 and 49 character measurements, respectively. In addition, the molecular markers consisting of the partial cytochrome c oxidase subunit I (from 105 sand flies: 15 specimens/collection site) and the partial internal transcribed spacer 2 (from 42 sand flies: six specimens/collection site) were compared. Multivariate analyses indicate that the low degree of variation between the grouped specimens from each collection site prevents the separation of any collection site into an entity that could be interpreted as a distinct population. The molecular analyses were in concordance with the morphometric study as no collection location grouped into a separate population based on the two partial markers. The grouped specimens from each collection site appear to be within the normal variance of the species, indicating a single population in the southeast United States. It is recommended that additional character analyses of L. shannoni based on more molecular markers, behavioral, ecological, and physiological characteristics, be conducted before ruling out the possibility of populations or a cryptic species complex within the southeastern United States. C1 [Florin, David A.; Davies, Stephen J.; Olsen, Cara; Schultz, George; Keep, Lisa] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Lawyer, Phillip] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Lipnick, Robert] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD 20910 USA. [Rowton, Edgar; Wilkerson, Richard] Walter Reed Army Inst Res, Div Entomol, Silver Spring, MD 20910 USA. RP Florin, DA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM david.florin@usuhs.mil RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011 OI Rowton, Edgar/0000-0002-1979-1485 FU Uniformed Services University of the Health Sciences [R087WB] FX We thank T. Mascari of Louisana State University and P. Obenauer of the United States Navy for providing sand flies from Baton Rouge, LA, and San Felasco Hammock State Preserve, FL, respectively. We also acknowledge F. Ruiz, Walter Reed Army Institute of Research, and Mike Flora, Uniformed Services University of the Health Sciences, for technical assistance. This work was supported by Uniformed Services University of the Health Sciences Intramural Grant R087WB: Risk for domestic transmission of leishmaniasis acquired by United States service members in Iraq/Afghanistan. NR 69 TC 9 Z9 9 U1 1 U2 6 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAR PY 2011 VL 48 IS 2 BP 154 EP 166 DI 10.1603/ME10199 PG 13 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 810JM UT WOS:000294121600007 PM 21485350 ER PT J AU Caro, JJ Coleman, CN Knebel, A DeRenzo, EG AF Caro, J. Jaime Coleman, C. Norman Knebel, Ann DeRenzo, Evan G. TI Unaltered Ethical Standards for Individual Physicians in the Face of Drastically Reduced Resources Resulting from an Improvised Nuclear Device Event SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID CRITICAL-CARE SUMMIT; MASS CRITICAL-CARE; JANUARY 26-27; TASK-FORCE; ALLOCATION; LIFE AB When disaster disrupts healthcare and other systems, the ethical allocation of resources should follow principles of justice, defined as fairness, established for normal clinical practice. Standards of clinical practice may be altered during disaster, but ethical standards must remain centered on prioritizing the treatment of patients according to need and the effectiveness of treatment. Should resources become extremely limited, it is fair to restrict their use to patients who have the highest needs, provided that the intervention is effective. When resources become more available, patients with lower priority can be increasingly accommodated. C1 [Caro, J. Jaime] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. [Caro, J. Jaime] McGill Univ, Div Gen Internal Med, Montreal, PQ, Canada. [Caro, J. Jaime] UnitedBiosource Corp, Lexington, MA USA. [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Washington, DC USA. [Coleman, C. Norman; Knebel, Ann] Off Assistant Secretary Preparedness & Response, Dept Hlth & Human Serv, Washington, DC USA. [DeRenzo, Evan G.] Washington Hosp Ctr, Ctr Eth, Washington, DC 20010 USA. [DeRenzo, Evan G.] Howard Univ, Sch Med, Washington, DC 20059 USA. RP Caro, JJ (reprint author), McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. EM Jaime.Caro@unitedbiosource.com NR 22 TC 5 Z9 5 U1 0 U2 1 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR PY 2011 VL 22 IS 1 BP 33 EP 41 PG 9 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 797XY UT WOS:000293164600005 PM 21595353 ER PT J AU Duggal, P Guo, XT Haque, R Peterson, KM Ricklefs, S Mondal, D Alam, F Noor, Z Verkerke, HP Marie, C Leduc, CA Chua, SC Myers, MG Leibel, RL Houpt, E Gilchrist, CA Sher, A Porcella, SF Petri, WA AF Duggal, Priya Guo, Xiaoti Haque, Rashidul Peterson, Kristine M. Ricklefs, Stacy Mondal, Dinesh Alam, Faisal Noor, Zannatun Verkerke, Hans P. Marie, Chelsea Leduc, Charles A. Chua, Streamson C., Jr. Myers, Martin G., Jr. Leibel, Rudolph L. Houpt, Eric Gilchrist, Carol A. Sher, Alan Porcella, Stephen F. Petri, William A., Jr. TI A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED PROTEIN-KINASE; PRESCHOOL-CHILDREN; DIARRHEAL ILLNESS; IMMUNE-RESPONSE; CELL-SURVIVAL; EXPRESSION; AMEBIASIS; SUSCEPTIBILITY; MALNUTRITION; MICE AB Malnutrition substantially increases susceptibility to Entamoeba histolytica in children. Leptin is a hormone produced by adipocytes that inhibits food intake, influences the immune system, and is suppressed in malnourished children. Therefore we hypothesized that diminished leptin function may increase susceptibility to E. histolytica infection. We prospectively observed a cohort of children, beginning at preschool age, for infection by the parasite E. histolytica every other day over 9 years and evaluated them for genetic variants in leptin (LEP) and the leptin receptor (LEPR). We found increased susceptibility to intestinal infection by this parasite associated with an amino acid substitution in the cytokine receptor homology domain 1 of LEPR. Children carrying the allele for arginine (223R) were nearly 4 times more likely to have an infection compared with those homozygous for the ancestral glutamine allele (223Q). An association of this allele with amebic liver abscess was also determined in an independent cohort of adult patients. In addition, mice carrying at least 1 copy of the R allele of Lepr were more susceptible to infection and exhibited greater levels of mucosal destruction and intestinal epithelial apoptosis after amebic infection. These findings suggest that leptin signaling is important in mucosal defense against amebiasis and that polymorphisms in the leptin receptor explain differences in susceptibility of children in the Bangladesh cohort to amebiasis. C1 [Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Guo, Xiaoti; Peterson, Kristine M.; Verkerke, Hans P.; Marie, Chelsea; Houpt, Eric; Gilchrist, Carol A.; Petri, William A., Jr.] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Haque, Rashidul; Mondal, Dinesh; Noor, Zannatun] Int Ctr Diarrheal Dis Res, Dhaka, Bangladesh. [Ricklefs, Stacy; Porcella, Stephen F.] NIAID, Rocky Mt Labs, Res Technol Sect, Genom Unit,NIH, Hamilton, MT 59840 USA. [Alam, Faisal] Rajshahi Med Coll, Rajshahi, Bangladesh. [Leduc, Charles A.; Leibel, Rudolph L.] Columbia Univ, Dept Pediat, Med Ctr, Div Mol Genet, New York, NY 10027 USA. [Leduc, Charles A.; Leibel, Rudolph L.] Columbia Univ, Med Ctr, Naomi Berrie Diabet Ctr, New York, NY USA. [Chua, Streamson C., Jr.] Albert Einstein Coll Med, Dept Med, New York, NY USA. [Chua, Streamson C., Jr.] Albert Einstein Coll Med, Dept Neurosci, New York, NY USA. [Myers, Martin G., Jr.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Myers, Martin G., Jr.] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. [Sher, Alan] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Duggal, P (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6539, Baltimore, MD 21205 USA. EM pduggal@jhsph.edu FU NIH [AI043596, R01 AI071373, R01 DK056731, R01 DK52431-17, 5P30 DK26687-29]; New York Obesity Research Center, Molecular Biology/Molecular Genetics Core; intramural division of the National Human Genome Research Institute; National Institutes of Allergy and Infectious Disease FX We thank the children and their families in Mirpur, Dhaka, Bangladesh for their participation in this study. We acknowledge the insight and assistance of Joan E. Bailey-Wilson. This work was supported by NIH grants AI043596 (to W.A. Petri), R01 AI071373 (to E. Houpt), R01 DK056731 (to M.G. Myers), R01 DK52431-17 (to R.L. Leibel), and 5P30 DK26687-29 New York Obesity Research Center, Molecular Biology/Molecular Genetics Core (to R.L. Leibel and S.C. Chua Jr.), and in parr by the intramural division of the National Human Genome Research Institute, the NIH, and the National Institutes of Allergy and Infectious Disease (to W.A. Petri). NR 38 TC 53 Z9 53 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2011 VL 121 IS 3 BP 1191 EP 1198 DI 10.1172/JCI45294 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 729YQ UT WOS:000287991000036 PM 21393862 ER PT J AU Ramaswamy, M Deng, M Siegel, RM AF Ramaswamy, Madhu Deng, Min Siegel, Richard M. TI Harnessing programmed cell death as a therapeutic strategy in rheumatic diseases SO NATURE REVIEWS RHEUMATOLOGY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAS-MEDIATED APOPTOSIS; MATURE T-LYMPHOCYTES; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; BH3 MIMETIC ABT-737; NF-KAPPA-B; IMMUNE-SYSTEM; TNF-ALPHA; SIGNALING COMPLEX; CROHNS-DISEASE AB Programmed cell death (PCD) is a key process in the regulation of immune cell development and peripheral immune homeostasis. Caspase-dependent apoptosis, as well as a number of alternative cell death mechanisms, account for immune cell PCD induced by cell-intrinsic and extrinsic pathways. In animal models, compelling evidence has emerged that genetic defects in PCD can result in autoimmune disease. Autoimmune disease can arise from single-gene mutations that affect PCD, and defective PCD has been observed in some tissues and cells from patients with rheumatic disease. Selectively inducing PCD in autoreactive B and T cells is very attractive as a therapeutic strategy because it offers the possibility of permanent elimination of these pathogenic cell subsets. In addition, the anti-inflammatory effects of apoptotic cells may add to the therapeutic benefit of induced PCD. Immune cell subsets vary widely in their sensitivity to specific inducers of cell death, and understanding these differences is key to predicting the outcome of inducing apoptosis for therapeutic means. Here, we review approaches that have been used to induce PCD in the treatment of autoimmune disease, and describe the prospects of bringing these experimental strategies into clinical practice. C1 [Ramaswamy, Madhu; Deng, Min; Siegel, Richard M.] NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMSD, Immunoregulat Sect, Autoimmun Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13C 103, Bethesda, MD 20892 USA. EM siegelr@mail.nih.gov FU NIAMS FX This work was supported by funds from the NIAMS intramural research program. We would like to thank Eric Hanson and Michael Ombrello for critical reading of this manuscript. Min Deng is a student in the Clinical Research Training program, a joint program of the NIH and Pfizer. NR 106 TC 8 Z9 8 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4790 J9 NAT REV RHEUMATOL JI Nat. Rev. Rheumatol. PD MAR PY 2011 VL 7 IS 3 BP 152 EP 160 DI 10.1038/nrrheum.2010.225 PG 9 WC Rheumatology SC Rheumatology GA 730DY UT WOS:000288014200005 PM 21283145 ER PT J AU Gilliam, M Allison, S Boyar, R Bull, S Guse, K Santelli, J AF Gilliam, Melissa Allison, Susannah Boyar, Robin Bull, Sheana Guse, Kylene Santelli, John TI New Media and Research: Considering Next Steps SO SEXUALITY RESEARCH AND SOCIAL POLICY LA English DT Article DE Sex education; Technology; Digital media; Adolescent; Evaluation and measurement; Behavior change theory AB This is an edited transcript of a roundtable discussion that was held on January 3, 2011. Six experts in the fields of new media and sexuality education discussed the most recent developments in the field, the opportunities presented by new technologies, measurement and evaluation strategies, and the theories that can be used to shape research in the field. C1 [Gilliam, Melissa; Guse, Kylene] Univ Chicago, Dept Obstet & Gynecol, Sect Family Planning & Contracept Res, Chicago, IL 60637 USA. [Allison, Susannah] NIMH, Infant Child & Adolescent Res Programs, Ctr Mental Hlth Res AIDS, Div AIDS & Hlth Behav Res,NIH, Bethesda, MA USA. [Boyar, Robin] Thinktank Res & Strategy, Berkeley, CA USA. [Bull, Sheana] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Community & Behav Hlth, Aurora, CO USA. [Santelli, John] Columbia Univ, Dept Populat & Family Hlth, Mailman Sch Publ Hlth, New York, NY USA. RP Gilliam, M (reprint author), Univ Chicago, Dept Obstet & Gynecol, Sect Family Planning & Contracept Res, 5841 S Maryland Ave,MC2050, Chicago, IL 60637 USA. EM mgilliam@babies.bsd.uchicago.edu NR 0 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-9884 J9 SEX RES SOC POLICY JI Sex. Res. Soc. Policy PD MAR PY 2011 VL 8 IS 1 BP 67 EP 72 DI 10.1007/s13178-011-0035-4 PG 6 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 769ED UT WOS:000290991400008 ER PT J AU Andrade, LR Arcanjo, KDS Martins, HSHL dos Reis, JSN Farina, M Borojevic, R Duarte, MEL AF Andrade, Leonardo Rodrigues Arcanjo, Katia Denise S. Martins, Humberto Saramago H. L. Nobre dos Reis, Joao Sergio Farina, Marcos Borojevic, Radovan Leite Duarte, Maria Eugenia TI Fine structure and molecular content of human chondrocytes encapsulated in alginate beads SO CELL BIOLOGY INTERNATIONAL LA English DT Article DE alginate; bioengineering; cartilage; electron microscopy; glycosaminoglycan ID ARTICULAR CHONDROCYTES; MATRIX SYNTHESIS; CARTILAGE; BONE; MICROCAPSULES; CULTURE AB Preservation of the chondrocytic phenotype in vitro requires a 3D (three-dimensional) culture model. Diverse biomaterials have been tested as scaffolds for culture of animal chondrocytes; however, to date, none is considered a gold standard in regenerative medicine. Here, we studied the fine structure and the GAGs (glycosaminoglycans) content of human chondrocytes encapsulated in alginate beads by using electron Microscopy and radioactive sulfate [(35)S] incorporation, respectively. Cells were obtained from human cartilage, encapsulated in alginate beads and cultured for 28 days. [(35)S]Na(2)SO(4) was added to the culture media and later isolated for quantification of the sulfated GAGs found in three compartments: IC (intracellular), IB (intra-bead) and EB (extra-bead). Round cells were seen isolated or forming small groups throughout the alginate. Human chondrocytes presented the features of active cells such as euchromatic nuclei, abundant RER (rough endoplasmic reticulum) and many transport vesicles. We observed an extracellular matrix rich in collagen fibres and electrondense material adjacent to the cells. Most of the GAGs produced (74%) were found in the culture medium (EB), indicating that alginate has a limited capacity to retain the GAGs. CS (chondroitin sulfate), the major component of aggrecan, was the most prominent GAG produced by the encapsulated cells. Human chondrocytes cultured in alginate can sustain their phenotype, confirming the potential application of this biomaterial for cartilage engineering. C1 [Andrade, Leonardo Rodrigues; Arcanjo, Katia Denise S.; Martins, Humberto Saramago H. L.; Nobre dos Reis, Joao Sergio; Farina, Marcos; Borojevic, Radovan] Univ Fed Rio de Janeiro, Ctr Hlth Sci, Inst Biomed Sci, Rio De Janeiro, Brazil. [Leite Duarte, Maria Eugenia] Natl Inst Traumatol & Orthopaed, Rio De Janeiro, Brazil. RP Andrade, LR (reprint author), NIDCD, Sect Struct Cell Biol, Lab Cell Struct & Dynam, NIH, 50 S Dr,Rm 4249, Bethesda, MD 20892 USA. EM andrade@histo.ufrj.br RI Andrade, Leonardo/C-9554-2011; Farina, Marcos/I-3744-2014; OI Andrade, Leonardo/0000-0002-0004-5677; Borojevic, Radovan/0000-0002-2393-7280 FU Fundacao Universitaria Josa Bonifacio (FUJB-UFRJ); Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) FX This work was supported by the Fundacao Universitaria Josa Bonifacio (FUJB-UFRJ) and Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ). NR 21 TC 4 Z9 4 U1 3 U2 15 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 1065-6995 J9 CELL BIOL INT JI Cell Biol. Int. PD MAR PY 2011 VL 35 IS 3 BP 293 EP 297 DI 10.1042/CBI20100273 PG 5 WC Cell Biology SC Cell Biology GA 759XR UT WOS:000290283300015 PM 20874706 ER PT J AU Sakakibara, N Kasiviswanathan, R Kelman, Z AF Sakakibara, Nozomi Kasiviswanathan, Rajesh Kelman, Zvi TI Mutational analysis of conserved aspartic acid residues in the Methanothermobacter thermautotrophicus MCM helicase SO EXTREMOPHILES LA English DT Article DE Archaea; DNA replication; MCM helicase; Methanothermobacter thermautotrophicus ID DNA-BINDING; PROTEIN; INSIGHTS; THERMOAUTOTROPHICUM; ARCHAEA; COMPLEX; DOMAIN AB Minichromosome maintenance (MCM) helicases are thought to function as the replicative helicases in archaea and eukarya, unwinding the duplex DNA in the front of the replication fork. The archaeal MCM helicase can be divided into three parts, the N-terminal, catalytic, and C-terminal regions. The N-terminal part of the protein is divided into three domains, A, B, and C, and was shown to be involved in protein multimerization and binding to single-and double-stranded DNA. Two Asp residues found in domain C are conserved among MCM proteins from different archaea. These residues are located in a loop at the interface with domain A. Mutations of these residues in the Methanothermobacter thermautotrophicus MCM protein, Asp202 and Asp203, to Asn result in a significant reduction in the ability of the enzyme to bind DNA and in lower thermal stability. However, the mutant proteins retained helicase and ATPase activities. Further investigation of the DNA binding revealed that the presence of ATP rescues the DNA binding deficiencies by these mutant proteins. Possible roles of these conserved residues in MCM function are discussed. C1 [Sakakibara, Nozomi; Kasiviswanathan, Rajesh] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. [Kelman, Zvi] Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. [Kelman, Zvi] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Sakakibara, N (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM sakakibaran@niaid.nih.gov RI Kasiviswanathan, Rajesh/D-2744-2012 FU NIST/UMD [70NANB9H9196]; National Science Foundation [MCB-0815646] FX We would like to thank Dr. Lori Kelman for her comments on the manuscript. Specialty oligonucleotide synthesis was supported as part of a NIST/UMD Joint Program in Bioscience Measurements (70NANB9H9196). This work was supported by a grant from the National Science Foundation (MCB-0815646). NR 25 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 1431-0651 J9 EXTREMOPHILES JI Extremophiles PD MAR PY 2011 VL 15 IS 2 BP 245 EP 252 DI 10.1007/s00792-010-0352-1 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 756TL UT WOS:000290037500012 PM 21274582 ER PT J AU Bae-Jump, V Yin, C Zong, X Van Dyke, T AF Bae-Jump, V. Yin, C. Zong, X. Van Dyke, T. TI Development of a preclinical serous ovarian cancer mouse model SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Bae-Jump, V.; Yin, C.; Zong, X.] Univ N Carolina, Chapel Hill, NC USA. [Van Dyke, T.] NCI, Frederick, MD 21701 USA. NR 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2011 VL 121 IS 1 SU 1 MA 44 BP S20 EP S20 DI 10.1016/j.ygyno.2010.12.051 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AF UT WOS:000290292300045 ER PT J AU Dinkelspiel, H Poitras, N Fetterman, B Kinney, W Cox, T Lorey, T Castle, P AF Dinkelspiel, H. Poitras, N. Fetterman, B. Kinney, W. Cox, T. Lorey, T. Castle, P. TI Pap-negative, human papillomavirus-positive screening results: Compliance with follow-up and results of follow-up SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Dinkelspiel, H.] Kaiser No Calif, Sacramento, CA USA. [Poitras, N.; Fetterman, B.; Kinney, W.; Lorey, T.] Kaiser Permanente Med Ctr, Oakland, CA USA. [Cox, T.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Castle, P.] NCI, Bethesda, MD 20892 USA. NR 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2011 VL 121 IS 1 SU 1 MA 61 BP S27 EP S28 DI 10.1016/j.ygyno.2010.12.068 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AF UT WOS:000290292300062 ER PT J AU Dinkelspiel, H Poitras, N Fetterman, B Kinney, W Cox, T Lorey, T Castle, P AF Dinkelspiel, H. Poitras, N. Fetterman, B. Kinney, W. Cox, T. Lorey, T. Castle, P. TI Cervical cancer rates in clinical practice with co-testing, interval extension and current evaluation of women with pap-negative, human papillomavirus-positive screening tests SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Dinkelspiel, H.] Kaiser No Calif, Sacramento, CA USA. [Poitras, N.; Fetterman, B.; Kinney, W.; Lorey, T.] Kaiser Permanente Med Ctr, Oakland, CA USA. [Cox, T.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Castle, P.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2011 VL 121 IS 1 SU 1 MA 41 BP S19 EP S19 DI 10.1016/j.ygyno.2010.12.048 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AF UT WOS:000290292300042 ER PT J AU Dinkelspiel, H Flanagan, T Kinney, W Fetterman, B Lorey, T Castle, P AF Dinkelspiel, H. Flanagan, T. Kinney, W. Fetterman, B. Lorey, T. Castle, P. TI Consequences of lengthening cervical cancer screening intervals on mammography rates SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Dinkelspiel, H.] Kaiser No Calif, Sacramento, CA USA. [Flanagan, T.; Kinney, W.; Fetterman, B.; Lorey, T.] Kaiser Permanente Med Ctr, Oakland, CA USA. [Castle, P.] NCI, Bethesda, MD 20892 USA. NR 0 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2011 VL 121 IS 1 SU 1 MA 246 BP S106 EP S107 DI 10.1016/j.ygyno.2010.12.253 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 760AF UT WOS:000290292300247 ER PT J AU Beydoun, HA Tamim, H Lincoln, AM Dooley, SD Beydoun, MA AF Beydoun, Hind A. Tamim, Hala Lincoln, Alicia M. Dooley, Suzanna D. Beydoun, May A. TI Association of physical violence by an intimate partner around the time of pregnancy with inadequate gestational weight gain SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Gestational weight gain; Violence; Body mass index; Pregnancy; Intimate partner violence ID SOCIAL SUPPORT; BIRTH-WEIGHT; HEALTH; OUTCOMES; ABUSE; WOMEN; RISK; BEHAVIORS; LIFE AB Intimate partner violence has been previously examined in relation to a variety of pregnancy, labor and delivery outcomes. We evaluated whether women who experienced physical violence by their intimate partners around the time of pregnancy were less likely to achieve weight gain according to the US Institute of Medicine (IOM) guidelines. A cross-sectional study was conducted using the 2000-2006 Oklahoma Pregnancy Risk Assessment Monitoring Survey (PRAMS) data for post-partum women, 20 years and older. Physical violence perpetrated by an intimate partner before and/or during pregnancy was prevalent in nearly 6.5% of women. Weight gain was adequate in 38.8%, deficient in 28.4% and excessive in 32.8% of these women, respectively. After adjusting for maternal age, marital status, education, pregnancy intention, stressful life events, third-trimester use of tobacco and alcohol and gestational age at delivery, physical violence by an intimate partner around the time of pregnancy was positively but non-significantly associated with excessive (but not deficient) gestational weight gain. After stratifying by age group, positive and significant associations between physical violence by an intimate partner around the time of pregnancy and inadequate gestational weight gain were observed only among women 35 years and older. With the exception of mothers >= 35 years of age, deficient and excessive gestational weight gains were not significantly related to experiences with physical violence by an intimate partner prior to delivery. Prospective cohort studies are needed to establish whether other forms of violence, including emotional and sexual abuse, can affect gestational weight gain and whether gestational weight gain can mediate the effect of physical, sexual and emotional abuse on pregnancy, labor and delivery outcomes. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA. [Tamim, Hala] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada. [Lincoln, Alicia M.; Dooley, Suzanna D.] Oklahoma Dept Hlth, Maternal & Child Hlth Serv, Oklahoma City, OK USA. [Beydoun, May A.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23507 USA. EM baydouha@evms.edu FU Centers for Disease Control and Prevention (CDC) [5UR6DP000483]; Oklahoma State Department of Health FX No funding was provided for this project. However, this research was supported in part by the intramural research program of the NIH, National Institute on Aging. Funding for The Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS) is provided in part by the Centers for Disease Control and Prevention (CDC) Grant Number 5UR6DP000483 and by the Oklahoma State Department of Health. NR 33 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 2011 VL 72 IS 6 BP 867 EP 873 DI 10.1016/j.socscimed.2011.01.006 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 757JA UT WOS:000290080100007 PM 21324411 ER PT J AU Evans, JD Zivin, K Weintraub, D Mamo, D Kales, HC AF Evans, Jovier D. Zivin, Kara Weintraub, Daniel Mamo, David Kales, Helen C. TI PSYCHOPHARMACOLOGY AND OLDER ADULTS: SAFETY, RISK, AND OPPORTUNITIES SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 18-21, 2011 CL San Antonio, TX SP Amer Assoc Geriat Psychiat C1 [Evans, Jovier D.] NIMH, Bethesda, MD 20892 USA. [Weintraub, Daniel] Univ Penn, Philadelphia, PA 19104 USA. [Zivin, Kara; Kales, Helen C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mamo, David] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2011 VL 19 IS 3 SU 1 BP S18 EP S18 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PD UT WOS:000289791000017 ER PT J AU Newhouse, P Resnick, SM Aizenstein, H Dumas, J Gunning-Dixon, F AF Newhouse, Paul Resnick, Susan M. Aizenstein, Howard Dumas, Julie Gunning-Dixon, Faith TI ADVANCES IN UNDERSTANDING COGNITIVE AND EMOTIONAL DISORDERS OF AGING THROUGH BRAIN IMAGING SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 18-21, 2011 CL San Antonio, TX SP Amer Assoc Geriat Psychiat C1 [Newhouse, Paul; Dumas, Julie] Univ Vermont, Burlington, VT USA. [Aizenstein, Howard] Univ Pittsburgh, Pittsburgh, PA USA. [Gunning-Dixon, Faith] Weill Cornell Med Coll, New York, NY USA. [Resnick, Susan M.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2011 VL 19 IS 3 SU 1 BP S39 EP S40 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PD UT WOS:000289791000046 ER PT J AU Niederehe, G Lee, FS Etkin, A Stanley, MA Shear, MK AF Niederehe, George Lee, Francis S. Etkin, Amit Stanley, Melinda A. Shear, M. Katherine TI TRANSLATIONAL RESEARCH ON AGING AND ANXIETY DISORDERS: MULTIPLE AVENUES SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 18-21, 2011 CL San Antonio, TX SP Amer Assoc Geriat Psychiat C1 [Niederehe, George] NIMH, Bethesda, MD 20892 USA. [Lee, Francis S.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Etkin, Amit] Stanford Univ, Stanford, CA 94305 USA. [Stanley, Melinda A.] Baylor Coll Med, Houston, TX 77030 USA. [Shear, M. Katherine] Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2011 VL 19 IS 3 SU 1 BP S44 EP S44 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PD UT WOS:000289791000052 ER PT J AU Resnick, SM Wassertheil-Smoller, S Goveas, JS Shih, R AF Resnick, Susan M. Wassertheil-Smoller, Sylvia Goveas, Joseph S. Shih, Regina TI ADVANCES IN THE UNDERSTANDING OF COGNITIVE AND MENTAL HEALTH IN POSTMENOPAUSAL WOMEN: EMERGING FINDINGS FROM THE WOMEN'S HEALTH INITIATIVE STUDIES SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Geriatric-Psychiatry CY MAR 18-21, 2011 CL San Antonio, TX SP Amer Assoc Geriat Psychiat C1 [Resnick, Susan M.] NIA, NIH, Baltimore, MD 21224 USA. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Goveas, Joseph S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Shih, Regina] RAND Corp, Arlington, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR PY 2011 VL 19 IS 3 SU 1 BP S35 EP S36 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 753PD UT WOS:000289791000040 ER PT J AU Keyak, J Jonsson, B Siggeirsdottir, K Eiriksdottir, G Gudnason, V Lang, T Sigurdsson, S Karlsdottir, G Oskarsdottir, D Sigmarsdottir, A Zhao, SJ Kornak, J Harris, T Sigurdsson, G AF Keyak, Joyce Jonsson, B. Siggeirsdottir, Kristin Eiriksdottir, Gudny Gudnason, V. Lang, Thomas Sigurdsson, Sigurdur Karlsdottir, Gyda Oskarsdottir, Diana Sigmarsdottir, Agusta Zhao, Shoujun Kornak, John Harris, Tamara Sigurdsson, Gunnar TI FORCE DIRECTIONS FOR OPTIMAL PROXIMAL FEMORAL STRENGTH AND HIP FRACTURE RISK ASSESSMENT IN MEN AND WOMEN: THE AGES-REYKJAVIK STUDY SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 1st IOF-ESCEO Pre-Clinical Symposium CY MAR 23-26, 2011 CL Valencia, SPAIN C1 [Keyak, Joyce] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA. [Siggeirsdottir, Kristin; Eiriksdottir, Gudny; Gudnason, V.; Sigurdsson, Sigurdur; Karlsdottir, Gyda; Oskarsdottir, Diana; Sigmarsdottir, Agusta; Sigurdsson, Gunnar] Iceland Heart Assoc, Kopavogur, Iceland. [Lang, Thomas; Zhao, Shoujun; Kornak, John] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Jonsson, B.] Malmo Univ Hosp, Malmo, Sweden. [Kornak, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Harris, Tamara] NIA, Dept Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Sigurdsson, Gunnar] Landspitalinn Univ Hosp, Reykjavik, Iceland. [Gudnason, V.; Sigurdsson, Gunnar] Univ Iceland, Reykjavik, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2011 VL 22 SU 1 BP 99 EP 99 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738SI UT WOS:000288662000138 ER PT J AU Ghorai, S Mukherjee, S Mukherjee, S Khowala, S AF Ghorai, Shakuntala Mukherjee, Sumana Mukherjee, Soumya Khowala, Suman TI Improved Production and Properties of beta-glucosidase Influenced by 2-deoxy-D-glucose in the Culture Medium of Termitomyces clypeatus SO BIOTECHNOLOGY AND BIOPROCESS ENGINEERING LA English DT Article DE beta-glucosidase; cellulolytic enzymes; 2-deoxy-D-glucose; Termitomyces clypeatus; saccharification ID TRICHODERMA-REESEI; CELLULOLYTIC ENZYMES; ENZYMATIC-HYDROLYSIS; CELLOBIASE; SECRETION; CELLULASE; 2-DEOXYGLUCOSE; FERMENTATION; PURIFICATION; ATROVIRIDE AB Increased production, secretion, and activity of beta-glucosidase in the filamentous fungus Termitomyces clypeatus was achieved in presence of the glycosylation inhibitor 2-deoxy-D-glucose (0.05%, w/v) during submerged fermentation. Enzyme activity increased to 163 U/mL by adding mannose (2 mg/mL) to the medium. Such a high enzyme activity has not been achieved without mutation or genetic manipulation. The K-m and V-max of the enzyme in culture medium were determined to be 0.092 mM and 35.54 U/mg, respectively, with p-nitrophenyl beta-D-glucopyranoside as substrate, confirming its high catalytic activity. The enzyme displayed optimum activity at pH 5.4 and 45 degrees C. The enzyme was fairly stable between acidic to alkaline pH and retained about 75 similar to 65% residual activities between pH 4 and 10.6 and demonstrated full activity at 45 degrees C for 3 days. The enzyme was also stable in the presence of Zn2+ and Mg2+ and 80% of the residual activity was observed in the presence of Mn2+, Ca2+, K+, Cu2+, EDTA, and sodium azide. Around 70% of the activity was retained in the presence of 2 M guanidium HCl and 3 M urea, whereas the activity was 5 and 2 times higher in the presence of 4 mM beta-mercaptoethanol and 50 mM DTI, respectively. The enzyme obtained from the culture filtrate showed potential cellulose saccharifying ability which increased further when supplemented with commercial cellulase. Thus, this enzyme could be used without any additional downstream processing for commercial cellulase preparation and production of bioethanol or for other biotechnological applications. C1 [Ghorai, Shakuntala; Mukherjee, Soumya; Khowala, Suman] Indian Inst Chem Biol, Drug Dev & Biotechnol Div, Kolkata 700032, India. [Mukherjee, Sumana] Natl Canc Inst Adv Technol Ctr, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Mukherjee, Sumana] Natl Canc Inst Adv Technol Ctr, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ghorai, S (reprint author), Indian Inst Chem Biol, Drug Dev & Biotechnol Div, Kolkata 700032, India. EM sumankhowala@iicb.res.in FU DBT; CSIR FX Financial support to SG by DBT and CSIR is duly acknowledged. NR 29 TC 2 Z9 2 U1 0 U2 2 PU KOREAN SOC BIOTECHNOLOGY & BIOENGINEERING PI SEOUL PA KOREAN SCIENCE TECHNOLOGY CENTER, #704 YEOGSAM-DONG, KANGNAM-KU, SEOUL 135-703, SOUTH KOREA SN 1226-8372 EI 1976-3816 J9 BIOTECHNOL BIOPROC E JI Biotechnol. Bioprocess Eng. PD MAR-APR PY 2011 VL 16 IS 2 BP 297 EP 304 DI 10.1007/s12257-010-0236-3 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 757FL UT WOS:000290070800011 ER PT J AU Ammary-Risch, NJ Huang, SS AF Ammary-Risch, Neyal J. Huang, Suber S. TI The Primary Care Physician's Role in Preventing Vision Loss and Blindness in Patients With Diabetes SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material DE diabetes; ophthalmic ID RETINOPATHY; PREVALENCE C1 [Ammary-Risch, Neyal J.] NEI, Natl Eye Hlth Educ Program, NIH, Bethesda, MD 20892 USA. [Huang, Suber S.] Case Western Reserve Univ, Sch Med, Dept Ophthalmol & Visual Sci, Cleveland, OH USA. [Huang, Suber S.] Case Western Reserve Univ, Sch Med, Ctr Retina & Macular Dis, Univ Hosp Eye Inst, Cleveland, OH USA. RP Ammary-Risch, NJ (reprint author), NEI, Natl Eye Hlth Educ Program, NIH, 31 Ctr Dr,Bldg 31-6A32, Bethesda, MD 20892 USA. EM ammaryn@nei.nih.gov NR 12 TC 1 Z9 2 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD MAR PY 2011 VL 103 IS 3 BP 281 EP 283 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 755UO UT WOS:000289964400013 PM 21671533 ER PT J AU Li, SW Thangapazham, RL Wang, JA Rajesh, S Kao, TC Sperling, L Moss, J Darling, TN AF Li, Shaowei Thangapazham, Rajesh L. Wang, Ji-an Rajesh, Sangeetha Kao, Tzu-Cheg Sperling, Leonard Moss, Joel Darling, Thomas N. TI Human TSC2-null fibroblast-like cells induce hair follicle neogenesis and hamartoma morphogenesis SO NATURE COMMUNICATIONS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; DERMAL PAPILLA CELLS; LUNG-TUMORS; STEM-CELLS; IN-VIVO; RAPAMYCIN; EXPRESSION; LESIONS; LYMPHANGIOLEIOMYOMATOSIS; ANGIOMYOLIPOMA AB Hamartomas are composed of cells native to an organ but abnormal in number, arrangement or maturity. In the tuberous sclerosis complex (TSC), hamartomas develop in multiple organs because of mutations in TSC1 or TSC2. Here we show that TSC2-null fibroblast-like cells grown from human TSC skin hamartomas induced normal human keratinocytes to form hair follicles and stimulated hamartomatous changes. Follicles were complete with sebaceous glands, hair shafts and inner and outer root sheaths. TSC2-null cells surrounding the hair bulb expressed markers of the dermal sheath and dermal papilla. Tumour xenografts recapitulated characteristics of TSC skin hamartomas with increased mammalian target of the rapamycin complex 1 (mTORC1) activity, angiogenesis, mononuclear phagocytes and epidermal proliferation. Treatment with an mTORC1 inhibitor normalized these parameters and reduced the number of tumour cells. These studies indicate that TSC2-null cells are the inciting cells for TSC skin hamartomas, and suggest that studies on hamartomas will provide insights into tissue morphogenesis and regeneration. C1 [Li, Shaowei; Thangapazham, Rajesh L.; Wang, Ji-an; Rajesh, Sangeetha; Sperling, Leonard; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. [Kao, Tzu-Cheg] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. EM tdarling@usuhs.mil OI Darling, Thomas/0000-0002-5161-1974 FU National Cancer Institute; Defense Medical Research and Development Program; Congressionally Directed Medical Research Programs; Tuberous Sclerosis Alliance; NIH, NHLBI FX This paper is dedicated to the memory of Jonathan Vogel, with continuing gratitude for his mentorship. We thank Jonathan Vogel and Atsushi Terunuma for training in creating and grafting dermal-epidermal composites. We thank the Tuberous Sclerosis Alliance and The LAM Foundation for patient referral, and Martha Vaughan, MD, for critical review of the manuscript. This work was supported by the National Cancer Institute, the Defense Medical Research and Development Program, and the Congressionally Directed Medical Research Programs (T.N.D.). S.L. was supported by a Junior Investigator Award from the Tuberous Sclerosis Alliance. J.M. was supported by the Intramural Research Program, NIH, NHLBI. NR 48 TC 14 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD MAR PY 2011 VL 2 AR 235 DI 10.1038/ncomms1236 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 756AC UT WOS:000289982600025 PM 21407201 ER PT J AU Chio, A Calvo, A Moglia, C Ossola, I Brunetti, M Sbaiz, L Lai, SL Abramzon, Y Traynor, BJ Restagno, G AF Chio, Adriano Calvo, Andrea Moglia, Cristina Ossola, Irene Brunetti, Maura Sbaiz, Luca Lai, Shiao-lin Abramzon, Yevgeniya Traynor, Bryan J. Restagno, Gabriella TI A de novo missense mutation of the FUS gene in a "true" sporadic ALS case SO NEUROBIOLOGY OF AGING LA English DT Article DE Amyotrophic lateral sclerosis; FUS; de novo mutation ID AMYOTROPHIC-LATERAL-SCLEROSIS AB Mutations in the Cu/Zn superoxide dismutase (SOD1) transactive response (TAR)-DNA binding protein (TARDBP) and fused in sarcoma (FUS) genes account for approximately 1 third of familial amyotrophic lateral sclerosis (ALS) cases. Mutations in these genes have been found in 1% to 2% of apparently sporadic cases. We present the first case of an AI,S patient carrying a de novo missense mutation of the FUS gene (c.1561C>T, p.R521C). This report highlights the importance of screening ALS patients, both familial and sporadic, for FUS mutations and also suggests that de novo Imitations is a relevant mechanism underlying sporadic neurodegenerative disease. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina] Univ Turin, ALS Ctr, Dept Neurosci, I-10126 Turin, Italy. [Ossola, Irene; Brunetti, Maura; Sbaiz, Luca; Restagno, Gabriella] ASO OIRM St Anna, Mol Genet Lab, Turin, Italy. [Lai, Shiao-lin; Abramzon, Yevgeniya; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Chio, A (reprint author), Univ Turin, ALS Ctr, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy. EM achio@usa.net RI Traynor, Bryan/G-5690-2010; Calvo, Andrea/K-4141-2016; Moglia, Cristina/K-4142-2016; OI Calvo, Andrea/0000-0002-5122-7243; Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341 FU Fondazione Vialli e Mauro for ALS Research Onlus; Federazione Italiana Giuoco Calcio (FICG); Ministero della Salute; NIH; National Institute on Aging [Z01 AG000949-02] FX This work was funded by grants of Fondazione Vialli e Mauro for ALS Research Onlus, Federazione Italiana Giuoco Calcio (FICG), and Ministero della Salute (Ricerca Sanitaria Finalizzata 2007) (Dr Chio); and Ministero della Salute (Ricerca Sanitaria Finalizzata 2007) (Dr Restagno). This work was supported in part by the Intramural Research Program of the NIH, and the National Institute on Aging (project Z01 AG000949-02). Funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 19 TC 12 Z9 14 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2011 VL 32 IS 3 AR 553.e23 DI 10.1016/j.neurobiolaging.2010.05.016 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 755PE UT WOS:000289944800039 PM 20598774 ER PT J AU Lai, SL Abramzon, Y Schymick, JC Stephan, DA Dunckley, T Dillman, A Cookson, M Calvo, A Battistini, S Giannini, F Caponnetto, C Luigi, G Spataro, R Monsurro, MR Tedeschi, G Marinou, K Sabatelli, M Conte, A Mandrioli, J Sola, P Salvi, F Bartolomei, I Lombardo, F Mora, G Restagno, G Chio, A Traynor, BJ AF Lai, Shiao-Lin Abramzon, Yevgeniya Schymick, Jennifer C. Stephan, Dietrich A. Dunckley, Travis Dillman, Allissa Cookson, Mark Calvo, Andrea Battistini, Stefania Giannini, Fabio Caponnetto, Claudia Luigi, Giovanni Spataro, Rossella Monsurro, Maria Rosaria Tedeschi, Gioacchino Marinou, Kalliopi Sabatelli, Mario Conte, Amelia Mandrioli, Jessica Sola, Patrizia Salvi, Fabrizio Bartolomei, Ilaria Lombardo, Federica Mora, Gabriele Restagno, Gabriella Chio, Adriano Traynor, Bryan J. CA ITALSGEN Consortium TI FUS mutations in sporadic amyotrophic lateral sclerosis SO NEUROBIOLOGY OF AGING LA English DT Article DE Amyotrophic lateral sclerosis; Sporadic disease; FUS; Italy; United States of America AB Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. Published by Elsevier Inc. C1 [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Lai, Shiao-Lin] Inst Neurol, Reta Lila Weston Inst Neurol Studies, London WC1 3BG, England. [Lai, Shiao-Lin] Inst Neurol, Dept Mol Neurosci, London WC1 3BG, England. [Lai, Shiao-Lin] Chang Gung Univ Coll Med & Hosp, Chiayi, Taiwan. [Schymick, Jennifer C.] Univ Oxford, Dept Clin Med, Oxford OX1 3QX, England. [Stephan, Dietrich A.] Navigenics, Foster City, CA 94404 USA. [Stephan, Dietrich A.] IGNITE Inst Individualized Hlth, Fairfax, VA 22042 USA. [Dunckley, Travis] Translat Genom Inst TGEN, Neurogenom Div, Phoenix, AZ 85004 USA. [Dillman, Allissa; Cookson, Mark] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA. [Calvo, Andrea; Chio, Adriano] Univ Turin, Dept Neurosci, I-10126 Turin, Italy. [Battistini, Stefania; Giannini, Fabio] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy. [Caponnetto, Claudia; Luigi, Giovanni] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Spataro, Rossella] Univ Palermo, Dept Clin Neurosci, I-90133 Palermo, Italy. [Monsurro, Maria Rosaria; Tedeschi, Gioacchino] Univ Naples 2, Dept Neurosci, Naples, Italy. [Monsurro, Maria Rosaria; Tedeschi, Gioacchino] Capodimonte Hermitage Inst, Naples, Italy. [Marinou, Kalliopi; Mora, Gabriele] Fdn Salvatore Maugeri, Milan, Italy. [Sabatelli, Mario; Conte, Amelia] Univ Cattolica Sacro Cuore, Neurol Inst, Rome, Italy. [Sabatelli, Mario; Conte, Amelia] ICOMM Assoc ALS Res, Rome, Italy. [Mandrioli, Jessica; Sola, Patrizia] Univ Modena, I-41100 Modena, Italy. [Mandrioli, Jessica; Sola, Patrizia] S Agostino Estense Hosp, Dept Neurosci, Modena, Italy. [Salvi, Fabrizio; Bartolomei, Ilaria] Bellaria Hosp, Ctr Diag & Cure Rare Dis, Dept Neurol, Bologna, Italy. [Lombardo, Federica; Restagno, Gabriella] ASO OIRM S Anna, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A-1000, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Traynor, Bryan/G-5690-2010; Battistini, Stefania/N-2596-2015; Calvo, Andrea/K-4141-2016; Spataro, Rossella/B-3656-2016; MANDRIOLI, JESSICA/K-7235-2016; mancardi, giovanni luigi/K-8656-2016; OI Battistini, Stefania/0000-0003-2887-7624; Calvo, Andrea/0000-0002-5122-7243; Spataro, Rossella/0000-0002-8910-3131; MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli, Mario/0000-0001-6635-4985; mancardi, giovanni luigi/0000-0001-8427-118X; Chio, Adriano/0000-0001-9579-5341 FU NIH, National Institute on Aging [Z01-AG000949-02]; Ministero della Salute, Ricerca Sanitaria Finalizzata; Fon-dazione Vialli e Mauro for ALS, Torino; Regione Piemonte, Progetti Finalizzati FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (Z01-AG000949-02). The work was also supported by Ministero della Salute, Ricerca Sanitaria Finalizzata 2007 (to AC, GR and GM); Fon-dazione Vialli e Mauro for ALS, Torino (to AC and GM); and Regione Piemonte, Progetti Finalizzati (to GR). NR 13 TC 11 Z9 12 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2011 VL 32 IS 3 AR 550.e1 DI 10.1016/j.neurobiolaging.2009.12.020 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 755PE UT WOS:000289944800030 PM 20138404 ER PT J AU Ramamoorthy, A Skaar, TC AF Ramamoorthy, Anuradha Skaar, Todd C. TI Gene copy number variations: it is important to determine which allele is affected SO PHARMACOGENOMICS LA English DT Editorial Material DE copy number variations; drug-metabolizing enzymes; pharmacogenetics ID HUMAN GENOME; DELETION POLYMORPHISMS; CYP2D6; JAPANESE; POPULATION C1 [Skaar, Todd C.] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. [Ramamoorthy, Anuradha] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Skaar, TC (reprint author), Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. EM tskaar@iupui.edu FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM088076, 1R01GM088076, R01 GM088076-02] NR 20 TC 11 Z9 11 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD MAR PY 2011 VL 12 IS 3 BP 299 EP 301 DI 10.2217/PGS.11.5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 752QL UT WOS:000289707400002 PM 21449666 ER PT J AU Vercruysse, T Pawar, S De Borggraeve, W Pardon, E Pavlakis, GN Pannecouque, C Steyaert, J Balzarini, J Daelemans, D AF Vercruysse, Thomas Pawar, Sonalika De Borggraeve, Wim Pardon, Els Pavlakis, George N. Pannecouque, Christophe Steyaert, Jan Balzarini, Jan Daelemans, Dirk TI Measuring cooperative Rev protein-protein interactions on Rev responsive RNA by fluorescence resonance energy transfer SO RNA BIOLOGY LA English DT Article DE Rev; RNA; Rev response element; multimerization; HIV-1; FRET ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MESSENGER-RNA; GENE-EXPRESSION REQUIRES; CYCLIC-PEPTIDES BEARING; NUCLEAR EXPORT SIGNAL; ARGININE RICH MOTIF; HIV-1 REV; FUNCTIONAL-ANALYSIS; TARGET SEQUENCE; IN-VITRO AB The export of viral RNA from the nucleus to the cytoplasm of the cellular host is a crucial step in the life cycle of HIV-1 that is mediated by the viral Rev protein. One aspect of the Rev function, its multimerization, is still unexplored as a target for antiviral therapy. This is partly due to the lack of a fast and solid system to measure Rev multimerization. We have developed a high throughput in vitro Rev multimerization assay based on fluorescence resonance energy transfer (FRET) in which real-time Rev-Rev interactions can be measured both in the absence and the presence of Rev specific RRE RNA. Well-characterized Rev multimerization deficient mutants showed reduced FRET as well as unlabeled Rev molecules were able to inhibit the FRET signal demonstrating the specificity of the assay. Upon multimerization along RRE RNA the FRET signal significantly increased but dropped again at equimolar Rev/RRE ratios suggesting that in this condition most Rev molecules are bound as monomers to the RRE. Furthermore, using this assay, we demonstrate that a previously selected llama heavy-chain only antibody was shown to not only prevent the development of Rev multimers but also disassemble the already formed complexes confirming the dynamic nature of the Rev-Rev interactions. The in vitro FRET based multimerization assay facilitates the further study of the basic mechanism of cooperative Rev multimerization along the RRE and is also widely applicable to study the assembly of other functional complexes involving protein homo-multimerization or cooperative protein-protein interactions on RNA or DNA. C1 [Vercruysse, Thomas; Pannecouque, Christophe; Balzarini, Jan; Daelemans, Dirk] Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. [Pawar, Sonalika; De Borggraeve, Wim] Katholieke Univ Leuven, Dept Chem, Louvain, Belgium. [Pardon, Els; Steyaert, Jan] Vrije Univ Brussel, VIB, Dept Mol Interact, Struct Biol Brussels Lab, Brussels, Belgium. [Pavlakis, George N.] NCI, Human Retrovirus Sect, NIH, Frederick, MD 21701 USA. RP Daelemans, D (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. EM dirk.daelemans@rega.kuleuven.be RI De Borggraeve, Wim/C-5179-2008; Steyaert, Jan/H-4662-2011 OI De Borggraeve, Wim/0000-0001-7813-6192; Steyaert, Jan/0000-0002-3825-874X FU Fonds voor Wetenschappelijk Onderzoek Vlaanderen [1.5.104.07, 1.5.165.10]; Institute for the Promotion of Innovation through Sciences and Technology in Flanders (IWT) FX This work was supported by the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (grants 1.5.104.07 and 1.5.165.10). Thomas Vercruysse was funded by a Ph.D. grant of the Institute for the Promotion of Innovation through Sciences and Technology in Flanders (IWT). NR 66 TC 10 Z9 11 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6286 J9 RNA BIOL JI RNA Biol. PD MAR-APR PY 2011 VL 8 IS 2 SI SI BP 316 EP 324 DI 10.4161/rna.8.2.13782 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 755MA UT WOS:000289934300018 PM 21358282 ER PT J AU Bogoslovsky, T Spatz, M Chaudhry, A Maric, D Luby, M Frank, J Warach, S AF Bogoslovsky, Tanya Spatz, Maria Chaudhry, Aneeka Maric, Dragan Luby, Marie Frank, Joseph Warach, Steven CA NINDS Nat Hist Stroke TI Stromal-Derived Factor-1 alpha Correlates With Circulating Endothelial Progenitor Cells and With Acute Lesion Volume in Stroke Patients SO STROKE LA English DT Article DE brain ischemia; cerebrovascular disease; endothelium; neuroregeneration ID COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; ACUTE ISCHEMIC-STROKE; BONE-MARROW; PERIPHERAL-BLOOD; STEM-CELLS; IN-VIVO; G-CSF; GROWTH-FACTOR; ANGIOGENESIS AB Background and Purpose-Endothelial progenitor cells (EPC) are important participants of neovascularization and are mobilized through signaling with stromal-derived factor (SDF-1 alpha), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and stem cell factor. The association between EPC levels and these growth factors (GF) in acute stroke has not been previously established. We aimed to determine the association between EPC and these GF, and to elucidate a relationship between these GF and stroke severity in acute stroke patients. Methods-Seventeen patients were selected from 175 patients with imaging-confirmed acute ischemic stroke. EPC were quantified using CD34, CD133, and VEGF-R2 markers. Plasma VEGF, SDF-1 alpha, granulocyte colony-stimulating factor, and stem cell factor were determined by enzyme-linked immunosorbent assay on days 1 and 3, and brain MRI was performed at baseline and on days 1 and 5 after the stroke onset. Results-Levels of SDF-1 alpha strongly (r=0.6) correlated with the numbers of EPC subsets CD133(+) VEFG-R2(+) (P<0.004), CD34(+) VEGF-R2(+) (P<0.01), and CD34(+) CD133(+) VEGF-R2(+) (P<0.01) on day 1. Stem cell factor strongly (r=0.5) correlated with CD133(+) VEGF-R2(+) (P<0.05). SDF-1 alpha moderately inversely (r=-0.49) correlated with baseline diffusion-weighted imaging lesion volumes (P<0.04). Median levels of SDF-1 alpha (1561 pg/mL) increased (P<0.04) on day 3 compared to day 1 (1379 pg/mL). Similarly, VEGF at day 3 (95 pg/mL) increased (P<0.03) compared to day 1 (64 pg/mL). Conclusions-These results indicate that SDF-1 alpha and stem cell factor correlate with an increase in EPC early in ischemic stroke patients. (Stroke. 2011;42:618-625.) C1 [Bogoslovsky, Tanya; Luby, Marie; Warach, Steven] Natl Inst Biomed Imaging & Bioengn, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD USA. [Spatz, Maria] Natl Inst Biomed Imaging & Bioengn, Stroke Branch, NIH, Bethesda, MD USA. [Maric, Dragan] NINDS, Flow Cytometry Core Facil, Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Chaudhry, Aneeka; Frank, Joseph] Natl Inst Biomed Imaging & Bioengn, Natl Inst Neurol Disorders & Stroke, Frank Lab, NIH, Bethesda, MD USA. [Chaudhry, Aneeka; Frank, Joseph] NCI, Ctr Clin, Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Bogoslovsky, T (reprint author), Uniformed Serv Univ Hlth Sci, NIH, NINR, CNRM, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM Tanya.Bogoslovsky.CTR@usuhs.mil FU National Institute of Neurological Disorders and Stroke, National Institutes of Health; Finnish Medical Foundation; Biomedicum Foundation FX This research was supported by the Division of Intramural Research of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, and by research grants from the Finnish Medical Foundation and the Biomedicum Foundation. NR 48 TC 36 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP 618 EP 625 DI 10.1161/STROKEAHA.110.596007 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401449 PM 21257825 ER PT J AU Anderson, CD Nalls, MA Biffi, A Rost, NS Greenberg, SM Singleton, AB Meschia, JF Rosand, J AF Anderson, Christopher D. Nalls, Michael A. Biffi, Alessandro Rost, Natalia S. Greenberg, Steven M. Singleton, Andrew B. Meschia, James F. Rosand, Jonathan TI The Effect of Survivorship Bias on Cross-Sectional Case-Control Genetic Studies of Highly Lethal Diseases SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Anderson, Christopher D.; Biffi, Alessandro; Rost, Natalia S.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nalls, Michael A.; Singleton, Andrew B.] NIH, Bethesda, MD 20892 USA. [Meschia, James F.] Mayo Clin, Jacksonville, FL 32224 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E186 EP E186 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400491 ER PT J AU Batra, A Song, SS Merino, JG Hsia, AW Lynch, JK Luby, M Latour, LL Warach, S AF Batra, Ayush Song, Shlee S. Merino, Jose G. Hsia, Amie W. Lynch, John K. Luby, Marie Latour, Lawrence L. Warach, Steven TI Older Patients are at Higher Risk for Blood-Brain Barrier Disruption Following Treatment with IV-tPA, Independent of Impaired Kidney Function SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Batra, Ayush; Song, Shlee S.; Merino, Jose G.; Hsia, Amie W.; Lynch, John K.; Luby, Marie; Latour, Lawrence L.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E253 EP E253 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401082 ER PT J AU Benson, RT Hsia, AW Pehlivanova, M Merino, J Latour, L Luby, M Song, S Lynch, J Ritter, CH Katcheves, A Warach, S AF Benson, Richard T. Hsia, Amie W. Pehlivanova, Marieta Merino, Jose Latour, Lawrence Luby, Marie Song, Shlee Lynch, John Ritter, Carsten H. Katcheves, Alexander Warach, Steve TI Heavy Alcohol Consumption: A Novel Predictor of Symptomatic Intracerebral Hemorrhage After IV t-PA? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Benson, Richard T.; Hsia, Amie W.; Latour, Lawrence; Luby, Marie; Song, Shlee; Lynch, John; Ritter, Carsten H.; Warach, Steve] NIH, Stroke Program, Washington, DC USA. [Pehlivanova, Marieta] MedStar Hlth Rsch Inst, Hyattsville, MD USA. [Merino, Jose] Suburban Hosp, NIH, Stroke Program, Bethesda, MD USA. [Katcheves, Alexander] Anne Arundel Med Cntr, Annapolis, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E265 EP E265 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401126 ER PT J AU Bogoslovsky, T Spatz, M Chaudhry, A Luby, M Maric, D Frank, J Warach, S AF Bogoslovsky, Tanya Spatz, Maria Chaudhry, Aneeka Luby, Marie Maric, Dragan Frank, Joseph Warach, Steven TI Circulating Endothelial Progenitor Cells CD133+CD34+Correlate With ICAM-1 In Early Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Bogoslovsky, Tanya; Spatz, Maria; Chaudhry, Aneeka; Luby, Marie; Maric, Dragan; Frank, Joseph; Warach, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E68 EP E68 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400095 ER PT J AU Davis, L Latour, L Song, S Ritter, CH Luby, M Mirasol, R Ku, K Shupenko, L Warach, S AF Davis, Lisa Latour, Lawrence Song, Shlee Ritter, Carsten H. Luby, Marie Mirasol, Raymond Ku, Katherine Shupenko, Leslie Warach, Steven CA NINDS LESION II Investigators TI A Clinical Trial Recruitment Dilemma: Imaging Entry Criteria Failure or Too Few Treatable Patients? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Davis, Lisa; Latour, Lawrence; Song, Shlee; Ritter, Carsten H.; Luby, Marie; Mirasol, Raymond; Ku, Katherine; Shupenko, Leslie; Warach, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E95 EP E95 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400187 ER PT J AU Famakin, BM Mou, YS Ruetzler, CA Lawal, MM Hallenbeck, JM AF Famakin, Bolanle M. Mou, Yongshan Ruetzler, Christl A. Lawal, Modinat M. Hallenbeck, John M. TI Cytokine Expression in the Brains and Serum of MyD88-/- and TRIF mutant mice following permanent Middle Cerebral Artery Occlusion SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Famakin, Bolanle M.; Lawal, Modinat M.] NINDS, NIH, Stroke Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E216 EP E217 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400596 ER PT J AU Freeman, JW Song, SS Merino, JG Hsia, AW Lynch, JK Luby, M Latour, LL Warach, S AF Freeman, Jason W. Song, Shlee S. Merino, Jose G. Hsia, Amie W. Lynch, John K. Luby, Marie Latour, Lawrence L. Warach, Steven TI Complete Reperfusion On MRI 5 Days After IV tPA Treatment Is Indicative Of Early Reperfusion: Evidence From The Lesion Project SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Freeman, Jason W.; Song, Shlee S.; Lynch, John K.; Luby, Marie; Latour, Lawrence L.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. [Merino, Jose G.] Suburban Hosp Stroke Program, Bethesda, MD USA. [Hsia, Amie W.] Washington Hosp Cntr, Stroke Cntr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E166 EP E166 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400410 ER PT J AU Haley, T Devereux, G Hodgson, K Swendsen, H Chatfield, F Conwit, R Starkman, S Saver, JL AF Haley, Theresa Devereux, Gillian Hodgson, Keta Swendsen, Heavenly Chatfield, Fiona Conwit, Robin Starkman, Sidney Saver, Jeffrey L. CA FAST-MAG Investigators Coordinator TI Challenges in Accessing Medical Records in a Multi-Site Stroke Trial SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Haley, Theresa; Devereux, Gillian; Hodgson, Keta; Swendsen, Heavenly; Chatfield, Fiona; Starkman, Sidney; Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Conwit, Robin] NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E296 EP E296 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401234 ER PT J AU Haley, T Gordon, M McCall, K Sanoff, R Lee, M Tran, A Chatfield, F Conwit, R Eckstein, M Stratton, S Pratt, F Starkman, S Saver, J AF Haley, Theresa Gordon, Miranda McCall, Kanika Sanoff, Randy Lee, Michael Tran, Ann Chatfield, Fiona Conwit, Robin Eckstein, Marc Stratton, Sam Pratt, Frank Starkman, Sidney Saver, Jeffrey CA FAST-MAG Investigators TI Paramedics and Prehospital Stroke Research Trials: Effective Education Strategies SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Eckstein, Marc] Univ Calif Los Angeles, Los Angeles Fire Dept, Los Angeles, CA USA. [Conwit, Robin] NIH, Baltimore, MD USA. [Stratton, Sam] Orange Cty EMS Agcy, Santa Ana, CA USA. [Pratt, Frank] LA Cty Fire Dept, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E207 EP E207 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400560 ER PT J AU Hernandez, DA Bokkers, RP Mirasol, RV Luby, M Henning, EC Merino, JG Warach, S Latour, LL AF Hernandez, Daymara A. Bokkers, Reinoud P. Mirasol, Raymond V. Luby, Marie Henning, Erica C. Merino, Jose G. Warach, Steven Latour, Lawrence L. TI Cerebral Blood Flow Quantification Utilizing Pseudo-Continuous Arterial Spin Labeling in Acute Stroke Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Hernandez, Daymara A.; Mirasol, Raymond V.; Luby, Marie; Henning, Erica C.; Warach, Steven; Latour, Lawrence L.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. [Bokkers, Reinoud P.] UMC Utrecht, Dept Radiol, Utrecht, Netherlands. [Merino, Jose G.] Suburban Hosp Stroke Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E286 EP E286 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401199 ER PT J AU Howard, G Lackland, DT Kleindorfer, DO Kissela, BM Moy, CS Safford, MM Cushman, M Glasser, SP Howard, VJ AF Howard, George Lackland, Daniel T. Kleindorfer, Dawn O. Kissela, Brett M. Moy, Claudia S. Safford, Monika M. Cushman, Mary Glasser, Steve P. Howard, Virginia J. TI Could Racial Differences In Susceptibility To Elevated Blood Pressures Contribute To The Excess Stroke Mortality In Blacks: The Reasons For Geographic And Racial Differences In Stroke (REGARDS) Study? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Howard, George; Safford, Monika M.; Glasser, Steve P.; Howard, Virginia J.] Univ Alabama, Birmingham, AL USA. [Lackland, Daniel T.] Med Univ S Carolina, Charleston, SC 29425 USA. [Kleindorfer, Dawn O.; Kissela, Brett M.] Univ Cincinnati, Cincinnati, OH USA. [Moy, Claudia S.] NINDS, NIH, Bethesda, MD 20892 USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E49 EP E49 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400033 ER PT J AU Hsia, AW Benson, RT Pehlivanova, M Merino, JG Latour, LL Luby, M Song, SS Lynch, JK Ritter, CH Katcheves, A Warach, S AF Hsia, Amie W. Benson, Richard T. Pehlivanova, Marieta Merino, Jose G. Latour, Larry L. Luby, Marie Song, Shlee S. Lynch, John K. Ritter, Carsten H. Katcheves, Alex Warach, Steven TI Evaluation Of Patients Treated With IV tPA At Regional Stroke Centers vs. Community Hospitals: Is There Opportunity For A Wider Stroke Population To Be Treated? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Hsia, Amie W.; Benson, Richard T.] Washington Hosp Cntr, Stroke Cntr, Washington, DC USA. [Pehlivanova, Marieta] Medstar Hlth Rsch Inst, Washington, DC USA. [Merino, Jose G.] Suburban Hosp, Stroke Cntr, Bethesda, MD USA. [Latour, Larry L.; Luby, Marie; Song, Shlee S.; Lynch, John K.; Ritter, Carsten H.; Katcheves, Alex; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E264 EP E264 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401123 ER PT J AU Kernan, WN Viscoli, CM Brass, LM Amatangelo, MP Birch, A Clark, W Conwit, R Furie, KL Gorman, M Hinnau, E Kleindorfer, D Lovejoy, AM Osborne, J Silliman, S Zweifler, RM Horwitz, RI AF Kernan, Walter N. Viscoli, Catherine M. Brass, Lawrence M. Amatangelo, Mary P. Birch, Ashley Clark, Wayne Conwit, Robin Furie, Karen L. Gorman, Mark Hinnau, Elizabeth Kleindorfer, Dawn Lovejoy, Anne M. Osborne, Jenny Silliman, Scott Zweifler, Richard M. Horwitz, Ralph I. CA IRIS Trial Investigators TI Local Hospital Networks for Clinical Trials in Stroke SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Kernan, Walter N.; Viscoli, Catherine M.; Brass, Lawrence M.; Hinnau, Elizabeth; Lovejoy, Anne M.] Yale Univ, Sch Med, New Haven, CT USA. [Amatangelo, Mary P.; Birch, Ashley; Furie, Karen L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clark, Wayne] Oregon Hlth & Sci Univ, Portland, OR USA. [Conwit, Robin] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Gorman, Mark] Univ Vermont, Burlington, VT USA. [Kleindorfer, Dawn; Osborne, Jenny] Univ Cincinnati, Cincinnati, OH USA. [Silliman, Scott] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Zweifler, Richard M.] Eastern Virginia Med Sch, Norfold, VA USA. [Horwitz, Ralph I.] Stanford Univ, Palo Alto, CA 94304 USA. RI Zweifler, Richard/K-1314-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E158 EP E159 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400386 ER PT J AU Kim, H Crago, E Kim, M Conley, Y Sherwood, P Poloyac, S Kerr, ME AF Kim, Hyungsuk Crago, Elizabeth Kim, Mirim Conley, Yvette Sherwood, Paula Poloyac, Samuel Kerr, Mary E. TI Genome-wide SNP Association For Cerebral Vasospasm In Subarachnoid Hemorrhage Patients SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Kim, Hyungsuk; Kim, Mirim; Poloyac, Samuel; Kerr, Mary E.] NINR, Bethesda, MD 20892 USA. [Crago, Elizabeth; Conley, Yvette; Sherwood, Paula] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E270 EP E270 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401144 ER PT J AU Kissela, BM Judd, S Safford, M Voeks, J Rhodes, D Kleindorfer, D Meschia, J Anderson, A Levine, D Moy, C Howard, VJ Howard, G AF Kissela, Brett M. Judd, Suzanne Safford, Monika Voeks, Jennifer Rhodes, David Kleindorfer, Dawn Meschia, James Anderson, Aaron Levine, Deborah Moy, Claudia Howard, Virginia J. Howard, George TI Effect of Diabetes (DM) on Ischemic Stroke Incidence and Case Fatality SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Kissela, Brett M.; Kleindorfer, Dawn] Univ Cincinnati, Cincinnati, OH USA. [Judd, Suzanne; Safford, Monika; Rhodes, David; Howard, Virginia J.; Howard, George] Univ Alabama, Birmingham, AL USA. [Voeks, Jennifer] Med Univ S Carolina, Charleston, SC 29425 USA. [Meschia, James] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Anderson, Aaron] Emory Univ, Atlanta, GA 30322 USA. [Levine, Deborah] Univ Michigan, Ann Arbor, MI 48109 USA. [Moy, Claudia] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E116 EP E117 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400241 ER PT J AU Liebeskind, DS Sanossian, N Villablanca, P Starkman, S Scalzo, F Hao, Q Hernandez, A Avelar, JL Chatfield, F Conwit, R Saver, JL AF Liebeskind, David S. Sanossian, Nerses Villablanca, Pablo Starkman, Sidney Scalzo, Fabien Hao, Qing Hernandez, Annel Avelar, Johanna L. Chatfield, Fiona Conwit, Robin Saver, Jeffrey L. CA FAST-MAG Investigators TI CT Findings at the Earliest Stages of Ischemia: Imaging from the FAST-MAG Prehospital Stroke Trial SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Liebeskind, David S.; Villablanca, Pablo; Starkman, Sidney; Scalzo, Fabien; Hao, Qing; Hernandez, Annel; Avelar, Johanna L.; Chatfield, Fiona; Saver, Jeffrey L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Sanossian, Nerses] USC, Los Angeles, CA USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E56 EP E57 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400055 ER PT J AU Luby, M Boparai, S Lynch, JK Merino, JG Latour, LL Song, SS Hsia, AW Warach, S AF Luby, Marie Boparai, Sundeep Lynch, John K. Merino, Jose G. Latour, Lawrence L. Song, Shlee S. Hsia, Amie W. Warach, Steven TI Does Threshold Based Segmentation of MRI Correlate with Visual Reading of Ischemia and Perfusion Deficit in Acute Scans? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Luby, Marie; Boparai, Sundeep; Lynch, John K.; Merino, Jose G.; Latour, Lawrence L.; Song, Shlee S.; Hsia, Amie W.; Warach, Steven] NINDS, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E280 EP E281 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401182 ER PT J AU McClure, LA Szychowski, JM Benavente, O Hart, RG Conwit, R Coffey, CS AF McClure, Leslie A. Szychowski, Jeff M. Benavente, Oscar Hart, Robert G. Conwit, Robin Coffey, Christopher S. TI The Use of an Unplanned Adaptive Design in an NIH-Sponsored Stroke Prevention Trial - Observations from SPS3 SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [McClure, Leslie A.; Szychowski, Jeff M.] Univ Alabama, Birmingham, AL USA. [Benavente, Oscar] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Hart, Robert G.] Univ Texas Hlth Sci Cntr, San Antonio, TX USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. [Coffey, Christopher S.] Univ Iowa, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E81 EP E81 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400139 ER PT J AU Merino, JG Latour, LL Tso, AR Lee, KY Kang, DW Davis, LA Warach, S AF Merino, Jose G. Latour, Lawrence L. Tso, Amy R. Lee, Kyung Y. Kang, Dong W. Davis, Lisa A. Warach, Steven CA CLOCS Investigators TI Blood-Brain Barrier Disruption After Cardiac Surgery SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Merino, Jose G.] Suburban Hosp Stroke Program, Bethesda, MD USA. [Latour, Lawrence L.; Davis, Lisa A.; Warach, Steven] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Tso, Amy R.] UCSF, Dept Neurol, San Francisco, CA USA. [Lee, Kyung Y.] Yonsei Univ, Coll Med, Seoul, South Korea. [Kang, Dong W.] Asan Med Cntr, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E90 EP E90 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400170 ER PT J AU Meschia, JF Nalls, MA Rich, SS Singleton, A Hardy, JA Brott, TG Brown, RD Kissela, B Worrall, BB AF Meschia, James F. Nalls, Michael A. Rich, Stephen S. Singleton, Andrew Hardy, John A. Brott, Thomas G. Brown, Robert D., Jr. Kissela, Brett Worrall, Bradford B. CA SWISS Investigators TI Genome-wide Search for Ischemic Stroke Genes: The Siblings with Ischemic Stroke Study (SWISS) SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Meschia, James F.; Brott, Thomas G.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Nalls, Michael A.; Singleton, Andrew] NIA, Neurogenet Lab, Intramural Rsch Program, Bethesda, MD 20892 USA. [Rich, Stephen S.] Univ Virginia, Cntr Publ Hlth Genom, Charlottesville, VA USA. [Hardy, John A.] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Kissela, Brett] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E269 EP E269 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401140 ER PT J AU Nadareishvili, Z Luby, M Lee, KY Latour, LL Warach, SW AF Nadareishvili, Zurab Luby, Marie Lee, Kyung-Yul Latour, Lawrence L. Warach, Steven Warach TI Surrogate Markers of Perfusion/Diffusion Mismatch In The Three To Twelve Hour Time Window From Stroke Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Nadareishvili, Zurab; Luby, Marie; Latour, Lawrence L.; Warach, Steven Warach] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Lee, Kyung-Yul] Yonsei Univ, Coll Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E69 EP E69 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400096 ER PT J AU Ritter, CH Chalela, JA Butman, JA Demchuk, AM Hill, MD Patronas, N Warach, S AF Ritter, Carsten H. Chalela, Julio A. Butman, John A. Demchuk, Andrew M. Hill, Michael D. Patronas, Nicholas Warach, Steven TI The Superiority of MRI over CT in the Diagnosis of Acute Ischemic Stroke Increases with Patient Age SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Ritter, Carsten H.; Butman, John A.; Patronas, Nicholas; Warach, Steven] NIH, Bethesda, MD 20892 USA. [Chalela, Julio A.] Med Univ S Carolina, Charleston, SC USA. [Demchuk, Andrew M.; Hill, Michael D.] Foothills Med Cntr, Calgary, AB, Canada. RI Demchuk, Andrew/E-1103-2012; Hill, Michael/C-9073-2012 OI Demchuk, Andrew/0000-0002-4930-7789; Hill, Michael/0000-0002-6269-1543 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E288 EP E288 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401206 ER PT J AU Ross, OA Soto-Ortolaza, AI Verbeeck, C Rich, SS Singleton, A Hardy, JA Brott, TG Brown, RD Kissela, B Worrall, BB Meschia, JF AF Ross, Owen A. Soto-Ortolaza, Alexandra I. Verbeeck, Christophe Rich, Stephen S. Singleton, Andrew Hardy, John A. Brott, Thomas G. Brown, Robert D., Jr. Kissela, Brett Worrall, Bradford B. Meschia, James F. CA SWISS Investigators TI Results of NOTCH3 Sequencing in Siblings with Ischemic Stroke Study Probands SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Rich, Stephen S.] Univ Virginia, Cntr Publ Hlth Genom, Charlottesville, VA USA. [Singleton, Andrew] NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Hardy, John A.] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Kissela, Brett] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. RI Singleton, Andrew/C-3010-2009; Ross, Owen/D-7573-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E269 EP E269 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401141 ER PT J AU Sanossian, N Starkman, S Hamilton, S Liebeskind, DS Eckstein, M Stratton, S Pratt, F Restrepo, L Ali, LK Conwit, R Saver, JL AF Sanossian, Nerses Starkman, Sidney Hamilton, Scott Liebeskind, David S. Eckstein, Marc Stratton, Samuel Pratt, Frank Restrepo, Lucas Ali, Latisha K. Conwit, Robin Saver, Jeffrey L. CA FAST-MAG Investigators & Coordinat TI Early Clinical Deterioration of Stroke Patients Assessed in the Field within Two Hours of Symptom Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sanossian, Nerses; Eckstein, Marc] Univ So Calif, Los Angeles, CA USA. [Starkman, Sidney; Liebeskind, David S.; Restrepo, Lucas; Ali, Latisha K.; Saver, Jeffrey L.] UCLA Stroke Cntr, Los Angeles, CA USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Stratton, Samuel] Univ Calif Los Angeles, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire Dept, Los Angeles, CA USA. [Conwit, Robin] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E291 EP E291 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401217 ER PT J AU Sanossian, N Kim, MA Hamilton, S Starkman, S Liebeskind, DS Eckstein, M Stratton, S Pratt, F Conwit, R Saver, JL AF Sanossian, Nerses Kim, May A. Hamilton, Scott Starkman, Sidney Liebeskind, David S. Eckstein, Marc Stratton, Samuel Pratt, Frank Conwit, Robin Saver, Jeffrey L. CA FAST-MAG Investigators Coordinator TI Frequency of Complete Resolution of Motor Symptoms among Stroke Patients Evaluated within 2 Hours of Symptom Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sanossian, Nerses; Kim, May A.; Eckstein, Marc] Univ So Calif, Los Angeles, CA USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Starkman, Sidney; Liebeskind, David S.; Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Cntr, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire Dept, Los Angeles, CA USA. [Conwit, Robin] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E210 EP E210 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400571 ER PT J AU Sanossian, N Eckstein, M Stratton, S Pratt, F Koenig, W Hamilton, S Conwit, R Sanoff, R Starkman, S Liebeskind, DS Saver, JL AF Sanossian, Nerses Eckstein, Marc Stratton, Samuel Pratt, Frank Koenig, William Hamilton, Scott Conwit, Robin Sanoff, Randy Starkman, Sidney Liebeskind, David S. Saver, Jeffrey L. CA FAST-MAG Investigators Coordinatr TI Recruitment of Stroke Patients into Prehospital Research Before and After Implementation of a System-Wide Stroke Triage Policy SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sanossian, Nerses; Eckstein, Marc] Univ So Calif, Los Angeles, CA USA. [Stratton, Samuel; Sanoff, Randy] Univ Calif Los Angeles, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire Dept, Los Angeles, CA USA. [Koenig, William] Los Angeles Cty Emergency Med Serv, Los Angeles, CA USA. [Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA. [Conwit, Robin] NIH, Bethesda, MD 20892 USA. [Starkman, Sidney; Liebeskind, David S.; Saver, Jeffrey L.] UCLA Stroke Cntr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E146 EP E146 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400345 ER PT J AU Sanossian, N Starkman, S Liebeskind, DS Restrepo, L Ali, LK Conwit, R Eckstein, M Stratton, S Pratt, F Saver, JL AF Sanossian, Nerses Starkman, Sidney Liebeskind, David S. Restrepo, Lucas Ali, Latisha K. Conwit, Robin Eckstein, Marc Stratton, Samuel Pratt, Frank Saver, Jeffrey L. CA FAST-MAG Investigators Coordinator TI Feasibility and Yield of a Brief Questionnaire to Help Identify Intracerebral Hemorrhage among Stroke Patients in the Field SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Sanossian, Nerses; Eckstein, Marc] Univ So Calif, Los Angeles, CA USA. [Starkman, Sidney; Liebeskind, David S.; Restrepo, Lucas; Ali, Latisha K.; Saver, Jeffrey L.] UCLA Stroke Cntr, Los Angeles, CA USA. [Conwit, Robin] NIH, Bethesda, MD 20892 USA. [Stratton, Samuel] Univ Calif Los Angeles, Los Angeles, CA USA. [Pratt, Frank] Los Angeles Cty Fire Dept, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E147 EP E147 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400347 ER PT J AU Saver, JL Sanossian, N Hamilton, S Liebeskind, DS Ali, L Restrepo, L Kim, MA Valdes-Sueiras, M Conwit, R Starkman, S AF Saver, Jeffrey L. Sanossian, Nerses Hamilton, Scott Liebeskind, David S. Ali, Latisha Restrepo, Lucas Kim, May A. Valdes-Sueiras, Miguel Conwit, Robin Starkman, Sidney CA FAST-MAG Investigators Coordinator TI Patient Versus Proxy Explicit Informed Consent for Enrollment in a Prehospital Stroke Treatment Trial SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Saver, Jeffrey L.; Liebeskind, David S.; Ali, Latisha; Restrepo, Lucas; Valdes-Sueiras, Miguel; Starkman, Sidney] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Hamilton, Scott] Stanford, Palo Alto, CA USA. [Sanossian, Nerses; Kim, May A.] USC, Los Angeles, CA USA. [Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E58 EP E58 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400060 ER PT J AU Shanbhag, DD Mullick, R Nath, S Luby, M Latour, LL Warach, S AF Shanbhag, Dattesh D. Mullick, Rakesh Nath, Sumit Luby, Marie Latour, Lawrence L. Warach, Steven TI Is There An Association Between The First Moment Method MTT And Tmax Based Mismatch Estimates In Acute Ischemic Stroke? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Shanbhag, Dattesh D.; Mullick, Rakesh; Nath, Sumit] GE Global Rsch, Bangalore, Karnataka, India. [Luby, Marie; Latour, Lawrence L.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E165 EP E166 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400409 ER PT J AU Song, SS Latour, LL Luby, M Wu, O Chalela, JA Butman, JA Demchuk, AM Hill, MD Patronas, N Warach, S AF Song, Shlee S. Latour, Lawrence L. Luby, Marie Wu, Ona Chalela, Julio A. Butman, John A. Demchuk, Andrew M. Hill, Michael D. Patronas, Nicholas Warach, Steven TI Negative CT in Witnessed Onset Acute Ischemic Stroke Patients is Not a Reliable Indicator for Early Stroke Onset SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Song, Shlee S.; Latour, Lawrence L.; Luby, Marie; Warach, Steven] NIH, Stroke Branch, Bethesda, MD 20892 USA. [Wu, Ona] Massachusetts Gen Hosp, Athinoula A Martinos Cntr, Dept Radiol, Charlestown, MA USA. [Chalela, Julio A.] Med Univ S Carolina, Charleston, SC 29425 USA. [Butman, John A.; Patronas, Nicholas] NIH Clin Cntr, Bethesda, MD USA. [Demchuk, Andrew M.; Hill, Michael D.] Univ Calgary, Calgary, AB T2N 1N4, Canada. RI Demchuk, Andrew/E-1103-2012; Hill, Michael/C-9073-2012 OI Demchuk, Andrew/0000-0002-4930-7789; Hill, Michael/0000-0002-6269-1543 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E137 EP E138 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400316 ER PT J AU Wadley, VG Letter, AJ Unverzagt, FW McClure, LA Howard, G Howard, VJ Cushman, M Kelley, BJ Moy, CS Kissela, B AF Wadley, Virginia G. Letter, Abraham J. Unverzagt, Frederick W. McClure, Leslie A. Howard, George Howard, Virginia J. Cushman, Mary Kelley, Brendan J. Moy, Claudia S. Kissela, Brett TI Lower Executive Function Increases Risk For Incident Stroke in the National REGARDS Cohort SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Wadley, Virginia G.; Letter, Abraham J.; McClure, Leslie A.; Howard, George; Howard, Virginia J.] Univ Alabama, Birmingham, AL USA. [Unverzagt, Frederick W.] Indiana Univ Purdue Univ, Indianapolis, IN 46202 USA. [Cushman, Mary] Univ Vermont, Burlington, VT USA. [Kelley, Brendan J.; Kissela, Brett] Univ Cincinnati, Cincinnati, OH USA. [Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E55 EP E56 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400051 ER PT J AU Warach, S Luby, M Lynch, JK Merino, JG Hsia, AW Song, SS Latour, LL AF Warach, Steven Luby, Marie Lynch, John K. Merino, Jose G. Hsia, Amie W. Song, Shlee S. Latour, Lawrence L. CA LESION Investigators TI The LESION Project Baseline Results Probability of Diffusion-Perfusion Mismatch, MCA Occlusion and their Relationship to Time Window SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Warach, Steven; Luby, Marie; Lynch, John K.; Merino, Jose G.; Hsia, Amie W.; Song, Shlee S.; Latour, Lawrence L.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E65 EP E65 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400084 ER PT J AU Willey, JZ Khatri, P Khoury, J Gonzales, NR Merino, J Rost, NS Ali, LK Ford, A Meyer, BC Broderick, JP AF Willey, Joshua Z. Khatri, Pooja Khoury, Jane Gonzales, Nichole R. Merino, Jose Rost, Natalia S. Ali, Latisha K. Ford, Andria Meyer, Brett C. Broderick, Joseph P. TI Variability In Treatment Of Acute Ischemic Stroke: Experience Across The Spotrias Consortium SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Willey, Joshua Z.] Columbia Univ, New York, NY USA. [Khatri, Pooja] Univ Cicinnati, Cincinnati, OH USA. [Khoury, Jane; Broderick, Joseph P.] Univ Cincinnati, Cincinnati, OH USA. [Gonzales, Nichole R.] Univ Texas Houston, Houston, TX USA. [Merino, Jose] NIH, Intramural Program, Washington, DC USA. [Rost, Natalia S.] Harvard Univ, Boston, MA 02115 USA. [Ali, Latisha K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Ford, Andria] Washington Univ, St Louis, MO USA. [Meyer, Brett C.] UCSD, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E66 EP E66 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479400085 ER PT J AU Wu, O Song, SS Ritter, C Latour, LL Yoo, AJ Lorenzano, S Chaudhry, ZA Sorensen, AG Schwamm, LH Warach, S AF Wu, Ona Song, Shlee S. Ritter, Carsten Latour, Lawrence L. Yoo, Albert J. Lorenzano, Svetlana Chaudhry, Zeshan A. Sorensen, A. G. Schwamm, Lee H. Warach, Steven CA MR WITNESS Investigators TI MRI As Witness: Ready For Prime-time? SO STROKE LA English DT Meeting Abstract CT International Stroke Conference CY FEB 08-10, 2011 CL Los Angeles, CA SP Amer Heart Assoc, Amer Stroke Assoc C1 [Wu, Ona; Yoo, Albert J.; Lorenzano, Svetlana; Chaudhry, Zeshan A.; Sorensen, A. G.; Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Song, Shlee S.; Ritter, Carsten; Latour, Lawrence L.; Warach, Steven] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2011 VL 42 IS 3 BP E285 EP E285 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 723AW UT WOS:000287479401197 ER PT J AU Mandelblatt, J Cronin, K Berry, D Feuer, E de Koning, H Lee, S Plevritis, S Schechter, C Stout, N van Ravesteyn, N Zelen, M AF Mandelblatt, J. Cronin, K. Berry, D. Feuer, E. de Koning, H. Lee, S. Plevritis, S. Schechter, C. Stout, N. van Ravesteyn, N. Zelen, M. TI Changing the guidelines for breast cancer screening: modeling mammography benefits and harms SO BREAST LA English DT Meeting Abstract C1 [Mandelblatt, J.] Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA. [Mandelblatt, J.] Lombardi Comprehens Canc Ctr, Dept Med, Washington, DC USA. [Cronin, K.; Feuer, E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Berry, D.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [de Koning, H.; van Ravesteyn, N.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Lee, S.; Zelen, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lee, S.] Inst Canc Res, Boston, MA USA. [Plevritis, S.] Stanford Univ, Dept Radiol, Palo Alto, CA 94304 USA. [Schechter, C.] Albert Einstein Coll Med, Dept Family & Social Med, Bronx, NY 10467 USA. [Schechter, C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Stout, N.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Stout, N.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Boston, MA USA. [Zelen, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD MAR PY 2011 VL 20 SU 1 BP S7 EP S8 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 747MM UT WOS:000289324100018 ER PT J AU Barsov, EV AF Barsov, Eugene V. TI Telomerase and primary T cells: biology and immortalization for adoptive immunotherapy SO IMMUNOTHERAPY LA English DT Review DE adoptive transfer; antigen-specific; immortalization; immunotherapy; retroviral vectors; T cells; telomerase ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-INFILTRATING LYMPHOCYTES; AKT SER(473) PHOSPHORYLATION; BLOOD MONONUCLEAR-CELLS; PRIMORDIAL GERM-CELLS; CANCER STEM-CELLS; NF-KAPPA-B; REVERSE-TRANSCRIPTASE; IN-VIVO; LIFE-SPAN AB Telomeres are specialized repeats, present at the end of chromosomes, whose loss during cell division is followed by growth arrest, a central mechanism of replicative senescence in human cells. Telomere length in stem cells is maintained by telomerase, a specialized reverse transcriptase, whose function is to restore shortening telomeres. Unlike most somatic cell types, human T lymphocytes are capable of briefly reactivating telomerase expression at the time of stimulation. Telomerase expression in T lymphocytes is modulated by a variety of external stimuli and by viral infections. However, telomerase reactivation in stimulated, proliferating human T lymphocytes is limited and cannot prevent the ultimate onset of senescence. Ectopic telomerase expression can rescue human and macaque antigen-specific T cells from senescence. Primary T cells have been engineered with telomerase to have substantially extended replicative lifespans without the loss of primary cell functions or malignant transformation. 'Immortal' antigen-specific T-cell lines and clones overexpressing telomerase are an invaluable source of well-characterized quasi-primary T cells for research of T-cell biology and are potentially useful for immunotherapy of cancer and AIDS. C1 NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Barsov, EV (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Bldg 535,Room 433, Frederick, MD 21702 USA. EM eugene.barsov@nih.gov FU National Cancer Institute, NIH [HHSN261200800001E, N01-CO-12400] FX This work has been funded in whole or in part with Federal funds from the National Cancer Institute, NIH, under Contracts No. HHSN261200800001E and No. N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 126 TC 9 Z9 10 U1 2 U2 10 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD MAR PY 2011 VL 3 IS 3 BP 407 EP 421 DI 10.2217/IMT.10.107 PG 15 WC Immunology SC Immunology GA 751AD UT WOS:000289588800014 PM 21395382 ER PT J AU Foley, AR Quijano-Roy, S Collins, J Straub, V Deconinck, N Mercuri, E D'Amico, A Bertini, E Ryan, M Muntoni, F Bonnemann, C AF Foley, A. R. Quijano-Roy, S. Collins, J. Straub, V. Deconinck, N. Mercuri, E. D'Amico, A. Bertini, E. Ryan, M. Muntoni, F. Boennemann, C. TI The identification of a viable outcome measure in the collagen VI myopathies promotes progress toward clinical trials SO NEUROMUSCULAR DISORDERS LA English DT Meeting Abstract CT United Kingdom Neuromuscular Translational Research Conference 2011 CY MAR 29-30, 2011 CL London, ENGLAND SP London Newcastle MRC Ctr Neuromuscular Dis, Muscular Dystrophy Campaign, Genzyme C1 [Foley, A. R.; Boennemann, C.] UCL, Dubowitz Neuromuscular Ctr, Inst Child Hlth, London, England. [Foley, A. R.; Boennemann, C.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [Quijano-Roy, S.] Hop Raymond Poincare, Neuromuscular Ctr, Garches, France. [Collins, J.] Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH USA. [Straub, V.] Newcastle Univ, Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Deconinck, N.] Hop Univ Enfants Reine Fabiola, Dept Neurol, Brussels, Belgium. [Mercuri, E.] Univ Cattolica Sacro Cuore, Dept Paediat Neurol, Rome, Italy. [D'Amico, A.; Bertini, E.] Bambino Gesu Pediat Hosp, Mol Med Unit, Rome, Italy. [Ryan, M.] Royal Childrens Hosp, Dept Neurol, Melbourne, Vic, Australia. [Boennemann, C.] Natl Inst Neurol Disorders & Stroke, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, Bethesda, MD USA. RI d'amico, adele/J-9203-2016 OI d'amico, adele/0000-0003-2438-2624 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 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD MAR PY 2011 VL 21 SU 1 BP S24 EP S24 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 749WJ UT WOS:000289501600081 ER PT J AU D'Adamo, CR Shardell, MD Hicks, GE Onvig, DL Hochberg, MC Semba, RD Yu-Yahiro, JA Ferrucci, L Magaziner, JS Miller, RR AF D'Adamo, Christopher R. Shardell, Michelle D. Hicks, Gregory E. Onvig, Denise L. Hochberg, Marc C. Semba, Richard D. Yu-Yahiro, Janet A. Ferrucci, Luigi Magaziner, Jay S. Miller, Ram R. TI Serum vitamin E concentrations among highly functioning hip fracture patients are higher than in nonfracture controls SO NUTRITION RESEARCH LA English DT Article DE Vitamin E; Tocopherols; Antioxidants; Micronutrients; Hip fracture; Older women ID MINI-MENTAL-STATE; GROWTH-FACTOR-I; ALPHA-TOCOPHEROL; GAMMA-TOCOPHEROL; NUTRITIONAL-STATUS; MICRONUTRIENT CONCENTRATIONS; MACULAR DEGENERATION; COGNITIVE FUNCTION; COLORECTAL-CANCER; CONTROLLED-TRIAL AB Malnutrition after hip fracture is common and associated with poor outcomes and protracted recovery. Low concentrations of vitamin E have been associated with incident decline in physical function among older adults and may, therefore, be particularly important to functionally compromised patients hip fracture patients. Serum concentrations of alpha-tocopherol and gamma-tocopherol, the 2 major forms of vitamin E, were assessed in 148 female hip fracture patients 65 years or older from the Baltimore Hip Studies cohort 4 around the time of fracture (baseline) and at 2, 6, and 12 month postfracture follow-up visits (recovery). It was hypothesized that mean concentrations of both forms of vitamin E among these hip fracture patients would be lowest at the baseline visit and increase at each study visit during the year after fracture. Linear regression and generalized estimating equations were used to assess changes in vitamin E concentrations after adjustment for covariates and to determine predictors of vitamin E concentrations at baseline and throughout recovery. It was also hypothesized that vitamin E concentrations shortly after hip fracture would be lower than those in nonfracture controls after adjustment for covariates. To evaluate this hypothesis, linear regression was used to perform adjusted comparisons of baseline vitamin E concentrations among Baltimore Hip Studies cohort 4 participants to 1076 older women without history of hip fracture from the Women's Health and Aging Study I, Invecchiare in Chianti Study, and the National Health and Nutrition Examination Surveys. Mean alpha-tocopherol was lowest at baseline, and time from fracture to blood draw was positively associated with baseline alpha-tocopherol (P = .005). Mean gamma-tocopherol did not change appreciably throughout the year after fracture, although it fluctuated widely within individuals. Serum concentrations of alpha-tocopherol and gamma-tocopherol were highest among the hip fracture population after adjustment (P < .0001). In general, highly cognitively and physically functioning hip fracture patients demonstrated higher vitamin E concentrations. Thus, the relatively high degree of function among this cohort of hip fracture patients may explain their higher-than-expected vitamin E concentrations. (C) 2011 Elsevier Inc. All rights reserved. C1 [D'Adamo, Christopher R.; Shardell, Michelle D.; Onvig, Denise L.; Magaziner, Jay S.; Miller, Ram R.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Hicks, Gregory E.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA. [Hochberg, Marc C.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Semba, Richard D.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Yu-Yahiro, Janet A.] Union Mem Hosp, Dept Orthoped Res, Baltimore, MD USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP D'Adamo, CR (reprint author), Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. EM cdadamo@compmed.umm.edu FU National Institute on Aging at the National Institutes of Health [R01 AG018668, R37 AG09901, R21HD057274, T32 AG00262, K12HD043489, K23 AG027746, P60 AG12583, P30 AG028747]; University of Maryland School of Medicine FX This work was supported by the National Institute on Aging at the National Institutes of Health (grant nos. R01 AG018668, R37 AG09901, R21HD057274, T32 AG00262, K12HD043489, K23 AG027746, P60 AG12583, and P30 AG028747) and a University of Maryland School of Medicine Intramural Award. NR 51 TC 2 Z9 2 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAR PY 2011 VL 31 IS 3 BP 205 EP 214 DI 10.1016/j.nutres.2011.03.005 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 754BF UT WOS:000289825400005 PM 21481714 ER PT J AU Uhl, GR Rose, JE AF Uhl, George R. Rose, Jed E. TI Individualized smoking cessation treatment: roles for sets of genomic markers SO PERSONALIZED MEDICINE LA English DT Editorial Material DE attributable risk; complex genetics; genotype score; SNP genotyping ID WIDE ASSOCIATION; SUCCESS PARTICIPANTS; NICOTINE REPLACEMENT; MOLECULAR-GENETICS; TRIAL; DEPENDENCE; BEHAVIOR; PATCH C1 [Uhl, George R.] NIDA, Mol Neurobiol Branch, NIH, IRP, Baltimore, MD 21224 USA. [Rose, Jed E.] Duke Univ, Dept Psychiat, Durham, NC 27705 USA. [Rose, Jed E.] Duke Univ, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27705 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, NIH, IRP, Box 5180, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov NR 22 TC 0 Z9 0 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAR PY 2011 VL 8 IS 2 BP 119 EP 121 DI 10.2217/PME.11.4 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 747SE UT WOS:000289338900003 ER PT J AU Menendez, D Shatz, M Azzam, K Garantziotis, S Fessler, MB Resnick, MA AF Menendez, Daniel Shatz, Maria Azzam, Kathleen Garantziotis, Stavros Fessler, Michael B. Resnick, Michael A. TI The Toll-Like Receptor Gene Family Is Integrated into Human DNA Damage and p53 Networks SO PLOS GENETICS LA English DT Article ID DIFFERENTIAL EXPRESSION; ALVEOLAR MACROPHAGES; PATTERN-RECOGNITION; ADAPTIVE IMMUNITY; TARGET GENES; ACTIVATION; RESPONSES; CELLS; MICE; TRANSACTIVATION AB In recent years the functions that the p53 tumor suppressor plays in human biology have been greatly extended beyond "guardian of the genome.'' Our studies of promoter response element sequences targeted by the p53 master regulatory transcription factor suggest a general role for this DNA damage and stress-responsive regulator in the control of human Toll-like receptor (TLR) gene expression. The TLR gene family mediates innate immunity to a wide variety of pathogenic threats through recognition of conserved pathogen-associated molecular motifs. Using primary human immune cells, we have examined expression of the entire TLR gene family following exposure to anti-cancer agents that induce the p53 network. Expression of all TLR genes, TLR1 to TLR10, in blood lymphocytes and alveolar macrophages from healthy volunteers can be induced by DNA metabolic stressors. However, there is considerable inter-individual variability. Most of the TLR genes respond to p53 via canonical as well as noncanonical promoter binding sites. Importantly, the integration of the TLR gene family into the p53 network is unique to primates, a recurrent theme raised for other gene families in our previous studies. Furthermore, a polymorphism in a TLR8 response element provides the first human example of a p53 target sequence specifically responsible for endogenous gene induction. These findings-demonstrating that the human innate immune system, including downstream induction of cytokines, can be modulated by DNA metabolic stress-have many implications for health and disease, as well as for understanding the evolution of damage and p53 responsive networks. C1 [Menendez, Daniel; Shatz, Maria; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Azzam, Kathleen; Fessler, Michael B.] NIEHS, Host Def Grp, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Garantziotis, Stavros] NIEHS, Clin Res Unit, NIH, Res Triangle Pk, NC 27709 USA. RP Menendez, D (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU NIEHS [Z01-ES065079, Z01 ES102005] FX This work was supported by intramural research funds from NIEHS as follows: to MAR, project Z01-ES065079; to MBF, project Z01 ES102005. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 48 Z9 51 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2011 VL 7 IS 3 AR e1001360 DI 10.1371/journal.pgen.1001360 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 743DD UT WOS:000288996600041 PM 21483755 ER PT J AU Hutchison, E Mattson, MP AF Hutchison, Emmette Mattson, Mark P. TI Eating less suppresses microRNA assassins in the brain SO AGING-US LA English DT Article ID DIETARY RESTRICTION; BDNF; MICE C1 [Hutchison, Emmette; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Hutchison, Emmette] Brown Univ, Grad Program Neurosci, Providence, RI 02906 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM MattsonM@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 10 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 2011 VL 3 IS 3 BP 179 EP 180 PG 2 WC Cell Biology SC Cell Biology GA 747HW UT WOS:000289311900001 PM 21389350 ER PT J AU Zhernakova, A Stahl, EA Trynka, G Raychaudhuri, S Festen, E Franke, L Fehrmann, RSN Kurreeman, FAS Thomson, B Gupta, N Romanos, J McManus, R Ryan, AW Turner, G Remmers, EF Greco, L Toes, R Grandone, E Mazzilli, MC Rybak, A Cukrowska, B Li, YH de Bakker, PIW Gregersen, PK Worthington, J Siminovitch, KA Klareskog, L Huizinga, TWJ Wijmenga, C Plenge, RM AF Zhernakova, Alexandra Stahl, Eli A. Trynka, Gosia Raychaudhuri, Soumya Festen, Eleanora Franke, Lude Fehrmann, Rudolf S. N. Kurreeman, Fina A. S. Thomson, Brian Gupta, Namrata Romanos, Jihane McManus, Ross Ryan, Anthony W. Turner, Graham Remmers, Elaine F. Greco, Luigi Toes, Rene Grandone, Elvira Mazzilli, Maria Cristina Rybak, Anna Cukrowska, Bozena Li, Yonghong de Bakker, Paul I. W. Gregersen, Peter K. Worthington, Jane Siminovitch, Katherine A. Klareskog, Lars Huizinga, Tom W. J. Wijmenga, Cisca Plenge, Robert M. TI META-ANALYSIS OF GENOME-WIDE ASSOCIATION STUDIES IN CELIAC DISEASE AND RHEUMATOID ARTHRITIS IDENTIFIES FOURTEEN NON-HLA SHARED LOCI SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 31st European Workshop for Rheumatology Research CY MAR 03-06, 2011 CL Amsterdam, NETHERLANDS C1 [Zhernakova, Alexandra; Kurreeman, Fina A. S.; Toes, Rene; Huizinga, Tom W. J.] Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. [Zhernakova, Alexandra] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Zhernakova, Alexandra; Stahl, Eli A.; Kurreeman, Fina A. S.; de Bakker, Paul I. W.; Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Stahl, Eli A.; Raychaudhuri, Soumya; Kurreeman, Fina A. S.; Thomson, Brian; Gupta, Namrata; de Bakker, Paul I. W.; Plenge, Robert M.] Broad Inst, Cambridge, MA USA. [Trynka, Gosia; Festen, Eleanora; Franke, Lude; Fehrmann, Rudolf S. N.; Romanos, Jihane; Wijmenga, Cisca] Univ Groningen, Groningen, Netherlands. [Trynka, Gosia; Festen, Eleanora; Franke, Lude; Fehrmann, Rudolf S. N.; Romanos, Jihane; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands. [Raychaudhuri, Soumya] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Franke, Lude] Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol, London, England. [McManus, Ross; Ryan, Anthony W.; Turner, Graham] St James Hosp, Trinity Coll Dublin, Dept Clin Med, Trinity Ctr Hlth Sci, Dublin 8, Ireland. [Remmers, Elaine F.] NIAMSD, Genet & Genom Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Greco, Luigi] Univ Naples Federico 2, European Lab Food Induced Dis, Naples, Italy. [Grandone, Elvira] IRCCS Casa Sollievo Sofferenza, Unita Aterosclerosi & Trombosi, Foggia, Italy. [Mazzilli, Maria Cristina] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Rybak, Anna] Childrens Mem Hlth Inst, Dept Gastroenterol Hepatol & Immunol, Warsaw, Poland. [Cukrowska, Bozena] Childrens Mem Hlth Inst, Dept Pathol, Warsaw, Poland. [Li, Yonghong] Celera, Alameda, CA USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA. [Worthington, Jane] Univ Manchester, Arthrit Res Campaign Epidemiol Unit, Manchester, Lancs, England. [Siminovitch, Katherine A.] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. [Siminovitch, Katherine A.] Univ Hlth Network, Toronto, ON, Canada. [Klareskog, Lars] Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden. [Klareskog, Lars] Karolinska Univ Hosp Solna, Stockholm, Sweden. RI Ryan, Anthony/A-1336-2010; Romanos, Jihane/F-7372-2012; Wijmenga, Cisca/D-2173-2009; de Bakker, Paul/B-8730-2009; Franke, Lude/P-7036-2016; Festen, Eleonora/S-3557-2016 OI de Bakker, Paul/0000-0001-7735-7858; Franke, Lude/0000-0002-5159-8802; NR 0 TC 0 Z9 0 U1 0 U2 3 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 MAR PY 2011 VL 70 SU 2 BP A21 EP A21 DI 10.1136/ard.2010.148965.20 PG 1 WC Rheumatology SC Rheumatology GA 724NE UT WOS:000287582400051 ER PT J AU Takikita, M Hu, N Shou, JZ Giffen, C Wang, QH Wang, CY Hewitt, SM Taylor, PR AF Takikita, Mikiko Hu, Nan Shou, Jian-Zhong Giffen, Carol Wang, Quan-Hong Wang, Chaoyu Hewitt, Stephen M. Taylor, Philip R. TI Fascin and CK4 as Biomarkers for Esophageal Squamous Cell Carcinoma SO ANTICANCER RESEARCH LA English DT Article DE Cytokeratin 4; fascin; biomarker; tissue microarray; squamous cell carcinoma; esophagus ID ACTIN-BUNDLING PROTEIN; HIGH-RISK POPULATION; GENE-EXPRESSION; GASTRIC-CARCINOMA; CDNA MICROARRAY; MESSENGER-RNA; SPARC; DIFFERENTIATION; OVEREXPRESSION; INVASIVENESS AB Background: Several studies have suggested that fascin, cytokeratin 14 and cytokeratin 4 may have significant roles as biomarkers for the progression and survival of esophageal squamous cell carcinoma (ESCC). Materials and Methods: This study performed immunohistochemistry in tissue microarrays, profiling premalignant lesions and invasive tumors. Results: Fascin increased across the following states as follows: normal-appearing epithelium (26%) to dysplasia (46%) to ESCC (6870), while CK4 was undetectable in ESCC (0%) compared to normal-appearing epithelium (45%) or dysplasia (41%). CK14 was elevated and invariant in expression. In regression analyses, compared to normal-appearing epithelium, higher fascin expression was associated with a 36% increased risk of dysplasia (odds ratio=1 36) and a 56% increased risk of invasive ESCC (odds ratio=1.56). Conclusion: Expression of fascin is upregulated in the transformation from normal-appearing epithelium, through dysplasia, into invasive carcinoma. Expression of CK4, CK14 and fascin did not correlate with patient survival. Fascin has a potential role as an early detection biomarker and CK4 as a tumor marker in ESCC. C1 [Takikita, Mikiko; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Hu, Nan; Wang, Chaoyu; Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shou, Jian-Zhong] Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100021, Peoples R China. [Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Wang, Quan-Hong] Shanxi Canc Hosp, Taiyuan 030013, Shanxi, Peoples R China. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov; ptaylor@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU NIH, National Cancer Institute, Division of Cancer Epidemiology and Prevention, and Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Prevention, and Center for Cancer Research. The Authors wish to thank Kimberly Parker, Langston Lim and Kris Ylaya for technical assistance. NR 33 TC 23 Z9 28 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR PY 2011 VL 31 IS 3 BP 945 EP 952 PG 8 WC Oncology SC Oncology GA 751JH UT WOS:000289612800027 PM 21498718 ER PT J AU Kummar, S Gutierrez, ME Maurer, BJ Reynolds, CP Kang, M Singh, H Crandon, S Murgo, AJ Doroshow, JH AF Kummar, Shivaani Gutierrez, Martin E. Maurer, Barry J. Reynolds, C. Patrick Kang, Min Singh, Hardeep Crandon, Sonja Murgo, Anthony J. Doroshow, James H. TI Phase I Trial of Fenretinide Lym-X-Sorb Oral Powder in Adults with Solid Tumors and Lymphomas SO ANTICANCER RESEARCH LA English DT Article DE Fenretinide; LXS oral powder; phase I; clinical trial ID RETINOL-BINDING-PROTEIN; N-(4-HYDROXYPHENYL) RETINAMIDE; CELL LINES; SECRETION; LIVER; NEUROBLASTOMA; APOPTOSIS; CHILDREN; COMPLEX; RATS AB Background: The synthetic retinoid fenretinide (N-(4-hydroxyphenyl)retinamide, 4-HPR) has shown promising anticancer activity in preclinical studies, but its limited oral bioavailability has hindered clinical assessment. A novel lipid matrix, Lym-X-Sorb (LXS), was evaluated to improve fenretinide bioavailability and attain higher plasma concentrations. Patients and Methods: Adults with refractory malignancies were administered fenretinide/LXS oral powder in 2 divided doses over 24 h for 7 consecutive days every 21 days in a standard phase 1 dose-escalation study with pharmacokinetic analysis. Results: The principal toxicities observed were diarrhea, reversible night blindness, and allergic reaction. The maximum tolerated dose regimens were 1,000 mg/m(2) /day divided into 2 daily doses for 7 days, every 21 days, and 800 mg/m(2)/day divided into 3 daily doses for 7 consecutive days, every 21 days. Conclusion: Better fenretinide formulations are needed to improve adult patient acceptability and compliance and to achieve the consistent systemic exposures associated with activity in preclinical models. C1 [Doroshow, James H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kummar, Shivaani; Murgo, Anthony J.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Maurer, Barry J.; Reynolds, C. Patrick; Kang, Min; Singh, Hardeep] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. RP Doroshow, JH (reprint author), NCI, Ctr Canc Res, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov FU Center for Cancer Research; Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health; Developmental Therapeutics Program; Cancer Prevention and Research Institute of Texas [RP10072] FX This research was supported by the Center for Cancer Research and the Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health; by a Developmental Therapeutics Program, Rapid Access to Intervention Development award to BJM; and by Grant RP10072 from the Cancer Prevention and Research Institute of Texas to CPR. 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 he U.S. Government. NR 18 TC 9 Z9 9 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR PY 2011 VL 31 IS 3 BP 961 EP 966 PG 6 WC Oncology SC Oncology GA 751JH UT WOS:000289612800030 PM 21498721 ER PT J AU Schmitz, KH Xie, DW Teal, V Ballard-Barbash, R Berrigan, D AF Schmitz, Kathryn H. Xie, Dawei Teal, Valerie Ballard-Barbash, Rachel Berrigan, David TI Association of IGF Axis Hormones with Waist-to-Hip Ratio Varies by Physical Activity SO IN VIVO LA English DT Article DE Insulin-like growth factor-I; insulin-like growth factor binding protein 3; exercise; central adiposity; obesity ID GROWTH-FACTOR-I; GLUCOSE-HOMEOSTASIS; BINDING PROTEIN-3; SERUM-LEVELS; BODY-MASS; EXERCISE; OBESITY; IGFBP-3; GENDER; FAT AB Background/Aim: Insulin-like growth factor (IGF) axis hormones ate associated with multiple chronic diseases. Reports of the relationship between adiposity and IGF-axis hormones vary widely. This study hypothesized that physical activity levels modify the association of IGF axis hormones with adiposity. Patients and Methods: Data from NHANES III were used to assess whether associations of adiposity, namely waist-to-hip ratio (WHR), with IGF axis hormones varied according to physical activity. Results: Among those in the lowest physical activity quintile, WHR had a substantive inverse association: bioavailable IGF-1 was 16% lower among those in the highest versus the lowest WHR quintiles among the least active subjects (p < 0.001). By comparison, among those in the highest physical activity quintile, IGF-1 did not vary by WHR. Conclusion: The association of bioavailable IGF-1 with central adiposity differs among active versus inactive adults in the U.S.A. This has relevance to understanding previously reported benefits of physical activity among overweight individuals. C1 [Schmitz, Kathryn H.; Xie, Dawei; Teal, Valerie] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Ballard-Barbash, Rachel; Berrigan, David] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. RP Schmitz, KH (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 903 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM Schmitz@mail.med.upenn.edu FU U.S.A. National Cancer Institute [263-MQ-612836] FX This study was supported by contract #263-MQ-612836 from the U.S.A. National Cancer Institute. NR 29 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD MAR-APR PY 2011 VL 25 IS 2 BP 245 EP 250 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 747LY UT WOS:000289322500015 PM 21471542 ER PT J AU Zhang, HY Jin, TY Zhang, GH Chen, LA Zou, WM Li, QQ AF Zhang, Haiying Jin, Taiyi Zhang, Gaohong Chen, Liang Zou, Weiming Li, Qingdi Quentin TI Polymorphisms in Heat-shock Protein 70 Genes Are Associated with Coal Workers' Pneumoconiosis in Southwestern China SO IN VIVO LA English DT Article DE Heat-shock protein 70; gene polymorphism; coal worker; pneumoconiosis ID HEAT-SHOCK PROTEINS; HSP70; EXPRESSION; SUSCEPTIBILITY; SILICOSIS; EXPOSURE; DISEASE; CELLS; RISK; TNF AB Background: Heat-shock proteins (HSPs) protect cells and tissues against different types of damage. This study investigated the relationship between the genetic variation in constitutive and inducible HSP70 genes and the risk for coal workers' pneumoconiosis (CWP) among miners in southwestern China. Patients and Methods: A job exposure matrix (JEM) was used to estimate the dust exposure level of individuals. A total of 225 CWP patients and 294 healthy individuals were assessed by genotyping for the single-nucleotide polymorphisms (SNPs) of the HSP70-1 (190 G/C), HSP70-2 (1267 A/G), and HSP70-hom (2437 T/C) genes. The association between these polymorphisms and the risk for CWP was assessed. Results: Polymerase chain reaction-restriction fragment length polymorphism analysis revealed no statistically significant differences between the dust exposure level and the polymorphisms of HSP70-1, HSP70-2 and HSP70-hom in individuals. However, there were significant differences in the distribution of the G allele for HSP70-2 among the different categories of CWP and in the genotype frequency for HSP70-hom between CWP patients and controls. Furthermore, five HSP haplotypes of the HSP70 genes (namely GAT, GAG, GGT, CAC and CGT) were examined and the frequencies of haplotypes GAT and GGT were significantly higher in the CWP than in the control group. Conclusion: The genotyping results of this study indicate that the G allele distribution of HSP70-2, the genotype frequency of HSP70-hom poly-morphisms and some haplotypes of the HSP70 genes are associated with the susceptibility to and severity of CWP, and may be involved in the pathogenesis and development of CWP in the southwestern Chinese Han population. C1 [Zhang, Haiying] Guangxi Med Univ, Sch Publ Hlth, Dept Occupat Hlth, Nanning 530021, Peoples R China. [Jin, Taiyi; Chen, Liang] Fudan Univ, Sch Publ Hlth, Dept Occupat Hlth, Shanghai 200433, Peoples R China. [Zhang, Gaohong] Panjiang Min Bur, Gen Hosp, Guiyang, Guizhou, Peoples R China. [Zou, Weiming] Guangxi Inst Prevent & Treatment Occupat Dis, Nanning, Peoples R China. [Li, Qingdi Quentin] Natl Inst Hlth, Bethesda, MD USA. RP Zhang, HY (reprint author), Guangxi Med Univ, Sch Publ Hlth, Dept Occupat Hlth, Nanning 530021, Peoples R China. EM billmamahyzhang@gmail.com FU Guangxi Science Foundation; Guangxi Provincial Department of Science and Technology, China [0832047] FX We thank all of the volunteers who participated in this study and the numerous medical personnel from the General Hospital of Heshan Mining Bureau, General Hospital of Panjiang Mining Bureau, Guangxi Institute for Prevention and Treatment of Occupational Diseases, and Guangxi Medical University School of Public Health. This project was supported in part by a grant from Guangxi Science Foundation for Young Scientists sponsored by Guangxi Provincial Department of Science and Technology (No. 0832047), China. NR 39 TC 3 Z9 5 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD MAR-APR PY 2011 VL 25 IS 2 BP 251 EP 257 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 747LY UT WOS:000289322500016 PM 21471543 ER PT J AU Kang, BT Kang, MH Lim, CY Kim, DY Park, HM AF Kang, Byeong-Teck Kang, Min-Hee Lim, Chae-Young Kim, Dae-Young Park, Hee-Myung TI F-18-FDG and C-11-MET Positron Emission Tomography Findings of Cutaneous Mast Cell Tumor in a Dog SO JOURNAL OF VETERINARY MEDICAL SCIENCE LA English DT Article DE canine; C-11-MET; F-18-FDG; mast cell tumor; PET ID CLINICAL-APPLICATIONS; HIGH-RESOLUTION; PET; CHEMOTHERAPY; DIAGNOSIS; LYMPHOMA; ONCOLOGY; BRAIN; FDG AB A 12-year-old intact male Maltese dog presented with an inguinal mass. Histopathology revealed a grade Ill mast cell tumor. Computed tomography demonstrated pulmonary and inguinal nodules and masses. Chemotherapy was performed using a vinblastine/prednisone protocol, and the inguinal mass disappeared 5 weeks later. Use of 2-deoxy-2-[F-18]fluoro-D-glucose (F-18-FDG) and L-[methyl-C-11]methionine (C-11-MET)-positron emission tomography (PET) demonstrated hypermetabolic areas in the lungs and inguinal region one week after initial chemotherapy. The standardized uptake values of F-18-FDG were not different between lung and inguinal lesions; however, the inguinal lesion had a higher C-11-MET standardized uptake value than the lung lesions. The hypermetabolic area was still visible on the second F-18-FDG-PET scan despite the disappearance of the mass. This is the first report of C-11-MET-PET findings associated with a cutaneous mast cell tumor in a dog. C1 [Kang, Byeong-Teck; Kang, Min-Hee; Lim, Chae-Young; Park, Hee-Myung] Konkuk Univ, Dept Vet Internal Med, Coll Vet Med, Seoul 143701, South Korea. [Kang, Byeong-Teck; Kang, Min-Hee; Lim, Chae-Young; Park, Hee-Myung] Konkuk Univ, Program Basic & Diagnost Vet Specialist Program A, Coll Vet Med, Seoul 143701, South Korea. [Kang, Byeong-Teck] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, NIH, Bethesda, MD 20892 USA. [Kim, Dae-Young] Univ Missouri, Vet Med Diagnost Lab, Coll Vet Med, Columbia, MO 65205 USA. RP Park, HM (reprint author), Konkuk Univ, Dept Vet Internal Med, Coll Vet Med, 1 Hwayang Dong, Seoul 143701, South Korea. EM parkhee@konkuk.ac.kr RI Park, Hee-Myung/D-6222-2011; Kang, Min Hee/D-6345-2011 FU Korean Government (MOEHRD) [KRF-2008-314-E00246] FX This work was supported by the Korean Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund)(KRF-2008-314-E00246). NR 22 TC 2 Z9 2 U1 0 U2 2 PU JAPAN SOC VET SCI PI TOKYO PA UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 103, JAPAN SN 0916-7250 EI 1347-7439 J9 J VET MED SCI JI J. Vet. Med. Sci. PD MAR PY 2011 VL 73 IS 3 BP 355 EP 359 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 748JO UT WOS:000289387100012 PM 20962463 ER PT J AU Ali, SF Onaivi, E Kim, HC Kuhar, MJ Koob, G AF Ali, Syed F. Onaivi, Emmanuel Kim, Hyoung-Chun Kuhar, Michael J. Koob, George TI New Research Frontiers and Advances in Drug Addiction PREFACE SO CURRENT NEUROPHARMACOLOGY LA English DT Editorial Material C1 [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Onaivi, Emmanuel] NIDA, Mol Neurobiol Branch, Baltimore, MD USA. [Onaivi, Emmanuel] William Paterson Univ, Wayne, NJ USA. [Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. [Koob, George] Scripps Res Inst, La Jolla, CA 92037 USA. [Kuhar, Michael J.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov; Onaivie@wpunj.edu; kimhc@kangwon.ac.kr; mkuhar@emory.edu; gkoob@scripps.edu RI koob, george/P-8791-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2011 VL 9 IS 1 BP 1 EP 1 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400001 ER PT J AU Ali, SF Onaivi, ES Dodd, PR Cadet, JL Schenk, S Kuhar, MJ Koob, GF AF Ali, S. F. Onaivi, E. S. Dodd, P. R. Cadet, J. L. Schenk, S. Kuhar, M. J. Koob, G. F. TI Understanding the Global Problem of Drug Addiction is a Challenge for IDARS Scientists SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE International Drug Abuse Research Society; IDARS; addiction; alcohol; marijuana; psychostimulants ID D2 RECEPTOR GENE; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC PARANOID PSYCHOSIS; CORTICAL NMDA RECEPTOR; ALCOHOL-DEPENDENCE; HUMAN BRAIN; MOLECULAR-GENETICS; SUBUNIT EXPRESSION; IONOPHORE COMPLEX; CEREBRAL-CORTEX AB IDARS is an acronym for the International Drug Abuse Research Society. Apart from our scientific and educational purposes, we communicate information to the general and scientific community about substance abuse and addiction science and treatment potential. Members of IDARS are research scientists and clinicians from around the world, with scheduled meetings across the globe. IDARS is developing a vibrant and exciting international mechanism not only for scientific interactions in the domain of addiction between countries but also ultimately as a resource for informing public policy across nations. Nonetheless, a lot more research needs to be done to better understand the neurobiological basis of drug addiction - A challenge for IDARS scientists. C1 [Ali, S. F.] US FDA, Neurochem Lab, NCTR, Jefferson, AR 72079 USA. [Onaivi, E. S.] William Paterson Univ, Wayne, NJ USA. [Onaivi, E. S.] NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA. [Dodd, P. R.] Univ Queensland, Brisbane, Qld, Australia. [Cadet, J. L.] NIDA, Mol Neuropsychiat Branch, NIH, US Dept HHS, Baltimore, MD USA. [Schenk, S.] Victoria Univ Wellington, Wellington, New Zealand. [Kuhar, M. J.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Koob, G. F.] Scripps Res Inst, La Jolla, CA 92037 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, NCTR, Jefferson, AR 72079 USA. EM Syed.Ali@fda.hhs.gov RI Dodd, Peter/A-4865-2010; koob, george/P-8791-2016 OI Dodd, Peter/0000-0001-5970-0181; FU William Paterson University center for research; National Health and Medical Research Council (NHMRC) [401551]; University of Sydney; Schizophrenia Research Institute; National Institutes of Alcoholism and Alcohol Abuse USA (NIAAA); NSW Department of Health; NIAAA under NIH [AA12404]; DHHS/NIH/NIDA; Neurological Foundation of New Zealand; Royal Society of New Zealand; Pearson Center for Alcoholism and Addiction Research; National Institutes of Health from the National Institute on Alcohol Abuse and Alcoholism [AA013517, AA006420, DA010072, DA004398, DA023597]; National Institute on Drug Abuse FX Dr. Onaivi acknowledges financial support from William Paterson University center for research, the Dean, Dr. Sandra DeYoung for continued student worker support and the Provost office for release time. Dr. Dodd's group in Australia are grateful to Neuropathologists from the Queensland Brain Bank, SCMB, University of Queensland, and from the NSW Tissue Resource Centre, for providing tissue samples; and to the next of kin, for informed written consent for the studies. The tissue banks are part of Australian Brain Bank Network supported by the National Health and Medical Research Council (NHMRC). The NSW Centre and Australian Brain Donor Program are supported by The University of Sydney, NHMRC, Schizophrenia Research Institute, National Institutes of Alcoholism and Alcohol Abuse USA (NIAAA), and NSW Department of Health. Financial support was provided by the NIAAA under grant NIH AA12404 and the NHMRC under grant #401551. Work in Dr. Cadet's laboratory is supported by the DHHS/NIH/NIDA Intramural Research Program. Dr. Schenk's studies on the behavioral and neurochemical consequences of MDMA self-administration are supported by the Neurological Foundation of New Zealand and the Royal Society of New Zealand Marsden Fund. Dr. Koob was supported by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA013517 and AA006420 from the National Institute on Alcohol Abuse and Alcoholism and DA010072, DA004398, and DA023597 from the National Institute on Drug Abuse. NR 96 TC 2 Z9 2 U1 3 U2 4 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 MAR PY 2011 VL 9 IS 1 BP 2 EP 7 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400002 PM 21886551 ER PT J AU Hodges, AB Ladenheim, B McCoy, MT Beauvais, G Cai, N Krasnova, IN Cadet, JL AF Hodges, A. B. Ladenheim, B. McCoy, M. T. Beauvais, G. Cai, N. Krasnova, I. N. Cadet, J. L. TI Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Methamphetamine; striatum; dopamine; preconditioning ID AMPHETAMINE ABUSE; TOLERANCE; BRAIN; MECHANISMS; DOPAMINE; NEUROTOXICITY; BINGE; CONSEQUENCES; DEATH; RAT AB Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH-induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems. C1 [Hodges, A. B.; Ladenheim, B.; McCoy, M. T.; Beauvais, G.; Cai, N.; Krasnova, I. N.; Cadet, J. L.] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Hodges, A. B.] Morgan State Univ, Dept Psychol, Baltimore, MD 21251 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Branch, US Dept HHS, NIH,IRP, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH/DHHS FX This research was financially supported by the Intramural Research Program of the National Institute on Drug Abuse, NIH/DHHS. NR 28 TC 5 Z9 6 U1 1 U2 2 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 MAR PY 2011 VL 9 IS 1 BP 35 EP 39 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400009 PM 21886558 ER PT J AU Hagino, Y Takamatsu, Y Yamamoto, H Iwamura, T Murphy, DL Uhl, GR Sora, I Ikeda, K AF Hagino, Y. Takamatsu, Y. Yamamoto, H. Iwamura, T. Murphy, D. L. Uhl, G. R. Sora, I. Ikeda, K. TI Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking Dopamine and/or Serotonin Transporters SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE MDMA; serotonin transporter; dopamine transporter; knockout; microdialysis ID RAT-BRAIN SLICES; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; KNOCKOUT MICE; NOREPINEPHRINE TRANSPORTER; PREFRONTAL CORTEX; RELEASE; ECSTASY; METHYLENEDIOXYMETHAMPHETAMINE; MICRODIALYSIS; STRIATUM AB 3,4-Methylendioxymethamphetamine (MDMA) has both stimulatory and hallucinogenic properties which make its psychoactive effects unique and different from those of typical psychostimulant and hallucinogenic agents. The present study investigated the effects of MDMA on extracellular dopamine (DA(ex)) and serotonin (5-HT(ex)) levels in the striatum and prefrontal cortex (PFC) using in vivo microdialysis techniques in mice lacking DA transporters (DAT) and/or 5-HT transporters (SERT). Subcutaneous injection of MDMA (3, 10 mg/kg) significantly increased striatal DA(ex) in wildtype mice, SERT knockout mice, and DAT knockout mice, but not in DAT/SERT double-knockout mice. The MDMA-induced increase in striatal DA(ex) in SERT knockout mice was significantly less than in wildtype mice. In the PFC, MDMA dose-dependently increased DA(ex) levels in wildtype, DAT knockout, SERT knockout and DAT/SERT doubleknockout mice to a similar extent. In contrast, MDMA markedly increased 5-HT(ex) in wildtype and DAT knockout mice and slightly increased 5-HT(ex) in SERT-KO and DAT/SERT double-knockout mice. The results confirm that MDMA acts at both DAT and SERT and increases DA(ex) and 5-HT(ex). C1 [Ikeda, K.] Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. [Iwamura, T.] Matsuyama Univ, Fac Pharmaceut Sci, Matsuyama, Ehime 7908578, Japan. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Uhl, G. R.] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Sora, I.] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikeda-kz@igakuken.or.jp FU MEXT of Japan [17025054]; MHLW of Japan [H17-pharmaco-001, H19-iyaku-023, 18A-3, 19A-8]; Smoking Research Foundation; Mitsubishi Foundation for Social Welfare Activities FX We acknowledge Mr. Michael Arends for his assistance with editing the manuscript and Ms. Junko Hasegawa for her assistance with genotyping mice. This work was supported by a research grant (17025054) from the MEXT of Japan, by grants from the MHLW of Japan (H17-pharmaco-001, H19-iyaku-023, and 18A-3 and 19A-8 for Nervous and Mental Disorders), by a grant from the Smoking Research Foundation, and by a grant from the Mitsubishi Foundation for Social Welfare Activities. NR 34 TC 14 Z9 14 U1 0 U2 2 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 MAR PY 2011 VL 9 IS 1 BP 91 EP 95 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400020 PM 21886569 ER PT J AU Onaivi, ES AF Onaivi, E. S. TI Commentary: Functional Neuronal CB2 Cannabinoid Receptors in the CNS SO CURRENT NEUROPHARMACOLOGY LA English DT Editorial Material DE Cannabinoid; CB1; CB2; endocannabinoids; CNS; immune system; cannabis; marijuana ID ENDOCANNABINOID SYSTEM; HUMAN BRAIN; ALZHEIMERS-DISEASE; RAT CEREBELLUM; EXPRESSION; ACTIVATION; ALCOHOL; LOCALIZATION; GENE; ANTAGONIST AB Cannabinoids are the constituents of the marijuana plant (Cannabis sativa). There are numerous cannabinoids and other natural compounds that have been reported in the cannabis plant. The recent progress in marijuana-cannabinoid research include the discovery of an endocannabinoid system with specific genes coding for cannabinoid receptors (CBRs) that are activated by smoking marijuana, and that the human body and brain makes its own marijuana-like substances called endocannabinoids that also activate CBRs. This new knowledge and progress about cannabinoids and endocannabinoids indicate that a balanced level of endocannabinoids is important for pregnancy and that the breast milk in animals and humans has endocannabinoids for the growth and development of the new born. There are two well characterized cannabinoid receptors termed CB1-Rs and CB2-Rs and these CBRs are perhaps the most abundant G-protein coupled receptors that are expressed at high levels in many regions of the mammalian brain. The expression of CB1-Rs in the brain and periphery and the identification of CB2-Rs in immune cells and during inflammation has been extensively studied and characterized. However, the expression of functional neuronal CB2-Rs in the CNS has been much less well established and characterized in comparison to the expression of abundant brain CB1-Rs and functional neuronal CB2-Rs has ignited debate and controversy. While the issue of the specificity of CB2-R antibodies remains, many recent studies have reported the discovery and functional characterization of functional neuronal CB2-Rs in the CNS beyond neuro-immuno cannabinoid activity. C1 [Onaivi, E. S.] William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. [Onaivi, E. S.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Baltimore, MD USA. RP Onaivi, ES (reprint author), William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. EM Onaivie@wpunj.edu NR 47 TC 20 Z9 20 U1 1 U2 4 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 MAR PY 2011 VL 9 IS 1 BP 205 EP 208 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400042 PM 21886591 ER PT J AU Onaivi, ES Benno, R Halpern, T Mehanovic, M Schanz, N Sanders, C Yan, X Ishiguro, H Liu, QR Berzal, AL Viveros, MP Ali, SF AF Onaivi, E. S. Benno, R. Halpern, T. Mehanovic, M. Schanz, N. Sanders, C. Yan, X. Ishiguro, H. Liu, Q-R Berzal, A. L. Viveros, M. P. Ali, S. F. TI Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Cannabinoid; Monoamines; Delta(9)-THC; Psychostimulants; MPTP; Behavior; Autism; BTBR T plus tf/J mice ID METHYLATION; BEHAVIOR; GENES AB Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Delta(9)-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs. C1 [Onaivi, E. S.] William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. [Onaivi, E. S.; Ishiguro, H.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Baltimore, MD USA. [Ishiguro, H.] Ikeda Hosp, Happoukai Med Corp, Ryugasaki, Japan. [Liu, Q-R] Natl Inst Drug Abuse, Behav Neurobiol Branch, NIH, Baltimore, MD USA. [Berzal, A. L.; Viveros, M. P.] Univ Complutense, Dept Fisiol Fisiol Anim 2, Fac Biol, E-28040 Madrid, Spain. [Ali, S. F.] US FDA, Neurochem Lab, NCTR, Jefferson, AR USA. RP Onaivi, ES (reprint author), William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. EM Onaivie@wpunj.edu RI Liu, Qing-Rong/A-3059-2012; Viveros, Maria-Paz/S-6855-2016 OI Liu, Qing-Rong/0000-0001-8477-6452; FU William Paterson University center; NIDA-NIH; Red de Trastornos adictivos [RD06/0001/1013]; GRUPOS UCM-BSCH [951579]; Plan Nacional sobre Drogas; Ministerio de Sanidad y Politica Social [PR10/09-16583] FX ESO acknowledges financial support from William Paterson University center for research, the Dean, Dr. Sandra DeYoung for continued student worker support and the Provost office for release time. ESO acknowledges Guest Scientist support at NIDA-NIH. QRL is supported by NIDA-NIH. ALB and MPV acknowledges support from Red de Trastornos adictivos RD06/0001/1013; GRUPOS UCM-BSCH: 951579; Plan Nacional sobre Drogas, Ministerio de Sanidad y Politica Social 2010-2012. Ref.: PR10/09-16583 NR 17 TC 10 Z9 10 U1 0 U2 5 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 MAR PY 2011 VL 9 IS 1 BP 209 EP 214 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400043 PM 21886592 ER PT J AU Kasai, S Yamamoto, H Kamegaya, E Uhl, GR Sora, I Watanabe, M Ikeda, K AF Kasai, Shinya Yamamoto, Hideko Kamegaya, Etsuko Uhl, George R. Sora, Ichiro Watanabe, Masahiko Ikeda, Kazutaka TI Quantitative Detection of mu Opioid Receptor: Western Blot Analyses Using mu Opioid Receptor Knockout Mice SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Knockout mice; mu opioid receptor; quantification; Western blot analysis ID POSITRON-EMISSION-TOMOGRAPHY; MESSENGER-RNA LEVELS; COCAINE TREATMENT; BRAIN; EXPRESSION; DEPENDENCE; OPIATE; DELTA AB Increasing evidence suggests that mu opioid receptor (MOP) expression is altered during the development of and withdrawal from substance dependence. Although anti-MOP antibodies have been hypothesized to be useful for estimating MOP expression levels, inconsistent MOP molecular weights (MWs) have been reported in studies using anti-MOP antibodies. In the present study, we generated a new anti-MOP antibody (N38) against the 1-38 amino acid sequence of the mouse MOP N-terminus and conducted Western blot analysis with wildtype and MOP knockout brain lysates to determine the MWs of intrinsic MOP. The N38 antibody detected migrating bands with relative MWs of 60-67 kDa in the plasma membrane fraction isolated from wildtype brain, but not from the MOP knockout brain. These migrating bands exhibited semi-linear density in the range of 3-30 mu g membrane proteins/lane. The N38 antibody may be useful for quantitatively detecting MOP. C1 [Ikeda, Kazutaka] Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. [Uhl, George R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Bethesda, MD 21224 USA. [Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Neurosci, Div Psychobiol, Sendai, Miyagi 9808574, Japan. [Watanabe, Masahiko] Hokkaido Univ, Grad Sch Med, Dept Anat & Embryol, Sapporo, Hokkaido 0608638, Japan. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikeda-kz@igakuken.or.jp RI WATANABE, Masahiko/A-4055-2012; Ikeda, Kazutaka/I-4694-2013 OI Ikeda, Kazutaka/0000-0001-8342-0278 FU Japanese Ministry of Health, Labour and Welfare [H17-pharmaco-001, 19-iyaku-023, H21-cancer-001, 18A-3, 19A-8]; Japanese Ministry of Education, Culture, Sports, Science, and Technology; Smoking Research Foundation; National Institute on Drug Abuse from the U.S. National Institutes of Health FX This study was supported by the Japanese Ministry of Health, Labour and Welfare (H17-pharmaco-001, 19-iyaku-023, H21-cancer-001, and 18A-3 and 19A-8 for Nervous and Mental Disorders), the Japanese Ministry of Education, Culture, Sports, Science, and Technology, the Smoking Research Foundation, and the National Institute on Drug Abuse Intramural Research Program from the U.S. National Institutes of Health. NR 14 TC 6 Z9 6 U1 0 U2 3 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 MAR PY 2011 VL 9 IS 1 BP 219 EP 222 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400045 PM 21886594 ER PT J AU Coleman, CN Weinstock, DM Casagrande, R Hick, JL Bader, JL Chang, F Nemhauser, JB Knebel, AR AF Coleman, C. Norman Weinstock, David M. Casagrande, Rocco Hick, John L. Bader, Judith L. Chang, Florence Nemhauser, Jeffrey B. Knebel, Ann R. TI Triage and Treatment Tools for Use in a Scarce Resources-Crisis Standards of Care Setting After a Nuclear Detonation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE nuclear detonation; triage; scarce resources; crisis standards of care ID BURN INJURIES; RADIATION; PROBABILITY; DEATH AB Based on background information in this special issue of the journal, possible triage recommendations for the first 4 days following a nuclear detonation, when response resources will be limited, are provided. The series includes: modeling for physical infrastructure damage; severity and number of injuries; expected outcome of triage to immediate, delayed, or expectant management; resources required for treating injuries of varying severity; and how resource scarcity (particularly medical personnel) worsens outcome. Four key underlying considerations are: 1.) resource adequacy will vary greatly across the response areas by time and location; 2.) to achieve fairness in resource allocation, a common triage approach is important; 3.) at some times and locations, it will be necessary to change from "conventional" to "contingency" or "crisis" standards of medical care (with a resulting change in triage approach from treating the "sickest first" to treating those "most likely to survive" first); and 4.) clinical reassessment and repeat triage are critical, as resource scarcity worsens or improves. Changing triage order and conserving and allocating resources for both lifesaving and palliative care can maintain fairness, support symptomatic care, and save more lives. Included in this article are printable triage cards that reflect our recommendations. These are not formal guidelines. With new research, data, and discussion, these recommendations will undoubtedly evolve. (Disaster Med Public Health Preparedness. 2011;5:S111-S121) C1 [Coleman, C. Norman; Bader, Judith L.; Knebel, Ann R.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Rockville, MD 20852 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Hick, John L.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. [Chang, Florence] Natl Inst Hlth, Specialized Informat Serv, Natl Lib Med, Bethesda, MD 20892 USA. [Nemhauser, Jeffrey B.] Ctr Dis Control & Prevent, Radiat Studies Branch, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Coleman, CN (reprint author), US Dept HHS, Off Assistant Secretary Preparedness & Response, 6130 Execut Blvd, Rockville, MD 20852 USA. EM ccoleman@mail.nih.gov FU US Department of Health and Human Services (DHHS) FX The US Department of Health and Human Services (DHHS) provided funding to support this publication and convene the authors. The contents of the articles represent the personal views of the individual authors and do not necessarily express the opinion or policy of DHHS or its components. No statement in the articles should be construed as an official position of DHHS or its components. NR 22 TC 21 Z9 21 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD MAR PY 2011 VL 5 SU 1 BP S111 EP S121 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 739VM UT WOS:000288748000012 PM 21402803 ER PT J AU DiCarlo, AL Maher, C Hick, JL Hanfling, D Dainiak, N Chao, N Bader, JL Coleman, CN Weinstock, DM AF DiCarlo, Andrea L. Maher, Carmen Hick, John L. Hanfling, Dan Dainiak, Nicholas Chao, Nelson Bader, Judith L. Coleman, C. Norman Weinstock, David M. TI Radiation Injury After a Nuclear Detonation: Medical Consequences and the Need for Scarce Resources Allocation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE nuclear detonation; radiation injury; acute radiation syndrome ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; WHOLE-BODY IRRADIATION; IONIZING-RADIATION; RHESUS-MONKEYS; SUPPORTIVE CARE; GAMMA-RADIATION; X-IRRADIATION; G-CSF; EXPOSURE AB A 10- kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network. (Disaster Med Public Health Preparedness. 2011;5:S32-S44) C1 [DiCarlo, Andrea L.] NIAID, Radiat Nucl Countermeasures Program, NIH, Bethesda, MD 20892 USA. [Maher, Carmen] US FDA, Off Counterterrorism & Emerging Threats, Rockville, MD 20857 USA. [Hick, John L.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. [Hanfling, Dan] George Washington Univ, Dept Emergency Med, Washington, DC 20052 USA. [Dainiak, Nicholas] Yale Univ, Sch Med, Bridgeport Hosp, New Haven, CT 06520 USA. [Chao, Nelson] Duke Univ, Bone Marrow & Stem Cell Transplant Program, Durham, NC 27706 USA. [Bader, Judith L.; Coleman, C. Norman] US Dept HHS, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weinstock, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 45 Brookline Ave,D510B, Boston, MA 02115 USA. EM DavidM_Weinstock@dfci.harvard.edu FU Genzyme; Novartis FX Dr Weinstock is a paid consultant by Genzyme and Novartis. NR 90 TC 68 Z9 69 U1 1 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD MAR PY 2011 VL 5 SU 1 BP S32 EP S44 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 739VM UT WOS:000288748000005 PM 21402810 ER PT J AU Douple, EB Mabuchi, K Cullings, HM Preston, DL Kodama, K Shimizu, Y Fujiwara, S Shore, RE AF Douple, Evan B. Mabuchi, Kiyohiko Cullings, Harry M. Preston, Dale L. Kodama, Kazunori Shimizu, Yukiko Fujiwara, Saeko Shore, Roy E. TI Long-term Radiation-Related Health Effects in a Unique Human Population: Lessons Learned from the Atomic Bomb Survivors of Hiroshima and Nagasaki SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE atomic bomb; ionizing radiation; cancer; genetics; health effects; epidemiology; excess relative risks ID NONCANCER DISEASE INCIDENCE; SOLID CANCER INCIDENCE; EXPOSED IN-UTERO; IONIZING-RADIATION; INFLAMMATORY RESPONSE; MENTAL-RETARDATION; PRENATAL EXPOSURE; GASTRIC-CANCER; YOUNG-CHILDREN; DOSE-RESPONSE AB For 63 years scientists in the Atomic Bomb Casualty Commission and its successor, the Radiation Effects Research Foundation, have been assessing the long-term health effects in the survivors of the atomic bombings of Hiroshima and Nagasaki and in their children. The identification and follow-up of a large population (approximately a total of 200 000, of whom more than 40% are alive today) that includes a broad range of ages and radiation exposure doses, and healthy representatives of both sexes; establishment of well-defined cohorts whose members have been studied longitudinally, including some with biennial health examinations and a high survivor-participation rate; and careful reconstructions of individual radiation doses have resulted in reliable excess relative risk estimates for radiation-related health effects, including cancer and noncancer effects in humans, for the benefit of the survivors and for all humankind. This article reviews those risk estimates and summarizes what has been learned from this historic and unique study. (Disaster Med Public Health Preparedness. 2011;5:S122-S133) C1 [Douple, Evan B.] Radiat Effects Res Fdn, Minami Ku, Hiroshima 7320815, Japan. [Mabuchi, Kiyohiko] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Preston, Dale L.] Hirosoft Int, Seattle, WA USA. RP Douple, EB (reprint author), Radiat Effects Res Fdn, Minami Ku, 5-2 Hijiyama Koen, Hiroshima 7320815, Japan. EM douple@rerf.or.jp FU Japan Ministry of Health, Labour and Welfare; US Department of Energy; National Cancer Institute [N02-CP-2009-00005]; National Institute for Allergy and Infectious Diseases FX The Radiation Effects Research Foundation is a private, nonprofit foundation funded primarily by the Japan Ministry of Health, Labour and Welfare and the US Department of Energy, the latter in part through the National Academy of Sciences. Additional support was received from the National Cancer Institute (contract N02-CP-2009-00005) and its Intramural Research Program, and the National Institute for Allergy and Infectious Diseases. NR 79 TC 29 Z9 29 U1 0 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD MAR PY 2011 VL 5 SU 1 BP S122 EP S133 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 739VM UT WOS:000288748000013 PM 21402804 ER PT J AU Koga, F Yoshida, S Tatokoro, M Kawakami, S Fujii, Y Kumagai, J Neckers, L Kihara, K AF Koga, F. Yoshida, S. Tatokoro, M. Kawakami, S. Fujii, Y. Kumagai, J. Neckers, L. Kihara, K. TI POTENTIAL ROLE OF HEAT SHOCK PROTEIN 90 INHIBITORS TO OVERCOME CHEMORADIOTHERAPY RESISTANCE ASSOCIATED WITH HER-2 AND NF-kappa B OVEREXPRESSION IN MUSCLE-INVASIVE BLADDER CANCER SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Meeting Abstract C1 [Koga, F.; Yoshida, S.; Tatokoro, M.; Kawakami, S.; Fujii, Y.; Kihara, K.] Tokyo Med & Dent Univ, Grad Sch, Dept Urol, Tokyo, Japan. [Kumagai, J.] Tokyo Med & Dent Univ, Grad Sch, Dept Pathol, Tokyo, Japan. [Neckers, L.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD MAR PY 2011 VL 10 IS 2 BP 167 EP 167 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 739KH UT WOS:000288715301424 ER PT J AU Vitiello, B Emslie, G Clarke, G Wagner, KD Asarnow, JR Keller, MB Birmaher, B Ryan, ND Kennard, B Mayes, TL DeBar, L Lynch, F Dickerson, J Strober, M Suddath, R McCracken, JT Spirito, A Onorato, M Zelazny, J Porta, G Iyengar, S Brent, DA AF Vitiello, Benedetto Emslie, Graham Clarke, Gregory Wagner, Karen Dineen Asarnow, Joan R. Keller, Martin B. Birmaher, Boris Ryan, Neal D. Kennard, Betsy Mayes, Taryn L. DeBar, Lynn Lynch, Frances Dickerson, John Strober, Michael Suddath, Robert McCracken, James T. Spirito, Anthony Onorato, Matthew Zelazny, Jamie Porta, Giovanna Iyengar, Satish Brent, David A. TI Long-Term Outcome of Adolescent Depression Initially Resistant to Selective Serotonin Reuptake Inhibitor Treatment: A Follow-Up Study of the TORDIA Sample SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT TREATMENT; TREATMENT RESPONSE; TADS; REMISSION; SUICIDE; SCALE; SSRI; VENLAFAXINE; PREDICTORS; DISORDERS AB Background: We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depressive disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive-behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while non-responders were given open treatment. Method: For the current study, patients were reassessed 48 (n = 116) and 72 (n = 130) weeks from intake. Data were gathered from February 2001 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology, and level of functioning were periodically administered. Remission was defined as >= 3 weeks with <= 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE]), and relapse, as 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed-effects regression models were applied to estimate remission, relapse, and functional recovery. Results: By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRIs had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (P<.03). Participants with more severe depression, greater dysfunction, and alcohol or drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of nonremitters by the first 6 weeks of treatment (P < .001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year. Conclusions: While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment. Trial Registration: clinicaltrials.gov Identifier: NCT00018902 Clin Psychiatry 2011;72(3):388-396 (C) Copyright 2010 Physicians Postgraduate Press,Inc. C1 [Vitiello, Benedetto] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Emslie, Graham; Kennard, Betsy; Mayes, Taryn L.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Clarke, Gregory; DeBar, Lynn; Lynch, Frances; Dickerson, John] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Wagner, Karen Dineen] Univ Texas Galveston, Dept Psychiat, Galveston, TX 77555 USA. [Asarnow, Joan R.; Strober, Michael; Suddath, Robert; McCracken, James T.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. [Keller, Martin B.; Spirito, Anthony] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Birmaher, Boris; Ryan, Neal D.; Onorato, Matthew; Zelazny, Jamie; Porta, Giovanna; Iyengar, Satish; Brent, David A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Vitiello, B (reprint author), NIMH, Div Serv & Intervent Res, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov FU National Institute of Mental Health [U01MH61835, U01 MH61856, U01MH 61864, U01MH61869, U01MH61958, U01MH62014]; Eli Lilly; Forest; Somerset; Pfizer; Philip Morris; Shire; McNeil; Bristol-Myers Squibb; Seaside FX Funded by the National Institute of Mental Health through grants U01MH61835 (University of Pittsburgh, Pennsylvania; PI: Dr Brent), U01 MH61856 (University of Texas, Galveston; PI: Dr Wagner), U01MH 61864 (University of California, Los Angeles; PI: Dr Asarnow), U01MH61869 (Kaiser Foundation, Portland, Oregon; PI: Dr Clarke), U01MH61958 (University of Texas, Dallas; PI: Dr Emslie), and U01MH62014 (Brown University, Providence, Rhode Island; PI: Dr Keller).; (Disclosures are relative to the last 12 months.) Dr Emslie has received research support from the National Institute of Mental Health, Eli Lilly, Forest, and Somerset; has been a consultant for Biobehavioral Diagnostics, Eli Lilly, Forest, GlaxoSmithKline, Pfizer, and Wyeth; and has been on the speakers bureau for Forest. Dr Clarke is an employee of Kaiser Permanente Northwest and has received grant/research support from the National Institute of Mental Health. Dr Wagner has received honoraria from CMP Medica, UMB Medics, Physicians Postgraduate Press, Contemporary Forums, and the National Institutes of Health. Dr Asarnow is an employee for the University of California in Los Angeles; has consulted for the California Institute of Mental Health and on cognitive behavior therapy and depression treatment quality improvement; received unrestricted funding from Philip Morris; and received honoraria from the University of Michigan. Dr Keller has received research support from Pfizer and the National Institute of Mental Health and is a consultant to Medtronic and Sierra. Dr Birmaher is an employee of the University of Pittsburgh and the University of Pittsburgh Medical Center/Western Psychiatric Institute and Clinic; is a consultant for Schering-Plough; receives research support from the National Institute of Mental Health; has participated in forums sponsored by Shire (provided training for an investigators meeting) and Forest (advisory board); and receives royalties from Random House and Lippincott Williams & Wilkins. Dr McCracken has received research support from Eli Lilly, McNeil, Bristol-Myers Squibb, Seaside, and Shire; has received honoraria from Continuing Medical Education Outfitters and Veritas; and is a consultant for Shire, Eli Lilly, McNeil, Pfizer, Janssen, Johnson & Johnson, Novartis, Shionogi, and Wyeth. The other authors report no relevant financial relationships. NR 29 TC 35 Z9 35 U1 4 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2011 VL 72 IS 3 BP 388 EP 396 DI 10.4088/JCp.09m05885blu PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 741BM UT WOS:000288838100016 PM 21208583 ER PT J AU Abbott, L Grady, C AF Abbott, Lura Grady, Christine TI A SYSTEMATIC REVIEW OF THE EMPIRICAL LITERATURE EVALUATING IRBs: WHAT WE KNOW AND WHAT WE STILL NEED TO LEARN SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Review DE institutional review boards; IRBs; evaluation; empirical data ID MULTICENTER CLINICAL-TRIALS; HEALTH-SERVICES RESEARCH; PEDIATRIC RESEARCH; STANDARD PROTOCOL; INFORMED-CONSENT; BOARD MEMBERS; UNITED-STATES; VARIABILITY; PARTICIPANTS; CHALLENGES AB INSTITUTIONAL REVIEW BOARDS (IRBS) are integral to the U.S. system of protection of human research participants. Evaluation of IRBs, although difficult, is essential. To date, no systematic review of IRB studies has been published. We conducted a systematic review of empirical studies of U.S. IRBs to determine what is known about the function of IRBs and to identify gaps in knowledge. A structured search in PubMed identified forty-three empirical studies evaluating U.S. IRBs. Studies were included if they reported an empirical investigation of the structure, process, outcomes, effectiveness, or variation of U.S. IRBs. The authors reviewed each study to extract information about study objectives, sample and methods, study results, and conclusions. Empirical evidence collected in forty-three published studies shows that for review of a wide range of types of research, U.S. IRBs differ in their application of the federal regulations, in the time they take to review studies, and in the decisions made. Existing studies show evidence of variation in multicenter review, inconsistent or ambiguous interpretation of the federal regulations, and inefficiencies in review. Despite recognition of a need to evaluate effectiveness of IRB review, no identified published study included an evaluation of IRB effectiveness. Multiple studies evaluating the structure, process, and outcome of IRB review in the United States have documented inconsistencies and inefficiencies. Efforts should be made to address these concerns. Additional research is needed to understand how IRBs accomplish their objectives, what issues they find important, what quality IRB review is, and how effective IRBs are at protecting human research participants. C1 [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Off Human Subjects Res,Div Intramural Res, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Off Human Subjects Res,Div Intramural Res, Bldg 10-1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov FU Clinical Center, Department of Bioethics, National Institutes of Health FX The authors acknowledge Nicole Newman and Karen Smith for their assistance in identifying empirical studies, and Frank Miller for his review and constructive comments. This work was supported by the Clinical Center, Department of Bioethics, National Institutes of Health. The views expressed are those of the authors and do not necessarily reflect those of the Clinical Center, the National Institutes of Health, the Public Health Service, or the U.S. Department of Health and Human Services. NR 65 TC 66 Z9 68 U1 1 U2 9 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2011 VL 6 IS 1 BP 3 EP 19 DI 10.1525/jer.2011.6.1.3 PG 17 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 742DE UT WOS:000288918900002 PM 21460582 ER PT J AU Brintnall-Karabelas, J Sung, S Cadman, ME Squires, C Whorton, K Pao, M AF Brintnall-Karabelas, Julie Sung, Susanna Cadman, Mary Ellen Squires, Carol Whorton, Katherine Pao, Maryland TI IMPROVING RECRUITMENT IN CLINICAL TRIALS: WHY ELIGIBLE PARTICIPANTS DECLINE SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS LA English DT Article DE recruitment; clinical trials; refusal to participate ID WILLINGNESS AB THERE IS A NEED TO EXPLORE WHY protocol-eligible subjects refuse participation in clinical trials. Without a clear understanding, participation by representative populations will be an ongoing obstacle to recruitment. This descriptive research study analyzes frequency data regarding a sample of 965 individuals who, despite being eligible for studies with the National Institute of Mental Health intramural program, declined research participation. Overall, responses regarding reasons for declining fell into the following five categories: a result of specific protocol issues; inconvenience; for other reasons not mentioned; financial reasons; and, lastly, decided to participate elsewhere. The results of this study identify common factors which suggest there are steps that investigators can take to better accommodate the needs of the public and, consequently, improve research participation. C1 [Brintnall-Karabelas, Julie] NIMH, Human Subjects Protect Unit, Off Clin Director, Bethesda, MD 20892 USA. [Pao, Maryland] Natl Inst Hlth, Hatfield Clin Res Ctr, Psychiat Consultat Liaison Serv, Bethesda, MD USA. RP Brintnall-Karabelas, J (reprint author), NIMH, Human Subjects Protect Unit, Off Clin Director, 9000 Rockville Pkwy,Bldg 10,Room 3N2 18, Bethesda, MD 20892 USA. EM brintnaj@mail.nih.gov FU National Institute of Mental Health FX This study was conducted with the support of the National Institute of Mental Health. Our gratitude goes to Dr. Donald Rosenstein, MD, for being one of the pioneers to spearhead CORE. We would like to thank Jean Murphy, RN, MSN, for the support and encouragement she gave to this research project and to Lisa Horowitz, PhD, for her editorial assistance. In addition, we would like to thank Dr. Christine Grady for highlighting the importance of recruitment issues and the need to better understand the desires of research participants during "The Ethical and Regulatory Aspects of Human Subject Research Conference" in 2002. NR 14 TC 10 Z9 11 U1 0 U2 3 PU UNIV CALIFORNIA PRESS PI BERKELEY PA C/O JOURNALS & DIGITAL PUBLISHING DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 1556-2646 J9 J EMPIR RES HUM RES JI J. Empir. Res. Hum. Res. Ethics PD MAR PY 2011 VL 6 IS 1 BP 69 EP 74 DI 10.1525/jer.2011.6.1.69 PG 6 WC Ethics; Medical Ethics SC Social Sciences - Other Topics; Medical Ethics GA 742DE UT WOS:000288918900010 PM 21460590 ER PT J AU Yang, MQ Laflamme, K Gotea, V Joiner, CH Seidel, NE Wong, C Petrykowska, HM Lichtenberg, J Lee, S Welch, L Gallagher, PG Bodine, DM Elnitski, L AF Yang, Mary Q. Laflamme, Karina Gotea, Valer Joiner, Clinton H. Seidel, Nancy E. Wong, Clara Petrykowska, Hanna M. Lichtenberg, Jens Lee, Stephen Welch, Lonnie Gallagher, Patrick G. Bodine, David M. Elnitski, Laura TI Genome-wide detection of a TFIID localization element from an initial human disease mutation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID II CORE PROMOTER; TRANSCRIPTION FACTOR IIB; HEREDITARY SPHEROCYTOSIS; GENE-EXPRESSION; CPG ISLAND; TATA; SP1; EVOLUTION; CHROMATIN; SYNERGY AB Eukaryotic core promoters are often characterized by the presence of consensus motifs such as the TATA box or initiator elements, which attract and direct the transcriptional machinery to the transcription start site. However, many human promoters have none of the known core promoter motifs, suggesting that undiscovered promoter motifs exist in the genome. We previously identified a mutation in the human Ankyrin-1 (ANK-1) promoter that causes the disease ankyrin-deficient Hereditary Spherocytosis (HS). Although the ANK-1 promoter is CpG rich, no discernable basal promoter elements had been identified. We showed that the HS mutation disrupted the binding of the transcription factor TFIID, the major component of the pre-initiation complex. We hypothesized that the mutation identified a candidate promoter element with a more widespread role in gene regulation. We examined 17 181 human promoters for the experimentally validated binding site, called the TFIID localization sequence (DLS) and found three times as many promoters containing DLS than TATA motifs. Mutational analyses of DLS sequences confirmed their functional significance, as did the addition of a DLS site to a minimal Sp1 promoter. Our results demonstrate that novel promoter elements can be identified on a genome-wide scale through observations of regulatory disruptions that cause human disease. C1 [Yang, Mary Q.; Gotea, Valer; Petrykowska, Hanna M.; Elnitski, Laura] NHGRI, Genome Technol Branch, NIH, Rockville, MD 20852 USA. [Laflamme, Karina; Seidel, Nancy E.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Rockville, MD 20852 USA. [Joiner, Clinton H.] Cincinnati Childrens Hosp Res Fdn, Div Hematol Oncol, Cincinnati, OH 45229 USA. [Wong, Clara; Gallagher, Patrick G.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Lichtenberg, Jens; Welch, Lonnie] Ohio Univ, Sch EECS, Athens, OH 45701 USA. [Lee, Stephen] Univ Idaho, Dept Stat, Moscow, ID 83844 USA. [Welch, Lonnie] Ohio Univ, Biomed Engn Program, Athens, OH 45701 USA. [Welch, Lonnie] Ohio Univ, Mol & Cellular Biol Program, Athens, OH 45701 USA. RP Elnitski, L (reprint author), NHGRI, Genome Technol Branch, NIH, Rockville, MD 20852 USA. EM elnitski@mail.nih.gov OI Gotea, Valer/0000-0001-7857-3309 FU NHGRI; Fonds de la recherche en sante du Quebec; Ohio University; Ohio University's Graduate Research and Education Board (GERB); Ohio Supercomputer Center; [DK60239]; [DK04015] FX NHGRI intramural funds (to L. E. and D. M. B.), DK60239, DK04015 (to P. G. G.); Fonds de la recherche en sante du Quebec (to K. L.); Ohio University Stocker Endowment, Ohio University's Graduate Research and Education Board (GERB); Ohio Supercomputer Center (to L. W., J.L.). Funding for open access charge: NHGRI intramural funds. NR 43 TC 5 Z9 9 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR PY 2011 VL 39 IS 6 BP 2175 EP 2187 DI 10.1093/nar/gkq1035 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 745LH UT WOS:000289166400025 PM 21071415 ER PT J AU Castro, K Bevans, M Miller-Davis, C Cusack, G Loscalzo, F Matlock, AM Mayberry, H Tondreau, L Walsh, D Hastings, C AF Castro, Kathleen Bevans, Margaret Miller-Davis, Claiborne Cusack, Georgie Loscalzo, Frances Matlock, Ann Marie Mayberry, Helen Tondreau, Linda Walsh, Diane Hastings, Clare TI Validating the Clinical Research Nursing Domain of Practice SO ONCOLOGY NURSING FORUM LA English DT Article AB Purpose/Objectives: To develop and validate a taxonomy for the domain of clinical research nursing. Design: Survey. Setting: Clinical research settings in the United States. Sample: A purposefully selected expert panel of 22 nurses who were actively practicing or supervising in a clinical research environment. Methods: A study team consisting of nurses with experience in clinical research synthesized peer-reviewed articles, academic curricula, professional guidelines, position descriptions, and expert opinion. Using the Delphi technique, three rounds of surveys were conducted to validate the taxonomy. The three sequential questionnaires were completed over five months. Main Research Variables: Activities performed by nurses in a clinical research setting. Findings: A taxonomy for clinical research nursing was validated with five dimensions and 52 activities: Clinical Practice (4 activities), Study Management (23 activities), Care Coordination and Continuity (10 activities), Human Subjects Protection (6 activities), and Contributing to the Science (9 activities). Conclusions: This study validated activities for direct care providers and nurses with the primary focus of research coordination. The findings identify a variety of activities that are unique to nurses in a clinical research setting. Implications for Nursing: Nurses play an integral role in the clinical research enterprise. Validating a taxonomy for the specialty of clinical research nursing allows for roles to be compared across settings, competency requirements to be defined, and nursing organizations to be guided in the development of specialty certification. C1 [Castro, Kathleen] NCI, Bethesda, MD 20892 USA. RP Castro, K (reprint author), NCI, Bethesda, MD 20892 USA. EM castrok@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 0 TC 11 Z9 12 U1 0 U2 2 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2011 VL 38 IS 2 BP 215 EP 215 DI 10.1188/11.ONF.E72-E80 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 736DM UT WOS:000288470700012 PM 21356644 ER PT J AU Wildman, DE AF Wildman, D. E. TI Review: Toward an integrated evolutionary understanding of the mammalian placenta SO PLACENTA LA English DT Article; Proceedings Paper CT 2010 Meeting of the International-Federation-of-Placenta-Associations (IFPA) CY 2010 CL Santiago de Chile, CHILE SP Int Federat Placenta Assoc, Placenta Assoc Amer, Latin Amer Soc Placenta Fetomaternal Res, SLIMP DE Evolution; Phylogeny; Gene duplication; Positive selection; Genomic imprinting ID GROWTH-HORMONE; PHYLOGENETIC ANALYSIS; GENES; PRIMATES; DIVERSIFICATION; ADAPTATION; PREGNANCY; SUBFAMILY; SELECTION; PATTERNS AB The placenta is fundamentally important for the success of pregnancy. Disruptions outside the normal range for placental function can result in pregnancy failure and other complications. The anatomy of the placenta varies greatly across mammals, as do key parameters in pregnancy such as neonatal body mass, length of gestation and number of offspring per pregnancy. An accurate understanding of the evolution of the mammalian placenta will require at minimum the integration of anatomical, developmental, physiological, genetic, and epigenetic data. Currently available data suggest that the placenta is a dynamic organ that has evolved rapidly in a lineage specific manner. Examination of the placenta from the perspective of human evolution shows that many anatomical features of the human placenta are relatively conserved. Despite the anatomical conservation of the human placenta there are many recently evolved placenta-specific genes (e.g. CGB, LGALS13, GH2) that are important in the development and function of the human placenta. Other mammalian genomes have also evolved specific suites of placenta-expressed genes. For example, rodents have undergone expansions of the cathepsin and prolactin families, and artiodactyls have expanded their suite of pregnancy-associated glycoproteins. In addition to lineage specific birth and death of gene family members, the pattern of imprinted loci varies greatly among species. Taken together, these studies suggest that a strategy reliant upon the sampling of placentally expressed and imprinted genes from a phylogenetically diverse range of species is appropriate for unraveling the conserved and derived aspects of placental biology. (C) 2011 Published by IFPA and Elsevier Ltd. C1 [Wildman, D. E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Wildman, D. E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA. RP Wildman, DE (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, 540 E Canfield Ave, Detroit, MI 48201 USA. EM dwildman@wayne.edu FU Intramural NIH HHS [ZIA HD002401-17] NR 45 TC 21 Z9 21 U1 2 U2 22 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD MAR PY 2011 VL 32 SU B BP S142 EP S145 DI 10.1016/j.placenta.2011.01.005 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 746SA UT WOS:000289266100012 PM 21306776 ER PT J AU Liu, JC Givi, B Wolden, S Kleinerman, RA Dunkel, IJ Lee, N Shah, JP Abramson, DH Kraus, DH AF Liu, Jeffrey C. Givi, Babak Wolden, Suzanne Kleinerman, Ruth A. Dunkel, Ira J. Lee, Nancy Shah, Jatin P. Abramson, David H. Kraus, Dennis H. TI Secondary Skull Base Malignancies in Survivors of Retinoblastoma: The Memorial Sloan Kettering Cancer Center Experience SO SKULL BASE-AN INTERDISCIPLINARY APPROACH LA English DT Article DE Skull base neoplasms; retinoblastoma; neoplasms; second primary; radiotherapy ID 2ND NONOCULAR TUMORS; FOLLOW-UP; RISK AB We report the pathology and outcome of secondary skull base tumors in patients previously treated with external beam radiation for retinoblastoma (Rb). Rb patients are at increased risk of second head and neck primary malignancies due to early radiation exposure during treatment and loss of RB1 protein in genetic carriers. An institutional database was reviewed for patients with retinoblastoma who had previously received radiation therapy and subsequently developed skull base tumors. Seventeen patients met the selection criteria. The median age of Rb diagnosis was 12 months. Thirteen cases underwent enucleation in addition to radiation therapy as part of initial Rb treatment. A median of 19 years elapsed between the diagnosis of Rb and diagnosis of skull base malignancy. The most common tumors were osteogenic sarcoma (39%) and leiomyosarcoma (22%). Eleven (71%) patients received postoperative chemotherapy, and 7 (41%) received postoperative radiotherapy. Three (24%) patients underwent salvage surgery for recurrent disease. Five-year survival was 68%, and 10-year survival was 51% by Kaplan-Meier analysis. Secondary malignancy in Rb patients is a well-defined event. The use of surgery with appropriate adjuvant therapy was associated with a 51% 10-year survival in this study population. C1 [Liu, Jeffrey C.; Givi, Babak; Wolden, Suzanne; Dunkel, Ira J.; Lee, Nancy; Shah, Jatin P.; Abramson, David H.; Kraus, Dennis H.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Kleinerman, Ruth A.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Liu, JC (reprint author), Mem Sloan Kettering Canc Ctr, Box 240, New York, NY 10065 USA. EM JCL2006@gmail.com OI Kleinerman, Ruth/0000-0001-7415-2478; Dunkel, Ira/0000-0001-8091-6067; Givi, Babak/0000-0002-8221-5077; Shah, Jatin/0000-0002-6444-6592 FU National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Cancer Institute [T32CA009685] FX This research was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics. The project described was supported by Award Number T32CA009685 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 9 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-5010 J9 SKULL BASE-INTERD AP JI Skull Base-Interdiscip. Appr. PD MAR PY 2011 VL 21 IS 2 BP 103 EP 107 DI 10.1055/s-0031-1275256 PG 5 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA 747KD UT WOS:000289317800008 PM 22451810 ER PT J AU Mroczkowski, MM Goes, FS Riddle, MA Grados, MA Bienvenu, OJ Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Knowles, JA Piacentini, J Cullen, B Rasmussen, SA Geller, DA Pauls, DL Liang, KY Nestadt, G Samuels, JF AF Mroczkowski, Megan M. Goes, Fernando S. Riddle, Mark A. Grados, Marco A. Bienvenu, O. Joseph, III Greenberg, Benjamin D. Fyer, Abby J. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Knowles, James A. Piacentini, John Cullen, Bernadette Rasmussen, Steven A. Geller, Daniel A. Pauls, David L. Liang, Kung-Yee Nestadt, Gerald Samuels, Jack F. TI SEPARATION ANXIETY DISORDER IN OCD SO DEPRESSION AND ANXIETY LA English DT Article DE obsessive-compulsive disorder; separation anxiety disorder; personality disorders ID OBSESSIVE-COMPULSIVE DISORDER; PERSONALITY-DISORDERS; COMORBIDITY; CHILDHOOD; ADOLESCENTS; PSYCHOPATHOLOGY; SCHIZOPHRENIA; RELIABILITY; ADULTHOOD; RATIONALE AB Background: A history of separation anxiety disorder (SAD) is frequently reported by patients with obsessive-compulsive disorder (OCD). The purpose of this study was to determine if there are clinical differences between OCD-affected individuals with, versus without, a history of SAD. Methods: Using data collected during the OCD Collaborative Genetic Study, we studied 470 adult OCD participants; 80 had a history of SAD, whereas 390 did not. These two groups were compared as to onset and severity of OCD, lifetime prevalence of Axis I disorders, and number of personality disorder traits. Results: OCD participants with a history of SAD were significantly younger than the non-SAD group (mean, 34.2 versus 42.2 years; P < .001). They had an earlier age of onset of OCD symptoms (mean, 8.0 versus 10.5 years; P < .003) and more severe OCD, as measured by the Yale-Brown Obsessive Compulsive Scale (mean, 27.5 versus 25.0; P < .005). In addition, those with a history of SAD had a significantly greater lifetime prevalence of agoraphobia (odds ratio (OR) 52.52, 95% confidence interval (CI) = 1.4-4.6, P < .003), panic disorder (OR51.84, CI = 1.03-3.3 P < .04), social phobia (OR = 1.69, CI 1.01-2.8, P < .048), after adjusting for age at interview, age at onset of OCD, and OCD severity in logistic regression models. There was a strong relationship between the number of dependent personality disorder traits and SAD (adjusted OR = 1.42, CI = 1.2-1.6, P < .001). Conclusions: A history of SAD is associated with anxiety disorders and dependent personality disorder traits in individuals with OCD. Depression and Anxiety 28:256-262, 2011. (C) 2011 Wiley-Liss, C1 [Mroczkowski, Megan M.; Goes, Fernando S.; Riddle, Mark A.; Grados, Marco A.; Bienvenu, O. Joseph, III; Cullen, Bernadette; Nestadt, Gerald; Samuels, Jack F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Liang, Kung-Yee] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. [Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [McCracken, James T.; Piacentini, John] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, Scott L.; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Rauch, Scott L.; Geller, Daniel A.; Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA. [Fyer, Abby J.; Knowles, James A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Fyer, Abby J.; Knowles, James A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 1629 Thames St,Suite 401, Baltimore, MD 21287 USA. EM gjacks@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; OI Samuels, Jack/0000-0002-6715-7905 NR 29 TC 10 Z9 10 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAR PY 2011 VL 28 IS 3 BP 256 EP 262 DI 10.1002/da.20773 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 734JZ UT WOS:000288331700011 PM 21308883 ER PT J AU Bornstein, MH Mash, C Arterberry, ME AF Bornstein, Marc H. Mash, Clay Arterberry, Martha E. TI Perception of Object-Context Relations: Eye-Movement Analyses in Infants and Adults SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE eye movement; scene perception; visual attention; infancy ID REAL-WORLD SCENES; RECOGNITION MEMORY; 6-MONTH-OLD INFANTS; ABSTRACT STIMULI; NATURAL SCENES; DYNAMIC FACES; VISUAL-SEARCH; RACE FACES; ATTENTION; PICTURES AB Twenty-eight 4-month-olds' and twenty-two 20-year-olds' attention to object context relations was investigated using a common eye-movement paradigm. Infants and adults scanned both objects and contexts. Infants showed equivalent preferences for animals and vehicles and for congruent and incongruent object-context relations overall, more fixations of objects in congruent object context relations, more fixations of contexts in incongruent object context relations, more fixations of objects than contexts in vehicle scenes, and more fixation shifts in incongruent than congruent vehicle scenes. Adults showed more fixations of congruent than incongruent scenes, vehicles than animals, and objects than contexts; equal fixations of animals and their contexts but more fixations of vehicles than their contexts: and more shifts of fixation when inspecting animals in context than vehicles in context. These findings for location, number, and order of eye movements indicate that object context relations play a dynamic role in the development and allocation of attention. C1 [Bornstein, Marc H.; Mash, Clay] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Arterberry, Martha E.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [Z01 HD001119-20] NR 107 TC 7 Z9 8 U1 3 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAR PY 2011 VL 47 IS 2 BP 364 EP 375 DI 10.1037/a0021059 PG 12 WC Psychology, Developmental SC Psychology GA 729NC UT WOS:000287956100006 PM 21244146 ER PT J AU Rezvani, K Yong, ASM Mielke, S Jafarpour, B Savani, BN Le, RQ Eniafe, R Musse, L Boss, C Kurlander, R Barrett, AJ AF Rezvani, Katayoun Yong, Agnes S. M. Mielke, Stephan Jafarpour, Behnam Savani, Bipin N. Le, Robert Q. Eniafe, Rhoda Musse, Laura Boss, Carol Kurlander, Roger Barrett, A. John TI Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8(+) T cells in myeloid malignancies SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE PR1; WT1; vaccine; leukemia; immunotherapy ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; EX-VIVO CHARACTERIZATION; CANCER-PATIENTS; CUTTING EDGE; IN-VITRO; LYMPHOCYTES; RESPONSES; MELANOMA AB Background We previously showed that vaccination with one dose of PR1 and WT1 peptides induces transient anti-leukemia immunity. We hypothesized that maintenance of a sustained anti-leukemia response may require frequent boost injections. Design and Methods Eight patients with myeloid malignancies were enrolled in this phase II study, and 6 completed 6 injections of PR1 and WT1 peptides in Montanide-adjuvant with GM-CSF, every two weeks. Results Both high- and low-avidity PR1 or WT1-specific CD8(+) T cells were detected in all evaluable patients after the first vaccine dose. Repeated vaccination led to selective deletion of high avidity PR1- and WT1-specific CD8(+) T cells and was not associated with significant reduction in WT1-expression. Additional boosting failed to increase vaccine-induced CD8(+) T-cell frequencies further and in all patients the response was lost before the 6(th) dose. PR1- or WT1-specific CD8(+) T cells were not detected in bone marrow samples, excluding their preferential localization to this site. Following a booster injection three months after the 6th vaccine dose, no high-avidity PR1 or WT1-specific CD8(+) T cells could be detected, whereas low-avidity T cells were readily expanded. Conclusions These data support the immunogenicity of PR1 and WT1 peptide vaccines. However, repeated delivery of peptides with Montanide-adjuvant and GM-CSF leads to rapid loss of high-avidity peptide-specific CD8(+) T cells. These results may offer an explanation for the lack of correlation between immune and clinical responses observed in a number of clinical trials of peptide vaccination. New approaches are needed to induce long-term high-avidity memory responses against leukemia antigens. (ClinicalTrials.gov Identifier: NCT00499772) C1 [Yong, Agnes S. M.; Jafarpour, Behnam; Le, Robert Q.; Eniafe, Rhoda; Musse, Laura; Boss, Carol; Barrett, A. John] Natl Heart Lung Blood Inst, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD USA. [Rezvani, Katayoun] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London W12 0NN, England. [Mielke, Stephan] Univ Wurzburg, Med Ctr, Div Hematol & Oncol, Dept Internal Med 2,Dept Lab Med, Wurzburg, Germany. [Savani, Bipin N.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Kurlander, Roger] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Hematol, Hammersmith Campus,4th Floor,Commonwealth Bldg,Du, London W12 0NN, England. EM k.rezvani@imperial.ac.uk FU NIH; National Institute for Health Research (NIHR) Biomedical Research Centre FX this study was supported by an NIH bench-to-bedside award. K.R. acknowledges the support of the National Institute for Health Research (NIHR) Biomedical Research Centre. NR 55 TC 55 Z9 57 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 EI 1592-8721 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAR PY 2011 VL 96 IS 3 BP 432 EP 440 DI 10.3324/haematol.2010.031674 PG 9 WC Hematology SC Hematology GA 740BQ UT WOS:000288767000014 PM 21134985 ER PT J AU Wilson, TM Maric, I Simakova, O Bai, Y Chan, EC Olivares, N Carter, M Maric, D Robyn, J Metcalfe, DD AF Wilson, Todd M. Maric, Irina Simakova, Olga Bai, Yun Chan, Eunice Ching Olivares, Nicolas Carter, Melody Maric, Dragan Robyn, Jamie Metcalfe, Dean D. TI Clonal analysis of NRAS activating mutations in KIT-D816V systemic mastocytosis SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE systemic mastocytosis; activating mutations; NRAS KIT ID ACUTE MYELOID-LEUKEMIA; GENE-MUTATIONS; RAS MUTATIONS; MAST-CELLS; PHASE-II; T-CELLS; C-KIT; DASATINIB; KITD816V; DISORDER AB Cooperating genetic events are likely to contribute to the phenotypic diversity of KIT-D816V systemic mastocytosis. In this study, 44 patients with KIT-D816V systemic mastocytosis were evaluated for coexisting NRAS, KRAS, HRAS or MRAS mutations. Activating NRAS mutations were identified in 2 of 8 patients with advanced disease. NRAS mutations were not found in patients with indolent systemic mastocytosis. To better understand the clonal evolution of mastocytosis, we evaluated the cell compartments impacted by the NRAS and KIT mutations. Clonal mast cells harbored both mutations. KIT-D816V was not detected in bone marrow CD34(+) progenitors, whereas the NRAS mutation was present. These findings suggest that NRAS mutations may have the potential to precede KIT-D816V in clonal development. Unlike other mature lineages, mast cell survival is dependent on KIT and the presence of these two activating mutations may have a greater impact on the expansion of this cell compartment and in resultant disease severity. C1 [Wilson, Todd M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Maric, Irina; Simakova, Olga; Olivares, Nicolas] Ctr Clin, Dept Lab Med, Bethesda, MD USA. [Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD USA. [Robyn, Jamie] Dept Vet Affairs, Springfield, OH USA. RP Wilson, TM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 12S235A, Bethesda, MD 20892 USA. EM twilson@niaid.nih.gov FU NIAID, NIH FX this study was funded by the Intramural Research Program of the NIAID, NIH. NR 24 TC 42 Z9 42 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 EI 1592-8721 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAR PY 2011 VL 96 IS 3 BP 459 EP 463 DI 10.3324/haematol.2010.031690 PG 5 WC Hematology SC Hematology GA 740BQ UT WOS:000288767000018 PM 21134978 ER PT J AU O'Meara, WP Tsofa, B Molyneux, S Goodman, C McKenzie, FE AF O'Meara, Wendy Prudhomme Tsofa, Benjamin Molyneux, Sassy Goodman, Catherine McKenzie, F. Ellis TI Community and facility-level engagement in planning and budgeting for the government health sector - A district perspective from Kenya SO HEALTH POLICY LA English DT Article DE Health planning; Decentralization; Community participation ID PARTICIPATION; DECENTRALIZATION; REFORM; TANZANIA; UGANDA AB Health systems reform processes have increasingly recognized the essential contribution of communities to the success of health programs and development activities in general. Here we examine the experience from Kilifi district in Kenya of implementing annual health sector planning guidelines that included community participation in problem identification, priority setting, and planning. We describe challenges in the implementation of national planning guidelines, how these were met, and how they influenced final plans and budgets. The broad-based community engagement envisaged in the guidelines did not take place due to the delay in roll out of the Ministry of Health-trained community health workers. Instead, community engagement was conducted through facility management committees, though in a minority of facilities, even such committees were not involved. Some overlap was found in the priorities highlighted by facility staff, committee members and national indicators, but there were also many additional issues raised by committee members and not by other groups. The engagement of the community through committees influenced target and priority setting, but the emphasis on national health indicators left many local priorities unaddressed by the final work plans. Moreover, it appears that the final impact on budgets allocated at district and facility level was limited. The experience in Kilifi highlights the feasibility of engaging the community in the health planning process, and the challenges of ensuring that this engagement feeds into consolidated plans and future implementation. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [O'Meara, Wendy Prudhomme] Duke Univ Sch Med, Durham, NC USA. [O'Meara, Wendy Prudhomme] Duke Global Hlth Inst, Durham, NC USA. [Tsofa, Benjamin; Molyneux, Sassy] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya. [Goodman, Catherine] KEMRI Wellcome Trust Res Programme, Nairobi, Kenya. [Goodman, Catherine] London Sch Hyg & Trop Med, Hlth Policy Unit, London WC1, England. [McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP O'Meara, WP (reprint author), Duke Univ Sch Med, Durham, NC USA. EM wendypomeara@gmail.com FU UK Department for International Development; Wellcome Trust [077092, WT 085418]; Fogarty International Center FX Special thanks to the Kilifi District Health Management Team. CG is a member of the Consortium for Research on Equitable Health Systems, which is funded by the UK Department for International Development. SM, CG and BT are members of the KEMRI-Wellcome Trust Research Programme, which is supported by a grant from the Wellcome Trust (#077092). SM is also supported by a fellowship from the Wellcome Trust (WT 085418). WPO was supported by the Fogarty International Center. This work is published with the permission of the Director, KEMRI. NR 27 TC 11 Z9 12 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD MAR PY 2011 VL 99 IS 3 BP 234 EP 243 DI 10.1016/j.healthpol.2010.08.027 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 728QA UT WOS:000287887500007 PM 20888061 ER PT J AU Ryan, JF Pang, K Moreland, RT Nguyen, A Nisc Wolfsberg, TG Mullikin, JC Martindale, MQ Baxevanis, AD AF Ryan, J. F. Pang, K. Moreland, R. T. Nguyen, A. Nisc Wolfsberg, T. G. Mullikin, J. C. Martindale, M. Q. Baxevanis, A. D. TI The Genome of the Ctenophore Mnemiopsis leidyi and its Implications on the History of Animals SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2011 CL Salt Lake City, UT SP Soc Integrat & Comparat Biol C1 [Ryan, J. F.; Pang, K.; Moreland, R. T.; Nguyen, A.; Nisc; Wolfsberg, T. G.; Mullikin, J. C.; Martindale, M. Q.; Baxevanis, A. D.] Univ Hawaii, NHGRI, NIH, Honolulu, HI 96822 USA. EM jfryan@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD MAR PY 2011 VL 51 SU 1 BP E120 EP E120 PG 1 WC Zoology SC Zoology GA 733QP UT WOS:000288278101170 ER PT J AU Simmons, D Pang, K Ryan, J Baxevanis, A Martindale, MQ AF Simmons, D. Pang, K. Ryan, J. Baxevanis, A. Martindale, M. Q. TI The Genomic Complement of the Ctenophore Nervous System SO INTEGRATIVE AND COMPARATIVE BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Integrative-and-Comparative-Biology CY JAN 03-07, 2011 CL Salt Lake City, UT SP Soc Integrat & Comparat Biol C1 Univ Hawaii, Honolulu, HI 96822 USA. NIH, Genome Technol Branch, Bethesda, MD USA. EM davidsim@hawaii.edu 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 1540-7063 J9 INTEGR COMP BIOL JI Integr. Comp. Biol. PD MAR PY 2011 VL 51 SU 1 BP E127 EP E127 PG 1 WC Zoology SC Zoology GA 733QP UT WOS:000288278101198 ER PT J AU Yao, JY Feathers, KL Khanna, H Thompson, D Tsilfidis, C Hauswirth, WW Heckenlively, JR Swaroop, A Zacks, DN AF Yao, Jingyu Feathers, Kecia L. Khanna, Hemant Thompson, Debra Tsilfidis, Catherine Hauswirth, William W. Heckenlively, John R. Swaroop, Anand Zacks, David N. TI XIAP Therapy Increases Survival of Transplanted Rod Precursors in a Degenerating Host Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTORECEPTOR PRECURSORS; INTEGRATION; MODEL; NRL; DISRUPTION; APOPTOSIS; MOUSE AB PURPOSE. To assess the survival of rod precursor cells transplanted into the Rd9 mouse, a model of X-linked retinal degeneration, and the effect of antiapoptotic therapy with X-linked inhibitor of apoptosis (MAP) on preventing cell loss. METHODS. Dissociated retinal cells from P4 Nrlp-GFP mice were transplanted into the subretinal space of 2-, 5-, and 8-month-old Rd9 mice. Histology, immunohistochemistry, and quantification of integrated cells were performed every month for up to 3 months after transplantation. XIAP delivery to donor cells was accomplished by transfection with adenoassociated virus (AAV-XIAP). Intraretinal activation of immune modulators was assessed using a quantitative real-time polymerase chain reaction-based immune response array. RESULTS. GFP-positive rod precursors were able to integrate into the outer nuclear layer (ONL) of the Rd9 retina. Transplanted cells underwent morphologic differentiation with the formation of inner and outer segments and synaptic projections to bipolar cells. Integration of donor cells into the ONL increased as a function of host age at the time of transplantation. The number of integrated cells was maximal at 1 month after transplantation and then decreased with time. Survival of integrated cells was significantly increased when donor cells were pretreated with AAV-XLAP. We did not detect any donor cell-specific activation of inflammation within the host retina. CONCLUSIONS. Survival of integrated cells decreases with time after transplantation but can be significantly increased with MAP antiapoptotic therapy. Preventing programmed cell death through MAP therapy may be an important component of future therapeutic retinal cell transplantation strategies. (Invest Ophthalmol Vis Sci, 2011;52:1567-1572) DOI:10.1167/iovs.1.0-5998 C1 [Yao, Jingyu; Feathers, Kecia L.; Khanna, Hemant; Thompson, Debra; Heckenlively, John R.; Swaroop, Anand; Zacks, David N.] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Khanna, Hemant] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA. [Tsilfidis, Catherine] Univ Ottawa, Inst Eye, Ottawa Hosp Res Inst, Ottawa, ON, Canada. [Hauswirth, William W.] Univ Florida, Coll Med, Dept Ophthalmol, Gainesville, FL 32610 USA. [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. RP Zacks, DN (reprint author), 1000 Wall St, Ann Arbor, MI 48105 USA. EM davzacks@umich.edu RI Zacks, David/I-4394-2013; OI Swaroop, Anand/0000-0002-1975-1141; Zacks, David/0000-0001-8592-5165 FU Foundation Fighting Blindness, Inc.; National Eye Institute [RO1-EY007961]; National Eye Institute Core Center for Vision Research [P30-REY007003] FX Supported by Foundation Fighting Blindness, Inc. (DNZ), National Eye Institute Grant RO1-EY007961 (HK), and National Eye Institute Core Center for Vision Research Grant P30-REY007003. NR 20 TC 25 Z9 25 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2011 VL 52 IS 3 BP 1567 EP 1572 DI 10.1167/iovs.10-5998 PG 6 WC Ophthalmology SC Ophthalmology GA 742SR UT WOS:000288965300044 PM 20926819 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI Understanding Autoimmune Uveitis through Animal Models The Friedenwald Lecture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID REGULATORY T-CELLS; OCULAR AUTOIMMUNITY; IMMUNE PRIVILEGE; TRANSGENIC MICE; HUMAN IRBP; IFN-GAMMA; UVEORETINITIS; ANTIGEN; DISEASE; TH1 C1 [Caspi, Rachel R.] NEI, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 FU National Eye Institute, National Institutes of Health; Casey Eye Institute, Oregon Health Science University FX I am extremely grateful to the National Eye Institute, National Institutes of Health, for funding and supporting my research for many years, and to my many trainees, collaborators and colleagues who are too numerous to mention individually, for their hard work, enthusiasm, encouragement and support. Thanks are due to James T. Rosenbaum, of Casey Eye Institute, Oregon Health Science University, who nominated me for this award; and of course to ARVO, for selecting me as its recipient. NR 41 TC 8 Z9 9 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2011 VL 52 IS 3 BP 1873 EP 1879 DI 10.1167/iovs.10-6909 PG 7 WC Ophthalmology SC Ophthalmology GA 742SR UT WOS:000288965300081 PM 21450922 ER PT J AU Bluemke, DA AF Bluemke, David A. TI ARVC: Imaging Diagnosis Is Still in the Eye of the Beholder SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE arrhythmogenic right ventricular cardiomyopathy; cardiac magnetic resonance; cardiomyopathy ID RIGHT-VENTRICULAR DYSPLASIA; CARDIOMYOPATHY/DYSPLASIA; DYSPLASIA/CARDIOMYOPATHY; MRI C1 Natl Inst Biomed Imaging & Bioengn, NIH Clin Ctr, Bethesda, MD 21287 USA. RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH Clin Ctr, 10 Ctr Dr, Bethesda, MD 21287 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 NR 15 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2011 VL 4 IS 3 BP 288 EP 291 DI 10.1016/j.jcmg.2011.01.007 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 744GN UT WOS:000289083000012 PM 21414578 ER PT J AU Amaruchkul, K Sae-Lim, P AF Amaruchkul, Kannapha Sae-Lim, Patipan TI Airline overbooking models with misspecification SO JOURNAL OF AIR TRANSPORT MANAGEMENT LA English DT Article DE Revenue management; Overbooking; Stochastic model applications ID AIR-CARGO OVERBOOKING AB This paper looks at static overbooking models. In theory, a random show demand follows a binomial distribution with each reservation showing up independently and with the same probability. However, in practice, some overbooking models assume that the show demand is the product of the overbooking level and the random show-up rate. The decision model embedded in a commercial revenue management system is misspecified. We explore the consequences of the modeling error and find that the performance of the model with misspecification decreases as show-up probability decreases. Among our three choices of show-up rate distributions, normal, beta and deterministic, the beta model performs best. We also identify situations in which an airline might prefer the deterministic model to the normal model. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Amaruchkul, Kannapha; Sae-Lim, Patipan] NIDA, Sch Appl Stat, Bangkok 10240, Thailand. RP Amaruchkul, K (reprint author), NIDA, Sch Appl Stat, 118 Serithai Rd, Bangkok 10240, Thailand. EM kamaruchkul@gmail.com NR 10 TC 8 Z9 8 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0969-6997 J9 J AIR TRANSP MANAG JI J. Air Transp. Manag. PD MAR PY 2011 VL 17 IS 2 BP 143 EP 147 DI 10.1016/j.jairtraman.2010.06.003 PG 5 WC Transportation SC Transportation GA 735LI UT WOS:000288415600017 ER PT J AU Mullinax, JE Allins, A Avital, I AF Mullinax, John E. Allins, Alexander Avital, Itzhak TI Laparoscopic Appendectomy for Amyand's Hernia: A Modern Approach to A Historic Diagnosis SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Appendicitis; Inguinal hernia; Laparoscopy ID APPENDICITIS; EXPERIENCE AB Objectives This study seeks to discuss the management and diagnosis of Amyand's hernia, an exceedingly rare diagnosis. Methods The case of a 60-year-old female found to have inguinal appendicitis on preoperative computed tomography imaging is presented. Results The patient underwent concomitant laparoscopic inguinal hernia repair and appendectomy. Discussion Laparoscopic management of Amyand's hernia should be strongly considered for repair and resection. C1 [Mullinax, John E.; Avital, Itzhak] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Allins, Alexander] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. RP Mullinax, JE (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,MSC 1201,CRC-10,Rm 3-3940, Bethesda, MD 20892 USA. EM john.mullinax@nih.gov; avitali@mail.nih.gov RI Mullinax, John/L-2509-2014 NR 9 TC 5 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR PY 2011 VL 15 IS 3 BP 533 EP 535 DI 10.1007/s11605-010-1386-5 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 740AA UT WOS:000288762700022 PM 21069473 ER PT J AU Kalisch, B Tschanen, D Lee, H AF Kalisch, Bea Tschanen, Dana Lee, Hyunhwa TI Does Missed Nursing Care Predict Job Satisfaction? SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID ORGANIZATIONAL CITIZENSHIP BEHAVIOR; PATIENT MORTALITY; EARLY MOBILIZATION; CLINICAL-PRACTICE; NURSES; OUTCOMES; QUALITY; ASSISTANTS; HOSPITALS; TURNOVER AB This study explores the impact of missed nursing care (required patient care that is omitted) on job satisfaction of nursing personnel. Data from 3,135 registered nurses (RNs) and 939 nursing assistants (NAs) on 110 patient care units in ten midwestern hospitals revealed that nursing staff who perceived less missed nursing care on the patient care unit where they work are more satisfied in their current position and occupation. Perceptions of staffing adequacy also significantly predicted both satisfaction variables. Focused interventions aimed at decreasing missed care and ensuring staffing adequacy are needed to improve job satisfaction and patient care. C1 [Kalisch, Bea; Tschanen, Dana] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Lee, Hyunhwa] NINR, NIH, Bethesda, MD USA. RP Kalisch, B (reprint author), Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. EM bkalisch@umich.edu NR 70 TC 27 Z9 28 U1 0 U2 8 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 EI 1944-7396 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD MAR-APR PY 2011 VL 56 IS 2 BP 117 EP 131 PG 15 WC Health Policy & Services SC Health Care Sciences & Services GA 738JB UT WOS:000288635000007 PM 21495530 ER PT J AU Fowler, KA Westen, D AF Fowler, Katherine A. Westen, Drew TI Subtyping Male Perpetrators of Intimate Partner Violence SO JOURNAL OF INTERPERSONAL VIOLENCE LA English DT Article DE intimate violence; personality; SWAP-II; subtyping; Q-factor analysis; domestic violence; cluster analysis ID PERSONALITY-DISORDER DIAGNOSIS; ASSESSING AXIS II; DSM-III; STATISTICAL PREDICTION; INTERNAL CONSISTENCY; BATTERER TYPOLOGY; EATING-DISORDERS; MEN; ADOLESCENCE; OFFENDERS AB Domestic violence is a serious problem with far-reaching consequences. This study applies a new methodology to derive subtypes of male perpetrators of intimate partner violence. As part of a larger National Institute of Mental Health (NIMH)-funded study, a national sample of randomly selected psychologists and psychiatrists describe 188 adult male patients (59 with a history of partner violence, 97 with a history of arrests but not partner violence, and 57 with neither partner violence nor arrests), using the Shedler-Westen Assessment Procedure-II (SWAP-II), a Q-sort procedure for assessing personality pathology. Using Q-factor analysis, the authors identify three personality constellations among the partner-violent men, two of which strongly resembled subtypes identified using different methods in prior research: psychopathic, hostile/controlling, and borderline/dependent. The authors compare these subtypes with each other and with nonarrested/nonviolent men and men with arrests but no partner violence on Axis I and II diagnoses, adaptive functioning, etiological variables, and response to treatment, providing initial validity data. C1 [Fowler, Katherine A.; Westen, Drew] Emory Univ, Atlanta, GA 30322 USA. RP Fowler, KA (reprint author), NIMH, 15K North Dr,Bldg 15K,Rm 300-C MSC 2670, Bethesda, MD 20892 USA. EM fowlerka@mail.nih.gov FU NIMH NIH HHS [R01-MH62377] NR 91 TC 22 Z9 22 U1 9 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0886-2605 J9 J INTERPERS VIOLENCE JI J. Interpers. Violence PD MAR PY 2011 VL 26 IS 4 BP 607 EP 639 DI 10.1177/0886260510365853 PG 33 WC Criminology & Penology; Family Studies; Psychology, Applied SC Criminology & Penology; Family Studies; Psychology GA 727ZP UT WOS:000287842300001 PM 20498380 ER PT J AU Devkota, KP Ratnayake, R Colburn, NH Wilson, JA Henrich, CJ McMahon, JB Beutler, JA AF Devkota, Krishna P. Ratnayake, Ranjala Colburn, Nancy H. Wilson, Jennifer A. Henrich, Curtis J. McMahon, James B. Beutler, John A. TI Inhibitors of the Oncogenic Transcription Factor AP-1 from Podocarpus latifolius SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MACROPHYLLUS D. DON; NORDITERPENE DILACTONES; TRANSFORMATION; PLANT; JUN AB An activator protein-1 (AP-1) based bioassay-guided phytochemical investigation on Podocarpus latifolius led to the isolation, of three new sempervirol-type diterpenes, cycloinumakiol (1), inumakal (2), and inumakoic acid (3), along with three known norditerpenes (4-6). Compounds 4 and 6 were responsible for the observed bioactivity. C1 [Devkota, Krishna P.; Ratnayake, Ranjala; Wilson, Jennifer A.; Henrich, Curtis J.; McMahon, James B.; Beutler, John A.] NCI, Mol Targets Lab, Mol Discovery Program, Frederick, MD 21702 USA. [Colburn, Nancy H.] NCI, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA. [Henrich, Curtis J.] SAIC Frederick Inc, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), NCI, Mol Targets Lab, Mol Discovery Program, Frederick, MD 21702 USA. EM beutlerj@mail.nih.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank T. McCloud, SAIC-Frederick, Inc., Frederick, MD, and the Natural Products Support Group for plant grinding and extraction, the CCR Biophysics Resource for providing technical assistance with HR-ELMS measurements, and K. Gustafson, Molecular Targets Laboratory, National Cancer Institute, Frederick, MD, for helpful comments. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 17 TC 9 Z9 9 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2011 VL 74 IS 3 BP 374 EP 377 DI 10.1021/np100736y PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 739DA UT WOS:000288691800011 PM 21306129 ER PT J AU Jenkins, J Bednash, G Malone, B AF Jenkins, Jean Bednash, Geraldine Malone, Beverly TI Bridging the Gap Between Genomics Discoveries and Clinical Care: Nurse Faculty are Key SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Editorial Material C1 [Jenkins, Jean] NHGRI, NIH, Bethesda, MD 20892 USA. [Bednash, Geraldine] Amer Assoc Coll Nursing, Washington, DC USA. [Malone, Beverly] Natl League Nursing, New York, NY USA. RP Jenkins, J (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM jean.jenkins@nih.gov NR 3 TC 6 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PD MAR PY 2011 VL 43 IS 1 BP 1 EP 2 DI 10.1111/j.1547-5069.2010.01362.x PG 2 WC Nursing SC Nursing GA 724NM UT WOS:000287583300001 PM 21342418 ER PT J AU Tudor-Locke, C Bassett, DR Shipe, MF McClain, JJ AF Tudor-Locke, Catrine Bassett, David R. Shipe, Michael F. McClain, James J. TI Pedometry Methods for Assessing Free-Living Adults SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Review DE walking; physical activity; measurement; protocols ID PHYSICAL-ACTIVITY INTERVENTION; 1ST STEP PROGRAM; ELECTRONIC PEDOMETERS; AMBULATORY ACTIVITY; OLDER-ADULTS; ENERGY-EXPENDITURE; WALKING; RELIABILITY; ACCURACY; VALIDITY AB Background: The purpose of this review is to update the methodological aspects of pedometry to encourage the consistent use of pedometers for assessment, to decrease sources of error, and to facilitate comparison and interpretation of results. Methods: The specific measurement topics addressed include: instrument choice, metric choice, validity, reliability, data collection and retrieval, time worn, day-to-day variability, monitoring time frame, reactivity, and data treatment. Results: A wide variety of valid and reliable instruments are commercially available and we can expect continued evolutions in value-added features as supporting technology improves. Data collection and retrieval has been achieved through various methods, including face-to-face contact, fax, e-mail, website, and conventional mail, and sometimes a combination of these. Day-to-day variation is not random, as would be expected from inconsistent pedometer performance, but rather exposes true behavior instability that can be explained by other factors and described using a coefficient of variation. Data reduction should be conducted cautiously and only after a full discovery (and disclosure) of its impact on aggregated group statistics and their relationship with other parameters. Conclusions: We have no doubt that research with pedometers will continue to yield new and important insights in the coming years. C1 [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. [Bassett, David R.] Univ Tennessee, Dept Exercise Sport & Leisure Studies, Knoxville, TN USA. [Shipe, Michael F.] Carson Newman Coll, Dept Hlth Phys Educ & Sport Sci, Jefferson, TN USA. [McClain, James J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Tudor-Locke, C (reprint author), Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. NR 61 TC 34 Z9 34 U1 3 U2 17 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAR PY 2011 VL 8 IS 3 BP 445 EP 453 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 734DI UT WOS:000288313000016 PM 21487145 ER PT J AU Gollenberg, AL Mumford, SL Cooney, MA Sundaram, R Louis, GMB AF Gollenberg, Audra L. Mumford, Sunni L. Cooney, Maureen A. Sundaram, Rajeshwari Louis, Germaine M. Buck TI Validity of Retrospectively Reported Behaviors During the Periconception Window SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE behavior; life style; preconception; pregnancy; validity of results ID MATERNAL RECALL; PREGNANCY; OUTCOMES; SMOKING; HEALTH; ALCOHOL; ORIGINS; DISEASE; COCAINE; BIRTH AB OBJECTIVE: To assess the validity of retrospectively reported maternal behaviors while attempting pregnancy. STUDY DESIGN: Participants in a prospective pregnancy cohort study with periconception enrollment were queried about. use of cigarettes, alcohol, vitamins and caffeine and the consumption of sport fish while attempting pregnancy. Prospective longitudinal data reported in daily diaries (gold standard) were compared with data obtained a decade later using a self-administered questionnaire. Agreement was assessed by percent agreement and Kappa coefficients. RESULTS: Among the 82 participating women, percent agreement ranged from 54-74% for the 5 behaviors. Validity was highest for smoking (Kappa = 0.43, 95% confidence interval [CI]: 0.22, 0.65) followed by fish consumption (Kappa = 0.32, 95% CI: 0.09, 0.55), caffeine (Kappa = 0.21, 95% CI: 0.09, 0.51) and alcohol (Kappa = 0.20, 95% CI: 0.08, 0.33). There were no systematic differences in agreement by time to pregnancy or pregnancy outcome. Associations between smoking and alcohol consumption and pregnancy outcomes were highly sensitive to the levels of misclassification observed in this study. CONCLUSION: Validity was poor to moderate for the 5 behaviors, though higher for more regular behaviors such as smoking and caffeine consumption. The potential for misreporting of periconception behaviors can affect inferences, and thus efforts to capture information prospectively should be promoted. (J Reprod Med 2011;56:130-137) C1 [Gollenberg, Audra L.; Mumford, Sunni L.; Cooney, Maureen A.; Sundaram, Rajeshwari; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Gollenberg, AL (reprint author), Shenandoah Univ, Dept Publ Hlth A&S, Henkel Hall 229,1460 Univ Dr, Winchester, VA 22601 USA. EM agollenb@su.edu OI Sundaram, Rajeshwari/0000-0002-6918-5002; Buck Louis, Germaine/0000-0002-1774-4490 FU Agency for Toxic Substances and Disease Registry [H751 ATH 298338]; Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health FX This Work was supported by the Agency for Toxic Substances and Disease Registry [H751 ATH 298338] and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health. NR 31 TC 4 Z9 4 U1 0 U2 5 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAR-APR PY 2011 VL 56 IS 3-4 BP 130 EP 137 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 743VE UT WOS:000289046000008 PM 21542530 ER PT J AU Tom, SE Cooper, R Patel, KV Guralnik, JM AF Tom, Sarah E. Cooper, Rachel Patel, Kushang V. Guralnik, Jack M. TI Menopausal Characteristics and Physical Functioning in Older Adulthood SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Tom, Sarah E.] Univ Texas Med Branch, Galveston, TX USA. [Cooper, Rachel] Univ Coll & Royal Free Med Sch, Med Res Council Unit Lifelong Hlth & Ageing, Dept Epidemiol & Publ Hlth, London, England. [Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2011 VL 20 IS 3 BP 481 EP 481 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 735RS UT WOS:000288435400093 ER PT J AU Comis, L Bernad, M Bondy, CA AF Comis, Leora Bernad, Martha Bondy, Carolyn A. TI Turner Syndrome: A Paradigm for Social Roles and Women's Health SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Bernad, Martha] Natl Inst Hlth, Occupat Therapy Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD USA. [Bondy, Carolyn A.] Natl Inst Hlth, Sect Epigenet & Dev, Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2011 VL 20 IS 3 MA P83 BP 485 EP 485 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 735RS UT WOS:000288435400103 ER PT J AU Lodish, M Dicker, S Ferguson, C Sinaii, N Sullivan, S Vanderhoof, VH Nelson, LM AF Lodish, Maya Dicker, Sarah Ferguson, Catherine Sinaii, Ninet Sullivan, Shannon Vanderhoof, Vien H. Nelson, Lawrence M. TI Compared to Adult Onset, Adolescent Onset of Primary Ovarian Insufficiency Is Not Associated with Increased Prevalence of Major Depressive Disorder, Yet Is Associated with a 9-Year Delay in Diagnosis SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Lodish, Maya; Dicker, Sarah; Ferguson, Catherine; Sullivan, Shannon; Vanderhoof, Vien H.; Nelson, Lawrence M.] NICHD NIH, Bethesda, MD 20892 USA. [Sinaii, Ninet] NIH, CC, Dept Biostat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2011 VL 20 IS 3 MA P103 BP 492 EP 492 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 735RS UT WOS:000288435400123 ER PT J AU Robertson, S Swan, LC Comis, LE Hodsdon, B Parks, R Nelson, L AF Robertson, Susan Swan, Lucy C. Comis, Leora E. Hodsdon, Bonnie Parks, Rebecca Nelson, Lawrence TI An Occupational Therapy Approach to Primary Ovarian Insufficiency SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Swan, Lucy C.; Comis, Leora E.; Hodsdon, Bonnie; Parks, Rebecca] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. [Nelson, Lawrence] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2011 VL 20 IS 3 MA P116 BP 496 EP 496 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 735RS UT WOS:000288435400136 ER PT J AU Jodar, L Mercken, EM Ariza, J Younts, C Gonzalez-Reyes, JA Alcain, FJ Buron, I de Cabo, R Villalba, JM AF Jodar, Laura Mercken, Evi M. Ariza, Julia Younts, Caitlin Gonzalez-Reyes, Jose A. Alcain, Francisco J. Buron, Isabel de Cabo, Rafael Villalba, Jose M. TI Genetic Deletion of Nrf2 Promotes Immortalization and Decreases Life Span of Murine Embryonic Fibroblasts SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Cellular immortalization; Life span; MEFs; Nrf2; Replicative senescence ID CELLULAR SENESCENCE; OXIDATIVE STRESS; PLASMA-MEMBRANE; SIGNALING PATHWAY; GENOMIC STABILITY; HEME OXYGENASE-1; DNA-DAMAGE; COENZYME-Q; CELLS; CANCER AB Nuclear factor E2 related factor-2 (Nrf2) transcription factor is one of the main regulators of intracellular redox balance and a sensor of oxidative and electrophilic stress. Low Nrf2 activity is usually associated with carcinogenesis, but Nrf2 is also considered as an oncogene because it increases survival of transformed cells. Because intracellular redox balance alterations :ire involved in both senescence and tumorigenesis, we investigated the impact of Nrf2 genetic deletion on cellular immortalization and life span of murine embryonic Fibroblasts. We report that Nrf2 genetic deletion promotes immortalization due to an early loss of p53-dependent gene expression. However, compared with control cells, immortalized Nrf2-/- murine embryonic fibroblasts exhibited decreased growth, lower cycl in E levels, and impaired expression of NQO1 and cytochrome b(5) reductase. Moreover, SirT1 was also significantly reduced in immortalized Nrf2-/- murine embryonic fibroblasts, and these cells exhibited shorter life span. Our results underscore the dual role of Nrf2 in protection against carcinogenesis and in the delay of cellular aging. C1 [Jodar, Laura; Ariza, Julia; Gonzalez-Reyes, Jose A.; Buron, Isabel; Villalba, Jose M.] Univ Cordoba, Fac Ciencias, Dept Biol Celular Fisiol & Inmunol, Cordoba 14014, Spain. [Mercken, Evi M.; Younts, Caitlin; Alcain, Francisco J.; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Villalba, JM (reprint author), Univ Cordoba, Fac Ciencias, Dept Biol Celular Fisiol & Inmunol, Campus Rabanales,Edificio Severo Ochoa,3A Planta, Cordoba 14014, Spain. EM jmvillalba@uco.es RI Gonzalez-Reyes, Jose A/K-1367-2014; de Cabo, Rafael/J-5230-2016; Alcain, Francisco /N-7503-2016; OI Gonzalez-Reyes, Jose A/0000-0003-1918-5490; de Cabo, Rafael/0000-0002-3354-2442; Alcain, Francisco /0000-0002-6833-7940; , rafael/0000-0003-2830-5693 FU Spanish Ministerio do Ciencia Tecnologia [BFU2008-00559/BMC]; Junta de Andalucia [BIO-276]; University of Cordoba [BIO-276]; National Institute on Aging FX This work was supported by grants BFU2008-00559/BMC (Spanish Ministerio do Ciencia Tecnologia), a Proyectos Internacionales grant from the Junta de Andalucia, BIO-276 (Junta de Andalucia and the University of Cordoba), and in part by the Intramural Research Program of the National Institute on Aging. L.J. was funded by Group BIO-276 (University of Cordoba and Junta de Andalucia). J.A. was recipient of a predoctoral contract funded by the Junta de Andalucia (Proyectos Internacionales grant). NR 54 TC 9 Z9 10 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2011 VL 66 IS 3 BP 247 EP 256 DI 10.1093/gerona/glq181 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 735LK UT WOS:000288415800001 PM 20974733 ER PT J AU Forrest, CB Bartek, RJ Rubinstein, Y Groft, SC AF Forrest, Christopher B. Bartek, Ronald J. Rubinstein, Yaffa Groft, Stephen C. TI The case for a global rare-diseases registry SO LANCET LA English DT Editorial Material C1 [Forrest, Christopher B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Forrest, Christopher B.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Bartek, Ronald J.] Friedreichs Ataxia Res Alliance, Springfield, VA USA. [Rubinstein, Yaffa; Groft, Stephen C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. RP Forrest, CB (reprint author), Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. EM forrestc@email.chop.edu NR 11 TC 38 Z9 40 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR-APR PY 2011 VL 377 IS 9771 BP 1057 EP 1059 DI 10.1016/S0140-6736(10)60680-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 743QY UT WOS:000289035000009 PM 20674966 ER PT J AU Liu, ZF Shi, JY Jia, B Yu, ZL Liu, Y Zhao, HY Li, F Tian, J Chen, XY Liu, SA Wang, F AF Liu, Zhaofei Shi, Jiyun Jia, Bing Yu, Zilin Liu, Yan Zhao, Huiyun Li, Fang Tian, Jie Chen, Xiaoyuan Liu, Shuang Wang, Fan TI Two Y-90-Labeled Multimeric RGD Peptides RGD4 and 3PRGD2 for Integrin Targeted Radionuclide Therapy SO MOLECULAR PHARMACEUTICS LA English DT Article DE integrin alpha(v)beta(3); Arg-Gly-Asp (RGD); Y-90; tumor; radionuclide therapy ID POSITRON-EMISSION-TOMOGRAPHY; IMPROVING TUMOR UPTAKE; SMALL-ANIMAL PET; ALPHA(V)BETA(3) INTEGRIN; CANCER-PATIENTS; PEG(4) LINKERS; ANGIOGENESIS; EXPRESSION; DIMERS; PHARMACOKINETICS AB We have recently developed a series of new Arg-Gly-Asp (RGD) dimeric peptides for specific targeting of integrin alpha(v)beta(3) with enhanced tumor uptake and improved pharmacokinetics. In this study, we investigated Y-90-labeled RGD tetramer (RGD4) and the new type of RGD dimer (3PRGD2), for the radionuclide therapy of integrin alpha(v)beta(3)-positive tumors. Biodistribution and gamma imaging studies of In-111 labeled RGD4 and 3PRGD2 were performed. Groups of nude mice were used to determine maximum tolerated dose (MTD) of Y-90-DOTA-RGD4 and Y-90-DOTA-3PRGD2. The radionuclide therapeutic efficacy of Y-90-DOTA-RGD4 and 90Y-DOTA-3PRGD2 was evaluated in U87MG tumor-bearing nude mice. The U87MG tumor uptake of In-111-DOTA-3PRGD2 was slightly lower than that of the In-111-DOTA-RGD4 (e.g., 6.13 +/- 0.82%ID/g vs 6.43 +/- 1.6%ID/g at 4 h post-injection), but the uptake of In-111-DOTA-3PRGD2 in normal organs, such as liver and kidneys, was much lower than that of In-111-DOTA-RGD4, which resulted in much higher tumor-to-nontumor ratios and lower toxicity. The MTD of Y-90-DOTA-RGD4 in nude mice is less than 44.4 MBq, while the MTD of Y-90-DOTA-3PRGD2 in mice is more than 55.5 MBq. Y-90-DOTA-3PRGD2 administration exhibited a similar tumor inhibition effect as compared with Y-90-DOTA-RGD4 at the same dose. The tumor vasculature in the Y-90-DOTA-3PRGD2 treatment group was much less than the control groups. Radionuclide therapy studies exhibited that both Y-90-DOTA-RGD4 and Y-90-DOTA-3PRGD2 caused significant tumor growth delay in the U87MG tumor model. Compared to Y-90-DOTA-RGD4, the low accumulation of Y-90-DOTA-3PRGD2 in normal organs led to lower toxicity and higher MTD in nude mice, which would make it more suitable for high dose or multiple-dose regimens, in order to achieve maximum therapeutic efficacy. C1 [Liu, Zhaofei; Shi, Jiyun; Jia, Bing; Yu, Zilin; Liu, Yan; Zhao, Huiyun; Wang, Fan] Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China. [Liu, Zhaofei; Shi, Jiyun; Jia, Bing; Yu, Zilin; Liu, Yan; Zhao, Huiyun; Wang, Fan] Peking Univ, Dept Radiat Med, Beijing 100191, Peoples R China. [Li, Fang] Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing 100857, Peoples R China. [Tian, Jie] Chinese Acad Sci, Med Image Proc Grp, Inst Automat, Beijing 100190, Peoples R China. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Liu, Shuang] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. RP Jia, B (reprint author), Peking Univ, Med Isotopes Res Ctr, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM jiabing@bjmu.edu.cn; wangfan@bjmu.edu.cn RI Jia, Bing/C-3796-2008; Tian, Jie/H-1190-2011; Tian, Jie/M-5675-2013 OI Tian, Jie/0000-0003-0498-0432; FU NSFC [30870728, 30930030, 30900373, 81000625, 81028009]; "863" project [2007AA02Z467]; "973" project [2011CB70-7703]; Ministry of Science and Technology of China [2009ZX09103-733, 2009ZX09301-010, 2009ZX-09103-746] FX This work was supported, in part, by NSFC projects (30870728, 30930030, 30900373, 81000625, and 81028009), an "863" project (2007AA02Z467), a "973" project (2011CB70-7703), and grants from the Ministry of Science and Technology of China (2009ZX09103-733, 2009ZX09301-010 and 2009ZX-09103-746). Parts of this manuscript were presented at the Society of Nuclear Medicine (SNM) Annual Meeting in Toronto, Canada, June 13-17, 2009. NR 24 TC 22 Z9 28 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAR-APR PY 2011 VL 8 IS 2 BP 591 EP 599 DI 10.1021/mp100403y PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 743HJ UT WOS:000289008600028 PM 21247151 ER PT J AU Yang, M Gao, HK Sun, XL Yan, YJ Quan, QM Zhang, WD Mohamedali, KA Rosenblum, MG Niu, G Chen, XY AF Yang, Min Gao, Haokao Sun, Xilin Yan, Yongjun Quan, Qimeng Zhang, Wendy Mohamedali, Khalid A. Rosenblum, Michael G. Niu, Gang Chen, Xiaoyuan TI Multiplexed PET Probes for Imaging Breast Cancer Early Response to VEGF(121)/rGel Treatment SO MOLECULAR PHARMACEUTICS LA English DT Article DE positron emission tomography (PET); F-18-FDG; F-18-FLT; F-18-FPPRGD2; F-18-FMISO; integrin; therapy response ID POSITRON-EMISSION-TOMOGRAPHY; FUSION TOXIN VEGF(121)/RGEL; SOLID TUMORS; THERAPY; HYPOXIA; GROWTH; BIODISTRIBUTION; REPRODUCIBILITY; F-18-AH111585; OXYGENATION AB In this study, we applied multiplexed positron emission tomography (PET) probes to monitor glucose metabolism, cellular proliferation, tumor hypoxia and angiogenesis during VEGF(121)/rGel therapy of breast cancer. Two doses of 12 mg/kg VEGF(121)/rGel, administered intraperitoneally, resulted in initial delay of tumor growth, but the growth resumed 4 days after tumor treatment was stopped. The average tumor growth rate expressed as V/V-0, were 1.11 +/- 0.07, 1.21 +/- 0.10, 1.58 +/- 0.36 and 2.64 +/- 0.72 at days 1, 3, 7 and 14, respectively. Meanwhile, the VEGF121/rGel treatment group showed V/V-0 ratios of 1.04 +/- 0.06, 1.05 +/- 0.11, 1.09 +/- 0.17 and 1.86 +/- 0.36 at days 1, 3, 7 and 14, respectively. VEGF(121)/rGel treatment led to significantly decreased uptake of F-18-FPPRGD2 at day 1(24.0 +/- 8.8%, p < 0.05) and day 3 (36.3 +/- 9.2%, p < 0.01), relative to the baseline, which slowly recovered to the baseline at day 14. F-18-FMISO uptake was increased in the treated tumors at day 1 (23.9 +/- 15.7%, p < 0.05) and day 3 (51.4 +/- 29.4%, p < 0.01), as compared to the control group. At days 7 and 14, F-18-FMISO uptake restored to the baseline level. The relative reductions in FLT uptake in treated tumors were approximately 13.0 +/- 4.5% at day 1 and 25.0 +/- 4.4% (p < 0.01) at day 3. No significant change of F-18-FDG uptake was observed in VEGF(121)/rGel treated tumors, compared with the control group. The imaging findings were supported by ex vivo analysis of related biomarkers. Overall, longitudinal imaging studies with 4 PET tracers demonstrated the feasibility and usefulness of multiplexed probes for quantitative measurement of antitumor effects of VEGF(121)/rGel at the early stage of treatment. This preclinical study should be helpful in accelerating anticancer drug development and promoting the clinical translation of molecular imaging. C1 [Yang, Min; Gao, Haokao; Sun, Xilin; Yan, Yongjun; Quan, Qimeng; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, NIH, Lab Mol Imaging & Nanomed, Bethesda, MD 20892 USA. [Yang, Min] Jiangsu Inst Nucl Med, Key Lab Nucl Med, Minist Hlth, Jiangsu Key Lab Mol Nucl Med, Wuxi 214063, Jiangsu, Peoples R China. [Gao, Haokao] Fourth Mil Med Univ, Dept Cardiol, Xijing Hosp, Xian 710032, Peoples R China. [Zhang, Wendy; Mohamedali, Khalid A.; Rosenblum, Michael G.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RP Niu, G (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Lab Mol Imaging & Nanomed, 31 Ctr Dr,Bldg 31,1C22, Bethesda, MD 20892 USA. EM niug@mail.nih.gov; shawn.chen@nih.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009]; Outstanding Professionals Foundation of Jiangsu Health Bureau [RC 2007096]; Radiology and Imaging Sciences Department, NIH Clinical Center; NIBIB, NIH FX This project was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) and the International Cooperative Program of National Science Foundation of China (NSFC) (81028009). M.Y. is partly supported by the Outstanding Professionals Foundation of Jiangsu Health Bureau (Grant No. RC 2007096). G.N. currently is an Imaging Sciences Training Program (ISTP) Fellow, jointly supported by the Radiology and Imaging Sciences Department, NIH Clinical Center and the Intramural Research Program, NIBIB, NIH. We acknowledge the NIH/CC cyclotron facility for isotope production and Dr. Henry S. Eden for proof-reading this manuscript. NR 33 TC 18 Z9 20 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAR-APR PY 2011 VL 8 IS 2 BP 621 EP 628 DI 10.1021/mp100446t PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 743HJ UT WOS:000289008600031 PM 21280671 ER PT J AU Pardini, M Krueger, F Hodgkinson, C Raymont, V Ferrier, C Goldman, D Strenziok, M Guida, S Grafman, J AF Pardini, M. Krueger, F. Hodgkinson, C. Raymont, V. Ferrier, C. Goldman, D. Strenziok, M. Guida, S. Grafman, J. TI Prefrontal cortex lesions and MAO-A modulate aggression in penetrating traumatic brain injury SO NEUROLOGY LA English DT Article ID MONOAMINE-OXIDASE-A; BORDERLINE PERSONALITY-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL-ABUSE; NEURAL MECHANISMS; HEAD-INJURY; BEHAVIOR; VIOLENCE; GENE; INVENTORY AB Objective: This study investigates the interaction between brain lesion location and monoamine oxidase A (MAO-A) in the genesis of aggression in patients with penetrating traumatic brain injury (PTBI). Methods: We enrolled 155 patients with PTBI and 42 controls drawn from the Vietnam Head Injury Study registry. Patients with PTBI were divided according to lesion localization (prefrontal cortex [PFC] vs non-PFC) and were genotyped for the MAO-A polymorphism linked to low and high transcriptional activity. Aggression was assessed with the aggression/agitation subscale of the Neuropsychiatric Inventory (NPI-a). Results: Patients with the highest levels of aggression preferentially presented lesions in PFC territories. A significant interaction between MAO-A transcriptional activity and lesion localization on aggression was revealed. In the control group, carriers of the low-activity allele demonstrated higher aggression than high-activity allele carriers. In the PFC lesion group, no significant differences in aggression were observed between carriers of the 2 MAO-A alleles, whereas in the non-PFC lesion group higher aggression was observed in the high-activity allele than in the low-activity allele carriers. Higher NPI-a scores were linked to more severe childhood psychological traumatic experiences and posttraumatic stress disorder symptomatology in the control and non-PFC lesion groups but not in the PFC lesion group. Conclusions: Lesion location and MAO-A genotype interact in mediating aggression in PTBI. Importantly, PFC integrity is necessary for modulation of aggressive behaviors by genetic susceptibilities and traumatic experiences. Potentially, lesion localization and MAO-A genotype data could be combined to develop risk-stratification algorithms and individualized treatments for aggression in PTBI. Neurology (R) 2011;76:1038-1045 C1 [Pardini, M.; Krueger, F.; Raymont, V.; Strenziok, M.; Grafman, J.] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. [Pardini, M.; Guida, S.] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Pardini, M.] Univ Genoa, Magnet Resonance Res Ctr Nervous Syst Dis, Genoa, Italy. [Krueger, F.] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Hodgkinson, C.; Ferrier, C.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Raymont, V.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. RP Grafman, J (reprint author), Kessler Fdn Res Ctr, Brain Injury Res Lab, 1199 Pleasant Valley Way, W Orange, NJ 07052 USA. EM jgrafman@kesslerfoundation.org RI Pardini, Matteo/F-8414-2010; Goldman, David/F-9772-2010; OI Pardini, Matteo/0000-0002-4740-1982; Goldman, David/0000-0002-1724-5405; Grafman, Jordan H./0000-0001-8645-4457 FU US National Institute of Neurological Disorders and Stroke; US Army Medical Research and Material Command; National Naval Medical Center; NIH; NIH/NINDS; Henry M. Jackson Foundation FX Supported by the US National Institute of Neurological Disorders and Stroke intramural research program and a project grant from the US Army Medical Research and Material Command administered by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year postinjury follow-up study).; The authors thank the Vietnam veterans who participated in this study. Without their long-term commitment to improving the health care of veterans, this study could not have been completed. The authors thank the National Naval Medical Center for their support and provision of their facilities and S. Bonifant, B. Cheon, C. Ngo, A. Greathouse, K. Reding, and G. Tasick for their help with the testing of participants and organization of this study.; Dr. Pardini and Dr. Krueger report no disclosures. Dr. Hodgkinson receives intramural research support from the NIH. Dr. Raymont and C. Ferrier report no disclosures. Dr. Goldman serves on the editorial boards of Biological Psychiatry and Addictions Biology. Dr. Strenziok and Dr. Guida report no disclosures. Dr. Grafman serves as Co-editor of Cortex and receives research support from the Intramural Research Program NIH/NINDS and the Henry M. Jackson Foundation. NR 32 TC 15 Z9 16 U1 6 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2011 VL 76 IS 12 BP 1038 EP 1045 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 741GW UT WOS:000288853200007 PM 21422455 ER PT J AU Matsuoka, M Jeang, KT AF Matsuoka, M. Jeang, K-T TI Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy SO ONCOGENE LA English DT Review DE human T-cell leukemia virus type 1 (HTLV-1); adult T-cell leukemia (ATL); Tax; HTLV-1 bZIP factor (HBZ); aneuploidy ID NF-KAPPA-B; DNA-DAMAGE RESPONSE; TROPICAL SPASTIC PARAPARESIS; SPINDLE ASSEMBLY CHECKPOINT; PROTEASOME INHIBITOR PS-341; 1ST HUMAN RETROVIRUS; I TAX; TRANSCRIPTIONAL ACTIVITY; MONOCLONAL-ANTIBODY; CYCLE PROGRESSION AB The human T-cell leukemia virus type 1 (HTLV-1) was the first retrovirus discovered to be causative of a human cancer, adult T-cell leukemia. The transforming entity of HTLV-1 has been attributed to the virally-encoded oncoprotein, Tax. Unlike the v-onc proteins encoded by other oncogenic animal retroviruses that transform cells, Tax does not originate from a c-onc counterpart. In this article, we review progress in our understanding of HTLV-1 infectivity, cellular transformation, anti-sense transcription and therapy, 30 years after the original discovery of this virus. Oncogene (2011) 30, 1379-1389; doi:10.1038/onc.2010.537; published online 29 November 2010 C1 [Jeang, K-T] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Matsuoka, M.] Kyoto Univ, Inst Virus Res, Kyoto 606, Japan. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Matsuoka, Masao/0000-0002-0473-754X FU NIAID; Ministry of Education, Science, Sports and Culture of Japan FX Work in KTJ's laboratory is supported in part by NIAID intramural funds, and work in MM's laboratory is supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. We thank Lauren Lee for preparation of manuscript and figures, and Junichiro Yasunaga and Linda Zane for discussions. NR 164 TC 99 Z9 102 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2011 VL 30 IS 12 BP 1379 EP 1389 DI 10.1038/onc.2010.537 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 739UM UT WOS:000288743800001 PM 21119600 ER PT J AU Durie, D Lewis, SM Liwak, U Kisilewicz, M Gorospe, M Holcik, M AF Durie, D. Lewis, S. M. Liwak, U. Kisilewicz, M. Gorospe, M. Holcik, M. TI RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation SO ONCOGENE LA English DT Article DE translation; internal initiation; ITAF; HuR; XIAP; cancer ID X-LINKED INHIBITOR; RIBOSOME-ENTRY-SITE; INCREASED CYCLOOXYGENASE-2 EXPRESSION; TRANS-ACTING FACTOR; MESSENGER-RNA; BREAST-CANCER; 5'-UNTRANSLATED REGION; APOPTOSIS PROTEIN; PROGNOSTIC-FACTOR; UP-REGULATION AB Expression of the intrinsic cellular caspase inhibitor XIAP is regulated primarily at the level of protein synthesis. The 50 untranslated region harbours an Internal Ribosome Entry Site (IRES) motif that supports cap-independent translation of XIAP mRNA during conditions of cellular stress. In this study, we show that the RNA-binding protein HuR, which is known to orchestrate an antiapoptotic cellular program, stimulates translation of XIAP mRNA through XIAP IRES. We further show that HuR binds to XIAP IRES in vitro and in vivo, and stimulates recruitment of the XIAP mRNA into polysomes. Importantly, protection from the apoptosis-inducing agent etoposide by overexpression of HuR requires the presence of XIAP, suggesting that HuR-mediated cytoprotection is partially executed through enhanced XIAP translation. Our data suggest that XIAP belongs to the HuR-regulated RNA operon of antiapoptotic genes, which, along with Bcl-2, Mcl-1 and ProT alpha, contributes to the regulation of cell survival. Oncogene (2011) 30, 1460-1469; doi:10.1038/onc.2010.527; published online 22 November 2010 C1 [Durie, D.; Lewis, S. M.; Liwak, U.; Kisilewicz, M.; Holcik, M.] Childrens Hosp Eastern Ontario, Res Inst, Apoptosis Res Ctr, Ottawa, ON K1H 8L1, Canada. [Durie, D.; Liwak, U.; Kisilewicz, M.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. [Holcik, M.] Univ Ottawa, Dept Paediat, Ottawa, ON, Canada. [Gorospe, M.] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Holcik, M (reprint author), Childrens Hosp Eastern Ontario, Res Inst, Apoptosis Res Ctr, 401 Smyth Rd, Ottawa, ON K1H 8L1, Canada. EM martin@mgcheo.med.uottawa.ca RI Lewis, Stephen/E-5533-2010; Holcik, Martin/E-5372-2011 OI Lewis, Stephen/0000-0001-9537-5822; FU Canadian Institutes of Health Research (CIHR) [MOP 89737]; National Institute on Aging, National Institutes of Health FX We thank Drs Nehal Thakor and Stephen Baird for critical discussions. We are grateful to Drs P Anderson and R Screaton for the gift of anti-TIA-1/TIAR and anti-GST antibodies, respectively, and to Dr I Gallouzi for the GFP-HuR, GFP-HuR(CP1), GFP-HuR(CP2), AP-HuR-GST, AP-HuR(CP1)-GST and AP-HuR(CP2)-GST overexpression constructs. This work was supported by an operating grant from the Canadian Institutes of Health Research to MH (CIHR; MOP 89737); MG was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. MH is the CHEO Volunteer Association Endowed Scholar. NR 50 TC 32 Z9 33 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR PY 2011 VL 30 IS 12 BP 1460 EP 1469 DI 10.1038/onc.2010.527 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 739UM UT WOS:000288743800008 PM 21102524 ER PT J AU Zhurkin, VB AF Zhurkin, Victor B. TI The first thirty years of nucleosome positioning Comment on "Cracking the chromatin code: Precise rule of nucleosome positioning" by Trifonov SO PHYSICS OF LIFE REVIEWS LA English DT Editorial Material ID NUCLEOTIDE-SEQUENCE; REPEATING UNIT; DNA; PROTEIN C1 NCI, NIH, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM zhurkin@nih.gov NR 18 TC 4 Z9 4 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1571-0645 J9 PHYS LIFE REV JI Phys. Life Rev. PD MAR PY 2011 VL 8 IS 1 BP 64 EP 66 DI 10.1016/j.plrev.2011.02.001 PG 3 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 743JY UT WOS:000289015800014 PM 21330223 ER PT J AU Brams, M Pandya, A Kuzmin, D van Elk, R Krijnen, L Yakel, JL Tsetlin, V Smit, AB Ulens, C AF Brams, Marijke Pandya, Anshul Kuzmin, Dmitry van Elk, Rene Krijnen, Liz Yakel, Jerrel L. Tsetlin, Victor Smit, August B. Ulens, Chris TI A Structural and Mutagenic Blueprint for Molecular Recognition of Strychnine and d-Tubocurarine by Different Cys-Loop Receptors SO PLOS BIOLOGY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; LIGAND-BINDING DOMAIN; CURARIFORM ANTAGONISTS BIND; GLYCINE RECEPTOR; ALPHA-SUBUNIT; PHARMACOLOGICAL-PROPERTIES; DIFFERENT ORIENTATIONS; CRYSTAL-STRUCTURE; 5HT(3) RECEPTOR; XENOPUS-OOCYTES AB Cys-loop receptors (CLR) are pentameric ligand-gated ion channels that mediate fast excitatory or inhibitory transmission in the nervous system. Strychnine and d-tubocurarine (d-TC) are neurotoxins that have been highly instrumental in decades of research on glycine receptors (GlyR) and nicotinic acetylcholine receptors (nAChR), respectively. In this study we addressed the question how the molecular recognition of strychnine and d-TC occurs with high affinity and yet low specificity towards diverse CLR family members. X-ray crystal structures of the complexes with AChBP, a well-described structural homolog of the extracellular domain of the nAChRs, revealed that strychnine and d-TC adopt multiple occupancies and different ligand orientations, stabilizing the homopentameric protein in an asymmetric state. This introduces a new level of structural diversity in CLRs. Unlike protein and peptide neurotoxins, strychnine and d-TC form a limited number of contacts in the binding pocket of AChBP, offering an explanation for their low selectivity. Based on the ligand interactions observed in strychnine-and d-TC-AChBP complexes we performed alanine-scanning mutagenesis in the binding pocket of the human alpha 1 GlyR and alpha 7 nAChR and showed the functional relevance of these residues in conferring high potency of strychnine and d-TC, respectively. Our results demonstrate that a limited number of ligand interactions in the binding pocket together with an energetic stabilization of the extracellular domain are key to the poor selective recognition of strychnine and d-TC by CLRs as diverse as the GlyR, nAChR, and 5-HT(3)R. C1 [Brams, Marijke; Krijnen, Liz; Ulens, Chris] KULeuven, Lab Struct Neurobiol, Louvain, Belgium. [Pandya, Anshul; Yakel, Jerrel L.] Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Kuzmin, Dmitry; Tsetlin, Victor] Russian Acad Sci, Dept Mol Basis Neurosignaling, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. [van Elk, Rene; Smit, August B.] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Mol & Cellular Neurobiol, Amsterdam, Netherlands. RP Brams, M (reprint author), KULeuven, Lab Struct Neurobiol, Louvain, Belgium. EM chris.ulens@med.kuleuven.be RI Smit, August /E-8410-2011; OI Kuzmin, Dmitry/0000-0002-4380-6018 FU EU [2020288]; RFBR; MCB RAS; NIEHS/NIH FX This research was supported by the following grants: EU FP7 2020288 NeuroCypres to CU, ABS, VT (http://www.neurocypres.eu). RFBR and MCB RAS grants to VT (http://www.rfbr.ru and http://www.ras.ru/presidium/documents/directions.aspx?ID=727c26ac-2098-4 45a-a7ab-344b5bb71165). NIEHS/NIH Intramural Research Program to JY. KULeuven Onderzoekstoelage OT/08/048 to CU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 46 Z9 46 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAR PY 2011 VL 9 IS 3 AR e1001034 DI 10.1371/journal.pbio.1001034 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 742KQ UT WOS:000288942200018 PM 21468359 ER PT J AU Cheng, KT Liu, XB Ong, HL Swaim, W Ambudkar, IS AF Cheng, Kwong Tai Liu, Xibao Ong, Hwei Ling Swaim, William Ambudkar, Indu S. TI Local Ca2+ Entry Via Orai1 Regulates Plasma Membrane Recruitment of TRPC1 and Controls Cytosolic Ca2+ Signals Required for Specific Cell Functions SO PLOS BIOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; OPERATED CALCIUM-CHANNELS; ACTIVATES CRAC CHANNELS; GLAND FLUID SECRETION; STORE DEPLETION; ENDOTHELIAL PERMEABILITY; B-LYMPHOCYTES; ACINAR-CELLS; PORE SUBUNIT; I-CRAC AB Store-operated Ca2+ entry (SOCE) has been associated with two types of channels: CRAC channels that require Orai1 and STIM1 and SOC channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC channels following Ca2+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct channels. We show that TRPC1/Orai1/STIM1-dependent I-SOC, activated in response to Ca2+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated I-CRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1((EE685)-E-684). In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and association of the channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca2+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 mu M Gd3+, removal of extracellular Ca2+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca2+-containing, but not Ca2+-free, medium. Consistent with this, I-CRAC is activated in cells pretreated with thapsigargin in Ca2+-free medium while I-SOC is activated in cells pretreated in Ca2+-containing medium. Significantly, TRPC1 function is required for sustained K-Ca activity and contributes to NFkB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca2+ store depletion. We suggest that coordinated regulation of the surface expression of TRPC1 by Orai1 and gating by STIM1 provides a mechanism for rapidly modulating and maintaining SOCE-generated Ca2+ signals. By recruiting ion channels and other signaling pathways, Orai1 and STIM1 concertedly impact a variety of critical cell functions that are initiated by SOCE. C1 [Cheng, Kwong Tai; Liu, Xibao; Ong, Hwei Ling; Swaim, William; Ambudkar, Indu S.] NIDCR, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Cheng, KT (reprint author), NIDCR, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. EM Indu.Ambudkar@nih.gov FU NIDCR, DIR FX This study was funded by NIDCR, DIR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: NR 65 TC 91 Z9 92 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAR PY 2011 VL 9 IS 3 AR e1001025 DI 10.1371/journal.pbio.1001025 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 742KQ UT WOS:000288942200012 PM 21408196 ER PT J AU Tsai, YC Weissman, AM AF Tsai, Yien Che Weissman, Allan M. TI Ubiquitylation in ERAD: Reversing to Go Forward? SO PLOS BIOLOGY LA English DT Editorial Material ID RETICULUM-ASSOCIATED DEGRADATION; UNFOLDED PROTEIN RESPONSE; UBIQUITIN-PROTEASOME PATHWAY; TO-CYTOSOL DISLOCATION; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEIN; QUALITY-CONTROL; MISFOLDED PROTEINS; LUMINAL PROTEIN; RETROTRANSLOCATION C1 [Tsai, Yien Che; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Tsai, YC (reprint author), NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. EM tsaiyien@mail.nih.gov; amw@nih.gov OI Tsai, Yien Che/0000-0001-9624-1092 FU Intramural NIH HHS NR 48 TC 19 Z9 19 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAR PY 2011 VL 9 IS 3 AR e1001038 DI 10.1371/journal.pbio.1001038 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 742KQ UT WOS:000288942200020 PM 21468305 ER PT J AU Cajas-Monson, LC Mkocha, H Munoz, B Quinn, TC Gaydos, CA West, SK AF Cajas-Monson, Luis Carlos Mkocha, Harran Munoz, Beatriz Quinn, Thomas C. Gaydos, Charlotte A. West, Sheila K. TI Risk Factors for Ocular Infection with Chlamydia trachomatis in Children 6 Months following Mass Treatment in Tanzania SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID HYPERENDEMIC COMMUNITY; AZITHROMYCIN AB Background: Trachoma is the leading infectious cause of blindness in the world, and for endemic communities, mass with azithromycin reduces the pool of infection. High coverage is essential, especially in children as they are the reservoir. However, infection remains post-mass treatment. We sought to determine risk factors for infection in post-mass treatment. Methodology: All children under 9 years in 4 villages in Tanzania were followed from baseline pre-mass treatment to six post treatment. 1,991 children under nine years were enrolled in the longitudinal study and data on individual and characteristics was collected at baseline. Clinical trachoma was determined by an ocular exam and infection by PCR of an eyelid swab. Azithromycin was offered and infection was reassessed at 6 months. A multilevel logistic model was used, accounting for household clustering of children for analysis. Principal Findings: Baseline infection was 23.7% and at 6 months was 10.4%, despite 95% coverage. Infection at baseline positively associated with infection at 6 months (OR = 3.31, 95% CI 2.40-4.56) and treatment had a protective effect (OR = 0.45, 95% CI 0.25-0.80). The age group 2-4 years had an increased risk of infection at 6 months. The household predictive of infection at 6 months were increasing number of children infected in the household at baseline increasing number of untreated children in the household. Conclusions: While one round of mass treatment with high coverage did decrease infection by over 50%, it appears that it is sufficient to eliminate infection. Findings that young children (ages 2-4 years) and households with increasing numbers infected and untreated children have a positive association with infection at 6 months suggest that such households be targeted for more intensive follow up. C1 [Cajas-Monson, Luis Carlos; Munoz, Beatriz; West, Sheila K.] Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. [Mkocha, Harran] Kongwa Trachoma Project, Kongwa, Tanzania. [Quinn, Thomas C.; Gaydos, Charlotte A.] Johns Hopkins Univ, Dept Infect Dis, Int Chlamydia Lab, Baltimore, MD 21218 USA. NIAID, Div Intramural Res, NIH, Bethesda, MD USA. RP Cajas-Monson, LC (reprint author), Johns Hopkins Univ, Wilmer Eye Inst, Dana Ctr Prevent Ophthalmol, Baltimore, MD 21218 USA. EM shwest@jhmi.edu FU Bill and Melinda Gates Foundation; National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [TL1 RR025007]; NIH Roadmap for Medical Research FX This study is funded by a grant from the Bill and Melinda Gates Foundation. Luis Carlos Cajas-Monson was supported by the Predoctoral Clinical Research Training Program at the Johns Hopkins University, which is funded by Grant Number TL1 RR025007 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 13 TC 9 Z9 9 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAR PY 2011 VL 5 IS 3 AR e978 DI 10.1371/journal.pntd.0000978 PG 6 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 742KI UT WOS:000288940800012 PM 21423645 ER PT J AU Sirot, LK Hardstone, MC Helinski, MEH Ribeiro, JMC Kimura, M Deewatthanawong, P Wolfner, MF Harrington, LC AF Sirot, Laura K. Hardstone, Melissa C. Helinski, Michelle E. H. Ribeiro, Jose M. C. Kimura, Mari Deewatthanawong, Prasit Wolfner, Mariana F. Harrington, Laura C. TI Towards a Semen Proteome of the Dengue Vector Mosquito: Protein Identification and Potential Functions SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID SEMINAL FLUID PROTEINS; AEDES-AEGYPTI L; ACCESSORY-GLAND SECRETIONS; HOST-SEEKING BEHAVIOR; DROSOPHILA-MELANOGASTER; REPRODUCTIVE PROTEINS; ANOPHELES-GAMBIAE; FEMALE MONOGAMY; SPERM MOTILITY; FLIGHT-ACTIVITY AB Background: No commercially licensed vaccine or treatment is available for dengue fever, a potentially lethal infection that impacts millions of lives annually. New tools that target mosquito control may reduce vector populations and break the cycle of dengue transmission. Male mosquito seminal fluid proteins (Sfps) are one such target since these proteins, in aggregate, modulate the reproduction and feeding patterns of the dengue vector, Aedes aegypti. As an initial step in identifying new targets for dengue vector control, we sought to identify the suite of proteins that comprise the Ae. aegypti ejaculate and determine which are transferred to females during mating. Methodology and Principal Findings: Using a stable-isotope labeling method coupled with proteomics to distinguish male-and female-derived proteins, we identified Sfps and sperm proteins transferred from males to females. Sfps were distinguished from sperm proteins by comparing the transferred proteins to sperm-enriched samples derived from testes and seminal vesicles. We identified 93 male-derived Sfps and 52 predicted sperm proteins that are transferred to females during mating. The Sfp protein classes we detected suggest roles in protein activation/inactivation, sperm utilization, and ecdysteroidogenesis. We also discovered that several predicted membrane-bound and intracellular proteins are transferred to females in the seminal fluids, supporting the hypothesis that Ae. aegypti Sfps are released from the accessory gland cells through apocrine secretion, as occurs in mammals. Many of the Ae. aegypti predicted sperm proteins were homologous to Drosophila melanogaster sperm proteins, suggesting conservation of their sperm-related function across Diptera. Conclusion and Significance: This is the first study to directly identify Sfps transferred from male Ae. aegypti to females. Our data lay the groundwork for future functional analyses to identify individual seminal proteins that may trigger female post-mating changes (e. g., in feeding patterns and egg production). Therefore, identification of these proteins may lead to new approaches for manipulating the reproductive output and vectorial capacity of Ae. aegypti. C1 [Sirot, Laura K.; Wolfner, Mariana F.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. [Hardstone, Melissa C.; Helinski, Michelle E. H.; Kimura, Mari; Deewatthanawong, Prasit; Harrington, Laura C.] Cornell Univ, Dept Entomol, Ithaca, NY USA. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Sirot, LK (reprint author), Coll Wooster, Dept Biol, Wooster, OH 44691 USA. EM Lsirot@wooster.edu OI Ribeiro, Jose/0000-0002-9107-0818 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [R21AI0176828]; HATCH project [NYC-139437]; National Institutes of Health National Research Service [F32GM074361]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was funded in part by grant R21AI0176828 from National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by NYC-139437 HATCH project to LCH and MFW. LKS was supported in part by a National Institutes of Health National Research Service Award fellowship F32GM074361. JMCR was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection NR 95 TC 49 Z9 49 U1 1 U2 29 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAR PY 2011 VL 5 IS 3 AR e989 DI 10.1371/journal.pntd.0000989 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 742KI UT WOS:000288940800022 PM 21423647 ER PT J AU Wood, SF Blehar, MC Mauery, DR AF Wood, Susan F. Blehar, Mary C. Mauery, D. Richard TI Policy Implications of a New National Institutes of Health Agenda for Women's Health Research, 2010-2020 SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID CLINICAL-TRIALS; GENDER; SEX; PARTICIPATION; CARE C1 [Wood, Susan F.; Mauery, D. Richard] George Washington Univ, Sch Publ Hlth & Hlth Serv, Jacobs Inst Womens Hlth, Washington, DC 20006 USA. [Blehar, Mary C.] Marjo Anal, Potomac, MD USA. [Blehar, Mary C.] NIMH, Womens Hlth Programs, NIH, Bethesda, MD 20892 USA. RP Mauery, DR (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Jacobs Inst Womens Hlth, 2021 K St NW,Suite 800, Washington, DC 20006 USA. EM rmauery@gwu.edu NR 28 TC 4 Z9 4 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAR-APR PY 2011 VL 21 IS 2 BP 99 EP 103 DI 10.1016/j.whi.2011.01.003 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 735NH UT WOS:000288422100001 PM 21353976 ER PT J AU Paek, SY Steinberg, SM Katz, SI AF Paek, So Yeon Steinberg, Seth M. Katz, Stephen I. TI Remission in Dermatitis Herpetiformis A Cohort Study SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MORTALITY; DISEASE; RISK AB Objectives: To determine the percentage of patients with dermatitis herpetiformis (DH) who experience at least 2 years of remission and to identify factors associated with DH remission. Design: Retrospective cohort study. Setting: National Institutes of Health (NIH). Patients: Patients seen at the NIH during the 1972-2010 period who had clinical findings consistent with DH, whose normal skin showed the presence of granular IgA deposits at the dermoepidermal junction on direct immunofluorescence (DIF) examination, whose age of disease onset was known, who hadDHfor at least 2 years, and who were followed up for at least 3 years after the initial NIH visit. Main Outcome Measure: Remission, defined as absence of skin lesions and symptoms of DH for more than 2 years while not taking sulfones (dapsone or sulfoxone), sulfapyridine, anti-tumor necrosis factor agents, or oral steroids and not adhering to a gluten-free diet. Results: Among 86 patients, in 10 (12%) the disease underwent remission (95% confidence interval, 6%-20%). Factors associated with DH remission included DH age of onset at 39 years or older vs onset at ages 8 to 38 years (unadjusted P=.02; adjusted P=.07) and DH onset year between 1960 and 1972 vs onset between 1935 and 1959 or after 1972 (P=.02 for global comparison of 4 onset-year groups). Conclusions: Dermatitis herpetiformis can go into remission. Clinicians should attempt to wean patients with well-controlled DH from a gluten-free diet and/or use of sulfones or other therapies to determine if the DH might have remitted. Our findings provide insight into the pathogenesis and course of this disease and may serve to guide long-term management of patients with DH. C1 [Paek, So Yeon; Katz, Stephen I.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov FU Clinical Research Training Program; NIH; Pfizer Inc; Center for Cancer Research, National Cancer Institute FX This study was supported in part by the Clinical Research Training Program (Ms Paek), a public-private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc), and by the Center for Cancer Research, National Cancer Institute (Ms Paek and Drs Steinbergand Katz). NR 17 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2011 VL 147 IS 3 BP 301 EP 305 DI 10.1001/archdermatol.2010.336 PG 5 WC Dermatology SC Dermatology GA 738AH UT WOS:000288611200006 PM 21079050 ER PT J AU Horvath, KA AF Horvath, Keith A. TI Local Antibiotics to Prevent Surgical Site Infections SO ARCHIVES OF SURGERY LA English DT Editorial Material ID OINTMENT C1 Suburban Hosp, NIH Heart Ctr, Bethesda, MD 20814 USA. RP Horvath, KA (reprint author), Suburban Hosp, NIH Heart Ctr, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA. EM khorvath@nih.gov NR 4 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAR PY 2011 VL 146 IS 3 BP 359 EP 360 PG 2 WC Surgery SC Surgery GA 738AI UT WOS:000288611300026 PM 21422369 ER PT J AU Boffetta, P Colditz, GA Potter, JD Kolonel, L Robson, PJ Malekzadeh, R Seminara, D Goode, EL Yoo, KY Demers, P Gallagher, R Prentice, R Yasui, Y O'Doherty, K Petersen, GM Ulrich, CM Csizmadi, I Amankwah, EK Brockton, NT Kopciuk, K McGregor, SE Kelemen, LE AF Boffetta, Paolo Colditz, Graham A. Potter, John D. Kolonel, Laurence Robson, Paula J. Malekzadeh, Reza Seminara, Daniela Goode, Ellen L. Yoo, Keun-Young Demers, Paul Gallagher, Richard Prentice, Ross Yasui, Yutaka O'Doherty, Kieran Petersen, Gloria M. Ulrich, Cornelia M. Csizmadi, Ilona Amankwah, Ernest K. Brockton, Nigel T. Kopciuk, Karen McGregor, S. Elizabeth Kelemen, Linda E. TI Cohorts and consortia conference: a summary report (Banff, Canada, June 17-19, 2009) SO CANCER CAUSES & CONTROL LA English DT Article DE Biobanks; Cohort studies; Consortia; Cancer; Ethics; Data harmonization; Molecular epidemiology ID CHILDHOOD-CANCER SURVIVOR; BREAST-CANCER; RESOURCE; BIOBANKS; DESIGN; HEALTH; INDIA AB Epidemiologic studies have adapted to the genomics era by forming large international consortia to overcome issues of large data volume and small sample size. Whereas both cohort and well-conducted case-control studies can inform disease risk from genetic susceptibility, cohort studies offer the additional advantages of assessing lifestyle and environmental exposure-disease time sequences often over a life course. Consortium involvement poses several logistical and ethical issues to investigators, some of which are unique to cohort studies, including the challenge to harmonize prospectively collected lifestyle and environmental exposures validly across individual studies. An open forum to discuss the opportunities and challenges of large-scale cohorts and their consortia was held in June 2009 in Banff, Canada, and is summarized in this report. C1 [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, Paolo] Int Prevent Res Inst, F-69006 Lyon, France. [Colditz, Graham A.] Washington Univ, Inst Publ Hlth, St Louis, MO 63110 USA. [Potter, John D.; Prentice, Ross; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kolonel, Laurence] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Robson, Paula J.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Edmonton, AB T5N 3T2, Canada. [Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran 14117, Iran. [Seminara, Daniela] NCI, Bethesda, MD 20892 USA. [Goode, Ellen L.; Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Yoo, Keun-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Demers, Paul] Univ British Columbia, Sch Environm Hlth, Vancouver, BC V6T 1Z2, Canada. [Gallagher, Richard] BC Canc Agcy, Canc Control Res Program, Vancouver, BC, Canada. [Yasui, Yutaka] Univ Alberta, Sch Publ Hlth, Edmonton, AB T5R 3B9, Canada. [O'Doherty, Kieran] Univ British Columbia, W Maurice Young Ctr Appl Eth, Vancouver, BC V6T 1Z2, Canada. [Ulrich, Cornelia M.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany. [Csizmadi, Ilona; Amankwah, Ernest K.; Brockton, Nigel T.; Kopciuk, Karen; McGregor, S. Elizabeth; Kelemen, Linda E.] Alberta Hlth Serv Canc Care, Dept Populat Hlth Res, Calgary, AB T2N 4N2, Canada. RP Boffetta, P (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM paolo.boffetta@i-pri.org RI Yoo, Keun-Young/J-5548-2012; Yasui, Yutaka/E-2564-2015; Colditz, Graham/A-3963-2009; OI Yasui, Yutaka/0000-0002-7717-8638; Colditz, Graham/0000-0002-7307-0291; Potter, John/0000-0001-5439-1500; Malekzadeh, Reza/0000-0003-1043-3814 FU Canadian Partnership Against Cancer; Canadian Institutes of Health Research; Canadian Breast Cancer Research Alliance; Canadian Cancer Society; Alberta Cancer Foundation/Alberta Cancer Research Institute; Alberta Heritage Foundation for Medical Research; University of Calgary FX The scientific and organizing committees would like to thank the conference speakers for their contributions: Paolo Boffetta, Graham Colditz, John Potter, Elio Riboli, Susan Hankinson, Laurence Kolonel, Michael Thun, Paula Robson, Rahman Jamal, Reza Malekzadeh, Zhengming Chen, Wei Zheng, Prabhat Jha, Daniela Seminara, Ellen Goode, Keun-Young Yoo, Paul Demers, Thomas Sellers, Isabel Fortier, Pierre Hainaut, Richard Gallagher, Jorn Olsen, Les Robison, Ross Prentice, Yutaka Yasui, Thomas Lumley, Kieran O'Doherty, Bartha Maria Knoppers, John McLaughlin, Louise Parker, John McPherson, Eric Paulos, and David Duggan. We gratefully acknowledge funding from the Canadian Partnership Against Cancer, the Canadian Institutes of Health Research, the Canadian Breast Cancer Research Alliance, the Canadian Cancer Society, Alberta Cancer Foundation/Alberta Cancer Research Institute, Alberta Heritage Foundation for Medical Research, and the University of Calgary. NR 32 TC 8 Z9 8 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2011 VL 22 IS 3 BP 463 EP 468 DI 10.1007/s10552-010-9717-0 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 737BH UT WOS:000288542400013 PM 21203821 ER PT J AU Friedenreich, CM Woolcott, CG McTiernan, A Terry, T Brant, R Ballard-Barbash, R Irwin, ML Jones, CA Boyd, NF Yaffe, MJ Campbell, KL McNeely, ML Karvinen, KH Courneya, KS AF Friedenreich, C. M. Woolcott, C. G. McTiernan, A. Terry, T. Brant, R. Ballard-Barbash, R. Irwin, M. L. Jones, C. A. Boyd, N. F. Yaffe, M. J. Campbell, K. L. McNeely, M. L. Karvinen, K. H. Courneya, K. S. TI Adiposity changes after a 1-year aerobic exercise intervention among postmenopausal women: a randomized controlled trial SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE clinical trial; exercise; body weight; breast neoplasms; biological mechanisms ID BREAST-CANCER RISK; RECREATIONAL PHYSICAL-ACTIVITY; VISCERAL FAT; INSULIN-RESISTANCE; WEIGHT-LOSS; CLINICAL-TRIAL; UNITED-STATES; ELDERLY-WOMEN; BODY-FAT; OBESITY AB Objective: We examined the effects of an aerobic exercise intervention on adiposity outcomes that may be involved in the association between physical activity and breast cancer risk. Design: This study was a two-centre, two-armed, randomized controlled trial. The 1-year-long exercise intervention included 45 min of moderate-to-vigorous aerobic exercise five times per week, with at least three of the sessions being facility based. The control group was asked not to change their activity and both groups were asked not to change their diet. Subjects: A total of 320 postmenopausal, sedentary, normal weight-to-obese women aged 50-74 years who were cancer-free, nondiabetic and nonhormone replacement therapy users were included in this study. Measurements: Anthropometric measurements of height, weight and waist and hip circumferences; dual energy X-ray absorptiometry measurements of total body fat; and computerized tomography measurements of abdominal adiposity were carried out. Results: Women in the exercise group exercised a mean of 3.6 days (s.d. = 1.3) per week and 178.5 min (s.d. = 76.1) per week. Changes in all measures of adiposity favored exercisers relative to controls (P < 0.001). The mean difference between groups was: -1.8 kg for body weight; -2.0 kg for total body fat; -14.9 cm(2) for intra-abdominal fat area; and -24.1 cm(2) for subcutaneous abdominal fat area. A linear trend of greater body fat loss with increasing volume of exercise was also observed. Conclusion: A 1-year aerobic exercise program consistent with current public health guidelines resulted in reduced adiposity levels in previously sedentary postmenopausal women at higher risk of breast cancer. International Journal of Obesity (2011) 35, 427-435; doi:10.1038/ijo.2010.147; published online 7 September 2010 C1 [Friedenreich, C. M.] Alberta Hlth Serv, Dept Populat Hlth Res, Calgary, AB T2N 4N2, Canada. [Woolcott, C. G.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [McTiernan, A.] Fred Hutchinson Canc Res Ctr, Prevent Ctr, Seattle, WA 98104 USA. [Terry, T.] Cross Canc Inst, Div Breast Imaging, Dept Oncol Imaging, Edmonton, AB T6G 1Z2, Canada. [Brant, R.] Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. [Ballard-Barbash, R.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Irwin, M. L.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Jones, C. A.] Univ Calgary, Dept Med, Calgary, AB, Canada. [Boyd, N. F.] Ontario Canc Inst, Div Epidemiol Stat & Behav Res, Toronto, ON M4X 1K9, Canada. [Yaffe, M. J.] Sunnybrook Res Inst, Toronto, ON, Canada. [Campbell, K. L.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V5Z 1M9, Canada. [McNeely, M. L.] Univ Alberta, Dept Phys Therapy, Edmonton, AB, Canada. [McNeely, M. L.] Univ Alberta, Dept Oncol, Edmonton, AB, Canada. [Karvinen, K. H.] E Carolina Univ, Dept Exercise & Sports Sci, Greenville, NC USA. [Courneya, K. S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB, Canada. RP Friedenreich, CM (reprint author), Alberta Hlth Serv, Dept Populat Hlth Res, 1331 29 St NW, Calgary, AB T2N 4N2, Canada. EM christine.friedenreich@albertahealthservices.ca OI Brant, Rollin/0000-0002-8026-2451 FU Canadian Breast Cancer Research Alliance [017468]; Canadian Institutes of Health Research; Alberta Heritage Foundation for Medical Research; Canada Research Chairs Program FX This study was funded by a research grant (no. 017468) from the Canadian Breast Cancer Research Alliance. Dr Friedenreich was funded by career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research. Dr Courneya is supported by the Canada Research Chairs Program. The study set up was carried out by Kim van der Hoek and Marla Orenstein, and the Study Coordinators were Rosemary Crosby and Ame-Lia Tamburrini. The Fitness Centre Managers were Ben Wilson, Lisa Workman and Diane Cook. The Exercise Trainers were Shannon Hutchins, Kathy Traptow, Shannon Brown, Susan Daniel, Parissa Gillani, Stephanie Sanden, Karen Mackay and Sandra Olsen. Data preparation and analysis was carried out by Sandra Blitz, Sony Brar and Qinggang Wang. NR 70 TC 15 Z9 16 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 2011 VL 35 IS 3 BP 427 EP 435 DI 10.1038/ijo.2010.147 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 736IJ UT WOS:000288486300014 ER PT J AU Rogers, JT Mikkilineni, S Cantuti-Castelvetri, I Smith, DH Huang, XD Bandyopadhyay, S Cahill, CM Maccecchini, ML Lahiri, DK Greig, NH AF Rogers, Jack T. Mikkilineni, Sohan Cantuti-Castelvetri, Ippolita Smith, Deborah H. Huang, Xudong Bandyopadhyay, Sanghamitra Cahill, Catherine M. Maccecchini, Maria L. Lahiri, Debomoy K. Greig, Nigel H. TI The alpha-synuclein 5 ' untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Parkinson's disease; Alpha-synuclein; 5 ' untranslated region; Transfection-based screen; Natural product; Translation blockers; Amyloid precursor protein; Posiphen; Phenserine ID AMYLOID PRECURSOR PROTEIN; IRON-RESPONSIVE ELEMENT; APP-MESSENGER-RNA; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; 5'-UNTRANSLATED REGION; LEWY BODIES; NEURODEGENERATIVE DISEASES; MYCOPHENOLATE-MOFETIL AB Increased brain alpha-synuclein (SNCA) protein expression resulting from gene duplication and triplication can cause a familial form of Parkinson's disease (PD). Dopaminergic neurons exhibit elevated iron levels that can accelerate toxic SNCA fibril formation. Examinations of human post mortem brain have shown that while mRNA levels for SNCA in PD have been shown to be either unchanged or decreased with respect to healthy controls, higher levels of insoluble protein occurs during PD progression. We show evidence that SNCA can be regulated via the 5'untranslated region (5'UTR) of its transcript, which we modeled to fold into a unique RNA stem loop with a CAGUGN apical loop similar to that encoded in the canonical iron-responsive element (IRE) of L- and H-ferritin mRNAs. The SNCA IRE-like stem loop spans the two exons that encode its 5'UTR, whereas, by contrast, the H-ferritin 5'UTR is encoded by a single first exon. We screened a library of 720 natural products (NPs) for their capacity to inhibit SNCA 5'UTR driven luciferase expression. This screen identified several classes of NPs, including the plant cardiac glycosides, mycophenolic acid (an immunosuppressant and Fe chelator), and, additionally, posiphen was identified to repress SNCA 5'UTR conferred translation. Western blotting confirmed that Posiphen and the cardiac glycoside, strophanthidine, selectively blocked SNCA expression (similar to 1 mu M IC(50)) in neural cells. For Posiphen this inhibition was accelerated in the presence of iron, thus providing a known APP-directed lead with potential for use as a SNCA blocker for PD therapy. These are candidate drugs with the potential to limit toxic SNCA expression in the brains of PD patients and animal models in vivo. C1 [Rogers, Jack T.; Mikkilineni, Sohan; Cantuti-Castelvetri, Ippolita; Huang, Xudong; Cahill, Catherine M.] Massachusetts Gen Hosp, Neurochem Lab, Charlestown, MA 02129 USA. [Cantuti-Castelvetri, Ippolita] Massachusetts Gen Hosp, MIND, Charlestown, MA 02129 USA. [Smith, Deborah H.] Yale Univ, New Haven, CT USA. [Bandyopadhyay, Sanghamitra] Indian Inst Toxicol Res CSIR, Lucknow, Uttar Pradesh, India. [Maccecchini, Maria L.] QR Pharma Inc, Radnor, PA 19087 USA. [Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Mol Neurogenet Lab, Indianapolis, IN USA. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Rogers, JT (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Charlestown, MA 02129 USA. EM Jrogers@partners.org OI Bandyopadhyay, Sanghamitra /0000-0002-1490-3599 FU Michael J. Fox Foundation; National Institute of Aging [R01 AG20181]; Alzheimer's Association [09-131352]; ISOA; QR Pharma Inc.; National Institutes of Health [AG18379, AG18884]; National Institute on Aging, National Institutes of Health (NHG); MGH/MIT Morris Udall Center of Excellence in PD Research [NIH NS38372]; APDA Advanced Center for Parkinson Research at MGH FX This research was supported by the Michael J. Fox Foundation Novel Drug Discoveries Award, National Institute of Aging R01 AG20181 (JTR), Alzheimer's Association Zenith Award 09-131352 (JTR), ISOA (JTR), QR Pharma Inc. (MLM), the National Institutes of Health Grants [AG18379 and AG18884 (DKL)] and the Intramural Research Program, National Institute on Aging, National Institutes of Health (NHG). ICC was supported by the MGH/MIT Morris Udall Center of Excellence in PD Research (NIH NS38372), and the APDA Advanced Center for Parkinson Research at MGH. We are indebted for the input and support of Professor Moussa Youdim, a pioneer in the fields of Parkinson's disease research, and an innovative drug discoverer and developer. NR 85 TC 18 Z9 19 U1 0 U2 6 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD MAR PY 2011 VL 118 IS 3 BP 493 EP 507 DI 10.1007/s00702-010-0513-5 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 737HB UT WOS:000288558600020 PM 21221670 ER PT J AU Tubbs, JT Kissling, GE Travlos, GS Goulding, DR Clark, JA King-Herbert, AP Blankenship-Paris, TL AF Tubbs, Jacquelyn T. Kissling, Grace E. Travlos, Greg S. Goulding, David R. Clark, James A. King-Herbert, Angela P. Blankenship-Paris, Terry L. TI Effects of Buprenorphine, Meloxicam, and Flunixin Meglumine as Postoperative Analgesia in Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID LOCOMOTOR-ACTIVITY; CORTICOSTERONE LEVELS; CIRCADIAN-RHYTHMS; LABORATORY MOUSE; OPIOID RECEPTOR; EMBRYO-TRANSFER; RATS; PAIN; BEHAVIOR; LAPAROTOMY AB C57BL/6NCrl male mice (n = 60; age, 6 to 7 wk) underwent partial hepatectomy or no surgery and were given 1 of 3 analgesics pre- and postoperatively. Food and water consumption, body weight, running wheel activity, locomotor activity, and serum corticosterone concentrations were measured before and after surgery. Mice that were surgically manipulated weighed significantly less on days 1 through 3 after surgery than did mice not manipulated surgically. On the day of surgery, the surgery groups consumed significantly less feed (-1.5 +/- 0.35 g) than did nonsurgery groups. There were no differences in water consumption on any day between surgery and nonsurgery groups or among the 3 analgesic groups. For running wheel activity, significant decreases in the surgery groups were seen at day 1 after surgery compared with baseline. Surgery groups that received buprenorphine and meloxicam returned to baseline activity levels on day 2 after surgery. Open-field testing revealed no significant differences in locomotor activity in any groups; however, posttreatment locomotor activity in the buprenorphine nonsurgery group was increased compared with baseline, and posttreatment locomotor activity in the flunixin meglumine surgery group was decreased compared with baseline. Serum corticosterone concentrations were within normal limits regardless of treatment in all groups. Comparison of the overall results indicated that meloxicam and buprenorphine, at the dose given, appear to be suitable postoperative analgesics for partial hepatectomy in mice. Flunixin meglumine at the given dosage (2.5 mg/kg) may not provide adequate analgesia for partial hepatectomy. C1 [Tubbs, Jacquelyn T.; Travlos, Greg S.; King-Herbert, Angela P.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Goulding, David R.; Clark, James A.; Blankenship-Paris, Terry L.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. RP Tubbs, JT (reprint author), NIEHS, Cellular & Mol Pathol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM tubbsj@niehs.nih.gov NR 56 TC 30 Z9 30 U1 1 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2011 VL 50 IS 2 BP 185 EP 191 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 738MJ UT WOS:000288643600005 PM 21439211 ER PT J AU Ahmet, I Tae, HJ Juhaszova, M Riordon, DR Boheler, KR Sollott, SJ Brines, M Cerami, A Lakatta, EG Talan, MI AF Ahmet, Ismayil Tae, Hyun-Jin Juhaszova, Magdalena Riordon, Daniel R. Boheler, Kenneth R. Sollott, Steven J. Brines, Michael Cerami, Anthony Lakatta, Edward G. Talan, Mark I. TI A Small Nonerythropoietic Helix B Surface Peptide Based upon Erythropoietin Structure is Cardioprotective against Ischemic Myocardial Damage SO MOLECULAR MEDICINE LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; CARDIAC MYOCYTES; PROTECTION; INFARCTION; RECEPTOR; UPDATE AB Strong cardioprotective properties of erythropoietin (EPO) reported over the last 10 years have been difficult to translate to clinical applications for ischemic cardioprotection owing to undesirable parallel activation of erythropoiesis and thrombogenesis. A pyroglutamate helix B surface peptide (pHBP), recently engineered to include only a part of the EPO molecule that does not bind to EPO receptor and thus, is not erythropoietic, retains tissue protective properties of EPO. Here we compared the ability of pHBP and EPO to protect cardiac myocytes from oxidative stress in vitro and cardiac tissue from ischemic damage in viva HBR similar to EPO, increased the reactive oxygen species (ROS) threshold for induction of the mitochondrial permeability transition by 40%, In an experimental model of myocardial infarction induced by permanent ligation of a coronary artery in rats, a single bolus injection of 60 mu g/kg of pHBP immediately after coronary ligation, similar to EPO, reduced apoptosis in the myocardial area at risk, examined 24 h later, by 80% and inflammation by 34%, Myocardial infarction (MI) measured 24 h after coronary ligation was similarly reduced by 50% in both pHBP- and EPO-treated rats. Two wks after surgery, left ventricular remodeling (ventricular dilation) and functional decline (fall in ejection fraction) assessed by echocardiography were significantly and similarly attenuated in pHBP- and EPO-treated rats, and MI size was reduced by 25%. The effect was retained during the 6-wk follow-up. A single bolus injection of pHBP immediately after coronary ligation was effective in reduction of MI size in a dose as low as 1 mu g/kg, but was ineffective at a 60 mu g/kg dose if administered 24 h after MI induction. We conclude that pHBP is equally cardioprotective with EPO and deserves further consideration as a safer alternative to rhEPO in the search for therapeutic options to reduce myocardial damage following blockade of the coronary circulation. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2010.00235 C1 [Ahmet, Ismayil; Tae, Hyun-Jin; Juhaszova, Magdalena; Riordon, Daniel R.; Boheler, Kenneth R.; Sollott, Steven J.; Lakatta, Edward G.; Talan, Mark I.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Brines, Michael; Cerami, Anthony] Araim Pharmaceut, Ossining, NY USA. RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov OI Brines, Michael/0000-0003-4151-4449 FU National Institute on Aging, NIH (Baltimore, MD, USA) FX The work was fully funded by the Intramural Research Program, National Institute on Aging, NIH (Baltimore, MD, USA). NR 20 TC 25 Z9 30 U1 0 U2 10 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR-APR PY 2011 VL 17 IS 3-4 BP 194 EP 200 DI 10.2119/molmed.2010.00235 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 737RW UT WOS:000288586900006 PM 21170473 ER PT J AU Shankar, EM Che, KF Messmer, D Lifson, JD Larsson, M AF Shankar, Esaki Muthu Che, Karlhans Fru Messmer, Davorka Lifson, Jeffrey D. Larsson, Marie TI Expression of a Broad Array of Negative Costimulatory Molecules and Blimp-1 in T Cells following Priming by HIV-1 Pulsed Dendritic Cells SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC VIRAL-INFECTION; HERPESVIRUS ENTRY MEDIATOR; TRANSCRIPTIONAL REPRESSOR BLIMP-1; LYMPHOCYTE ATTENUATOR; DISEASE PROGRESSION; B-LYMPHOCYTE; IN-VIVO; INHIBITS ACTIVATION; IMMUNE-RESPONSES AB Accumulating evidence indicates that immune impairment in persistent viral infections could lead to T-cell exhaustion. To evaluate the potential contribution of induction of negative costimulatory molecules to impaired T-cell responses, we primed naive T cells with mature monocyte-derived dendritic cells (MDDCs) pulsed with HIV-1 in vitro. We used quantitative real-time polymerase chain reaction and flow cytometry, respectively, to compare the gene and surface-protein expression profiles of naive T cells primed with HIV-pulsed or mock-pulsed DCs. We detected elevated expressions of negative costimulatory molecules, including lymphocyte activation gene-3 (LAG-3). CD160, cytolytic T-lymphocyte antigen-4 (CTLA-4). T-cell immunoglobulin mucin-containing domain-3 (TIM-3), programmed death-1 (PD-1) and TRAIL (tumor necrosis-factor-related apoptosis-inducing ligand) in T cells primed by HIV-pulsed DCs. The PD-1(+) T-cell population also coexpressed TIM-3, LAG-3, and CTLA-4. Interestingly, we also found an increase in gene expression of the transcriptional repressors Blimp-1 (B-lymphocyte-induced maturation protein-1) and Foxp3 (forkhead transcription factor) in T-cells primed by HIV-pulsed DCs; Blimp-1 expression was directly proportional to the expression of the negative costimulatory molecules. Furthermore, levels of the effector cytokines interleukin-2, tumor necrosis factor-alpha and interferon-gamma, and perforin and granzyme B were decreased in T-cell populations primed by HIV-pulsed DCs. In conclusion, in vitro priming of halve T-cells with HIV-pulsed DC leads to expansion of T cells with coexpression of a broad array of negative costimulatory mclecules and Blimp-1, with potential deleterious consequences for T-cell responses. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2010.00175 C1 [Shankar, Esaki Muthu] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Mol Virol Lab, S-58185 Linkoping, Sweden. [Messmer, Davorka] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Shankar, EM (reprint author), Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Mol Virol Lab, 1 Plan 13, S-58185 Linkoping, Sweden. EM esakimuthu.shankar@liu.se RI Muthu , Shankar/G-6444-2011; OI Esaki Muthu, Shankar/0000-0002-7866-9818 FU Swedish Research Council; Swedish, Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; National Cancer Institute, National Institutes of Health [NO1-CO-124000, HHSN266200400088C]; [AI52731] FX We thank the Biological Products Core of the AIDS and Cancer Virus Program, SAIC Frederick, National Cancer Institute, Frederick, MD, USA, for generously providing HIV. This work has been supported by grants through: M Larsson: AI52731, the Swedish Research Council, the Swedish, Physicians against AIDS Research Foundation, the Swedish International Development Cooperation Agency; SIDA SARC, VINNMER for Vinnova, Linkoping University Hospital Research Fund, CALF, and the Swedish Society of Medicine. JD Lifson was supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts NO1-CO-124000 and HHSN266200400088C. NR 78 TC 29 Z9 31 U1 0 U2 5 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAR-APR PY 2011 VL 17 IS 3-4 BP 229 EP 240 DI 10.2119/molmed.2010.00175 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 737RW UT WOS:000288586900010 PM 21103670 ER PT J AU Mahringer, A Miller, D Fricker, G AF Mahringer, A. Miller, D. Fricker, G. TI Genomic regulation of ABC transporters by the aryl hydrocarbon receptor (AhR) in kidney tubules SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 77th Annual Meeting on German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 30-APR 01, 2011 CL Frankfurt, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Mahringer, A.; Fricker, G.] Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. [Miller, D.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2011 VL 383 SU 1 BP 17 EP 17 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737MO UT WOS:000288573100070 ER PT J AU Reinartz, MT Wainer, IW Seifert, R AF Reinartz, M. T. Wainer, I. W. Seifert, R. TI Molecular Interaction of the Fenoterol Stereoisomers with the beta(2)-Adrenoceptor SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract CT 77th Annual Meeting on German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology CY MAR 30-APR 01, 2011 CL Frankfurt, GERMANY SP German Soc Expt & Clin Pharmacol & Toxicol C1 [Reinartz, M. T.; Seifert, R.] Hannover Med Sch, Pharmakol OE 5320, D-30623 Hannover, Germany. [Wainer, I. W.] NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2011 VL 383 SU 1 BP 18 EP 19 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 737MO UT WOS:000288573100077 ER PT J AU Backinger, CL Pilsner, AM Augustson, EM Frydl, A Phillips, T Rowden, J AF Backinger, Cathy L. Pilsner, Alison M. Augustson, Erik M. Frydl, Andrea Phillips, Todd Rowden, Jessica TI YouTube as a source of quitting smoking information SO TOBACCO CONTROL LA English DT Article ID IMPACT AB Objective To conduct analyses to determine the extent to which YouTube videos posted specific to smoking cessation were actually about quitting smoking and if so, whether or not they portrayed evidence-based practices (EBPs). Methods In August 2008, researchers identified YouTube videos by search strategies, 'relevance' and 'view count' using the following three search terms: 'stop smoking', 'quit smoking' and 'smoking cessation (n = 296 for full sample and n = 191 for unique videos). Results Overall, almost 60% of videos contained a message about quitting smoking. Differences were found across search terms for videos about quitting smoking, with 'stop smoking' yielding the highest percentage (80.8%) of videos about quitting smoking. Almost half of the videos (48.9%) contained EBPs for cessation strategies; however, a significant portion contained either non-EBPs (28.4%) or both EBPs and non-EBPs (22.7%). The number of views per an individual video across the six categories ranged from a low of 8 in the 'relevance' strategy and 'smoking cessation' search term to a high of 1 247 540 in the 'view count' strategy and 'stop smoking' search term. Of the top three most viewed videos by strategy and search term, 66.7% included a specific mention of quitting smoking and, of these, the majority included EBPs. Conclusion Results highlight the need to develop and upload videos containing EBPs both to increase the overall proportion of EBP videos in all categories, particularly in 'quit smoking' and 'stop smoking.' Research is needed to study whether YouTube videos influence knowledge, attitudes and behaviours regarding quitting smoking. C1 [Backinger, Cathy L.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Pilsner, Alison M.] DB Consulting Grp Inc, Silver Spring, MD USA. [Phillips, Todd; Rowden, Jessica] Acad Educ Dev, Washington, DC USA. RP Backinger, CL (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4050, Rockville, MD 20852 USA. EM backingc@mail.nih.gov FU National Cancer Institute, Tobacco Control Research Branch FX Funding for this study was provided by the National Cancer Institute, Tobacco Control Research Branch. NR 16 TC 26 Z9 27 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD MAR PY 2011 VL 20 IS 2 BP 119 EP 122 DI 10.1136/tc.2009.035550 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 724JW UT WOS:000287573000016 PM 20966132 ER PT J AU Jacobson, O Zhu, L Ma, Y Weiss, ID Sun, XL Niu, G Kiesewetter, DO Chen, XY AF Jacobson, Orit Zhu, Lei Ma, Ying Weiss, Ido D. Sun, Xilin Niu, Gang Kiesewetter, Dale O. Chen, Xiaoyuan TI Rapid and Simple One-Step F-18 Labeling of Peptides SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ALPHA(V)BETA(3) INTEGRIN EXPRESSION; RGD PEPTIDE; PET; CHEMISTRY AB Labeling biomolecules with (18)F is usually done through coupling with prosthetic groups, which requires several time-consuming radiosynthesis steps and therefore in low labeling yield. In this study, we designed a simple one-step (18)F-labeling strategy to replace the conventional complex and the long process of multiple-step radiolabeling procedure. Both monomeric and dimeric cyclic RGD peptides were modified to contain 4-NO(2)-3-CF(3) arene as precursors for direct 18F labeling. Binding of the two functionalized peptides to integrin alpha(v)beta(3) was tested in vitro using the MDA-MB-435 human breast cell line. The most promising functionalized peptide, the dimeric cyclic RGD, was further evaluated in vivo in an orthotopic MDA-MB-435 tumor xenograft model. The use of relatively low amount of precursor (similar to 0.5 mu mol) gave reasonable yield, ranging from 7 to 23% (decay corrected, calculated from the start of synthesis) after HPLC purification. Overall reaction time was 40 man, and the specific activity of the labeled peptide was high. Modification of RGD peptides did not significantly change the biological binding affinities of the modified peptides. Small animal PET and biodistribution studies revealed integrin specific tumor uptake and favorable biokinetics. We have developed a novel one-step (18)F radiolabeling strategy for peptides that contain a specific arene group, which shortens reaction time and labor significantly, requires low amount of precursor, and results in specific activity of 79 +/- 13 GBq/mu mol. Successful introduction of 4-fluoro-3-trifluoromethylbenzamide into RGD peptides may be a general strategy applicable to other biologically active peptides and proteins. C1 [Jacobson, Orit; Zhu, Lei; Ma, Ying; Sun, Xilin; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Jilin Univ, Key Lab Mol Enzymol & Enzyme Engn, Minist Educ, Changchun 130000, Jilin, Peoples R China. [Weiss, Ido D.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This research was supported by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 26 TC 43 Z9 46 U1 3 U2 25 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 MAR PY 2011 VL 22 IS 3 BP 422 EP 428 DI 10.1021/bc100437q PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 735GM UT WOS:000288401400014 PM 21338096 ER PT J AU Qin, J Liang, KY AF Qin, Jing Liang, Kung-Yee TI Hypothesis Testing in a Mixture Case-Control Model SO BIOMETRICS LA English DT Article DE Case-control; Chi-squared distribution; Clinical trial; Gene mutation; Microarray study; Mixture models ID PROSTATE-CANCER; NONPARAMETRIC-ESTIMATION; EMPIRICAL LIKELIHOOD; NUISANCE PARAMETER; GENETIC-LINKAGE; MALARIA; RATIO; DISTRIBUTIONS; PROPORTIONS; EXPRESSION AB We consider a problem of testing mixture proportions using two-sample data, one from group one and the other from a mixture of groups one and two with unknown proportion, lambda, for being in group two. Various statistical applications, including microarray study, infectious epidemiological studies, case-control studies with contaminated controls, clinical trials allowing "nonresponders," genetic studies for gene mutation, and fishery applications can be formulated in this setup. Under the assumption that the log ratio of probability (density) functions from the two groups is linear in the observations, we propose a generalized score test statistic to test the mixture proportion. Under some regularity conditions, it is shown that this statistic converges to a weighted chi-squared random variable under the null hypothesis of lambda = 0, where the weight depends only on the sampling fraction of both groups. The permutation method is used to provide more reliable finite sample approximation. Simulation results and two real data applications are presented. C1 [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Liang, Kung-Yee] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Qin, J (reprint author), NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. EM kyliang@jhsph.edu RI Liang, Kung-Yee/F-8299-2011 FU National Institutes of Health [HL090577] FX Comments from the editor, associate editor, the referee are greatly appreciated. This work is supported in part by Grant HL090577 (K-YL) of the National Institutes of Health. NR 42 TC 3 Z9 3 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2011 VL 67 IS 1 BP 182 EP 193 DI 10.1111/j.1541-0420.2010.01409.x PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 735AW UT WOS:000288386800020 PM 20345497 ER PT J AU Zhou, HB Song, R Wu, YS Qin, J AF Zhou, Haibo Song, Rui Wu, Yuanshan Qin, Jing TI Statistical Inference for a Two-Stage Outcome-Dependent Sampling Design with a Continuous Outcome SO BIOMETRICS LA English DT Article DE Biased sampling; Empirical likelihood; Outcome dependent; Sample size; Two-stage design ID EMPIRICAL LIKELIHOOD METHOD; REGRESSION-MODELS; EXPOSURE; 2-PHASE; DISEASE AB The two-stage case-control design has been widely used in epidemiology studies for its cost-effectiveness and improvement of the study efficiency (White, 1982, American Journal of Epidemiology 115, 119-128; Breslow and Cain, 1988, Biometrika 75, 11-20). The evolution of modern biomedical studies has called for cost-effective designs with a continuous outcome and exposure variables. In this article, we propose a new two-stage outcome-dependent sampling (ODS) scheme with a continuous outcome variable, where both the first-stage data and the second-stage data are from ODS schemes. We develop a semiparametric empirical likelihood estimation for inference about the regression parameters in the proposed design. Simulation studies were conducted to investigate the small-sample behavior of the proposed estimator. We demonstrate that, for a given statistical power, the proposed design will require a substantially smaller sample size than the alternative designs. The proposed method is illustrated with an environmental health study conducted at National Institutes of Health. C1 [Zhou, Haibo; Wu, Yuanshan] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Song, Rui] Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA. [Wu, Yuanshan] Wuhan Univ, Sch Math & Stat, Wuhan 430072, Hubei, Peoples R China. [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Zhou, HB (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM zhou@bios.unc.edu; song@stat.colostate.edu; yswu@bios.unc.edu; jingqin@niaid.nih.gov FU National Institutes of Health [R01 CA 079949] FX The authors would like to thank the editor, the associate editor, and the referees for their thoughtful comments and constructive suggestions. This research is supported by the National Institutes of Health grant R01 CA 079949 (H.Z., R.S., and Y.W.). NR 22 TC 7 Z9 7 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2011 VL 67 IS 1 BP 194 EP 202 DI 10.1111/j.1541-0420.2010.01446.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 735AW UT WOS:000288386800021 PM 20560938 ER PT J AU Solomon, BD Patel, A Cheung, SW Pineda-Alvarez, DE AF Solomon, Benjamin D. Patel, Ankita Cheung, Sau Wai Pineda-Alvarez, Daniel E. TI VACTERL Association and Mitochondrial Dysfunction SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE VACTERL; VACTERL association; VATER; VATER association; mitochondria ID RESPIRATORY-CHAIN DEFICIENCY; NP-3243 POINT MUTATION; VATER ASSOCIATION; PATIENT; MALFORMATIONS; DELETION; GENE AB BACKGROUND: VACTERL association includes the presence of malformations affecting the vertebrae, anus, heart, trachea and esophagus, kidneys, and limbs. The causes remain largely unknown, but rare patients with mitochondrial dysfunction have been reported. Although clinical signs and symptoms consistent with possible mitochondrial disease are not uncommon in patients with VACTERL association, the necessary testing to confirm mitochondrial dysfunction is infrequently performed. METHODS: We describe a patient with relatively classic signs of VACTERL association who had an onset of clinical signs of mitochondrial dysfunction at 13 months of age. These signs included progressive muscle weakness, autonomic dysregulation, episodic hypoglycemia, and exocrine pancreatic dysfunction. The patient was later shown to have evidence of mitochondrial dysfunction (cytochrome c oxidase deficiency). CONCLUSIONS: Abnormal mitochondrial function may be associated with VACTERL association, and clinicians who encounter patients with VACTERL association should have a low threshold for considering mitochondrial dysfunction. Birth Defects Research (Part A) 91:192-194, 2011. (c) 2011 Wiley-Liss, Inc. C1 [Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Patel, Ankita; Cheung, Sau Wai] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717,Bldg 35,Room 1B-207, Bethesda, MD 20892 USA. EM solomonb@mail.nih.gov FU Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health and Human Services, United States of America FX This research was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health and Human Services, United States of America. NR 21 TC 12 Z9 13 U1 0 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 MAR PY 2011 VL 91 IS 3 BP 192 EP 194 DI 10.1002/bdra.20768 PG 3 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 735DU UT WOS:000288394400008 PM 21308977 ER PT J AU Desvigne-Nickens, P AF Desvigne-Nickens, Patrice TI Heart Failure Prevention Is the Best Option To Stem High Costs and Disease Burden Research for More Effective Heart Failure Treatment Is Needed SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Editorial Material DE Editorials; healthcare disparities; heart failure; hypertension; prevention ID ISOSORBIDE DINITRATE; MORTALITY; HYPERTENSION; HYDRALAZINE; BLACKS; RACE C1 NHLBI, Heart Failure & Arrhythmia Branch, Div Cardiovas Sci, Bethesda, MD 20892 USA. RP Desvigne-Nickens, P (reprint author), NHLBI, Heart Failure & Arrhythmia Branch, Div Cardiovas Sci, 2 Rockledge Ctr,Room 8176, Bethesda, MD 20892 USA. EM desvignp@mail.nih.gov NR 21 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2011 VL 4 IS 2 BP 143 EP 145 DI 10.1161/CIRCOUTCOMES.111.960641 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 734WN UT WOS:000288372200003 PM 21406669 ER PT J AU Seeff, LB Everson, GT Morgan, TR Curto, TM Lee, WM Ghany, MG Shiffman, ML Fontana, RJ Di Bisceglie, AM Bonkovsky, HL Dienstag, JL AF Seeff, Leonard B. Everson, Gregory T. Morgan, Timothy R. Curto, Teresa M. Lee, William M. Ghany, Marc G. Shiffman, Mitchell L. Fontana, Robert J. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Dienstag, Jules L. TI Percutaneous Liver Biopsy Reply SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Letter C1 [Seeff, Leonard B.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Richmond, VA USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Dept Mol & Struct Biol, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Gastrointestinal Unit,Med, Boston, MA USA. RP Seeff, LB (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2011 VL 9 IS 3 BP 278 EP 279 DI 10.1016/j.cgh.2010.12.006 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 737FY UT WOS:000288555700026 ER PT J AU Nam, KA Kim, S Lee, H Kim, HL AF Nam, K. A. Kim, S. Lee, H. Kim, H. L. TI Employed women with depression in Korea SO JOURNAL OF PSYCHIATRIC AND MENTAL HEALTH NURSING LA English DT Article DE depressive symptoms; employment; Korean women; stressful life events; work stress ID NURSING PRACTICE PARADIGM; SOCIAL SUPPORT; PHYSICAL-ACTIVITY; RURAL WOMEN; LIFE EVENTS; HEALTH; SYMPTOMS; EPIDEMIOLOGY; PREVALENCE; EXPERIENCE AB Accessible summary Depression is a major mental health problem with a higher incidence in women than in men, which is also observed in Korea. Work-related factors, along with other known social and familial factors, have been reported to greatly affect women's mental health. Hauenstein's Nursing Practice Paradigm for Depressed Rural Women (NPP) is an explicit paradigm for holistic interventions to prevent depression by emphasizing the importance of resources available to depressed women - physiological, psychological, and social resources. In this study, after modifying Hauenstein's NPP for culturally competent result, we employed the framework for exploring the predictors of depression and the possible moderating effects of resources on the stress-depression relationship in a community-based sample of employed Korean women. Abstract Korean women have been reported to be more susceptible to depressive symptoms than men. In this study we explored the important predictors of depression among employed Korean women using modified Hauenstein's Nursing Practice Paradigm for Depressed Rural Women, focusing on the relationship of stressful life events and three resources (physiological, social, and psychological). In particular, we examined the moderating effects of resources on the stress-depression relationship among a community-based sample of employed Korean women. In this cross-sectional study, survey data were collected with 767 employed women in Korea over a 2-month period in 2006. Of these respondents, 286 depressed participants' data were analysed to test moderating effects of the three resources on depression. Our hierarchical multiple regression results revealed that stressful life events directly affected depression. However, after including the product terms of the three resources (i.e. regular exercise, self-efficacy, and closeness) and stressful life events, the main effect of stressful life events disappeared, confirming significant moderating effects of the resources. The findings would contribute to development of a body of culturally sensitive knowledge for clinical practice with depressed employed Korean women. C1 [Lee, H.] NINR, NIH, Bethesda, MD 20892 USA. [Nam, K. A.] Hallym Univ, Div Nursing, Chunchon, Gangwon Do, South Korea. [Kim, S.; Kim, H. L.] Yonsei Univ, Coll Nursing, Seoul 120749, South Korea. RP Lee, H (reprint author), NINR, NIH, 9 Ctr Dr,Rm 1W121, Bethesda, MD 20892 USA. EM mizbeanhh@gmail.com NR 37 TC 5 Z9 6 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-0126 J9 J PSYCHIATR MENT HLT JI J. Psychiatr. Ment. Health Nurs. PD MAR PY 2011 VL 18 IS 2 BP 139 EP 145 DI 10.1111/j.1365-2850.2010.01641.x PG 7 WC Nursing; Psychiatry SC Nursing; Psychiatry GA 718BZ UT WOS:000287096200009 PM 21299726 ER PT J AU Maruri-Avidal, L Domi, A Weisberg, AS Moss, B AF Maruri-Avidal, Liliana Domi, Arban Weisberg, Andrea S. Moss, Bernard TI Participation of Vaccinia Virus L2 Protein in the Formation of Crescent Membranes and Immature Virions SO JOURNAL OF VIROLOGY LA English DT Article ID GOLGI INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; INITIATE MORPHOGENESIS; EXTERNAL SCAFFOLD; ENVELOPE PROTEIN; MATURE VIRION; F10 KINASE; H5R GENE; BIOGENESIS; RIFAMPICIN AB Morphogenesis of vaccinia virus begins with the appearance of crescent-shaped membrane precursors of immature virions in cytoplasmic factories. During the initial characterization of the product of the L2R reading frame, we discovered that it plays an important role in crescent formation. The L2 protein was expressed early in infection and was associated with the detergent-soluble membrane fraction of mature virions, consistent with two potential membrane-spanning domains. All chordopoxviruses have L2 homologs, suggesting an important function. Indeed, we were unable to isolate an infectious L2R deletion mutant. Consequently, we constructed an inducible mutant with a conditional lethal phenotype. When L2 expression was repressed, proteolytic processing of the major core proteins and the A17 protein, which is an essential component of the immature virion membrane, failed to occur, suggesting an early block in viral morphogenesis. At 8 h after infection in the presence of inducer, immature and mature virions were abundantly seen by electron microscopy. In contrast, those structures were rare in the absence of inducer and were replaced by large, dense aggregates of viroplasm. A minority of these aggregates had short spicule-coated membranes, which resembled the beginnings of crescent formation, at their periphery. These short membrane segments at the edge of the dense viroplasm increased in number at later times, and some immature virions were seen. Although the L2 protein was not detected under nonpermissive conditions, minute amounts could account for stunted and delayed viral membrane formation. These findings suggested that L2 is required for the formation or elongation of crescent membranes. C1 [Maruri-Avidal, Liliana; Domi, Arban; Weisberg, Andrea S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research, NIAID, NIH FX The research was supported by the Division of Intramural Research, NIAID, NIH. NR 48 TC 19 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 2504 EP 2511 DI 10.1128/JVI.02505-10 PG 8 WC Virology SC Virology GA 735AT UT WOS:000288386500003 PM 21228235 ER PT J AU Fabozzi, G Nabel, CS Dolan, MA Sullivan, NJ AF Fabozzi, Giulia Nabel, Christopher S. Dolan, Michael A. Sullivan, Nancy J. TI Ebolavirus Proteins Suppress the Effects of Small Interfering RNA by Direct Interaction with the Mammalian RNA Interference Pathway SO JOURNAL OF VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; SECONDARY STRUCTURE PREDICTION; RIG-I; ANTIVIRAL IMMUNITY; 5'-TRIPHOSPHATE RNA; INHIBITORY DOMAIN; STRUCTURAL BASIS; BINDING PROTEIN; VIRUS-INFECTION; VP35 PROTEIN AB Cellular RNA interference (RNAi) provides a natural response against viral infection, but some viruses have evolved mechanisms to antagonize this form of antiviral immunity. To determine whether Ebolavirus (EBOV) counters RNAi by encoding suppressors of RNA silencing (SRSs), we screened all EBOV proteins using an RNAi assay initiated by exogenously delivered small interfering RNAs (siRNAs) against either an EBOV or a reporter gene. In addition to viral protein 35 (VP35), we found that VP30 and VP40 independently act as SRSs. Here, we present the molecular mechanisms of VP30 and VP35. VP30 interacts with Dicer independently of siRNA and with one Dicer partner, TRBP, only in the presence of siRNA. VP35 directly interacts with Dicer partners TRBP and PACT in an siRNA-independent fashion and in the absence of effects on interferon (IFN). Taken together, our findings elucidate a new mechanism of RNAi suppression that extends beyond the role of SRSs in double-stranded RNA (dsRNA) binding and IFN antagonism. The presence of three suppressors highlights the relevance of host RNAi-dependent antiviral immunity in EBOV infection and illustrates the importance of RNAi in shaping the evolution of RNA viruses. C1 [Fabozzi, Giulia; Nabel, Christopher S.; Sullivan, Nancy J.] NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Sullivan, NJ (reprint author), NIAID, Biodef Res Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40-2509, Bethesda, MD 20892 USA. EM njsull@mail.nih.gov FU Vaccine Research Center, NIAID, NIH FX This work was supported by the Intramural Research Program, Vaccine Research Center, NIAID, NIH. NR 65 TC 57 Z9 60 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 2512 EP 2523 DI 10.1128/JVI.01160-10 PG 12 WC Virology SC Virology GA 735AT UT WOS:000288386500004 PM 21228243 ER PT J AU Changela, A Wu, XL Yang, YP Zhang, BS Zhu, JA Nardone, GA O'Dell, S Pancera, M Gorny, MK Phogat, S Robinson, JE Stamatatos, L Zolla-Pazner, S Mascola, JR Kwong, PD AF Changela, Anita Wu, Xueling Yang, Yongping Zhang, Baoshan Zhu, Jiang Nardone, Glenn A. O'Dell, Sijy Pancera, Marie Gorny, Miroslaw K. Phogat, Sanjay Robinson, James E. Stamatatos, Leonidas Zolla-Pazner, Susan Mascola, John R. Kwong, Peter D. TI Crystal Structure of Human Antibody 2909 Reveals Conserved Features of Quaternary Structure-Specific Antibodies That Potently Neutralize HIV-1 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; TYROSINE SULFATION SITES; ENVELOPE GLYCOPROTEIN; GP120; SEQUENCE; EPITOPE; DESIGN; BROAD; IDENTIFICATION; SOFTWARE AB Monoclonal antibody 2909 belongs to a class of potently neutralizing antibodies that recognize quaternary epitopes on HIV-1. Some members of this class, such as 2909, are strain specific, while others, such as antibody PG16, are broadly neutralizing; all, however, recognize a region on the gp120 envelope glycoprotein that includes two loops (V2 and V3) and forms appropriately only in the oligomeric HIV-1 spike (gp120(3)/gp41(3)). Here we present the crystal structure of 2909 and report structure-function analysis with antibody chimeras composed of 2909 and other members of this antibody class. The 2909 structure was dominated by a heavy-chain third-complementarity-determining region (CDR H3) of 21 residues, which comprised 36% of the combining surface and formed a beta-hairpin club extending similar to 20 angstrom beyond the rest of the antibody. Sequence analysis and mass spectrometry identified sites of tyrosine sulfation at the middle and top of CDR H3; substitutions with phenylalanine either ablated (middle substitution) or substantially diminished (top substitution) neutralization. Chimeric antibodies composed of heavy and light chains, exchanged between 2909 and other members of the class, indicated a substantial lack of complementation. Comparison of 2909 to PG16 (which is tyrosine sulfated and the only other member of the class for which a structure has previously been reported) showed that both utilize protruding, anionic CDR H3s for recognition. Thus, despite some diversity, members of this class share structural and functional similarities, with conserved features of the CDR H3 subdomain likely reflecting prevalent solutions by the human immune system for recognition of a quaternary site of HIV-1 vulnerability. C1 [Changela, Anita; Wu, Xueling; Yang, Yongping; Zhang, Baoshan; Zhu, Jiang; O'Dell, Sijy; Pancera, Marie; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Nardone, Glenn A.] NIAID, Res Technol Branch, NIH, Rockville, MD 20852 USA. [Gorny, Miroslaw K.; Zolla-Pazner, Susan] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Phogat, Sanjay] Int AIDS Vaccine Initiat, AIDS Vaccine Design & Dev Lab, Brooklyn, NY 11226 USA. [Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA. [Stamatatos, Leonidas] Seattle BioMed, Seattle, WA 98109 USA. [Stamatatos, Leonidas] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA. [Zolla-Pazner, Susan] New York Vet Affairs Med Ctr, New York, NY 10010 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA. EM pdkwong@nih.gov OI Gorny, Miroslaw/0000-0002-2714-8780 FU NIH [AI36085, AI 27742]; Department of Veterans Affairs; U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38] FX Support for this work was provided by the International AIDS Vaccine Initiative (IAVI), by the Intramural Research Program of the NIH, by grants from the NIH (AI36085 and AI 27742), and by research funds from the Department of Veterans Affairs. Use of sector 22 (Southeast Region Collaborative Access team) at the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no W-31-109-Eng-38. NR 49 TC 29 Z9 29 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 2524 EP 2535 DI 10.1128/JVI.02335-10 PG 12 WC Virology SC Virology GA 735AT UT WOS:000288386500005 PM 21191009 ER PT J AU Kang, JG Pripuzova, N Majerciak, V Kruhlak, M Le, SY Zheng, ZM AF Kang, Jeong-Gu Pripuzova, Natalia Majerciak, Vladimir Kruhlak, Michael Le, Shu-Yun Zheng, Zhi-Ming TI Kaposi's Sarcoma-Associated Herpesvirus ORF57 Promotes Escape of Viral and Human Interleukin-6 from MicroRNA-Mediated Suppression SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; GENE-EXPRESSION; CASTLEMANS-DISEASE; RNA EXPORT; IN-VITRO; PROTEIN; VIRUS; CYTOKINE; CELLS; KSHV AB Kaposi's sarcoma-associated herpesvirus (KSHV) lytic infection increases the expression of viral and human interleukin-6 (vIL-6 and hIL-6, respectively), an important factor for cell growth and pathogenesis. Here, we report genome-wide analysis of viral RNA targets of KSHV ORF57 by a novel UV-cross-linking and immunoprecipitation (CLIP) assay. We identified 11 viral transcripts as putative ORF57 targets and demonstrate that vIL-6 mRNA is an authentic target of ORF57. Disrupting the ORF57 gene in the KSHV genome leads to inefficient expression of vIL-6. With transient transfection, the expression of vIL-6 could be enhanced greatly in the presence of ORF57 in a dose-dependent manner. We found that the open reading frame (ORF) region of vIL-6 RNA contains an MRE (MTA [ORF57]-responsive element) composed of two motifs, MRE-A and MRE-B, and binding of ORF57 to these two motifs stabilizes vIL-6 RNA and promotes vIL-6 translation. We demonstrate that vIL-6 MRE-B bears an miR-1293 binding site and that, mechanistically, ORF57 competes with miR-1293 for the same binding site to interact with vIL-6 RNA, thereby preventing vIL-6 RNA from association with the miR-1293-specified RNA-induced silencing complex (RISC). Consistent with this, ORF57 also interacts with an miR-608 binding site in the hIL-6 ORF and prevents miR-608 repression of hIL-6. Collectively, our results identify a novel function of ORF57 in being responsible for stabilization of viral and human IL-6 RNAs and the corresponding enhancement of RNA translation. In addition, our data provide the first evidence that a tumor virus may use a viral protein to interfere with microRNA (miRNA)-mediated repression of an miRNA target to induce cell proliferation and tumorigenesis during virus infection. C1 [Kang, Jeong-Gu; Pripuzova, Natalia; Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Le, Shu-Yun] NCI, Nanobiol Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Rm 6N106, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU NCI, Center for Cancer Research, National Institutes of Health FX This work was supported by the Intramural Research Program of the NCI, Center for Cancer Research, National Institutes of Health. NR 47 TC 42 Z9 43 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 2620 EP 2630 DI 10.1128/JVI.02144-10 PG 11 WC Virology SC Virology GA 735AT UT WOS:000288386500014 PM 21209110 ER PT J AU Feng, NG Sen, A Wolf, M Vo, P Hoshino, Y Greenberg, HB AF Feng, Ningguo Sen, Adrish Wolf, Marie Vo, Phuoc Hoshino, Yasutaka Greenberg, Harry B. TI Roles of VP4 and NSP1 in Determining the Distinctive Replication Capacities of Simian Rotavirus RRV and Bovine Rotavirus UK in the Mouse Biliary Tract SO JOURNAL OF VIROLOGY LA English DT Article ID HOST-RANGE RESTRICTION; OUTER CAPSID PROTEINS; MODEL; INTERFERON; GENE; MICE; VIRULENCE; ATRESIA; CHOLANGIOCYTES; EXPRESSION AB Rotavirus replication and virulence are strongly influenced by virus strain and host species. The rotavirus proteins VP3, VP4, VP7, NSP1, and NSP4 have all been implicated in strain and species restriction of replication; however, the mechanisms have not been fully determined. Simian (RRV) and bovine (UK) rota-viruses have distinctive replication capacities in mouse extraintestinal organs such as the biliary tract. Using reassortants between UK and RRV, we previously demonstrated that the differential replication of these viruses in mouse embryonic fibroblasts is determined by the respective NSP1 proteins, which differ substantially in their abilities to degrade interferon (IFN) regulatory factor 3 (IRF3) and suppress the type I IFN response. In this study, we used an in vivo model of rotavirus infection of mouse gallbladder with UK x RRV reassortants to study the genetic and mechanistic basis of systemic rotavirus replication. We found that the low-replication phenotype of UK in biliary tissues was conferred by UK VP4 and that the high-replication phenotype of RRV was conferred by RRV VP4 and NSP1. Viruses with RRV VP4 entered cultured mouse cholangiocytes more efficiently than did those with UK VP4. Reassortants with RRV VP4 and UK NSP1 genes induced high levels of expression of IRF3-dependent p54 in biliary tissues, and their replication was increased 3-fold in IFN-alpha/beta and -gamma receptor or STAT1 knockout (KO) mice compared to wild-type mice. Our data indicate that systemic rotavirus strain-specific replication in the murine biliary tract is determined by both viral entry mediated by VP4 and viral antagonism of the host innate immune response mediated by NSP1. C1 [Feng, Ningguo; Sen, Adrish; Wolf, Marie; Vo, Phuoc; Greenberg, Harry B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. [Feng, Ningguo; Sen, Adrish; Wolf, Marie; Vo, Phuoc; Greenberg, Harry B.] Stanford Univ, Stanford, CA 94305 USA. [Hoshino, Yasutaka] NIAID, NIH, Bethesda, MD 20892 USA. RP Greenberg, HB (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave,MC154C, Palo Alto, CA 94304 USA. EM hbgreen@stanford.edu FU VA Merit Award; NIH [R01 AI021362, P30DK56339] FX This study was supported in part by a VA Merit Award and NIH grants R01 AI021362 and P30DK56339. NR 28 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 2686 EP 2694 DI 10.1128/JVI.02408-10 PG 9 WC Virology SC Virology GA 735AT UT WOS:000288386500019 PM 21191030 ER PT J AU Harford, JB AF Harford, Joe B. TI Breast-cancer early detection in low-income and middle-income countries: do what you can versus one size fits all SO LANCET ONCOLOGY LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; SCREENING MAMMOGRAPHY; GUIDELINE IMPLEMENTATION; HEALTH-CARE; WOMEN; AGE; MORTALITY; OVERDIAGNOSIS; DIAGNOSIS; BENEFITS AB In general, rates of breast cancer are lower in low-income and middle-income countries (LMCs) than they are in more industrialised countries of North America and Europe. This lower incidence means that screening programmes aimed at early detection in asymptomatic women would have a lower yield-ie, substantially more women would need to be examined to find a true case of breast cancer. Because the average age of breast cancer is generally younger in LMCs, it has been suggested that breast-cancer screening programmes begin at an earlier age in these settings. However, the younger average age of breast cancer is mainly driven by the age distribution of the population, and fewer older women with breast cancer, rather than by higher age-specific incidence rates in younger women. Resources in LMCs might be better used to raise awareness and encourage more women with palpable breast lumps to seek and receive treatment in a timely manner. C1 NCI, Off Int Affairs, Bethesda, MD 20892 USA. RP Harford, JB (reprint author), NCI, Off Int Affairs, Bethesda, MD 20892 USA. EM harfordj@nih.gov NR 51 TC 47 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2011 VL 12 IS 3 BP 306 EP 312 DI 10.1016/S1470-2045(10)70273-4 PG 7 WC Oncology SC Oncology GA 736HY UT WOS:000288483500029 PM 21376292 ER PT J AU Brill, LM AF Brill, Laurence M. TI Responding to Data Analysis and Evaluation Challenges in Mass Spectrometry-Based Methods for High-Throughput Proteomics SO LC GC NORTH AMERICA LA English DT Article ID SHOTGUN PROTEOMICS; STATISTICAL-MODEL; PROTEINS AB Technology implemented in proteomics studies has recently been scrutinized for its effectiveness. As reported in a recent Nature Methods paper, questions have been raised about sample preparation, sample handling, data analysis, and data evaluation with the latter two being highlighted most. This article presents a new data management method that is specifically designed to handle the large amounts of data produced in proteomics studies. Experimental methods and data are presented from a recent study conducting proteomics profiling of Schizosaccharomyces pombe (S. pombe) (published in Methods) to demonstrate the effectiveness of the data management solution. The results demonstrate enhanced data search speeds as well as effective data analysis. C1 NCI, Canc Ctr Prote Facil, Sanford Burnham Med Res Inst, La Jolla, CA USA. RP Brill, LM (reprint author), NCI, Canc Ctr Prote Facil, Sanford Burnham Med Res Inst, La Jolla, CA USA. NR 8 TC 0 Z9 0 U1 1 U2 4 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1527-5949 J9 LC GC N AM JI LC GC N. AM. PD MAR PY 2011 SU S BP 36 EP 39 PG 4 WC Chemistry, Analytical SC Chemistry GA 736CK UT WOS:000288467400006 ER PT J AU Romm, H Wilkins, RC Coleman, CN Lillis-Hearne, PK Pellmar, TC Livingston, GK Awa, AA Jenkins, MS Yoshida, MA Oestreicher, U Prasanna, PGS AF Romm, Horst Wilkins, Ruth C. Coleman, C. Norman Lillis-Hearne, Patricia K. Pellmar, Terry C. Livingston, Gordon K. Awa, Akio A. Jenkins, Mark S. Yoshida, Mitsuaki A. Oestreicher, Ursula Prasanna, Pataje G. S. TI Biological Dosimetry by the Triage Dicentric Chromosome Assay: Potential Implications for Treatment of Acute Radiation Syndrome in Radiological Mass Casualties SO RADIATION RESEARCH LA English DT Article ID CRITICALITY ACCIDENT; BIODOSIMETRY; NETWORK; LABORATORIES; CYTOGENETICS; ABERRATIONS; LYMPHOCYTES; EVENTS AB Biological dosimetry is an essential tool for estimating radiation dose. The dicentric chromosome assay (DCA) is currently the tool of choice. Because the assay is labor-intensive and time-consuming, strategies are needed to increase throughput for use in radiation mass casualty incidents. One such strategy is to truncate metaphase spread analysis for triage dose estimates by scoring 50 or fewer metaphases, compared to a routine analysis of 500 to 1000 metaphases, and to increase throughput using a large group of scorers in a biodosimetry network. Previously, the National Institutes for Allergies and Infectious Diseases (NIAID) and the Armed Forces Radiobiology Research Institute (AFRRI) sponsored a double-blinded interlaboratory comparison among five established international cytogenetic biodosimetry laboratories to determine the variability in calibration curves and in dose measurements in unknown, irradiated samples. In the present study, we further analyzed the published data from this previous study to investigate how the number of metaphase spreads influences dose prediction accuracy and how this information could be of value in the triage and management of people at risk for the acute radiation syndrome (ARS). Although, as expected, accuracy decreased with lower numbers of metaphase spreads analyzed, predicted doses by the laboratories were in good agreement and were judged to be adequate to guide diagnosis and treatment of ARS. These results demonstrate that for rapid triage, a network of cytogenetic biodosimetry laboratories can accurately assess doses even with a lower number of scored metaphases. (C) 2011 by Radiation Research Society C1 [Prasanna, Pataje G. S.] NCI, Div Canc Treatment & Diag, Radiat Res Program, Bethesda, MD 20892 USA. [Romm, Horst; Oestreicher, Ursula] Bundesamt Strahlenschutz, D-38226 Salzgitter, Germany. [Wilkins, Ruth C.] Hlth Canada, Consumer & Clin Radiat Protect Bur, Ottawa, ON K1A 1C1, Canada. [Coleman, C. Norman; Prasanna, Pataje G. S.] Off Assistant Secretary Preparedness & Response, Dept Hlth & Human Serv, Washington, DC USA. [Lillis-Hearne, Patricia K.; Pellmar, Terry C.] Armed Forces Radiobiol Res Inst, Bethesda, MD USA. [Livingston, Gordon K.; Awa, Akio A.; Jenkins, Mark S.] Oak Ridge Associated Univ, REACITS, Oak Ridge, TN USA. [Yoshida, Mitsuaki A.] Natl Inst Radiol Sci, Ctr Radiat Res, Inage Ku, Chiba 260, Japan. RP Prasanna, PGS (reprint author), NCI, Div Canc Treatment & Diag, Radiat Res Program, 6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. EM Pat.Prasanna@nih.gov OI Romm, Horst/0000-0003-4921-685X FU NIAID, NIH; AFRRI, Uniformed Services University of the Health Sciences; Chemical, Biological, Radiological and Nuclear Research and Technology Initiative [0027RD]; Department of Energy (DOE) National Nuclear Security Administration; Nuclear Regulatory Commission; DOE Office of Environment, Safety and Health FX Financial support was provided by an interagency agreement between the NIAID, NIH and the AFRRI, Uniformed Services University of the Health Sciences. National Cancer Institute's Radiation Research Program supported manuscript preparation. Work at Health Canada was partially supported by the Chemical, Biological, Radiological and Nuclear Research and Technology Initiative, Project No. 0027RD. Work at the REAC/TS was partially supported by the Department of Energy (DOE) National Nuclear Security Administration, the Nuclear Regulatory Commission and DOE Office of Environment, Safety and Health. Special thanks to Dr. V. Nagy (AFRRI) for dosimetry support and Dr. M. Moroni, U. Subramanian, K. Krasnopolsky, P. R. Martin (AFRRI), C. Ferrarotto (Health Canada), S. Wenzel and D. Westfahl (BfS) and M. Akiyama (NIRS) for technical assistance. NR 29 TC 36 Z9 37 U1 0 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAR PY 2011 VL 175 IS 3 BP 397 EP 404 DI 10.1667/RR2321.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 734SM UT WOS:000288358100016 PM 21388284 ER PT J AU Iwamoto, S Lin, X Iwamoto, A Yufit, T Carson, P Fiore, D Kobrin, K Morgan, J Zak, F Hammerman, S Greer, D Falanga, V AF Iwamoto, S. Lin, X. Iwamoto, A. Yufit, T. Carson, P. Fiore, D. Kobrin, K. Morgan, J. Zak, F. Hammerman, S. Greer, D. Falanga, V. TI GCSF-INDUCED MOBILIZATION OF BONE MARROW STEM CELLS ACCELERATES HEALING OF EXPERIMENTAL MOUSE WOUNDS SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Iwamoto, S.; Lin, X.; Yufit, T.; Carson, P.; Fiore, D.; Kobrin, K.; Zak, F.; Hammerman, S.; Falanga, V.] Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Providence, RI USA. [Iwamoto, S.; Lin, X.; Iwamoto, A.; Yufit, T.; Carson, P.; Fiore, D.; Kobrin, K.; Morgan, J.; Zak, F.; Greer, D.; Falanga, V.] Roger Williams Med Ctr, NIH Ctr Biomed Res Excellence, Providence, RI USA. [Iwamoto, S.; Lin, X.; Falanga, V.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Falanga, V.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2011 VL 19 IS 2 BP A28 EP A28 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 728ML UT WOS:000287878100080 ER PT J AU Lin, X Fiore, D Lu, M Yufit, T Kwak, T Carson, P Falanga, V AF Lin, X. Fiore, D. Lu, M. Yufit, T. Kwak, T. Carson, P. Falanga, V. TI AN IN VITRO PRIMING STRATEGY ACTIVATES AN ESTABLISHED TISSUE ENGINEERING CONSTRUCT AND LEADS TO GREATER EFFICACY AND A DRAMATIC BURST IN LEVELS OF GENES ASSOCIATED WITH EPIDERMAL GROWTH AND MIGRATION SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Lin, X.; Fiore, D.; Lu, M.; Yufit, T.; Kwak, T.; Carson, P.; Falanga, V.] Roger Williams Med Ctr, Dept Dermatol & Skin Surg, Providence, RI USA. [Lin, X.; Fiore, D.; Lu, M.; Yufit, T.; Kwak, T.; Carson, P.; Falanga, V.] NIH, Ctr Biomed Res Excellence COBRE, Roger Williams Med Ctr, Providence, RI USA. [Lin, X.; Falanga, V.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Falanga, V.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 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 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2011 VL 19 IS 2 BP A34 EP A34 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 728ML UT WOS:000287878100104 ER PT J AU Komarow, HD Myles, IA Uzzaman, A Metcalfe, DD AF Komarow, Hirsh D. Myles, Ian A. Uzzaman, Ashraf Metcalfe, Dean D. TI Impulse oscillometry in the evaluation of diseases of the airways in children SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID FORCED OSCILLATION TECHNIQUE; TOTAL RESPIRATORY RESISTANCE; ASTHMATIC PRESCHOOL-CHILDREN; WHOLE-BODY PLETHYSMOGRAPHY; PULMONARY-FUNCTION; INTERRUPTER TECHNIQUE; REFERENCE VALUES; BRONCHIAL RESPONSIVENESS; EXPIRATORY MANEUVERS; CLINICAL-APPLICATION AB Objective: To provide an overview of impulse oscillometry and its application to the evaluation of children with diseases of the airways. Data Sources: Medline and PubMed search, limited to English language and human disease, with keywords forced oscillation, impulse oscillometry, and asthma. Study Selections: The opinions of the authors were used to select studies for inclusion in this review. Results: Impulse oscillometry is a noninvasive and rapid technique requiring only passive cooperation by the patient. Pressure oscillations are applied at the mouth to measure pulmonary resistance and reactance. It is employed by health care professionals to help diagnose pediatric pulmonary diseases such asthma and cystic fibrosis; assess therapeutic responses; and measure airway resistance during provocation testing. Conclusions: Impulse oscillometry provides a rapid, noninvasive measure of airway impedance. It may be easily employed in the diagnosis and management of diseases of the airways in children. Ann Allergy Asthma Immunol. 2011;106:191-199. C1 [Komarow, Hirsh D.; Myles, Ian A.; Uzzaman, Ashraf; Metcalfe, Dean D.] NIAID, LAD, NIH, Bethesda, MD 20892 USA. RP Komarow, HD (reprint author), NIAID, LAD, NIH, Bldg 10,Room 1C129A1,10 Ctr Dr, Bethesda, MD 20892 USA. EM komarowh@niaid.nih.gov FU NIAID FX This work was supported by the DIR Intramural Research Program of the NIAID. NR 50 TC 37 Z9 42 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 2011 VL 106 IS 3 BP 191 EP 199 DI 10.1016/j.anai.2010.11.011 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 733WN UT WOS:000288295300003 PM 21354020 ER PT J AU Lynch, FL Dickerson, JF Clarke, G Vitiello, B Porta, G Wagner, KD Emslie, G Asarnow, JR Keller, MB Birmaher, B Ryan, ND Kennard, B Mayes, T Debar, L McCracken, JT Strober, M Suddath, RL Spirito, A Onorato, M Zelazny, J Iyengar, S Brent, D AF Lynch, Frances L. Dickerson, John F. Clarke, Greg Vitiello, Benedetto Porta, Giovanna Wagner, Karen D. Emslie, Graham Asarnow, Joan Rosenbaum, Jr. Keller, Martin B. Birmaher, Boris Ryan, Neal D. Kennard, Betsy Mayes, Taryn DeBar, Lynn McCracken, James T. Strober, Michael Suddath, Robert L. Spirito, Anthony Onorato, Matthew Zelazny, Jamie Iyengar, Satish Brent, David TI Incremental Cost-effectiveness of Combined Therapy vs Medication Only for Youth With Selective Serotonin Reuptake Inhibitor-Resistant Depression Treatment of SSRI-Resistant Depression in Adolescents Trial Findings SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; ROUTINE SPECIALIST CARE; ADJUSTED LIFE-YEAR; MAJOR DEPRESSION; PREVENT DEPRESSION; HEALTH-CARE; TADS; OUTCOMES; MODERATORS AB Context: Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective. Objective: To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI. Design: Randomized controlled trial. Setting: Six US academic and community clinics. Patients: Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression. Intervention: Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy. Main Outcome Measures: Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs DFD-QALYs). Costs of intervention, nonprotocol services, and families were included. Results: Combined treatment achieved 8.3 additional DFDs (P =. 03), 0.020 more DFD-QALYs (P =. 03), and 11.0 more DIDs (P =. 04). Combined therapy cost $1633 more (P =. 01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER]= $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78 948 per DFD-QALY (ICER = $78 948; 95% CI, -$9261 to $677 448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100 000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions. Conclusions: For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups. C1 [Lynch, Frances L.; Dickerson, John F.; Clarke, Greg; DeBar, Lynn] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97212 USA. [Vitiello, Benedetto] NIMH, Child & Adolescent Treatment, Bethesda, MD 20892 USA. [Vitiello, Benedetto] NIMH, Prevent Intervent Res Branch, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Porta, Giovanna; Birmaher, Boris; Ryan, Neal D.; Onorato, Matthew; Brent, David] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Zelazny, Jamie] Univ Pittsburgh, Univ Pittsburgh Hosp, Shadyside Sch Nursing, Pittsburgh, PA 15261 USA. [Iyengar, Satish] Univ Pittsburgh, Dept Stat, Pittsburgh, PA USA. [Wagner, Karen D.] Univ Texas Med Branch, Dept Pediat, Galveston, TX USA. [Wagner, Karen D.] Univ Texas Med Branch, Div Child & Adolescent Psychiat, Dept Psychiat & Behav Sci, Galveston, TX USA. [Emslie, Graham; Kennard, Betsy; Mayes, Taryn] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX USA. [Emslie, Graham; Kennard, Betsy; Mayes, Taryn] Univ Texas SW Med Ctr Dallas, Grad Sch Biomed Sci, Dallas, TX USA. [Asarnow, Joan Rosenbaum, Jr.; McCracken, James T.; Strober, Michael; Suddath, Robert L.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Keller, Martin B.; Spirito, Anthony] Brown Univ, Dept Psychiat & Human Behav, Div Biol & Med, Providence, RI 02912 USA. RP Lynch, FL (reprint author), Kaiser Permanente NW, Ctr Hlth Res, 3800 N Interstate, Portland, OR 97212 USA. EM frances.lynch@kpchr.org FU Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb; Eli Lilly; Forest Laboratories GlaxoSmithKline; Johnson Johnson; Novartis; Organon; Pfizer; Wyeth-Ayerst; Biobehavioral Diagnostics Inc; Shire; Somerset; Philip Morris; Wyeth Pharmaceuticals; Abbott; Bristol-Meyers Squibb; CENEREX; Cephalon; Cypress Bioscience; Cyberonics; GlaxoSmithKline; Janssen; JDS; Medtronic; Sierra Neuropharmaceuticals; Solvay; Wyeth; Abcomm Inc; Solvay Pharmaceuticals Inc; McNeil; National Institute of Mental Health [MH61835, MH61856, MH61864, MH61869, MH61958, MH62014]; Advanced Center for Early-Onset Mood and Anxiety Disorders [MH66371] FX Dr Wagner reports receiving past research support from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories GlaxoSmithKline, Johnson & Johnson, Novartis, Organon, Pfizer, and Wyeth-Ayerst and is a consultant/advisory board member for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Novartis, Organon, Ortho-McNeil, Otsuka, Pfizer, Solvay, UCB Pharma, and Wyeth Ayerst. Dr Emslie reports receiving research support from Biobehavioral Diagnostics Inc, Eli Lilly, Forest Laboratories, Organon, Shire, and Somerset; consulting for Biobehavioral Diagnostics Inc, Eli Lilly, GlaxoSmithKline, Shire, and Wyeth-Ayerst; and is on the speaker's bureau for McNeil. Dr Asarnow reports consulting on CBT and CBT for depression supported by an unrestricted grant from Pfizer and has funding from Philip Morris; a family member has funding from Bristol-Myers Squibb and has consulted for Roche. Dr Keller reports receiving research support from Pfizer and Wyeth Pharmaceuticals; receiving consulting fees from Abbott, Bristol-Meyers Squibb, CENEREX, Cephalon, Cypress Bioscience, Cyberonics, Forest Laboratories, GlaxoSmithKline, Janssen, JDS, Medtronic, Organon, Novartis, Pfizer, Roche, Sierra Neuropharmaceuticals, Solvay, and Wyeth; and serving on advisory boards for Abbott Laboratories, Bristol-Myers Squibb, CENEREX, Cyberonics, Cypress Bioscience, Forest Laboratories, Janssen, Neuronetics, Novartis, Organon, and Pfizer. Dr Birmaher reports participating in forums sponsored by Abcomm Inc and Solvay Pharmaceuticals Inc; presenting on bipolar disorders in children at a meeting sponsored by Solvay; and receiving royalties from Random House Inc. Dr McCracken reports receiving research support from Bristol-Myers Squibb, Eli Lilly, McNeil, and Shire and consulting fees from Eli Lilly, Janssen, Johnson & Johnson, McNeil, Novartis, Pfizer, Shire, and Wyeth.; This work was supported by grants MH61835 (Pittsburgh site), MH61856 (Galveston site), MH61864 (UCLA site), MH61869 (Portland site), MH61958 (Dallas site), and MH62014 (Brown University site) from the National Institute of Mental Health and by grant MH66371 from the Advanced Center for Early-Onset Mood and Anxiety Disorders (Dr Brent). NR 51 TC 22 Z9 22 U1 1 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2011 VL 68 IS 3 BP 253 EP 262 DI 10.1001/archgenpsychiatry.2011.9 PG 10 WC Psychiatry SC Psychiatry GA 731DQ UT WOS:000288086900005 PM 21383263 ER PT J AU Compton, CC Sobin, LH AF Compton, Carolyn C. Sobin, Leslie H. TI Residual Tumor (R) Classification in Colorectal Cancer: Reduced, Expanded, or Not Uniform? Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 [Compton, Carolyn C.] Amer Joint Comm Canc, Chicago, IL 60611 USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Sobin, Leslie H.] Int Union Canc, TNM Prognost Factors Project, Geneva, Switzerland. RP Compton, CC (reprint author), Amer Joint Comm Canc, Chicago, IL 60611 USA. NR 5 TC 0 Z9 0 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 MAR PY 2011 VL 135 IS 3 BP 289 EP 289 PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 732AQ UT WOS:000288153600002 ER PT J AU Kraut, EH Rhoades, C Zhang, YL Cheng, H Aimiumu, J Chen, P Lang, J Young, DC Agrawal, A Dancey, J Chan, KK Grever, MR AF Kraut, Eric H. Rhoades, Christopher Zhang, Yilong Cheng, Hao Aimiumu, Josephine Chen, Ping Lang, James Young, Donn C. Agrawal, Amit Dancey, Janet Chan, Kenneth K. Grever, Michael R. TI Phase I and pharmacokinetic study of erlotinib (OSI-774) in combination with docetaxel in squamous cell carcinoma of the head and neck (SSCHN) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Erlotinib; Squamous cell carcinoma of the head and neck; OSI-774; Phase I ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; SOLID TUMORS; ACTIVE-DRUG; CANCER; MALIGNANCIES; RECURRENT; EFFICACY; EVALUATE; THERAPY AB This phase I study determined the maximal-tolerated dose, dose-limiting toxicities, pharmacokinetics, and recommended dose of erlotinib with docetaxel. Twenty-eight patients with head and neck cancer were enrolled. Patients were orally given erlotinib (50 mg) daily plus 35 mg/m(2) of docetaxel intravenously weekly x 3 every 4 weeks. Dose escalation of erlotinib was in 50-mg increments until toxicity. Pharmacokinetics were studied with LC-MS/MS, standard, and population pharmacokinetic methods. Ninety-five courses were successfully given (median 3, range 1-6). The most frequent side effects were diarrhea, fatigue, skin rash, anemia, and hypoalbuminemia. Dose de-escalation for both erlotinib and docetaxel was due to skin rash, neutropenia and/or severe infection with docetaxel to 25 mg/m(2) and erlotinib to starting dose of 50 mg and re-escalation of docetaxel to 35 mg/m(2). Responses were observed in 4/26 evaluable patients (100 mg erlotinib). In 24 patients, the mean Cmax and AUC erlotinib values increased with dose and following cumulative dosing (days 7 and 8 vs. day1, p < 0.05). The CL/F (similar to 7 L/h), V/F (similar to 140 L), and t1/2 (similar to 20 h) for erlotinib were similar to the reported. The mean AUC ratio of metabolite OSI-420 to erlotinib following repetitive dosing at 100 mg (+ or - docetaxel) showed a similar to 50% increase (p < 0.02), possibly suggesting self-enzyme induction. Population pharmacokinetic studies showed no significant covariate affecting erlotinib pharmacokinetics. The combination of erlotinib and docetaxel was associated with significant toxicity, which limited the amount of administered erlotinib. Dosing for phase II trials was docetaxel 35 mg/m(2) and erlotinib 50 mg. The reason for excessive toxicity is not clear, but not due to change in pharmacokinetics. C1 [Kraut, Eric H.; Rhoades, Christopher; Lang, James; Young, Donn C.; Agrawal, Amit; Chan, Kenneth K.; Grever, Michael R.] Arthur G James Canc Hosp, Columbus, OH USA. [Kraut, Eric H.; Rhoades, Christopher; Lang, James; Young, Donn C.; Agrawal, Amit; Chan, Kenneth K.; Grever, Michael R.] Richard J Solove Res Inst, Coll Med, Columbus, OH USA. [Kraut, Eric H.; Rhoades, Christopher; Lang, James; Young, Donn C.; Agrawal, Amit; Chan, Kenneth K.; Grever, Michael R.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Zhang, Yilong; Cheng, Hao; Aimiumu, Josephine; Chen, Ping] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Dancey, Janet] NCI, Canc Therapy & Evaluat Program, Bethesda, MD 20892 USA. RP Kraut, EH (reprint author), Arthur G James Canc Hosp, Columbus, OH USA. EM Eric.Kraut@osumc.edu FU National Cancer Institute [U01-CA76576] FX The project described was supported by Grant Number U01-CA76576 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer institute or the National Institutes of Health. NR 24 TC 10 Z9 10 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2011 VL 67 IS 3 BP 579 EP 586 DI 10.1007/s00280-010-1332-y PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 724LU UT WOS:000287578500010 PM 20490801 ER PT J AU Colloca, L Miller, FG AF Colloca, Luana Miller, Franklin G. TI Role of expectations in health SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE clinical outcomes; conditioning; nocebo effect; placebo effect; psychiatry; verbal suggestion ID BALANCED-PLACEBO DESIGN; DOUBLE-BLIND; CONTROLLED-TRIALS; MAJOR DEPRESSION; NOCEBO RESPONSES; ANTIDEPRESSANT; BRAIN; METAANALYSIS; EXPECTANCY; ANALGESIA AB Purpose of review Considerable progress has been made in the neurobiological understanding of expectations in physiological and pathological processes. This article is aimed at presenting an overview of the role of expectations in producing health-related effects. We selected recent laboratory and clinical studies in the field of the placebo effect, with a particular focus on psychiatric disorders. Recent findings Recent scientific research indicates that expectations have the potential for relieving many symptoms. This research relies mostly on the study of placebo and nocebo phenomena which influence physiological and pathological functions. The findings from placebo and nocebo research have important implications for the design and interpretation of clinical trials and for clinical practice. Summary The studies of expectations in the field of psychiatry and in other fields of medicine suggest that placebo effects are likely to be an important aspect of any treatment. The application of research on health-related expectations has the potential for promoting wellness, improving health, and benefiting patient care. C1 [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA. [Colloca, Luana; Miller, Franklin G.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Colloca, L (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM luana.colloca@nih.gov OI Colloca, Luana/0000-0002-6503-4709 FU National Center for Complementary and Alternative Medicine (NCCAM); NIH; International Association for Study of Pain (IASP); European Federation of IASP Chapter and Grunenthal Grant (EFIC-EGG) FX This research was supported by the Intramural Research Program of the National Center for Complementary and Alternative Medicine (NCCAM), NIH, International Association for Study of Pain (IASP), and European Federation of IASP Chapter and Grunenthal Grant (EFIC-EGG). NR 56 TC 33 Z9 33 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 2011 VL 24 IS 2 BP 149 EP 155 DI 10.1097/YCO.0b013e328343803b PG 7 WC Psychiatry SC Psychiatry GA 715IH UT WOS:000286876300011 PM 21248640 ER PT J AU Yao, HHC Archambeault, D Tomaszewski, J AF Yao, Humphrey H-C Archambeault, Denise Tomaszewski, Jessica TI TESTICULAR DYSGENESIS: FETAL ORIGINS OF ADULT REPRODUCTIVE DEFICIENCY SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of Genes and Harmones - State-of-the-Art Reproductive and Sexual Development CY APR 02-05, 2011 CL Hyatt Regency Montreal, Montreal, CANADA HO Hyatt Regency Montreal C1 [Yao, Humphrey H-C; Tomaszewski, Jessica] Univ Illinois, Urbana, IL 61801 USA. [Yao, Humphrey H-C] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2011 SU S BP 30 EP 31 PG 2 WC Andrology SC Endocrinology & Metabolism GA 724AZ UT WOS:000287549800024 ER PT J AU Chakravorty, S Aladegbami, B Thoms, K Lee, JS Lee, EG Rajan, V Cho, EJ Kim, H Kwak, H Kurepina, N Cho, SN Kreiswirth, B Via, LE Barry, CE Alland, D AF Chakravorty, Soumitesh Aladegbami, Bola Thoms, Kimberley Lee, Jong Seok Lee, Eun Gae Rajan, Vignesh Cho, Eun-Jin Kim, Hyunchul Kwak, Hyunkyung Kurepina, Natalia Cho, Sang-Nae Kreiswirth, Barry Via, Laura E. Barry, Clifton E., III Alland, David TI Rapid Detection of Fluoroquinolone-Resistant and Heteroresistant Mycobacterium tuberculosis by Use of Sloppy Molecular Beacons and Dual Melting-Temperature Codes in a Real-Time PCR Assay SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIFAMPIN RESISTANCE; GYRA MUTATIONS; DNA GYRASE; IDENTIFICATION; STRAINS; GENES; SEQUENCE AB Fluoroquinolones (FQ) are important second-line drugs to treat tuberculosis; however, FQ resistance is an emerging problem. Resistance has been mainly attributed to mutations in a 21-bp region of the Mycobacterium tuberculosis gyrA gene, often called the quinolone resistance-determining region (QRDR). We have developed a simple, rapid, and specific assay to detect FQ resistance-determining QRDR mutations. The assay amplifies the M. tuberculosis gyrA QRDR in an asymmetrical PCR followed by probing with two sloppy molecular beacons (SMBs) spanning the entire QRDR. Mutations are detected by melting temperature (T(m)) shifts that occur when the SMBs bind to mismatched sequences. By testing DNA targets corresponding to all known QRDR mutations, we found that one or both of the SMBs produced a T(m) shift of at least 3.6 degrees C for each mutation, making mutation detection very robust. The assay was also able to identify mixtures of wild-type and mutant DNA, with QRDR mutants identified in samples containing as little as 5 to 10% mutant DNA. The assay was blindly validated for its ability to identify the QRDR mutations on DNA extracted from clinical M. tuberculosis strains. Fifty QRDR wild-type samples, 34 QRDR mutant samples, and 8 heteroresistant samples containing mixtures of wild-type and mutant DNA were analyzed. The results showed 100% concordance to conventional DNA sequencing, including a complete identification of all of the mixtures. This SMB T(m) shift assay will be a valuable molecular tool to rapidly detect FQ resistance and to detect the emergence of FQ heteroresistance in clinical samples from tuberculosis patients. C1 [Chakravorty, Soumitesh; Aladegbami, Bola; Thoms, Kimberley; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Div Infect Dis, Dept Med, Newark, NJ 07103 USA. [Chakravorty, Soumitesh; Aladegbami, Bola; Thoms, Kimberley; Alland, David] Univ Med & Dent New Jersey, New Jersey Med Sch, Ruy V Lourenco Ctr Study Emerging & Reemerging Pa, Newark, NJ 07103 USA. [Lee, Jong Seok; Cho, Eun-Jin; Kim, Hyunchul; Kwak, Hyunkyung; Cho, Sang-Nae] Int TB Res Ctr, Dept Microbiol, Chang Won, Gyeongsang, South Korea. [Lee, Eun Gae; Cho, Sang-Nae] Yonsei Univ, Sch Med, Dept Microbiol, Seoul 120749, South Korea. [Lee, Eun Gae; Rajan, Vignesh; Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. [Kurepina, Natalia; Kreiswirth, Barry] Univ Med & Dent New Jersey, New Jersey Med Sch, Publ Hlth Res Inst, Newark, NJ 07103 USA. RP Alland, D (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Div Infect Dis, Dept Med, 185 S Orange Ave,MSB A920C, Newark, NJ 07103 USA. EM allandda@umdnj.edu RI Barry, III, Clifton/H-3839-2012; OI Via, Laura/0000-0001-6074-9521 FU National Institutes of Health [AI082174, AI080653]; Northeast Bio-Defense Career training grant [3185-07]; NIAID, NIH; South Korean Ministry of Health, Welfare and Family Affairs FX This work was supported by National Institutes of Health grants AI082174 and AI080653 (to D. A., K. T., and S. C.); Northeast Bio-Defense Career training grant 3185-07 (to B. A.); funding from the Intramural Research Program of the NIAID, NIH (to C. E. B.); and the South Korean Ministry of Health, Welfare and Family Affairs (to S.-N.C. and C. E. B.). NR 31 TC 32 Z9 35 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2011 VL 49 IS 3 BP 932 EP 940 DI 10.1128/JCM.02271-10 PG 9 WC Microbiology SC Microbiology GA 729RA UT WOS:000287967100026 PM 21191047 ER PT J AU Grogan, RH Pacak, K Pasche, L Huynh, TT Greco, RS AF Grogan, Raymon H. Pacak, Karel Pasche, Lezlee Huynh, Thanh T. Greco, Ralph S. TI Bilateral Adrenal Medullary Hyperplasia Associated With an SDHB Mutation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; RET PROTOONCOGENE; PHEOCHROMOCYTOMA; PARAGANGLIOMA; CLONALITY; CARCINOMA; LINKAGE; TYPE-2A; BENIGN; TUMOR C1 [Grogan, Raymon H.; Pasche, Lezlee; Greco, Ralph S.] Stanford Univ, Stanford, CA 94305 USA. [Pacak, Karel; Huynh, Thanh T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Grogan, RH (reprint author), Stanford Univ, Stanford, CA 94305 USA. NR 23 TC 9 Z9 9 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 MAR PY 2011 VL 29 IS 8 BP E200 EP E202 DI 10.1200/JCO.2010.32.2156 PG 3 WC Oncology SC Oncology GA 732CN UT WOS:000288161000006 PM 21172883 ER PT J AU Pinn, VW Kravitz, JY AF Pinn, Vivian W. Kravitz, Joslyn Yudenfreund TI Expanding the Evidence Base for Women's Health Across the Lifespan SO JOURNAL OF DENTAL EDUCATION LA English DT Editorial Material ID ESTROGEN PLUS PROGESTIN; RANDOMIZED-CONTROLLED-TRIAL; BREAST-CANCER INCIDENCE; POSTMENOPAUSAL WOMEN; TEMPOROMANDIBULAR-JOINT; DISORDER; RISK; PAIN C1 [Pinn, Vivian W.; Kravitz, Joslyn Yudenfreund] US Natl Inst Hlth, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA. EM ORWH-Research@od.nih.gov NR 44 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD MAR PY 2011 VL 75 IS 3 SU S BP S11 EP S19 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 732NK UT WOS:000288192000003 PM 21368241 ER PT J AU Whitehead, T Metayer, C Gunier, RB Ward, MH Nishioka, MG Buffler, P Rappaport, SM AF Whitehead, Todd Metayer, Catherine Gunier, Robert B. Ward, Mary H. Nishioka, Marcia G. Buffler, Patricia Rappaport, Stephen M. TI Determinants of polycyclic aromatic hydrocarbon levels in house dust SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE cancer; child exposure/health; empirical/statistical models; environmental monitoring; polycyclic aromatic hydrocarbons ID CANCER-RISK; RESPIRATORY SYMPTOMS; HISTORICAL EXPOSURE; PRENATAL EXPOSURE; INDOOR AIR; POLLUTANTS; CHILDREN; SMOKING; PESTICIDES; BIOMARKERS AB Estimation of human exposures to polycyclic aromatic hydrocarbons (PAHs) is often desired for the epidemiological studies of cancer. One way to obtain information about indoor levels of PAHs is to measure these chemicals in house dust. In this study, we evaluated the predictive value of self-reported and geographic data for estimating measured levels of nine PAHs in house dust from 583 households in the Northern California Childhood Leukemia Study (NCCLS). Using multivariable linear regression models, we evaluated the effects on house-dust PAH concentrations from the following covariates: residential heating sources, smoking habits, house characteristics, and outdoor emission sources. House dust was collected from 2001 to 2007, using both high-volume surface samplers and household vacuum cleaners, and was analyzed for nine PAHs using gas chromatography-mass spectrometry. All nine PAHs were detected in more than 93% of dust samples, with median concentrations ranging from 14 to 94 ng/g dust. Statistically significant effects on PAH concentrations in house dust were found for gas heating, outdoor PAH concentrations, and residence age. Yet, the optimal regression model only explained 15% of the variation in PAH levels in house dust. As self-reported data and outdoor PAH sources were only marginally predictive of observed PAH levels, we recommend that PAH concentrations be measured directly in dust samples for use in epidemiological studies. Journal of Exposure Science and Environmental Epidemiology (2011) 21, 123-132; doi:10.1038/jes.2009.68; published online 30 December 2009 C1 [Whitehead, Todd; Metayer, Catherine; Buffler, Patricia; Rappaport, Stephen M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Gunier, Robert B.] No Calif Canc Ctr, Berkeley, CA USA. [Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH 43201 USA. RP Whitehead, T (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Hall,MC 7360, Berkeley, CA 94720 USA. EM toddpwhitehead@berkeley.edu OI Gunier, Robert/0000-0001-5485-9919 FU National Institute of Environmental Health Sciences [R01ES009137, P42ES0470518]; National Cancer Institute, National Institute of Health [7590-S-04, 7590-S-01]; National Cancer Institute [N02-CP-11015]; Berkeley Fellowship for Graduate Study FX This work was supported by the National Institute of Environmental Health Sciences (Grant numbers R01ES009137 and P42ES0470518); the Intramural Research Program of the National Cancer Institute, National Institute of Health (subcontracts 7590-S-04 and 7590-S-01); the National Cancer Institute (contract N02-CP-11015) and the Berkeley Fellowship for Graduate Study. We thank the families for their participation. We also thank the clinical investigators at the following collaborating hospitals for help in recruiting patients: University of California Davis Medical Center (Dr. Jonathan Ducore), University of California San Francisco (Dr. Mignon Loh and Dr. Katherine Matthay), Children's Hospital of Central California (Dr. Vonda Crouse), Lucile Packard Children's Hospital (Dr. Gary Dahl), Children's Hospital Oakland (Dr. James Feusner), Kaiser Permanente Roseville (Dr. Kent Jolly and Dr. Vincent Kiley), Kaiser Permanente Santa Clara (Dr. Alan Wong and Dr. Carolyn Russo), Kaiser Permanente San Francisco (Dr. Kenneth Leung) and Kaiser Permanente Oakland (Dr. Daniel Kronish and Dr. Stacy Month). Finally, we acknowledge the entire Northern California Childhood Leukemia Study staff and the UCB Survey Research Center for their effort and dedication. NR 44 TC 19 Z9 19 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD MAR-APR PY 2011 VL 21 IS 2 BP 123 EP 132 DI 10.1038/jes.2009.68 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 730SN UT WOS:000288054700004 PM 20040932 ER PT J AU Ekhterae, D Hinmon, R Matsuzaki, K Noma, M Zhu, WZ Xiao, RP Gorman, RC Gorman, JH AF Ekhterae, Daryoush Hinmon, Robin Matsuzaki, Kanji Noma, Mio Zhu, Weizhong Xiao, Rui-Ping Gorman, Robert C. Gorman, Joseph H., III TI Infarction Induced Myocardial Apoptosis and ARC Activation SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE cardiomyopathy; apoptosis; heart failure; remodeling; myocardial infarction ID CASPASE RECRUITMENT DOMAIN; FAILING HUMAN HEART; CELL-DEATH; CARDIOMYOPATHY; INHIBITION; REPRESSOR; FAILURE; PROTECTS; GEOMETRY; STRETCH AB Background. Apoptosis is thought to play a role in infarction induced ventricular remodeling. Apoptosis repressor with caspase recruitment domain (ARC) has been shown to limit cardiomyocytes apoptosis; however, its role in the pathogenesis of heart failure is not established. This study examines the regional and temporal relationships of apoptosis, ARC, and remodeling. Methods. Myocardium was harvested from the infarct borderzone and remote regions of the left ventricle (LV) at 2 (n = 8), 8 (n = 6), and 32 (n = 5) wk after MI. Activated ARC was compared with myocardial apoptosis in each region at each time. Both were then compared with the progression of remodeling. Results. LV systolic volume increased by a factor 1.56 +/- 0.06 and 2.09 +/- 0.07 at 2 and 8 wk, respectively then stabilized by 32 wk (2.08 +/- 0.18). Activated ARC was elevated at 2 wk, diminished at 8 wk, and increased again at 32 wk in both regions. Apoptosis was elevated at 2 wk, and further increased at 8 wk. By 32 wk, apoptosis had diminished significantly. Conclusions. In a large animal infarction model, remodeling varied directly with the degree of apoptosis and inversely with ARC activation, suggesting that ARC acts as a natural regulatory phenomenon that limits apoptosis induced ventricular remodeling. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ekhterae, Daryoush; Hinmon, Robin; Matsuzaki, Kanji; Noma, Mio; Gorman, Robert C.; Gorman, Joseph H., III] Univ Penn, Sch Med, Gorman Cardiovasc Res Grp, Philadelphia, PA 19104 USA. [Zhu, Weizhong; Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, NIH, Bethesda, MD 20892 USA. RP Ekhterae, D (reprint author), Univ Penn, Sch Med, 500 S Ridgeway Ave, Glenolden, PA 19036 USA. EM dekhterae@gmail.com; gormanj@uphs.upenn.edu FU National Institutes of Health (Bethesda, MD) [HL63954, HL76560, HL71137]; W. W. Smith Charitable Trust (West Conshohocken, PA); Mary L. Smith Charitable Trust (West Conshohocken, PA); NIH, National Institute on Aging FX The authors acknowledge support for this research by the National Institutes of Health (Bethesda, MD) grants HL63954, HL76560, HL71137, and grants from the W. W. Smith Charitable Trust (West Conshohocken, PA) and the Mary L. Smith Charitable Trust (West Conshohocken, PA). This research was also supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 26 TC 8 Z9 9 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAR PY 2011 VL 166 IS 1 BP 59 EP 67 DI 10.1016/j.jss.2009.05.002 PG 9 WC Surgery SC Surgery GA 732EI UT WOS:000288167300020 PM 19815236 ER PT J AU Merikangas, KR AF Merikangas, Kathleen Ries TI What Is a Case? New Lessons From the Great Smoky Mountains Study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DISORDERS C1 NIMH, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM Kathleen.merikangas@nih.gov NR 10 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2011 VL 50 IS 3 BP 213 EP 215 DI 10.1016/j.jaac.2011.01.003 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 727FR UT WOS:000287783700003 PM 21334561 ER PT J AU Toner, CD Davis, CD Milner, JA AF Toner, Cheryl D. Davis, Cindy D. Milner, John A. TI UVB-Vitamin D-Cancer Hypothesis Response SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Letter ID MORTALITY C1 [Toner, Cheryl D.; Davis, Cindy D.; Milner, John A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. [Toner, Cheryl D.] CDT Consulting LLC, Fairfax, VA USA. RP Toner, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2011 VL 111 IS 3 BP 366 EP 366 DI 10.1016/j.jada.2011.01.020 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 730RC UT WOS:000288050800007 ER PT J AU Erinosho, TO Thompson, OM Moser, RP Yaroch, AL AF Erinosho, Temitope O. Thompson, Olivia M. Moser, Richard P. Yaroch, Amy L. TI Fruit and Vegetable Intake of US Adults: Comparing Intake by Mode of Survey Administration SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID TELEPHONE INTERVIEWS; HEALTH; RISK; NONRESPONSE; DISEASE; MAIL; WEB AB Modes for collecting dietary data vary across studies and include in-person/interviewer-administered surveys, mail, and telephone surveys. Few studies use mixed modes to assess dietary intakes. Using data from the 2007 Health Information National Trends Survey, we compared fruit and vegetable intake of adults measured through dual modes (mail and random-digit dial [RDD] telephone), and discussed potential factors that could account for mode differences. The Health Information National Trends Survey data were collected through mailed (n=3,582), and RDD (n=4,092) surveys from December 2007 to May 2008. Data were weighted and analyzed in SUDAAN. Unadjusted mean fruit and vegetable intake was 0.48 servings higher (P < 0.001) among mail (mean 5.40) vs RDD (mean 4.09) participants. In a multivariate model that controlled for other predictors, the odds of consuming >= 5 servings of fruit and vegetables per day was 83% higher among mail respondents compared to RDD (odds ratio 1.83, 95% confidence interval 1.62 to 2.07). Other predictors of fruit and vegetable intake were sex, education, participation in physical activity, self-rated health, and knowledge of the fruit and vegetable recommendation. Methodologic issues may account for modal differences in fruit and vegetable intake. Different measures (cups, servings) were used to assess fruit and vegetable intake in both modes, details about portion sizes were provided on the mail mode vs RDD, and closed-ended responses were provided on the mail vs open-ended responses for RDD. We cannot recommend one mode over the other nor attribute mode differences to real differences in reported fruit and vegetable intake between participants from both modes. Future research that uses dual modes needs to use identical methods of dietary assessment to minimize these potential sources of error. Further research is needed to validate the use of dual modes to assess dietary intake and inform research practice. J Am Diet Assoc. 2011;111:408-413. C1 [Erinosho, Temitope O.] Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC 27599 USA. [Erinosho, Temitope O.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA. [Erinosho, Temitope O.] NCI, Hlth Promot Res Branch, Rockville, MD USA. [Thompson, Olivia M.] Univ Nebraska Med Ctr, Dept Hlth Promot & Social & Behav Hlth, Coll Publ Hlth, Omaha, NE USA. [Moser, Richard P.] NCI, Behav Res Program, Rockville, MD USA. [Yaroch, Amy L.] Ctr Human Nutr, Omaha, NE USA. RP Erinosho, TO (reprint author), Univ N Carolina, Ctr Hlth Promot & Dis Prevent, 1700 Martin Luther King Jr Blvd,2nd Fl,CB 7426, Chapel Hill, NC 27599 USA. EM tope_erinosho@unc.edu FU Cancer Research Training Award (CRTA) FX T. O. Erinosho is a postdoctoral research associate, Department of Nutrition and Center for Health Promotion and Disease Prevention, University of North Carolina at Chapel Hill; at the time of the study, she was a Cancer Research Training Award (CRTA) fellow, Health Promotion Research Branch, National Cancer Institute, Rockville, MD. O. M. Thompson is an assistant professor, Department of Health Promotion and Social and Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha. R. P. Moser is a research psychologist, Behavioral Research Program, National Cancer Institute, Rockville, MD. A. L. Yaroch is executive director, Center for Human Nutrition, Omaha, NE. NR 23 TC 8 Z9 8 U1 0 U2 3 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2011 VL 111 IS 3 BP 408 EP 413 DI 10.1016/j.jada.2010.11.013 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 730RC UT WOS:000288050800013 PM 21338740 ER PT J AU Han, PKJ Klein, WMP Lehman, T Killam, B Massett, H Freedman, AN AF Han, Paul K. J. Klein, William M. P. Lehman, Tom Killam, Bill Massett, Holly Freedman, Andrew N. TI Communication of Uncertainty Regarding Individualized Cancer Risk Estimates: Effects and Influential Factors SO MEDICAL DECISION MAKING LA English DT Article DE numeracy; shared decision making; risk communication or risk perception; provider decision making; patient decision making; decision aids; physician-patient communication ID BREAST-CANCER; HEALTH-RISK; GRAPHICAL DISPLAYS; DECISION-MAKING; INFORMATION; AMBIGUITY; RESPONSES; WOMEN; AVOIDANCE; FORMATS AB Objective. To examine the effects of communicating uncertainty regarding individualized colorectal cancer risk estimates and to identify factors that influence these effects. Methods. Two Web-based experiments were conducted, in which adults aged 40 years and older were provided with hypothetical individualized colorectal cancer risk estimates differing in the extent and representation of expressed uncertainty. The uncertainty consisted of imprecision (otherwise known as "ambiguity") of the risk estimates and was communicated using different representations of confidence intervals. Experiment 1 (n = 240) tested the effects of ambiguity (confidence interval v. point estimate) and representational format (textual v. visual) on cancer risk perceptions and worry. Potential effect modifiers, including personality type (optimism), numeracy, and the information's perceived credibility, were examined, along with the influence of communicating uncertainty on responses to comparative risk information. Experiment 2 (n = 135) tested enhanced representations of ambiguity that incorporated supplemental textual and visual depictions. Results. Communicating uncertainty led to heightened cancer-related worry in participants, exemplifying the phenomenon of "ambiguity aversion." This effect was moderated by representational format and dispositional optimism; textual (v. visual) format and low (v. high) optimism were associated with greater ambiguity aversion. However, when enhanced representations were used to communicate uncertainty, textual and visual formats showed similar effects. Both the communication of uncertainty and use of the visual format diminished the influence of comparative risk information on risk perceptions. Conclusions. The communication of uncertainty regarding cancer risk estimates has complex effects, which include heightening cancer-related worry-consistent with ambiguity aversion- and diminishing the influence of comparative risk information on risk perceptions. These responses are influenced by representational format and personality type, and the influence of format appears to be modifiable and content dependent. C1 [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04101 USA. [Klein, William M. P.; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lehman, Tom] Acad Educ Dev, Ctr Social Mkt & Behav Change, Washington, DC USA. [Massett, Holly] NCI, Off Market Res & Evaluat, Bethesda, MD 20892 USA. [Killam, Bill] User Centered Design, Ashburn, VA USA. RP Han, PKJ (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 39 Forest Ave, Portland, ME 04101 USA. EM hanp@mmc.org OI Han, Paul/0000-0003-0165-1940 FU National Cancer Institute FX Received 15 October 2009 from Center for Outcomes Research and Evaluation, Maine Medical Center, Portland, Maine (PKJH); Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland (WMPK, ANF); Center for Social Marketing and Behavior Change, Academy for Educational Development, Washington, DC (TL); User-Centered Design, Ashburn, Virginia (BK); and Office of Market Research and Evaluation, National Cancer Institute, Bethesda, Maryland (HM). Financial support for this study was provided by intramural research funds from the National Cancer Institute. The authors thank Barbara Barry and Erin Nomiyama for their assistance in programming and developing the visual representations tested in this study. Revision accepted for publication 3 April 2010. NR 44 TC 30 Z9 30 U1 1 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR-APR PY 2011 VL 31 IS 2 BP 354 EP 366 DI 10.1177/0272989X10371830 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 732QT UT WOS:000288204500017 PM 20671211 ER PT J AU Tryndyak, VP Han, T Muskhelishvili, L Fuscoe, JC Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Han, Tao Muskhelishvili, Levan Fuscoe, James C. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Coupling global methylation and gene expression profiles reveal key pathophysiological events in liver injury induced by a methyl-deficient diet SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Gene expression; Gene methylation; Liver injury; Methyl-deficient diet; Mice ID DNA METHYLATION; S-ADENOSYLHOMOCYSTEINE; CHOLINE DEFICIENCY; HUMAN-DISEASE; GC-RICH; HYPOMETHYLATION; CARCINOGENESIS; HOMOCYSTEINE; MICE; ADENOSYLMETHIONINE AB Scope: A methyl-deficient diet induces liver injury similar to human nonalcoholic steatohepatitis, one of the main risk factors for the development of hepatocellular carcinoma. Previous studies have demonstrated that this diet perturbs DNA methylation by causing a profound loss of global cytosine methylation, predominantly at heavily methylated repetitive sequences. However, whether methyl deficiency affects the methylation status of gene promoters has not been explored. Methods and results: Mouse gene expression and CpG island microarrays were used to characterize the gene expression and CpG island methylation profiles in the livers of C57BL/6J mice fed a methyl-deficient diet. We detected 164 genes that were differentially expressed and exhibited an inverse relationship between the gene expression and the extent of CpG island methylation. Furthermore, these genes were associated with altered lipid and glucose metabolism, DNA damage and repair, apoptosis, the development of fibrosis, and liver tissue remodeling. Although there were both increased and decreased levels of CpG island methylation, the number of hypomethylated genes was substantially greater than the number of hypermethylated genes. Conclusion: The results this study demonstrate that pairing methylation profiles with gene expression profiles is a powerful approach to identify dysregulated high-priority fundamental pathophysiological pathways associated with disease development. C1 [Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao; Fuscoe, James C.] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 43 TC 25 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD MAR PY 2011 VL 55 IS 3 BP 411 EP 418 DI 10.1002/mnfr.201000300 PG 8 WC Food Science & Technology SC Food Science & Technology GA 732IE UT WOS:000288177400007 PM 20938992 ER PT J AU Nicholson, CE AF Nicholson, Carol E. TI Early exchange and pheresis therapies in critical pertussis SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Editorial Material DE Bordetella pertussis; leukapheresis; pediatric intensive care unit; exchange transfusion; pulmonary hypertension; leukostasis ID TRANSFUSION; CHILDREN; HYPERLEUKOCYTOSIS; LEUKAPHERESIS; LEUKEMIA; INFANTS C1 NIH, Bethesda, MD 20892 USA. RP Nicholson, CE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAR PY 2011 VL 12 IS 2 BP 240 EP 241 DI 10.1097/PCC.0b013e3181fe293f PG 2 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 730BY UT WOS:000288006100031 PM 21646959 ER PT J AU Meert, KL Eggly, S Berger, J Zimmerman, J Anand, KJS Newth, CJL Harrison, R Carcillo, J Dean, JM Willson, DF Nicholson, C AF Meert, Kathleen L. Eggly, Susan Berger, John Zimmerman, Jerry Anand, K. J. S. Newth, Christopher J. L. Harrison, Rick Carcillo, Joseph Dean, J. Michael Willson, Douglas F. Nicholson, Carol CA Eunice Kennedy Shriver Natl Inst TI Physicians' experiences and perspectives regarding follow-up meetings with parents after a child's death in the pediatric intensive care unit SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE bereavement; parent; critical care; communication; qualitative methods ID OF-LIFE CARE; PALLIATIVE CARE; HOSPITAL STAFF; END; ONCOLOGY; PATIENT; ABANDONMENT; GUIDELINES; FAMILIES AB Objective: To investigate critical care physicians' experiences and perspectives regarding follow-up meetings with parents after a child's death in the pediatric intensive care unit. Parents of children who die in the pediatric intensive care unit often desire a follow-up meeting with the physicians who cared for their child. Design: Semistructured, audio-recorded telephone interviews. Setting: Six clinical centers affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Participants: Seventy critical care physicians (i.e., attendings and fellows) practicing or training at a Child Health and Human Development Collaborative Pediatric Critical Care Research Network clinical center between February 1, 2008 and June 30, 2008. Measurements and Main Results: Twenty-three (33%) physicians reported never participating in a follow-up meeting with bereaved parents; 22 (31%) participated in one to five meetings; and 25 (36%) participated in more than five meetings. Of those with prior experience, 44 (94%) met with parents at the hospital and 40 (85%) met within 3 months of the death. Meeting content included discussing autopsy, parent questions, hospital course, cause of death, genetic risk, bereavement services, and legal or administrative issues; providing emotional support; and receiving parent feedback. Forty (85%) physicians perceived the meetings to be beneficial to families, and 35 (74%) to physicians. Barriers included time and scheduling, family and physician unwillingness, distance and transportation, language and cultural issues, parent anger, and lack of a system for meeting initiation and planning. Conclusions: Critical care physicians have a wide range of experience conducting follow-up meetings with bereaved parents. Although physicians perceive benefits to follow-up meetings, barriers exist that interfere with their implementation in clinical practice. (Pediatr Crit Care Med 2011; 12:e64-e68) C1 [Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA. [Eggly, Susan] Karmanos Canc Inst, Detroit, MI USA. [Berger, John] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA. [Anand, K. J. S.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Harrison, Rick] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Carcillo, Joseph] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. [Dean, J. Michael] Univ Utah, Salt Lake City, UT USA. [Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA USA. [Nicholson, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Meert, KL (reprint author), Childrens Hosp Michigan, Detroit, MI 48201 USA. EM kmeert@med.wayne.edu OI Anand, Kanwaljeet/0000-0001-6498-1483; Eggly, Susan/0000-0002-8137-6098 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10HD050096, U10HD049981, U10HD500009, U10HD049945, U10HD049983, U10HD050012, U01HD049934]; Department of Health and Human Services; National Institutes of Health (NIH); CPCCRN FX The study was funded, in part, by cooperative agreements U10HD050096, U10HD049981, U10HD500009, U10HD049945, U10HD049983, U10HD050012, and U01HD049934 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Department of Health and Human Services. The following authors received grant support from the National Institutes of Health (NIH): Drs. Meert, Berger, Zimmerman, Anand, Newth, Carcillo, and Dean. Dr. Nicholson is employed by the NIH. Dr. Harrison also received financial support from CPCCRN. The remaining authors have not disclosed any potential conflicts of interest. NR 27 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAR PY 2011 VL 12 IS 2 BP E64 EP E68 DI 10.1097/PCC.0b013e3181e89c3a PG 5 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 730BY UT WOS:000288006100037 PM 20581729 ER PT J AU Lang, PJ Wangelin, BC Bradley, MM Versace, F Davenport, PW Costa, VD AF Lang, Peter J. Wangelin, Bethany C. Bradley, Margaret M. Versace, Francesco Davenport, Paul W. Costa, Vincent D. TI Threat of suffocation and defensive reflex activation SO PSYCHOPHYSIOLOGY LA English DT Article DE Respiratory distress; Threat versus safe; Fear; Startle ID OBSTRUCTIVE PULMONARY-DISEASE; ANXIETY; FEAR; EMOTION; STARTLE AB The current study examined emotional reflex reactions of participants threatened with respiratory distress caused by imposing a resistive load at inspiration. Cues signaling threat (breathing MAY be difficult) and safe periods were intermixed while startle reflexes, heart rate, skin conductance, and facial EMG activity were measured. Compared to safe cues, threat cues elicited significant startle potentiation, enhanced skin conductance, heightened corrugator EMG changes, and pronounced "fear bradycardia" consistent with defensive activation in the context of threatened respiratory dysfunction. These data indicate that anticipating respiratory resistance activates defensive responding, which may mediate symptomatology in patients with panic and other anxiety disorders. C1 [Lang, Peter J.] Univ Florida, NIMH CSEA, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA. [Bradley, Margaret M.; Versace, Francesco; Costa, Vincent D.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Davenport, Paul W.] Univ Florida, Dept Physiol Sci, Gainesville, FL 32611 USA. RP Lang, PJ (reprint author), Univ Florida, NIMH CSEA, Dept Clin & Hlth Psychol, POB 112766, Gainesville, FL 32611 USA. EM plang@phhp.ufl.edu RI Costa, Vincent/A-2086-2015 OI Costa, Vincent/0000-0002-5412-8945 FU NIMH [P50 MH072850-04] FX This research was supported in part by NIMH grant P50 MH072850-04 to Peter J. Lang. Francesco Versace is now at the MD Anderson Cancer Center, Houston, Texas. NR 23 TC 15 Z9 15 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAR PY 2011 VL 48 IS 3 BP 393 EP 396 DI 10.1111/j.1469-8986.2010.01076.x PG 4 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 718RR UT WOS:000287144300012 PM 20667037 ER PT J AU Baranowski, T Baranowski, JC Watson, KB Martin, S Beltran, A Islam, N Dadabhoy, H Adame, SH Cullen, K Thompson, D Buday, R Subar, A AF Baranowski, Tom Baranowski, Janice C. Watson, Kathleen B. Martin, Shelby Beltran, Alicia Islam, Noemi Dadabhoy, Hafza Adame, Su-heyla Cullen, Karen Thompson, Debbe Buday, Richard Subar, Amy TI Children's accuracy of portion size estimation using digital food images: effects of interface design and size of image on computer screen SO PUBLIC HEALTH NUTRITION LA English DT Article DE Portion size estimation; Children; Food images ID PHOTOGRAPHS; VALIDITY; AIDS AB Objective: To test the effect of image size and presence of size cues on the accuracy of portion size estimation by children. Design: Children were randomly assigned to seeing images with or without food size cues (utensils and checked tablecloth) and were presented with sixteen food models (foods commonly eaten by children) in varying portion sizes, one at a time. They estimated each food model's portion size by selecting a digital food image. The same food images were presented in two ways: (i) as small, graduated portion size images all on one screen or (ii) by scrolling across large, graduated portion size images, one per sequential screen. Setting: Laboratory-based with computer and food models. Subjects: Volunteer multi-ethnic sample of 120 children, equally distributed by gender and ages (8 to 13 years) in 2008-2009. Results: Average percentage of correctly classified foods was 60.3%. There were no differences in accuracy by any design factor or demographic characteristic. Multiple small pictures on the screen at once took half the time to estimate portion size compared with scrolling through large pictures. Larger pictures had more overestimation of size. Conclusions: Multiple images of successively larger portion sizes of a food on one computer screen facilitated quicker portion size responses with no decrease in accuracy. This is the method of choice for portion size estimation on a computer. C1 [Baranowski, Tom; Baranowski, Janice C.; Watson, Kathleen B.; Martin, Shelby; Beltran, Alicia; Islam, Noemi; Dadabhoy, Hafza; Adame, Su-heyla; Cullen, Karen; Thompson, Debbe] Baylor Coll Med, Dept Pediat, USDA ARS Childrens Nutr Res Ctr, Houston, TX 77030 USA. [Subar, Amy] NCI, Bethesda, MD 20892 USA. [Buday, Richard] Archimage Inc, Houston, TX USA. RP Baranowski, T (reprint author), Baylor Coll Med, Dept Pediat, USDA ARS Childrens Nutr Res Ctr, 1100 Bates St, Houston, TX 77030 USA. EM tbaranow@bcm.tmc.edu OI Baranowski, Tom/0000-0002-0653-2222 FU National Cancer Institute [5 U01 CA130762-02]; USDA/ARS [58-6250-6001] FX Sources of funding: This research was funded primarily by a grant from the National Cancer Institute (5 U01 CA130762-02). This work is also a publication of the United States Department of Agriculture/Agricultural Research Service (USDA/ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, and has been funded in part with federal funds from the USDA/ARS under Cooperative Agreement No. 58-6250-6001. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products or organizations imply endorsement from the US government. NR 17 TC 9 Z9 9 U1 0 U2 14 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD MAR PY 2011 VL 14 IS 3 BP 418 EP 425 DI 10.1017/S1368980010002193 PG 8 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 730RA UT WOS:000288050600006 PM 21073772 ER PT J AU Gabriel, KP McClain, JJ Schmid, KK Storti, KL Ainsworth, BE AF Gabriel, Kelley Pettee McClain, James J. Schmid, Kendra K. Storti, Kristi L. Ainsworth, Barbara E. TI Reliability and convergent validity of the past-week Modifiable Activity Questionnaire SO PUBLIC HEALTH NUTRITION LA English DT Article DE Psychometrics; Self-report; Physical activity; Women ID MIDDLE-AGED WOMEN; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; COMPUTER-SCIENCE; ACCELEROMETER; CALIBRATION; THERAPY; INDIANS; RECALL; LIFE AB Objective: To examine the reliability and convergent validity of physical activity (PA) and inactivity estimates obtained with the past-week Modifiable Activity Questionnaire (PWMAQ). Design: The PWMAQ, an interviewer-administered questionnaire, was administered twice, one week apart, during visits 3 and 4 of six total visits. Intra-class correlation coefficients (ICC) between administrations of the PWMAQ were used to assess the reliability of summary estimates. Spearman rank-order correlation coefficients (p) were used to examine the associations of PWMAQ summary estimates with temporally matched and averaged accelerometer data in all participants and then stratified by whether the data were reflective of usual PA. Setting: Data were obtained from the Evaluation of Physical Activity Measures in Middle-Aged Women (PAW) study. Subjects: Sixty-six women, mean age 52.6 (SD 5.4) years. Results: The reliability of the PWMAQ physical inactivity estimate suggested substantial agreement over one week (ICC = 0.77, 95% CI 0.57, 0.82; P < 0.0001). With the exception of light-intensity PA, the PWMAQ leisure PA estimate was significantly associated with averaged accelerometer data (rho = 0.33-0.76; P < 0.05). For both temporally matched and averaged accelerometer data, correlation coefficients were higher between the PWMAQ estimate and moderate-walk-to vigorous-intensity PA in those who indicated that reported activity was reflective of usual PA; however, the association with moderate-lifestyle-intensity PA was higher in those reporting that data were not reflective. Conclusions: The PWMAQ is a reliable and valid measure of leisure PA levels in middle-aged women and supports subsequent studies evaluating this questionnaire in other population subgroups. C1 [Gabriel, Kelley Pettee] Univ Texas Austin, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Austin, TX 78701 USA. [McClain, James J.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Schmid, Kendra K.] Univ Nebraska Med Ctr, Dept Biostat, Omaha, NE USA. [Storti, Kristi L.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ainsworth, Barbara E.] Arizona State Univ, Program Exercise & Wellness, Healthy Lifestyles Res Ctr, Mesa, AZ USA. RP Gabriel, KP (reprint author), Univ Texas Austin, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Austin Reg Campus,Univ Texas Adm Bldg UTA,1616 Gu, Austin, TX 78701 USA. EM Kelley.P.Gabriel@uth.tmc.edu FU American College of Sports Medicine FX Sources of funding: This work was supported by the American College of Sports Medicine, Paffenbarger-Blair Endowment for Epidemiological Research on Physical Activity that was awarded to K.P.G. while working as a post-doctoral research associate at Arizona State University. The results of the present study do not constitute endorsement by the American College of Sports Medicine. NR 28 TC 13 Z9 13 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 EI 1475-2727 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD MAR PY 2011 VL 14 IS 3 BP 435 EP 442 DI 10.1017/S1368980010002612 PG 8 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 730RA UT WOS:000288050600008 ER PT J AU Addington, J Cornblatt, BA Cadenhead, K Cannon, T McGlashan, TH Perkins, D Seidman, LJ Tsuang, M Walker, E Woods, S Heinssen, R AF Addington, Jean Cornblatt, Barbara A. Cadenhead, Kristin Cannon, Tyrone McGlashan, Thomas H. Perkins, D. Seidman, Larry J. Tsuang, M. Walker, E. Woods, Scott Heinssen, R. TI CONVERSION IN NAPLS: THOSE WHO DO NOT CONVERT TO PSYCHOSIS SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Addington, Jean] Univ Calgary, Calgary, AB, Canada. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Long Isl City, NY USA. [Cadenhead, Kristin; Tsuang, M.] UCSD, San Diego, CA USA. [Cannon, Tyrone] Univ Calif Los Angeles, Los Angeles, CA USA. [McGlashan, Thomas H.; Woods, Scott] Yale Univ, New Haven, CT USA. [Perkins, D.] Univ N Carolina, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA USA. [Walker, E.] Emory Univ, Atlanta, GA 30322 USA. [Heinssen, R.] NIMH, Div Adult Translat Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 1 EP 1 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000002 ER PT J AU Pogorelov, V Nomura, J Krasnova, I Elmer, G Cadet, JL Pletnikov, M AF Pogorelov, Vladimir Nomura, Jun Krasnova, I. Elmer, G. Cadet, Jean Lud Pletnikov, Mikhail TI SEX DIFFERENCES IN THE INVOLVEMENT OF DISRUPTED-IN-SCHIZOPHRENIA-1 IN THE BEHAVIORAL EFFECTS OF METHAMPHETAMINE IN MICE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Pogorelov, Vladimir; Nomura, Jun; Pletnikov, Mikhail] Johns Hopkins Univ, Baltimore, MD USA. [Krasnova, I.; Cadet, Jean Lud] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. [Elmer, G.] MPRC Sch Med, Baltimore, MD USA. RI Nomura, Jun/C-2411-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 20 EP 20 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000058 ER PT J AU Warren, KR Buchanan, RW Feldman, S Conley, R Linthicum, J Ball, MP Liu, F McMahon, R Gorelick, D Kelly, DL AF Warren, Kimberly R. Buchanan, Robert W. Feldman, S. Conley, R. Linthicum, J. Ball, M. Patricia Liu, F. McMahon, R. Gorelick, D. Kelly, Deanna L. TI EFFECTS OF THE CANNABINOID-1 RECEPTOR ANTAGONIST RIMONABANT ON SATIETY SIGNALING IN OVERWEIGHT PEOPLE WITH SCHIZOPHRENIA: A RANDOMIZED, DOUBLE-BLIND PILOT STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Warren, Kimberly R.; Buchanan, Robert W.; Feldman, S.; Linthicum, J.; Ball, M. Patricia; Liu, F.; McMahon, R.; Kelly, Deanna L.] Univ Maryland, Sch Med, Psychiat MPRC, Baltimore, MD 21201 USA. [Conley, R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Gorelick, D.] NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 29 EP 29 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000082 ER PT J AU Hodgkinson, C AF Hodgkinson, Colin TI USE OF NEXT-GENERATION SEQUENCING PLATFORMS TO IDENTIFY SCHIZOPHRENIA GENES SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Hodgkinson, Colin] NIAAA, LNG, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 71 EP 71 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000204 ER PT J AU Sanders, AR Goring, HH Shi, J Duan, J Gejman, PV AF Sanders, Alan R. Goering, H. H. Shi, J. Duan, J. Gejman, Pablo V. TI JOINT MAPPING OF GENOME-WIDE GENE EXPRESSION AND ASSOCIATION IN A SCHIZOPHRENIA DATASET SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Sanders, Alan R.; Duan, J.; Gejman, Pablo V.] NorthShore Univ HealthSyst, Res Inst, Evanston, IL USA. [Goering, H. H.] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Shi, J.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 76 EP 77 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000222 ER PT J AU Decot, H Zhang, F Weinberger, DR Apud, J AF Decot, Heather Zhang, F. Weinberger, Daniel R. Apud, J. TI EFFECT OF PLACEBO AND REINTRODUCTION OF ANTIPSYCHOTICS IN PATIENTS WITH SCHIZOPHRENIA BASED ON COMT VAL108/158MET POLYMORPHISM SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Decot, Heather; Zhang, F.; Weinberger, Daniel R.; Apud, J.] NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 84 EP 85 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000245 ER PT J AU Fortgang, R Straub, R Vakkalanka, R Feng, N Weinberger, DR Dickinson, D AF Fortgang, Rebecca Straub, R. Vakkalanka, R. Feng, N. Weinberger, Daniel R. Dickinson, D. TI KIBRA AND COGNITION: EXPLORING THE ASSOCIATION OF WWC1 SNPS WITH COGNITION IN SCHIZOPHRENIA AND HEALTHY SAMPLES SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Fortgang, Rebecca; Straub, R.; Vakkalanka, R.; Feng, N.; Weinberger, Daniel R.; Dickinson, D.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 86 EP 86 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000249 ER PT J AU Hong, E Zhang, X Hodgkinson, CA Yang, Y Sampath, H Ross, TJ Buchholz, B Salmeron, BJ Thaker, GK Goldman, D Stein, EA AF Hong, Elliot Zhang, X. Hodgkinson, C. A. Yang, Y. Sampath, H. Ross, T. J. Buchholz, B. Salmeron, B. J. Thaker, G. K. Goldman, D. Stein, E. A. TI MODULATION OF A CINGULATE CORTEX CONNECTIVITY: INFLUENCE OF NICOTINE, GENETICS AND SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Hong, Elliot; Sampath, H.; Buchholz, B.; Thaker, G. K.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Zhang, X.; Yang, Y.; Ross, T. J.; Salmeron, B. J.; Stein, E. A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Baltimore, MD USA. [Hodgkinson, C. A.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RI Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 87 EP 87 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000252 ER PT J AU Lipska, BK AF Lipska, Barbara K. TI ASSOCIATION OF DLG4 VARIANTS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Lipska, Barbara K.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 89 EP 89 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000257 ER PT J AU Wallwork, RS Straub, R Vakkalanka, R Feng, N Weinberger, DR Dickinson, D AF Wallwork, Rachel Shere Straub, R. Vakkalanka, R. Feng, N. Weinberger, D. R. Dickinson, D. TI INITIAL INVESTIGATION OF THE RELATIONSHIP OF KYNU AND CORTICAL KYNURENINE PATHWAY METABOLISM TO COGNITION IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Wallwork, Rachel Shere; Straub, R.; Vakkalanka, R.; Feng, N.; Weinberger, D. R.; Dickinson, D.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 93 EP 94 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000271 ER PT J AU Weinberger, DR AF Weinberger, Daniel R. TI SUSCEPTIBILITY GENES DO NOT RESPECT DSM-IV CRITERIA OR NEURAL CIRCUIT SPECIFICITY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Weinberger, Daniel R.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 94 EP 95 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000274 ER PT J AU Weinberger, DR AF Weinberger, Daniel R. TI GENETIC ARCHITECTURE OF COGNITION IN SCHIZOPHRENIA: WITHER WORKING MEMORY? SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Weinberger, Daniel R.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 94 EP 94 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000273 ER PT J AU Kannan, G Xiao, J Sabunciyan, S Krasnova, I Cadet, JL Yolken, RH Jones-Brando, L Pletnikov, M AF Kannan, Geetha Xiao, J. Sabunciyan, S. Krasnova, I. Cadet, Jean Lud Yolken, Robert H. Jones-Brando, L. Pletnikov, Mikhail TI T. GONDII MAY CONTRIBUTE TO SCHIZOPHRENIA GENDER DIFFERENCES THROUGH THE MODULATION OF PROLACTIN SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Kannan, Geetha] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Program, Baltimore, MD USA. [Xiao, J.; Sabunciyan, S.; Yolken, Robert H.; Jones-Brando, L.] Johns Hopkins Univ, Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA. [Krasnova, I.; Cadet, Jean Lud] Natl Inst Drug Abuse, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 108 EP 108 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000311 ER PT J AU Moran, LV Sampath, H Yang, YH Ross, TJ Salmeron, BJ Buchholz, B Thaker, GK Stein, EA Hong, E AF Moran, Lauren V. Sampath, Hemalatha Yang, Yihong Ross, Thomas J. Salmeron, Betty Jo Buchholz, Brittany Thaker, Gunvant K. Stein, Elliot A. Hong, Elliot TI INSULA, DORSAL ANTERIOR CINGULATE AND VENTRAL STRIATUM RESTING STATE FUNCTIONAL CONNECTIVITY NETWORK IN NICOTINE ADMINISTRATION, NICOTINE ADDICTION AND SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Moran, Lauren V.; Sampath, Hemalatha; Buchholz, Brittany; Thaker, Gunvant K.; Hong, Elliot] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Yang, Yihong; Ross, Thomas J.; Salmeron, Betty Jo; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RI Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 147 EP 148 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000419 ER PT J AU Pietersen, CY Kim, S Lim, M Chen, J Stephens, R Sonntag, KC McCarley, RM Woo, TUW AF Pietersen, Charmaine Y. Kim, Susie Lim, Maribel Chen, Jack Stephens, Robert Sonntag, Kai C. McCarley, Robert M. Woo, Tsung-Ung Wilson TI MRNA AND MICRORNA EXPRESSION PROFILING OF PYRAMIDAL NEURONS IN LAYER 3 OF THE SUPERIOR TEMPORAL GYRUS IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Pietersen, Charmaine Y.; Kim, Susie; Lim, Maribel; Sonntag, Kai C.; Woo, Tsung-Ung Wilson] McLean Hosp, Belmont, MA 02178 USA. [Pietersen, Charmaine Y.; Sonntag, Kai C.; McCarley, Robert M.; Woo, Tsung-Ung Wilson] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Jack; Stephens, Robert] NCI, SAIC Frederick, NIH, Bethesda, MD 20892 USA. [McCarley, Robert M.] VA Boston Healthcare Syst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 185 EP 186 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000523 ER PT J AU Hyde, TM AF Hyde, Thomas Michael TI GABA SIGNALING MOLECULES IN DEVELOPMENT AND SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Hyde, Thomas Michael] NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Hyde, Thomas Michael] Lieber Inst Brain Dev, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 191 EP 191 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000538 ER PT J AU Kleinman, JE AF Kleinman, Joel E. TI GENETIC NEUROPATHOLOGY OF SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Kleinman, Joel E.] NIMH, CBDB, GCAP, IRP,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 192 EP 192 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000540 ER PT J AU Abazyan, B Nomura, J Kannan, G Ishizuka, K Tamashiro, K Nucifora, F Pogorelov, V Ladenheim, B Yanq, CX Krasnova, I Cadet, JL Pardo, C Mori, S Kamiya, A Vogel, M Sawa, A Ross, CA Pletnikov, M AF Abazyan, Bagrat Nomura, Jun Kannan, Geetha Ishizuka, Koko Tamashiro, Kellie Nucifora, Frederick Pogorelov, Vladimir Ladenheim, Bruce Yanq, Chunxia Krasnova, Irina Cadet, Jean Luc Pardo, Carlos Mori, Susumu Kamiya, Atsushi Vogel, Michel Sawa, Akira Ross, Christopher A. Pletnikov, Mikhail TI INTERACTION OF MUTANT DISC1 AND PRENATAL IMMUNE ACTIVATION: TIMING OF THE NEUROBEHAVIORAL EFFECTS OF MUTANT DISC1 SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Abazyan, Bagrat; Nomura, Jun; Kannan, Geetha; Nucifora, Frederick; Pogorelov, Vladimir; Yanq, Chunxia; Ross, Christopher A.; Pletnikov, Mikhail] JHU Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD USA. [Ladenheim, Bruce; Krasnova, Irina; Cadet, Jean Luc] NIDA, Mol Neuropsychiat Branch, NIH, DHHS, Baltimore, MD USA. [Vogel, Michel] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RI Nomura, Jun/C-2411-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 198 EP 198 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000559 ER PT J AU Cadet, JL AF Cadet, Jean Lud TI THE PRIMACY OF COGNITIVE DISTURBANCES IN MARIJUANA ABUSE: NEUROBIOLOGICAL PERSPECTIVES SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Cadet, Jean Lud] NIDA, NIH, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 202 EP 203 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000571 ER PT J AU Hahn, B Harvey, AN Robinson, BM Kaiser, ST Leonard, CJ Stein, EA Luck, SJ Gold, JM AF Hahn, Britta Harvey, A. N. Robinson, B. M. Kaiser, S. T. Leonard, C. J. Stein, E. A. Luck, S. J. Gold, J. M. TI VISUOSPATIAL ATTENTION IN SCHIZOPHRENIA: DEFICITS IN BROAD MONITORING SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Hahn, Britta; Harvey, A. N.; Robinson, B. M.; Kaiser, S. T.; Gold, J. M.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Leonard, C. J.; Luck, S. J.] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. [Leonard, C. J.; Luck, S. J.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Stein, E. A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 209 EP 209 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000592 ER PT J AU Karlsson, RM Kircher, DM Shaham, Y O'Donnell, P AF Karlsson, Rose-Marie Kircher, Daniel M. Shaham, Yavin O'Donnell, Patricio TI ENHANCED CUE-INDUCED RELAPSE TO COCAINE SEEKING IN THE NEONATAL VENTRAL HIPPOCAMPAL LESION (NVHL) RAT MODEL OF SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Karlsson, Rose-Marie; Kircher, Daniel M.; O'Donnell, Patricio] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Shaham, Yavin] Natl Inst Drug Abuse, Behav Neurosci Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 214 EP 214 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000605 ER PT J AU Waltz, JA Kasanova, Z Ross, TJ Salmeron, BJ Gold, J Stein, EA AF Waltz, James A. Kasanova, Z. Ross, T. J. Salmeron, B. J. Gold, James Stein, E. A. TI INVESTIGATING THE NEURAL SUBSTRATES OF NEGATIVE SYMPTOMS: RESULTS FROM FMRI STUDIES OF OUTCOME PROCESSING IN SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Waltz, James A.; Kasanova, Z.; Gold, James] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Ross, T. J.; Salmeron, B. J.; Stein, E. A.] NIDA, Neuroimaging Res Branch, IRP, Baltimore, MD USA. RI Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 232 EP 232 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000658 ER PT J AU Wehring, H Kelly, DL McMahon, RP Bordnick, P Bellack, A Holcomb, HH Fischer, BA Rowland, LM Turner, H Taylor, R Liu, F Heishman, SJ AF Wehring, Heidi Kelly, Deanna L. McMahon, R. P. Bordnick, P. Bellack, A. Holcomb, H. H. Fischer, B. A. Rowland, L. M. Turner, H. Taylor, R. Liu, F. Heishman, S. J. TI ASSESSMENT OF TOBACCO CRAVING IN SMOKERS WITH SCHIZOPHRENIA USING VIRTUAL REALITY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Wehring, Heidi; Kelly, Deanna L.; McMahon, R. P.; Holcomb, H. H.; Fischer, B. A.; Rowland, L. M.; Turner, H.; Liu, F.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Bordnick, P.] Univ Houston, Grad Coll Social Work, Houston, TX USA. [Bellack, A.] Baltimore Vet Adm Med Ctr, MIRECC, VA Capital Hlth Care Network, Baltimore, MD USA. [Bellack, A.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Taylor, R.; Heishman, S. J.] Natl Inst Drug Abuse, Clin Pharmacol & Therapeut Branch, NIH Intramural Res Program, Baltimore, MD USA. RI McMahon, Robert/C-5462-2009 NR 0 TC 0 Z9 0 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 256 EP 257 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000727 ER PT J AU Fink-Jensen, A Nielsen, D Wortwein, G Woldbye, DP Wess, J Weikop, P AF Fink-Jensen, Anders Nielsen, D. Woertwein, G. Woldbye, D. P. Wess, J. Weikop, P. TI ROLE OF M4 MUSCARINIC CHOLINERGIC RECEPTORS IN PSYCHOSTIMULANT-MEDIATED EFFECTS IN MICE SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Fink-Jensen, Anders; Nielsen, D.; Woertwein, G.; Woldbye, D. P.; Weikop, P.] Univ Copenhagen, Lab Neuropsychiat, Psychiat Ctr Copenhagen, Copenhagen, Denmark. [Fink-Jensen, Anders; Nielsen, D.; Woertwein, G.; Woldbye, D. P.; Weikop, P.] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark. [Wess, J.] NIDDKD, Mol Signaling Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 288 EP 288 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000819 ER PT J AU Buchanan, RW Boggs, DL Conley, R Gorelick, D McMahon, R Gold, J Linthicum, J Huestis, M Liu, F Kelly, DL AF Buchanan, Robert W. Boggs, D. L. Conley, R. Gorelick, D. McMahon, R. Gold, James Linthicum, J. Huestis, M. Liu, F. Kelly, Deanna L. TI A PILOT STUDY EVALUATING THE COGNITIVE EFFECTS OF RIMONABANT IN PEOPLE WITH SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Buchanan, Robert W.; Boggs, D. L.; McMahon, R.; Gold, James; Linthicum, J.; Liu, F.; Kelly, Deanna L.] Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Conley, R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Gorelick, D.; Huestis, M.] NIDA, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 297 EP 298 PG 2 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000844 ER PT J AU Kelly, DL Gorelick, D Conley, R Boggs, DL Linthicum, J Liu, F Feldman, S Ball, MP Wehring, H McMahon, R Huestis, M Heishman, S Warren, K Buchanan, R AF Kelly, Deanna L. Gorelick, D. Conley, R. Boggs, Douglas Lee Linthicum, J. Liu, F. Feldman, S. Ball, M. P. Wehring, Heidi McMahon, R. Huestis, M. Heishman, S. Warren, K. Buchanan, R. TI EFFECTS OF THE CANNABINOID-1 RECEPTOR ANTAGONIST RIMONABANT ON PSYCHIATRIC SYMPTOMS IN OVERWEIGHT PEOPLE WITH SCHIZOPHRENIA: A RANDOMIZED, DOUBLE-BLIND PILOT STUDY SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 13th International Congress on Schizophrenia Research (ICSR) CY APR 02-06, 2011 CL Colorado Springs, CO C1 [Kelly, Deanna L.; Boggs, Douglas Lee; Linthicum, J.; Liu, F.; Feldman, S.; Ball, M. P.; Wehring, Heidi; McMahon, R.; Warren, K.; Buchanan, R.] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Gorelick, D.; Huestis, M.; Heishman, S.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. [Conley, R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 SU 1 BP 310 EP 310 PG 1 WC Psychiatry SC Psychiatry GA 726SI UT WOS:000287746000878 ER PT J AU Wang, CCC Friedman, L Kennedy, GC Wang, H Kebebew, E Steward, DL Zeiger, MA Westra, WH Wang, YC Khanafshar, E Fellegara, G Rosai, J LiVolsi, V Lanman, RB AF Wang, Chung-Che Charles Friedman, Lyssa Kennedy, Giulia C. Wang, Hui Kebebew, Electron Steward, David L. Zeiger, Martha A. Westra, William H. Wang, Yongchun Khanafshar, Elham Fellegara, Giovanni Rosai, Juan LiVolsi, Virginia Lanman, Richard B. TI A Large Multicenter Correlation Study of Thyroid Nodule Cytopathology and Histopathology SO THYROID LA English DT Article ID FINE-NEEDLE-ASPIRATION; OBSERVER VARIATION; UNITED-STATES; INCREASING INCIDENCE; SCIENCE CONFERENCE; CANCER; CYTOLOGY; LESIONS; EXPERIENCE; DIAGNOSIS AB Background: Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed. Methods: Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U. S.-based thyroid FNA studies. Results: FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%). Conclusions: Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens. C1 [Wang, Chung-Che Charles; Friedman, Lyssa; Lanman, Richard B.] Veracyte Inc, Dept Med & Clin Affairs, San Francisco, CA 94080 USA. [Kennedy, Giulia C.; Wang, Hui] Veracyte Inc, Dept Res & Dev, San Francisco, CA 94080 USA. [Kebebew, Electron] NCI, Surg Branch, Endocrine Surg Sect, Bethesda, MD 20892 USA. [Steward, David L.] Univ Cincinnati, Coll Med, Dept Otolaryngol Head & Neck Surg, Cincinnati, OH USA. [Zeiger, Martha A.; Wang, Yongchun] Johns Hopkins Univ, Sch Med, Dept Surg, Endocrine Surg Sect, Baltimore, MD 21205 USA. [Westra, William H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Khanafshar, Elham] Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. [Fellegara, Giovanni; Rosai, Juan] Int Ctr Oncol Pathol Consultat, Cent Diagnost Italiano, Milan, Italy. [LiVolsi, Virginia] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. RP Wang, CCC (reprint author), Veracyte Inc, Dept Med & Clin Affairs, 7000 Shoreline Court,Suite 250, San Francisco, CA 94080 USA. EM c.charles.wang@gmail.com OI Lanman, Richard/0000-0001-8122-4329 FU Veracyte, Inc. FX Drs. C. Charles Wang, Giulia C. Kennedy, Hui Wang, Richard B. Lanman, and Lyssa Friedman are employees of Veracyte, Inc. Drs. Electron Kebebew, Virginia LiVolsi, Juan Rosai, Giovanni Fellegara, David L. Steward, and Martha A. Zeiger have received research grant support from Veracyte, Inc. The other authors have no competing financial interests. NR 39 TC 128 Z9 133 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2011 VL 21 IS 3 BP 243 EP 251 DI 10.1089/thy.2010.0243 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 730GG UT WOS:000288021200006 PM 21190442 ER PT J AU Moalem, J Choi, DX Khanafshar, E Ruan, DT Woeber, KA Clark, OH Kebebew, E AF Moalem, Jacob Choi, Daniel X. Khanafshar, Elham Ruan, Daniel T. Woeber, Kenneth A. Clark, Orlo H. Kebebew, Electron TI Metastatic Papillary Thyroid Cancer Misdiagnosed as Small Cell Lung Cancer SO THYROID LA English DT Article ID TRANSCRIPTION FACTOR-I; DISTANT METASTASES; CARCINOMA; GLAND; TUMOR AB Background: Thyroid and lung cancers, two malignancies with similar immunohistological characteristics, have vastly different biologic behaviors and treatment approaches. As thyroid cancers commonly spread to the lungs, metastatic thyroid cancer should be included in the differential diagnosis of a pulmonary lesion or lesions. Summary: A 54-year-old woman with a remote history of stage IV nonsmall cell lung cancer was found to have FDG avidity in the thyroid and right cervical lymph nodes. Subsequent ultrasonographic findings and FNA cytology led to a total thyroidectomy, bilateral central lymphadenectomy, and right modified radical lymph node dissection for primary thyroid cancer. Reviews and comparisons of the pulmonary and cervical surgical specimens revealed that the patient had been misdiagnosed for the previous 6 years; she had metastatic papillary thyroid cancer to the lung. The patient's original diagnosis of stage IV lung cancer was based upon the original lung biopsy showing positive thyroid transcription factor-1 (TTF-1) immunostaining. The original diagnosis was questioned because of her long survival when she was diagnosed with locally advanced papillary thyroid cancer. Further analyses of the immunohistological characteristics of both surgical specimens-including staining for TTF-1, thyroglobulin, CD57, S-100, and CEA-documented the correct diagnosis. Conclusions: A thorough understanding of the natural history and surgical pathology, including immunohistology, of lung and thyroid cancers is necessary for a correct and timely diagnosis and appropriate treatment. Because TTF-1 expression is seen in both thyroid and lung cancers, careful consideration should be given to both malignancies when evaluating patients with thyroid and pulmonary nodules. C1 [Moalem, Jacob; Choi, Daniel X.] Univ Rochester, Dept Surg, Div Surg Oncol, Rochester, NY 14642 USA. [Khanafshar, Elham] UCSF Med Ctr Mt Zion, Dept Pathol, San Francisco, CA USA. [Ruan, Daniel T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Woeber, Kenneth A.] UCSF Med Ctr Mt Zion, Div Endocrinol, San Francisco, CA USA. [Clark, Orlo H.] UCSF Med Ctr Mt Zion, Dept Surg, San Francisco, CA USA. [Kebebew, Electron] NCI, Clin Res Ctr, Bethesda, MD 20892 USA. RP Moalem, J (reprint author), Univ Rochester, Dept Surg, Div Surg Oncol, 601 Elmwood Ave,Box SURG, Rochester, NY 14642 USA. EM jacob_moalem@urmc.rochester.edu NR 23 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAR PY 2011 VL 21 IS 3 BP 319 EP 323 DI 10.1089/thy.2010.0395 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 730GG UT WOS:000288021200016 PM 21254936 ER PT J AU Brzezinski, K Walejko, P Baj, A Witkowski, S Dauter, Z AF Brzezinski, Krzysztof Walejko, Piotr Baj, Aneta Witkowski, Stanislaw Dauter, Zbigniew TI 2,2,5,7,8-Pentamethylchroman-6-yl 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranoside from synchrotron data SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID VITAMIN-E; ALPHA-TOCOPHEROL; ANTIOXIDANT AB The crystal structure of the title compound, C28H38O11, solved and refined against synchrotron diffraction data, contains two formula units in the asymmetric unit. In both molecules, the dihydropyran ring along with its methyl substituents is disordered and adopts two alternative half-chair conformations. The occupancy of the major conformers of the two molecules refined to 0.858 (5) and 0.523 (5). C1 [Brzezinski, Krzysztof; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA. [Walejko, Piotr; Baj, Aneta; Witkowski, Stanislaw] Univ Bialystok, Inst Chem, PL-15443 Bialystok, Poland. RP Brzezinski, K (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab,Biosci Div, Bldg 202, Argonne, IL 60439 USA. EM kbrzezinski@anl.gov FU NIH, National Cancer Institute, Center for Cancer Research; US Department of Energy [W-31-109-Eng-38] FX This work was in part supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. X-ray data were collected at the NECAT 24ID-C beamline of the Advanced Photon Source, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy under contract No. W-31-109-Eng-38. NR 9 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD MAR PY 2011 VL 67 BP O718 EP U2631 DI 10.1107/S160053681100626X PN 3 PG 21 WC Crystallography SC Crystallography GA 727RX UT WOS:000287820000233 PM 21522460 ER PT J AU Forooghian, F Chew, EY Meyerle, CB Cukras, C Wong, WT AF Forooghian, Farzin Chew, Emily Y. Meyerle, Catherine B. Cukras, Catherine Wong, Wai T. TI Investigation of the role of neutralizing antibodies against bevacizumab as mediators of tachyphylaxis SO ACTA OPHTHALMOLOGICA LA English DT Letter ID MACULAR DEGENERATION; RANIBIZUMAB C1 [Wong, Wai T.] NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA. [Forooghian, Farzin; Chew, Emily Y.; Meyerle, Catherine B.; Cukras, Catherine] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Off Sci Director, NIH, 7 Mem Dr,Bldg 7,Room 217, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Intramural NIH HHS [NIH0010073583, ZIE EY000487-01] NR 6 TC 19 Z9 19 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD MAR PY 2011 VL 89 IS 2 BP E206 EP E207 DI 10.1111/j.1755-3768.2009.01773.x PG 2 WC Ophthalmology SC Ophthalmology GA 725RV UT WOS:000287664700019 PM 19900197 ER PT J AU Xue, L Mei, YA AF Xue, Lei Mei, Yan-ai TI Synaptic vesicle recycling at the calyx of Held SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE endocytosis; calyx of Held; kiss-and-run; bulk endocytosis; compound fusion; PTP ID FROG NEUROMUSCULAR JUNCTION; KISS-AND-RUN; POSTTETANIC POTENTIATION; TRANSMITTER RELEASE; NERVE-TERMINALS; MEDIAL NUCLEUS; TRAPEZOID BODY; NEUROTRANSMITTER RELEASE; CAPACITANCE MEASUREMENTS; PRESYNAPTIC CAPACITANCE AB Efficient endocytosis is crucial for maintaining synaptic transmission because of its role in retrieving constituent membrane and associated proteins. In the past three decades three modes of endocytosis have been proposed involving the central nervous system: clathrin-mediated endocytosis, kiss-and-run endocytosis and bulk endocytosis. These forms of endocytosis can be induced under different conditions, but their detailed molecular mechanisms and functions are largely unknown. Here, we review the existence and initiation of all three modes of endocytosis at a giant glutamatergic synapse, the calyx of Held. The possibility of direct electrophysiology recording in this synapse allows for accurate tracking of exocytosis and endocytosis via capacitance measurements. Future aims will be focused on identifying the molecules that undergo the different mechanisms of endocytosis and the conditions under which different forms of endocytosis predominate. C1 [Xue, Lei; Mei, Yan-ai] Fudan Univ, Inst Brain Sci, Sch Life Sci, Shanghai 200433, Peoples R China. [Xue, Lei; Mei, Yan-ai] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Xue, Lei] NINDS, NIH, Bethesda, MD 20892 USA. RP Mei, YA (reprint author), Fudan Univ, Inst Brain Sci, Sch Life Sci, Shanghai 200433, Peoples R China. EM yamei@fudan.edu.cn NR 40 TC 4 Z9 4 U1 1 U2 7 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD MAR PY 2011 VL 32 IS 3 BP 280 EP 287 DI 10.1038/aps.2010.212 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 730BH UT WOS:000288003200002 PM 21258358 ER PT J AU Schwilke, EW Gullberg, RG Darwin, WD Chiang, CN Cadet, JL Gorelick, DA Pope, HG Huestis, MA AF Schwilke, Eugene W. Gullberg, Rod G. Darwin, William D. Chiang, C. Nora Cadet, Jean Lud Gorelick, David A. Pope, Harrison G. Huestis, Marilyn A. TI Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users SO ADDICTION LA English DT Article DE New cannabis use; predictive model; residual drug excretion; urine cannabinoids ID CREATININE RATIO; 11-NOR-9-CARBOXY-DELTA(9)-TETRAHYDROCANNABINOL; PROFILES; DELTA(9)-THC-COOH; MARIJUANA; HUMANS AB Aims To develop and validate empirically a mathematical model for identifying new cannabis use in chronic, daily cannabis smokers. Design Models were based on urinary creatinine-normalized (CN) cannabinoid excretion in chronic cannabis smokers. Setting For model development, participants resided on a secure research unit for 30 days. For model validation, participants were abstinent with daily observed urine specimens for 28 days. Participants A total of 48 (model development) and 67 (model validation) daily cannabis smokers were recruited. Measurements All voided urine was collected and analyzed for 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THCCOOH) by gas chromatography-mass spectrometry (GCMS; limit of quantification 2.5 ng/ml) and creatinine (mg/ml). Urine THCCOOH was normalized to creatinine, yielding ng/mg CN-THCCOOH concentrations. Urine concentration ratios were determined from 123 513 specimen pairs collected 2-30 days apart. Findings A mono-exponential model (with two parameters, initial urine specimen CN-THCCOOH concentration and time between specimens), based on the Marquardt-Levenberg algorithm, provided a reasonable data fit. Prediction intervals with varying probability levels (80, 90, 95, 99%) provide upper ratio limits for each urine specimen pair. Ratios above these limits suggest cannabis re-use. Disproportionate numbers of ratios were higher than expected for some participants, prompting development of two additional rules that avoid misidentification of re-use in participants with unusual CN-THCCOOH excretion patterns. Conclusions For the first time, a validated model is available to aid in the differentiation of new cannabis use from residual creatinine-normalized 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (CN-THCCOOH) excretion in chronic, daily cannabis users. These models are valuable for clinicians, toxicologists and drug treatment staff and work-place, military and criminal justice drug-testing programs. C1 [Schwilke, Eugene W.; Darwin, William D.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21146 USA. [Gullberg, Rod G.] Washington State Patrol, Breath Test Sect, Seattle, WA USA. [Chiang, C. Nora] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Rockville, MD USA. [Cadet, Jean Lud] Natl Inst Drug Abuse, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD USA. [Gorelick, David A.] Natl Inst Drug Abuse, Off Sci Director, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD USA. [Pope, Harrison G.] Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 200,Room 05A 721, Baltimore, MD 21146 USA. EM mhuestis@intra.nida.nih.gov FU National Institutes of Health, National Institute on Drug Abuse [N01DA-1-8817]; NIDA [RO1-06522, R01-DA10346] FX This research was supported by the Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse, contract N01DA-1-8817 to BRCI and by NIDA grants RO1-06522 and R01-DA10346 to Dr Pope. We thank the participants and clinical research staff and Ms An-Ting Wei for providing statistical support. NR 18 TC 13 Z9 13 U1 3 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2011 VL 106 IS 3 BP 499 EP 506 DI 10.1111/j.1360-0443.2010.03228.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 717GV UT WOS:000287032500010 PM 21134021 ER PT J AU Roh, S Matsushita, S Hara, S Maesato, H Matsui, T Suzuki, G Miyakawa, T Ramchandani, VA Li, TK Higuchi, S AF Roh, Sungwon Matsushita, Sachio Hara, Sachiko Maesato, Hitoshi Matsui, Toshifumi Suzuki, Go Miyakawa, Tomohiro Ramchandani, Vijay A. Li, Ting-Kai Higuchi, Susumu TI Role of GABRA2 in Moderating Subjective Responses to Alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE GABA; GABRA2; Alcohol; Subjective Response; Alcohol Clamping; ALDH2 ID GABA(A) RECEPTOR; PHYSIOLOGICAL-RESPONSES; VENTRAL PALLIDUM; DRINKING HISTORY; ASIAN-AMERICANS; FAMILY-HISTORY; LOW-LEVEL; DEPENDENCE; SONS; RISK AB Background: Human twin studies have shown that certain responses to alcohol, including subjective perceptions, are genetically influenced. Previous studies have provided evidence that a low level of response to alcohol predicts future alcohol use disorders in humans. Recent genetic studies suggest an association between alcohol dependence and genetic variation in the gamma-aminobutyric acid A (GABA(A)) receptor alpha 2 subunit gene (GABRA2). Based on a haplotypic association of alcohol dependence with GABRA2, we investigated whether GABRA2 alleles are associated with the subjective responses to clamped alcohol concentration. Methods: One hundred and ten healthy social drinkers (53 men) underwent the alcohol clamp. Fifteen minutes after the start of an intravenous infusion of alcohol, the breath alcohol concentration was clamped at a target of 50 +/- 5 mg/dl for 165 minutes. Subjective physiologic responses to alcohol and stimulant and sedative effects of alcohol were measured repeatedly during the alcohol clamp. Because aldehyde dehydrogenase 2 (ALDH2) has been shown to have a great impact on the subjective responses to alcohol, we divided subjects by ALDH2 genotype for further analyses. To examine the role of genetic variation in GABRA2, 7 single nucleotide polymorphisms (SNPs) that were informative in association studies were included as factors in the analysis. Results: Among these 7 SNPs, 3 SNPs (rs279869, rs279858, and rs279837) located in the middle of the GABRA2 gene showed significant associations with subjective effects of alcohol. Subjects with 1 or 2 copies of the more common allele showed greater subjective responses to alcohol than did individuals homozygous for the alcohol dependence associated allele regardless of ALDH2 genotype. Conclusions: These findings confirm and extend the observation that the GABRA2 alleles affect the subjective responses to alcohol, and suggest that the genetic variations in GABRA2 might play a role in the risk of alcohol use disorders by moderating the subjective effects of alcohol. C1 [Matsushita, Sachio; Maesato, Hitoshi; Suzuki, Go; Miyakawa, Tomohiro; Higuchi, Susumu] Natl Hosp Org, Kurihama Alcoholism Ctr, Dept Psychiat, Kanagawa 2390841, Japan. [Roh, Sungwon; Hara, Sachiko] Natl Hosp Org, Kurihama Alcoholism Ctr, Div Clin Res, Kanagawa 2390841, Japan. [Matsui, Toshifumi] Natl Hosp Org, Kurihama Alcoholism Ctr, Dept Internal Med, Kanagawa 2390841, Japan. [Ramchandani, Vijay A.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. [Li, Ting-Kai] NIAAA, Off Director, Bethesda, MD USA. RP Higuchi, S (reprint author), Natl Hosp Org, Kurihama Alcoholism Ctr, Dept Psychiat, 5-3-1 Nobi, Kanagawa 2390841, Japan. EM h-susumu@db3.so-net.ne.jp RI Suzuki, Go/E-5081-2011 OI Suzuki, Go/0000-0003-3120-8683 FU Ministry of Health, Labour and Welfare, Japan FX This study was supported by a block grant to the Division of Clinical Research, National Hospital Organization Kurihama Alcoholism Center funded by the Ministry of Health, Labour and Welfare, Japan. The authors gratefully acknowledge the expert technical assistance of Ms. Imazeki. NR 54 TC 30 Z9 30 U1 8 U2 16 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 MAR PY 2011 VL 35 IS 3 BP 400 EP 407 DI 10.1111/j.1530-0277.2010.01357.x PG 8 WC Substance Abuse SC Substance Abuse GA 731XF UT WOS:000288143100004 PM 21118274 ER PT J AU Coates, PM Dwyer, JT AF Coates, Paul M. Dwyer, Johanna T. TI Mary Frances Picciano, PhD 1946-2010 In Memoriam SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Biographical-Item ID DIETARY-SUPPLEMENT USE; FUTURE-DIRECTIONS; UNITED-STATES; INFANTS; FOLATE; HEALTH; MILK C1 [Coates, Paul M.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd, Bethesda, MD 20892 USA. EM coatesp@od.nih.gov NR 13 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2011 VL 93 IS 3 BP 479 EP 480 DI 10.3945/ajcn.110.010389 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 722ZN UT WOS:000287475000001 ER PT J AU Brosens, I Pijnenborg, R Vercruysse, L Romero, R AF Brosens, Ivo Pijnenborg, Robert Vercruysse, Lisbeth Romero, Roberto TI The "Great Obstetrical Syndromes" are associated with disorders of deep placentation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE adverse pregnancy outcome; physiological transformation; placental vascular bed; spiral artery ID FOR-GESTATIONAL-AGE; ANTI-ANGIOGENIC FACTORS; EARLY HUMAN-PREGNANCY; FACTOR RECEPTOR-1 CONCENTRATION; MATERNAL PLASMA-CONCENTRATIONS; FETAL GROWTH-RETARDATION; ARTERY BLOOD-FLOW; SPIRAL ARTERIES; SOLUBLE ENDOGLIN; TROPHOBLASTIC INVASION AB Defective deep placentation has been associated with a spectrum of complications of pregnancy including preeclampsia, intrauterine growth restriction, preterm labor, preterm premature rupture of membranes, late spontaneous abortion, and abruptio placentae. The disease of the placental vascular bed that underpins these complications is commonly investigated with targeted biopsies. In this review, we critically evaluate the biopsy technique to summarize the salient types of defective deep placentation, and propose criteria for the classification of defective deep placentation into 3 types based on the degree of restriction of remodeling and the presence of obstructive lesions in the myometrial segment of the spiral arteries. C1 [Brosens, Ivo] Katholieke Univ Leuven, Leuven Inst Fertil & Embryol, Louvain, Belgium. [Pijnenborg, Robert; Vercruysse, Lisbeth] Katholieke Univ Leuven Hosp, Dept Woman & Child, Louvain, Belgium. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA. [Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Brosens, I (reprint author), Katholieke Univ Leuven, Leuven Inst Fertil & Embryol, Louvain, Belgium. FU Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health/Department of Health and Human Services FX Supported, in part, by the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health/Department of Health and Human Services. NR 78 TC 234 Z9 249 U1 2 U2 22 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 MAR PY 2011 VL 204 IS 3 BP 193 EP 201 DI 10.1016/j.ajog.2010.08.009 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 730CY UT WOS:000288010300010 PM 21094932 ER PT J AU Kido, T Tomita, T Okamoto, M Cai, Y Matsumoto, Y Vinson, C Maru, Y Kimura, S AF Kido, Taketomo Tomita, Takeshi Okamoto, Minoru Cai, Yan Matsumoto, Yoshimi Vinson, Charles Maru, Yoshiro Kimura, Shioko TI FOXA1 plays a role in regulating secretoglobin 1a1 expression in the absence of CCAAT/enhancer binding protein activities in lung in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE cc10; lung specific; tetracycline regulation; CCSP; dominant-negative ID C/EBP TRANSCRIPTION FACTORS; GENE-EXPRESSION; EPITHELIAL-CELLS; ALPHA; MICE; DIFFERENTIATION; DELTA; LIVER; PROLIFERATION; UTEROGLOBIN AB Kido T, Tomita T, Okamoto M, Cai Y, Matsumoto Y, Vinson C, Maru Y, Kimura S. FOXA1 plays a role in regulating secretoglobin 1a1 expression in the absence of CCAAT/enhancer binding protein activities in lung in vivo. Am J Physiol Lung Cell Mol Physiol 300: L441-L452, 2011. First published December 17, 2010; doi:10.1152/ajplung.00435.2009.-Secretoglobin (SCGB) 1A1, also called Clara cell secretor protein (CCSP) or Clara cell-specific 10-kDa protein (CC10), is a small molecular weight secreted protein mainly expressed in lung, with anti-inflammatory/immunomodulatory properties. Previous in vitro studies demonstrated that CCAAT/enhancer-binding proteins (C/EBPs) are the major transcription factors for the regulation of Scbg1a1 gene expression, whereas FOXA1 had a minimum effect on the transcription. To determine the in vivo role of C/EBPs in the regulation of SCGB1A1 expression, experiments were performed in which A-C/EBP, a dominant-negative form of C/EBP that interferes with DNA binding activities of all C/EBPs, was specifically expressed in lung. Surprisingly, despite the in vitro findings, expression of SCGB1A1 mRNA was not decreased in vivo in the absence of C/EBPs. This may be due to a compensatory role assumed by FOXA1 in the regulation of Scgb1a1 gene expression in lung in the absence of active C/EBPs. This disconnect between in vitro and in vivo results underscores the importance of studies using animal models to determine the role of specific transcription factors in the regulation of gene expression in intact multicellular complex organs such as lung. C1 [Kido, Taketomo; Tomita, Takeshi; Okamoto, Minoru; Cai, Yan; Matsumoto, Yoshimi; Vinson, Charles; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Tomita, Takeshi; Maru, Yoshiro] Tokyo Womens Med Univ, Dept Pharmacol, Tokyo, Japan. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3106, Bethesda, MD 20892 USA. EM kimuras@mail.nih.gov RI Cai, Yan/P-4383-2015 FU National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research. NR 31 TC 6 Z9 7 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAR PY 2011 VL 300 IS 3 BP 441 EP 452 DI 10.1152/ajplung.00435.2009 PG 12 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 728ZX UT WOS:000287915100014 ER PT J AU Fee, E AF Fee, Elizabeth TI Charles E. Terry (1878-1945): Early Campaigner Against Drug Addiction SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM changb@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2011 VL 101 IS 3 BP 451 EP 451 DI 10.2105/AJPH.2010.191171 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 724JL UT WOS:000287571800015 PM 21307375 ER PT J AU Roth, GA Fee, E AF Roth, Ginny A. Fee, Elizabeth TI The Invention of Braille SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Roth, Ginny A.; Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20984 USA. RP Roth, GA (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,MSC 3819,Bldg 38,Room 1E-21, Bethesda, MD 20984 USA. EM changb@mail.nih.gov NR 1 TC 2 Z9 2 U1 1 U2 6 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 MAR PY 2011 VL 101 IS 3 BP 454 EP 454 DI 10.2105/AJPH.2010.200865 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 724JL UT WOS:000287571800017 PM 21307377 ER PT J AU Emmanuel, B Kawira, E Ogwang, MD Wabinga, H Magatti, J Nkrumah, F Neequaye, J Bhatia, K Brubaker, G Biggar, RJ Mbulaiteye, SM AF Emmanuel, Benjamin Kawira, Esther Ogwang, Martin D. Wabinga, Henry Magatti, Josiah Nkrumah, Francis Neequaye, Janet Bhatia, Kishor Brubaker, Glen Biggar, Robert J. Mbulaiteye, Sam M. TI African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID EPSTEIN-BARR-VIRUS; PLASMODIUM-FALCIPARUM INFECTIONS; SICKLE-CELL TRAIT; SEASONAL-VARIATION; CANCER INCIDENCE; UGANDA; AREA; TRANSMISSION; CHILDREN; GHANA AB African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated age-specific pat terns of 2,602 cases of African Burkitt lymphoma (60% male, mean +/- SD age = 7.1 +/- 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma. C1 NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kawira, Esther] Shirati Hlth Educ & Dev Fdn, Shirati, Tanzania. [Ogwang, Martin D.] St Marys Hosp, Dept Surg, Lacor, Gulu, Uganda. [Wabinga, Henry] Makerere Univ, Kampala Canc Registry, Makerere Coll Hlth Sci, Dept Pathol, Kampala, Uganda. [Emmanuel, Benjamin; Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Magatti, Josiah; Brubaker, Glen] Interchurch Med Assistance, New Windsor, MD USA. Shirati Hosp, Shirati, North Mara, Tanzania. [Nkrumah, Francis] Univ Ghana, Noguchi Mem Inst, Legon, Ghana. [Neequaye, Janet] Korle Bu Univ, Teaching Hosp, Dept Child Hlth, Korle Bu, Accra, Ghana. [Biggar, Robert J.] Staten Serum Inst, Dept Epidemiol Res, Copenhagen S, Denmark. Emeritus Prof Noguchi Mem Inst, Accra, Ghana. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S,Room 7080, Rockville, MD 20852 USA. EM emmanuelb@mail.nih.gov; elkawira@gmail.com; ogwang.martin@lacorhospital.org; hwabinga@med.mak.ac.ug; jomagati2000@yahoo.com; fnkrumah@noguchi.mimcom.org; janet.neequaye@yahoo.com; bhatiak@mail.nih.gov; grb176@comcast.net; rjbiggar@gmail.com; mbulaits@mail.nih.gov FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services [HHSN26120090068P, HHSN261200555004C, N02-CP-31003, N01-CO-12400] FX The study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (grants HHSN26120090068P, HHSN261200555004C, N02-CP-31003, and N01-CO-12400). NR 39 TC 10 Z9 10 U1 0 U2 3 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 MAR PY 2011 VL 84 IS 3 BP 397 EP 401 DI 10.4269/ajtmh.2011.10-0450 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 730AK UT WOS:000287995600007 PM 21363976 ER PT J AU Felt, SA Wasfy, MO El-Tras, WF Samir, A Rahaman, BA Boshra, M Parker, TM Hatem, ME El-Bassiouny, AA Murray, CK Pimentel, G AF Felt, Stephen A. Wasfy, Momtaz O. El-Tras, Wael F. Samir, Ahmed Rahaman, Bassem Abdel Boshra, Marie Parker, Tina M. Hatem, Mahmoud Essam El-Bassiouny, Ahmed Ahmed Murray, Clinton K. Pimentel, Guillermo TI Cross-Species Surveillance of Leptospira in Domestic and Pen-Domestic Animals in Mahalla City, Gharbeya Governorate, Egypt SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ACUTE FEBRILE ILLNESS; PATHOGENIC LEPTOSPIRES; CANINE LEPTOSPIROSIS; INFECTION; SHEEP; EAST; FARM; DOGS; PCR AB A survey of 179 animals (black rats, dogs, sheep, buffaloes, cattle, donkeys, weasels, and cats) for Leptospira infection was conducted in Mahalla City (Lower Egypt). Blood, urine, and kidney were collected and tested by culture, microscopic agglutination test (MAT), and/or polymerase chain reaction (PCR). Among rats, 26% were positive by PCR, including 7% that were also positive by culture for L. interrogans serovars Grippotyphosa, Pyrogenes, and Icterohaemorrhagiae. L. borpetersenii serovar Polonica was isolated for the first time in Egypt in three rats. MAT titers >= 1:800 were observed in 11% of rats and 12% of dogs. L. interrogans serovar Grippotyphosa was detected in one cat. Sheep and donkeys were negative for leptospirosis by all methods. Buffaloes and cattle were seropositive in 20% and 44% of animals, respectively. Data indicate that several pathogenic serovars are circulating in the animals, which may pose exposure risks and account for high rates of acute febrile illness. C1 [Wasfy, Momtaz O.; Rahaman, Bassem Abdel; Boshra, Marie; Pimentel, Guillermo] USN, Med Res Unit 3, Lab Unit, Cairo 11517, Egypt. [Felt, Stephen A.] Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA. [Parker, Tina M.] NIAID, TB Leprosy & Other Mycobacterial Dis Resp Dis Bra, DMID, NIH,DHHS, Bethesda, MD 20892 USA. [El-Tras, Wael F.; El-Bassiouny, Ahmed Ahmed] Kafr El Sheik Univ, Fac Vet Med, Dept Hyg & Prevent Med, Kafr Al Sheikh, Egypt. [Samir, Ahmed] Cairo Univ, Fac Vet, Dept Microbiol, Coll Med, Cairo, Egypt. [Hatem, Mahmoud Essam] Cairo Univ, Fac Vet Med, Dept Microbiol, Cairo, Egypt. [Murray, Clinton K.] Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. RP Wasfy, MO (reprint author), USN, Med Res Unit 3, Lab Unit, 3A Imtidad Ramses St, Cairo 11517, Egypt. EM felt@stanford.edu; momtaz.wasfy.eg@med.navy.mil; wael_tras@yahoo.com; ahmedsamir121@hotmail.com; bassem.abdel-rahman.eg@med.navy.mil; marie.boshra@gmail.com; parkerti@niaid.nih.gov; essamhatem@yahoo.com; bassiounya@yahoo.com; clinton.murray@us.army.mil OI El-Tras, Wael/0000-0003-1276-7164; Pimentel, Guillermo/0000-0003-2464-1526 FU Global Emerging Infections Surveillance (GEIS); Institutional Animal Care and Use Committee of the US Naval Medical Research Unit-3 (NAMU-3); Accreditation of the International Association of Assessment of Laboratory Animal Care (AAALAC) FX The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the US Navy Department or Egypt. Copyright statement: some of the authors are employees of the US Government, and this work was prepared as part of their official duties. Title 17 U.S.C. 105 provides that "copyright protection under this title is not available for any work of the United States Government." Title 17 U.S.C. 001 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties. This work was funded by Global Emerging Infections Surveillance (GEIS) in compliance with the regulations of the Institutional Animal Care and Use Committee of the US Naval Medical Research Unit-3 (NAMU-3) and Accreditation of the International Association of Assessment of Laboratory Animal Care (AAALAC). NR 39 TC 16 Z9 16 U1 0 U2 7 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 MAR PY 2011 VL 84 IS 3 BP 420 EP 425 DI 10.4269/ajtmh.2011.10-0393 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 730AK UT WOS:000287995600011 PM 21363980 ER PT J AU Wendler, D Rid, A AF Wendler, David Rid, Annette TI Systematic Review: The Effect on Surrogates of Making Treatment Decisions for Others SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID INTENSIVE-CARE-UNIT; OF-LIFE CARE; INTERNATIONAL CONSENSUS CONFERENCE; FAMILY-MEMBERS; ADVANCE DIRECTIVES; HEALTH-CARE; SUSTAINING TREATMENTS; POSTTRAUMATIC STRESS; QUALITATIVE RESEARCH; CRITICALLY-ILL AB Background: Clinical practice relies on surrogates to make or help to make treatment decisions for incapacitated adults; however, the effect of this practice on surrogates has not been evaluated. Purpose: To assess the effect on surrogates of making treatment decisions for adults who cannot make their own decisions. Data Sources: Empirical studies published in English and listed in MEDLINE, EMBASE, CINAHL, BIOETHICSLINE, PsycINFO, or Scopus before 1 July 2010. Study Selection: Eligible studies provided quantitative or qualitative empirical data, by evaluating surrogates, regarding the effect on surrogates of making treatment decisions for an incapacitated adult. Data Extraction: Information on study location, number and type of surrogates, timing of data collection, type of decisions, patient setting, methods, main findings, and limitations. Data Synthesis: 40 studies, 29 using qualitative and 11 using quantitative methods, provided data on 2854 surrogates, more than one half of whom were family members of the patient. Most surrogates were surveyed several months to years after making treatment decisions, the majority of which were end-of-life decisions. The quantitative studies found that at least one third of surrogates experienced a negative emotional burden as the result of making treatment decisions. The qualitative studies reported that many or most surrogates experienced negative emotional burden. The negative effects on surrogates were often substantial and typically lasted months or, in some cases, years. The most common negative effects cited by surrogates were stress, guilt over the decisions they made, and doubt regarding whether they had made the right decisions. Nine of the 40 studies also reported beneficial effects on a few surrogates, the most common of which were supporting the patient and feeling a sense of satisfaction. Knowing which treatment is consistent with the patient's preferences was frequently cited as reducing the negative effect on surrogates. Limitations: Thirty-two of the 40 articles reported data collected in the United States. Because the study populations were relatively homogenous, it is unclear whether the findings apply to other groups. In some cases, the effect of making treatment decisions could not be isolated from that of other stressors, such as grief or prognostic uncertainty. Nine of the studies had a response rate less than 50%, and 9 did not report a response rate. Many of the studies had a substantial interval between the treatment decisions and data collection. Conclusion: Making treatment decisions has a negative emotional effect on at least one third of surrogates, which is often substantial and typically lasts months (or sometimes years). Future research should evaluate ways to reduce this burden, including methods to identify which treatment options are consistent with the patient's preferences. C1 [Wendler, David] NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Biomed Eth, CH-8032 Zurich, Switzerland. RP Wendler, D (reprint author), NIH, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov FU National Institutes of Health; Swiss National Science Foundation [PA00B-117505/2]; National Institutes of Health Clinical Center FX Primary Funding Source: National Institutes of Health.r Grant Support: By the National Institutes of Health Clinical Center. Dr. Rid is supported by a grant from the Swiss National Science Foundation (PA00B-117505/2). NR 74 TC 157 Z9 157 U1 8 U2 30 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 1 PY 2011 VL 154 IS 5 BP 336 EP + DI 10.7326/0003-4819-154-5-201103010-00008 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 727LA UT WOS:000287799900006 PM 21357911 ER PT J AU Li, MH Luo, YH Lin, CF Chang, YT Lu, SL Kuo, CF Hong, JS Lin, YS AF Li, Ming-Han Luo, Yueh-Hsia Lin, Chiou-Feng Chang, Yu-Tzu Lu, Shiou-Ling Kuo, Chih-Feng Hong, Jau-Shyong Lin, Yee-Shin TI Dextromethorphan Efficiently Increases Bactericidal Activity, Attenuates Inflammatory Responses, and Prevents Group A Streptococcal Sepsis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INFECTED EPITHELIAL-CELLS; PYROGENIC EXOTOXIN-B; HUMAN NEUTROPHILS; OXIDATIVE STRESS; MOUSE MODEL; PYOGENES; APOPTOSIS; ACTIVATION; PATHOGENS; DISEASE AB Group A streptococcus ( GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-1 beta and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study. C1 [Li, Ming-Han; Luo, Yueh-Hsia; Lin, Chiou-Feng; Lu, Shiou-Ling; Lin, Yee-Shin] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 701, Taiwan. [Lin, Chiou-Feng] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 701, Taiwan. [Chang, Yu-Tzu] Natl Cheng Kung Univ Hosp, Dept Internal Med, Tainan 70428, Taiwan. [Lu, Shiou-Ling] Natl Cheng Kung Univ, Coll Med, Inst Basic Med Sci, Tainan 701, Taiwan. [Kuo, Chih-Feng] I Shou Univ, Dept Nursing, Kaohsiung Cty, Taiwan. [Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, Res Triangle Pk, NC USA. RP Lin, YS (reprint author), Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, 1 Univ Rd, Tainan 701, Taiwan. EM yslin1@mail.ncku.edu.tw FU National Health Research Institutes, Taiwan [NHRI-EX95-9429SP]; NIEHS, NIH FX This work was supported by grant NHRI-EX95-9429SP from the National Health Research Institutes, Taiwan. This research was supported in part by the Intramural Research Program of the NIEHS, NIH. NR 44 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2011 VL 55 IS 3 BP 967 EP 973 DI 10.1128/AAC.00950-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 726AD UT WOS:000287687100004 PM 21199930 ER PT J AU Newman, ZL Sirianni, N Mawhinney, C Lee, MS Leppla, SH Moayeri, M Johansen, LM AF Newman, Zachary L. Sirianni, Nicole Mawhinney, Christina Lee, Margaret S. Leppla, Stephen H. Moayeri, Mahtab Johansen, Lisa M. TI Auranofin Protects against Anthrax Lethal Toxin-Induced Activation of the Nlrp1b Inflammasome SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GOLD SODIUM THIOMALATE; KAPPA-B KINASE; POTASSIUM CHANNEL; INTERLEUKIN-1 PRODUCTION; CASPASE-1 ACTIVATION; MEDIATED ACTIVATION; CEREBRAL-ISCHEMIA; FRIEDREICH ATAXIA; MONOCYTES INVITRO; CELL-DEATH AB Anthrax lethal toxin (LT) is the major virulence factor for Bacillus anthracis. The lethal factor (LF) component of this bipartite toxin is a protease which, when transported into the cellular cytoplasm, cleaves mitogen-activated protein kinase kinase (MEK) family proteins and induces rapid toxicity in mouse macrophages through activation of the Nlrp1b inflammasome. A high-throughput screen was performed to identify synergistic LT-inhibitory drug combinations from within a library of approved drugs and molecular probes. From this screen we discovered that auranofin, an organogold compound with anti-inflammatory activity, strongly inhibited LT-mediated toxicity in mouse macrophages. Auranofin did not inhibit toxin transport into cells or MEK cleavage but inhibited both LT-mediated caspase-1 activation and caspase-1 catalytic activity. Thus, auranofin inhibited LT-mediated toxicity by preventing activation of the Nlrp1b inflammasome and the downstream actions that occur in response to the toxin. Idebenone, an analog of coenzyme Q, synergized with auranofin to increase its protective effect. We found that idebenone functions as an inhibitor of voltage-gated potassium channels and thus likely mediates synergy through inhibition of the potassium fluxes which have been shown to be required for Nlrp1b inflammasome activation. C1 [Sirianni, Nicole; Mawhinney, Christina; Lee, Margaret S.; Johansen, Lisa M.] Zalicus Inc, Cambridge, MA 02142 USA. [Newman, Zachary L.; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, NIH, Bethesda, MD 20892 USA. RP Johansen, LM (reprint author), Zalicus Inc, 245 1st St, Cambridge, MA 02142 USA. EM ljohansen@zalicus.com FU NIH, National Institute of Allergy and Infectious Diseases; National Institute for Allergy and Infectious Diseases [5 U01 AI061345] FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases, and a grant from the National Institute for Allergy and Infectious Diseases (5 U01 AI061345) awarded to L.M.J. NR 52 TC 14 Z9 16 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2011 VL 55 IS 3 BP 1028 EP 1035 DI 10.1128/AAC.00772-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 726AD UT WOS:000287687100011 PM 21149629 ER PT J AU Bilusic, M Dahut, WL AF Bilusic, Marijo Dahut, William L. TI Cabazitaxel: a new drug for metastatic prostate cancer SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID DOCETAXEL; MITOXANTRONE; PREDNISONE; INFUSION C1 [Bilusic, Marijo; Dahut, William L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 0 Z9 0 U1 1 U2 6 PU SHANGHAI INST MATERIA MEDICA PI SHANGHAI PA 555 ZU CHONG ZHI RD, ZHANG JIANG HI-TECH PARK, SHANGHAI, PUDONG 201203, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD MAR PY 2011 VL 13 IS 2 BP 185 EP 186 DI 10.1038/aja.2010.161 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 730YV UT WOS:000288074400005 PM 21151153 ER PT J AU Koh, KK Sakuma, I Quon, MJ AF Koh, Kwang Kon Sakuma, Ichiro Quon, Michael J. TI Differential metabolic effects of distinct statins SO ATHEROSCLEROSIS LA English DT Review DE Statins; Insulin resistance; Diabetes ID C-REACTIVE PROTEIN; ASSESSING INSULIN SENSITIVITY; DEPENDENT DIABETES-MELLITUS; RANDOMIZED CONTROLLED-TRIAL; IMPAIRED FASTING GLUCOSE; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; HYPERCHOLESTEROLEMIC PATIENTS; NONDIABETIC PATIENTS; ENDOTHELIAL DYSFUNCTION AB Reciprocal relationships between endothelial dysfunction and insulin resistance suggest that therapies improving endothelial dysfunction will simultaneously improve insulin sensitivity and other metabolic parameters. However, previous studies with some statins either did not alter insulin sensitivity or promoted insulin resistance despite significant improvements in endothelial dysfunction and decreases in circulating pro-inflammatory markers. This may be due to pleiotropic or off-target effects of some statins to cause insulin resistance by diverse mechanisms unrelated to endothelial dysfunction. Indeed, there is evidence of other differential metabolic actions of distinct statins including effects on hydroxymethylglutaryl-CoA reductase inhibition, isoprotenoid synthesis, calcium release, glucose transport, insulin secretion, and/or insulin resistance. Pravastatin increases expression of adiponectin mRNA, enhances adiponectin secretion, increases plasma levels of adiponectin, and enhances insulin sensitivity in mice and humans. Clinical studies including large scale randomized controlled trials demonstrate potential differences between individual statins, with pravastatin promoting risk reduction for new onset of diabetes. Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk. Given the frequent concordance of metabolic diseases including diabetes, obesity, and metabolic syndrome with cardiovascular diseases associated with hyperlipidemia, it is important to understand the potential metabolic risks and benefits of therapies with distinct statins. In this review, we discuss these differential effects of statins on metabolic homeostasis and insulin sensitivity. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon] Gachon Univ, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, Inchon 405760, South Korea. [Sakuma, Ichiro] Hokko Mem Clin, Sapporo, Hokkaido, Japan. [Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Univ, Vasc Med & Atherosclerosis Unit, Gil Med Ctr, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Gachon University Gil Hospital [2008-1, 2009-1]; National Center for Complementary and Alternative Medicine, National Institutes of Health FX This study was supported by grants from established investigator award (2008-1, 2009-1) (K.K. Koh), Gachon University Gil Hospital and by the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health (M.J. Quon). NR 74 TC 70 Z9 74 U1 2 U2 19 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 MAR PY 2011 VL 215 IS 1 BP 1 EP 8 DI 10.1016/j.atherosclerosis.2010.10.036 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 730CN UT WOS:000288008700001 PM 21130454 ER PT J AU Wullschleger, S Wasserman, DH Gray, A Sakamoto, K Alessi, DR AF Wullschleger, Stephan Wasserman, David H. Gray, Alex Sakamoto, Kei Alessi, Dario R. TI Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P-2 in regulating insulin sensitivity defined by knock-in analysis SO BIOCHEMICAL JOURNAL LA English DT Article DE insulin signalling; phosphoinositide 3-kinase (PI3K); pleckstrin homology domain (PH domain); protein tyrosine phosphatase; tandem pleckstrin homology-domain-containing protein (TAPP) ID PLECKSTRIN HOMOLOGY DOMAINS; PROTEIN TAPP1; PH-DOMAIN; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; PHOSPHATASE; RESISTANCE; RECEPTOR; MICE; ACTIVATION AB Insulin sensitivity is critically dependent on the activity of PI3K (phosphoinositide 3-kinase) and generation of the PtdIns(3,4,5)P-3 second messenger. PtdIns(3,4,5)P-3 can be broken down to PtdIns(3,4)P-2 through the action of the SHIPs (Src-homology-2-domain-containing inositol phosphatases). As PtdIns(3,4)P-2 levels peak after those of PtdIns(3,4,5)P-3, it has been proposed that PtdIns(3,4)P-2 controls a negative-feedback loop that down-regulates the insulin and PI3K network. Previously, we identified two related adaptor proteins termed TAPP [tandem PH (pleckstrin homology)-domain-containing protein] 1 and TAPP2 that specifically bind to PtdIns(3,4)P-2 through their C-terminal PH domain. To determine whether TAPP1 and TAPP2 play a role in regulating insulin sensitivity, we generated knock-in mice that express normal endogenous levels of mutant TAPP1 and TAPP2 that are incapable of binding PtdIns(3,4)P-2. These homozygous TAPP1(R211L/R211L)TAPP2(R218L)/R-218L double knock-in mice are viable and exhibit significantly enhanced activation of Akt, a key downstream mediator of insulin signalling. Consistent with increased PI3K and Akt activity, the double knock-in mice display enhanced whole body insulin sensitivity and disposal of glucose uptake into muscle tissues. We also generated wild-type and double TAPP1(R211L/R211L)TAPP2(R218L/R218L) knock-in embryonic fibroblasts and found that insulin triggered enhanced production of PtdIns(3,4,5)P-3 and Akt activity in the double knock-in fibroblasts. These observations provide the first genetic evidence to support the notion that binding of TAPP1 and TAPP2 adaptors to PtdIns(3,4)P-2 function as negative regulators of the insulin and PI3K signalling pathways. C1 [Wullschleger, Stephan; Sakamoto, Kei; Alessi, Dario R.] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. [Wasserman, David H.] Vanderbilt Univ, Vanderbilt NIH Mouse Metab Phenotyping Ctr, Sch Med, Nashville, TN 37232 USA. [Gray, Alex] Univ Dundee, Coll Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland. RP Wullschleger, S (reprint author), Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee DD1 5EH, Scotland. EM s.wullschleger@dundee.ac.uk; d.r.alessi@dundee.ac.uk OI Alessi, Dario/0000-0002-2140-9185 FU Medical Research Council; AstraZeneca; Boehringer-Ingelheim; GlaxoSmithKline; Merck KGaA; Pfizer; National Institutes of Health [U24 DK059637, R01 DK054902] FX We thank the Medical Research Council and the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA and Pfizer) for financial support. The research was also supported by the National Institutes of Health [grant numbers U24 DK059637 and R01 DK054902]. NR 45 TC 22 Z9 23 U1 0 U2 6 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 MAR 1 PY 2011 VL 434 BP 265 EP 274 DI 10.1042/BJ20102012 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 727XA UT WOS:000287835200009 PM 21204784 ER PT J AU Tran, SD Redman, RS Barrett, AJ Pavletic, SZ Key, S Liu, YN Carpenter, A Nguyen, HM Sumita, Y Baum, BJ Pillemer, SR Mezey, E AF Tran, Simon D. Redman, Robert S. Barrett, A. John Pavletic, Steven Z. Key, Sharon Liu, Younan Carpenter, Ashley Nguyen, Hieu M. Sumita, Yoshinori Baum, Bruce J. Pillemer, Stanley R. Mezey, Eva TI Microchimerism in Salivary Glands after Blood- and Marrow-Derived Stem Cell Transplantation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Salivary glands; Microchimerism; Bone marrow stem cells; Blood stem cells; Transplantation ID EPITHELIAL-CELLS; BONE-MARROW; CHIMERISM; TOLERANCE; RECIPIENT AB Blood- and marrow-derived stem cells (BMDSCs) provide disease-ameliorating effects for cardiovascular and autoimmune diseases. Microchimerism from donor BMDSCs has been reported in several recipient tissues. We hypothesized that this finding suggests a potential use of BMDSCs in the treatment of salivary dysfunctions. We investigated the presence of Y chromosome-positive cells in salivary gland biopsies of 5 females who had received a marrow or blood stem cell transplant from male donors. One to 16 years after transplantation, all recipients exhibited scattered Y chromosome-positive cells in the acini, ducts, and Stroma of their salivary glands (mean of 1.01%). Potentially, these cells can be markers of transplantation tolerance, contribute to neoplastic epithelial tissues, or engraft at sites of injury. In addition, transplantation of BMDSCs could be used for treatment of Sjogren's syndrome and salivary glands damaged by therapeutic irradiation for cancers of the head and neck. Biol Blood Marrow Transplant 17: 429-433 (2011) (C) 2011 American Society for Blood and Marrow Transplantation C1 [Tran, Simon D.; Liu, Younan; Nguyen, Hieu M.; Sumita, Yoshinori] McGill Univ, Fac Dent, Montreal, PQ H3A 2B2, Canada. [Redman, Robert S.] Dept Vet Affairs Med Ctr, Oral Pathol Res Lab, Washington, DC USA. [Barrett, A. John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Pavletic, Steven Z.; Carpenter, Ashley] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Key, Sharon; Baum, Bruce J.; Mezey, Eva] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Sumita, Yoshinori] Nagasaki Univ, Dept Regenerat Oral Surg, Nagasaki, Japan. [Pillemer, Stanley R.] MacroGenics Inc, Rockville, MD USA. RP Tran, SD (reprint author), McGill Univ, Fac Dent, 3640 Univ St,Room M-43, Montreal, PQ H3A 2B2, Canada. EM simon.tran@mcgill.ca FU NCI; NIDCR; NHLBI; Canadian Institutes of Health Research; Department of Veterans Affairs FX Roseanne Leakan, Peiman Hematti, David Kleinman, Jane Atkinson, Amalia Dutra, Evgenia Pak, Vidya Sankar, Kathy Kalinyak, and for donating the Na+-K+-2Cl- cotransporter antibody, R. James Turner (NIDCR). This study was supported in part by research funding from the Intramural Research Programs of NCI, NIDCR, and NHLBI, the Canadian Institutes of Health Research, and the Department of Veterans Affairs. NR 21 TC 11 Z9 12 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2011 VL 17 IS 3 BP 429 EP 433 DI 10.1016/j.bbmt.2010.09.021 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 725GM UT WOS:000287633200017 PM 20940057 ER PT J AU Parekh, SH Chatterjee, K Lin-Gibson, S Moore, NM Cicerone, MT Young, MF Simon, CG AF Parekh, Sapun H. Chatterjee, Kaushik Lin-Gibson, Sheng Moore, Nicole M. Cicerone, Marcus T. Young, Marian F. Simon, Carl G., Jr. TI Modulus-driven differentiation of marrow stromal cells in 3D scaffolds that is independent of myosin-based cytoskeletal tension SO BIOMATERIALS LA English DT Article DE Three-dimensional culture; Bone marrow stromal cell; Cytoskeleton; Hydrogels; Matrix modulus ID MESENCHYMAL STEM-CELLS; INTERMEDIATE-FILAMENTS; EXTRACELLULAR-MATRIX; STIFFNESS; BONE; MECHANOTRANSDUCTION; MICROTUBULES; TRANSFORM; INTEGRINS; SUBSTRATE AB Proliferation and differentiation of cells are known to be influenced by the physical properties of the extracellular environment. Previous studies examining biophysics underlying cell response to matrix stiffness utilized a two-dimensional (2D) culture format, which is not representative of the three-dimensional (3D) tissue environment in vivo. We report on the effect of 3D matrix modulus on human bone marrow stromal cell (hBMSC) differentiation. hBMSCs underwent osteogenic differentiation in poly (ethylene glycol) hydrogels of all modulus (300-fold modulus range, from 0.2 kPa to 59 kPa) in the absence of osteogenic differentiation supplements. This osteogenic differentiation was modulus-dependent and was enhanced in stiffer gels. Osteogenesis in these matrices required integrin-protein ligation since osteogenesis was inhibited by soluble Arginine-Glycine-Aspartate-Serine peptide, which blocks integrin receptors. Immunostained images revealed lack of well-defined actin filaments and microtubules in the encapsulated cells. Disruption of mechanosensing elements downstream of integrin binding that have been identified from 2D culture such as actin filaments, myosin II contraction, and RhoA kinase did not abrogate hBMSC material-driven osteogenic differentiation in 3D. These data show that increased hydrogel modulus enhanced osteogenic differentiation of hBMSCs in 3D scaffolds but that hBMSCs did not use the same mechanosensing pathways that have been identified in 2D culture. Published by Elsevier Ltd. C1 [Parekh, Sapun H.; Chatterjee, Kaushik; Lin-Gibson, Sheng; Moore, Nicole M.; Cicerone, Marcus T.; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Chatterjee, Kaushik; Young, Marian F.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Simon, CG (reprint author), NIST, Div Polymers, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM carl.simon@nist.gov FU National Research Council of the National Academy of Sciences; NIST; NIH-NIBIB [R21 EB006497-01]; NIH-NIDCR FX K.C., S.H.P., and N.M.M. were supported by Research Associateship Awards from the National Research Council of the National Academy of Sciences. This work was supported by NIST, NIH-NIBIB R21 EB006497-01 and the Intramural Program of the NIH-NIDCR. The Tulane Center for Gene Therapy provided hBMSCs (NCRR/NIH P40RR017447). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH or NIST. Certain equipment and instruments or materials are identified in the paper to adequately specify the experimental details. Such identification does not imply recommendation by NIST, nor does it imply the materials are necessarily the best available for the purpose. NR 42 TC 53 Z9 55 U1 2 U2 38 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 MAR PY 2011 VL 32 IS 9 BP 2256 EP 2264 DI 10.1016/j.biomaterials.2010.11.065 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 722JI UT WOS:000287428100003 PM 21176956 ER PT J AU Huang, CY Qin, J AF Huang, Chiung-Yu Qin, Jing TI Nonparametric estimation for length-biased and right-censored data SO BIOMETRIKA LA English DT Article DE Backward and forward recurrence time; Cross-sectional sampling; Partial likelihood; Random truncation; Renewal process ID PRODUCT-LIMIT ESTIMATOR; PREVALENT COHORT DATA; SURVIVAL-DATA; TRUNCATION AB This paper considers survival data arising from length-biased sampling, where the survival times are left truncated by uniformly distributed random truncation times. We propose a nonparametric estimator that incorporates the information about the length-biased sampling scheme. The new estimator retains the simplicity of the truncation product-limit estimator with a closed-form expression, and has a small efficiency loss compared with the nonparametric maximum likelihood estimator, which requires an iterative algorithm. Moreover, the asymptotic variance of the proposed estimator has a closed form, and a variance estimator is easily obtained by plug-in methods. Numerical simulation studies with practical sample sizes are conducted to compare the performance of the proposed method with its competitors. A data analysis of the Canadian Study of Health and Aging is conducted to illustrate the methods and theory. C1 [Huang, Chiung-Yu; Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Huang, CY (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM huangchi@niaid.nih.gov; jingqin@niaid.nih.gov NR 20 TC 14 Z9 16 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD MAR PY 2011 VL 98 IS 1 BP 177 EP 186 DI 10.1093/biomet/asq069 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 726XA UT WOS:000287759000013 ER PT J AU Tasevska, N Midthune, D Potischman, N Subar, AF Cross, AJ Bingham, SA Schatzkin, A Kipnis, V AF Tasevska, Natasa Midthune, Douglas Potischman, Nancy Subar, Amy F. Cross, Amanda J. Bingham, Sheila A. Schatzkin, Arthur Kipnis, Victor TI Use of the Predictive Sugars Biomarker to Evaluate Self-Reported Total Sugars Intake in the Observing Protein and Energy Nutrition (OPEN) Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRES; PARA-AMINOBENZOIC ACID; MEASUREMENT ERROR; URINARY SUCROSE; DIETARY-INTAKE; NITROGEN; EPIDEMIOLOGY; VALIDATION; WEIGHT; MARKER AB Background: A predictive biomarker for intake of total sugars was recently developed under controlled conditions. We used this biomarker to assess measurement error (ME) structure in self-reported intake of total sugars in free-living individuals. Methods: The Observing Protein and Energy Nutrition (OPEN) study involved 484 participants aged 40 to 69 years. Diet was assessed using two administrations of a food frequency questionnaire (FFQ) and two nonconsecutive 24-hour dietary recalls (24HDR). Two 24-hour urine samples checked for completeness were analyzed on sucrose and fructose. We applied the biomarker calibrated in a feeding study to OPEN data to assess the ME structure and the attenuation factors (AF) for intakes of absolute total sugars and sugars density for the FFQ and 24HDR. Results: The AFs for absolute sugars were similar for a single FFQ and 24HDR, but attenuation decreased with repeated 24HDRs. For sugars density, the AFs for FFQ (men: 0.39; women: 0.33) were greater than for single 24HDR (men: 0.30; women: 0.24), and similar to two 24HDRs (men: 0.41; women: 0.35). The attenuation associated with both instruments was greater in women than in men. Conclusions: Both the FFQ and 24HDR were found to be biased; hence, incorporation of the sugars biomarker in calibration studies within the cohorts may be necessary to more reliably estimate associations of sugars and disease. Impact: In this article, we propose a new dietary reference instrument based on the recently defined class of predictive biomarkers. Using sugars biomarker, we quantify ME in the FFQ- and 24HDR-reported absolute total sugars and total sugars density. Cancer Epidemiol Biomarkers Prev; 20(3); 490-500. (C)2011 AACR. C1 [Tasevska, Natasa; Potischman, Nancy; Subar, Amy F.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Tasevska, Natasa; Cross, Amanda J.; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Midthune, Douglas; Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Bingham, Sheila A.] MRC, Dunn Nutr Unit, Cambridge CB4 1XJ, England. RP Tasevska, N (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 6130 Executive Blvd,EPN-3121, Bethesda, MD 20892 USA. EM tasevskan@mail.nih.gov RI Trivedi, Kruti/E-7558-2015 FU National Cancer Institute, NIH, U.S. Department of Health and Human Services FX Supported by the Intramural Research Program of the National Cancer Institute, NIH, U.S. Department of Health and Human Services. NR 44 TC 15 Z9 15 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2011 VL 20 IS 3 BP 490 EP 500 DI 10.1158/1055-9965.EPI-10-0820 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 730WO UT WOS:000288067200011 PM 21278329 ER PT J AU de Castro, A Jones, HE Johnson, RE Gray, TR Shakleya, DM Huestis, MA AF de Castro, Ana Jones, Hendree E. Johnson, Rolley E. Gray, Teresa R. Shakleya, Diaa M. Huestis, Marilyn A. TI Maternal Methadone Dose, Placental Methadone Concentrations, and Neonatal Outcomes SO CLINICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; ABSTINENCE SYNDROME; SIMULTANEOUS QUANTIFICATION; WITHDRAWAL SYNDROME; PLASMA; EXPOSURE; 2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE; MAINTENANCE; METABOLITES; MECONIUM AB BACKGROUND: Few investigations have used placenta as an alternative matrix to detect in utero drug exposure, despite its availability at the time of birth and the large amount of sample. Methadone-maintained opioid-dependent pregnant women provide a unique opportunity to examine the placental disposition of methadone and metabolite [2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)], to explore their correlations with maternal methadone dose and neonatal outcomes, and to test the ability to detect in utero exposure to illicit drugs. METHODS: We calculated the correlations of placental methadone and EDDP concentrations and their correlations with maternal methadone doses and neonatal outcomes. Cocaine-and opiate-positive placenta results were compared with the results for meconium samples and for urine samples collected throughout gestation. RESULTS: Positive correlations were found between placental methadone and EDDP concentrations (r = 0.685), and between methadone concentration and methadone dose at delivery (r = 0.542), mean daily dose (r = 0.554), mean third-trimester dose (r = 0.591), and cumulative daily dose (r = 0.639). The EDDP/methadone concentration ratio was negatively correlated with cumulative daily dose (r = -0.541) and positively correlated with peak neonatal abstinence syndrome (NAS) score (r = 0.513). Placental EDDP concentration was negatively correlated with newborn head circumference (r = -0.579). Cocaine and opiate use was detected in far fewer placenta samples than in thrice-weekly urine and meconium samples, a result suggesting a short detection window for placenta. CONCLUSIONS: Quantitative methadone and EDDP measurement may predict NAS severity. The placenta reflects in utero drug exposure for a shorter time than meconium but may be useful when meconium is unavailable or if documentation of recent exposure is needed. (C) 2010 American Association for Clinical Chemistry C1 [Huestis, Marilyn A.] Natl Inst Drug Abuse, IRP, NIH, Baltimore, MD 21224 USA. [de Castro, Ana] Univ Santiago de Compostela, Inst Legal Med, Santiago De Compostela, Spain. [Jones, Hendree E.; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Johnson, Rolley E.] Reckitt Benckiser Pharmaceut, Richmond, VA USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov RI DE CASTRO, ANA/M-5159-2015 OI DE CASTRO, ANA/0000-0002-9832-012X FU National Institute on Drug Abuse, NIH [DA12220, DA12403] FX Research Funding: Intramural Research Program, and Extramural Grants DA12220 and DA12403 from the National Institute on Drug Abuse, NIH. NR 34 TC 15 Z9 16 U1 0 U2 5 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 MAR PY 2011 VL 57 IS 3 BP 449 EP 458 DI 10.1373/clinchem.2010.154864 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 727ME UT WOS:000287803400017 PM 21245372 ER PT J AU van Deventer, HE Miller, WG Myers, GL Sakurabayashi, I Bachmann, LM Caudill, SP Dziekonski, A Edwards, S Kimberly, MM Korzun, WJ Leary, ET Nakajima, K Nakamura, M Shamburek, RD Vetrovec, GW Warnick, GR Remaley, AT AF van Deventer, Hendrick E. 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 Shamburek, Robert D. Vetrovec, George W. Warnick, G. Russell Remaley, Alan T. TI Non-HDL Cholesterol Shows Improved Accuracy for Cardiovascular Risk Score Classification Compared to Direct or Calculated LDL Cholesterol in a Dyslipidemic Population SO CLINICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-HEART-DISEASE; APOLIPOPROTEIN-A-I; VASCULAR-DISEASE; ARTERY DISEASE; LIPID MEASURES; PLASMA; EVENTS; WOMEN; STANDARDIZATION AB BACKGROUND: Our objective was to evaluate the accuracy of cardiovascular disease (CVD) risk score classification by direct LDL cholesterol (dLDL-C), calculated LDL cholesterol (cLDL-C), and non-HDL cholesterol (non-HDL-C) compared to classification by reference measurement procedures (RMPs) performed at the CDC. METHODS: We examined 175 individuals, including 138 with CVD or conditions that may affect LDL-C measurement. dLDL-C measurements were performed using Denka, Kyowa, Sekisui, Serotec, Sysmex, UMA, and Wako reagents. cLDL-C was calculated by the Friedewald equation, using each manufacturer's direct HDL-C assay measurements, and total cholesterol and triglyceride measurements by Roche and Siemens (Advia) assays, respectively. RESULTS: For participants with triglycerides < 2.26 mmol/L (< 200 mg/dL), the overall misclassification rate for the CVD risk score ranged from 5% to 17% for cLDL-C methods and 8% to 26% for dLDL-C methods when compared to the RMP. Only Wako dLDL-C had fewer misclassifications than its corresponding cLDL-C method (8% vs 17%; P < 0.05). Non-HDL-C assays misclassified fewer patients than dLDL-C for 4 of 8 methods (P < 0.05). For participants with triglycerides >= 2.26 mmol/L (>= 200 mg/dL) and < 4.52 mmol/L (< 400 mg/dL), dLDL-C methods, in general, performed better than cLDL-C methods, and non-HDL-C methods showed better correspondence to the RMP for CVD risk score than either dLDL-C or cLDL-C methods. CONCLUSIONS: Except for hypertriglyceridemic individuals, 7 of 8 dLDL-C methods failed to show improved CVD risk score classification over the corresponding cLDL-C methods. Non-HDL-C showed overall the best concordance with the RMP for CVD risk score classification of both normal and hypertriglyceridemic individuals. (C) 2010 American Association for Clinical Chemistry C1 [Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [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.] Ctr Dis Control Prevent, Atlanta, GA USA. [Sakurabayashi, Ikunosuke] Jichi Med Univ, Shimotsuke, Tochigi, Japan. [Leary, Elizabeth T.] Pacific Biomarkers & Pacific Biometr Res Fdn, Seattle, WA USA. [Nakajima, Katsuyuki] Otsuka Pharmaceut Co Ltd, Tokyo, Japan. [Nakamura, Masakazu] Osaka Med Ctr Hlth Sci & Promot, Osaka, Japan. [Warnick, G. Russell] Hlth Diagnost Lab, Richmond, VA USA. RP Remaley, AT (reprint author), NIH, Dept Lab Med, Bldg 10,Room 2C-433,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM aremaley1@cc.nih.gov FU Denka Seiken; Kyowa Medex; Sekisui Medical; Serotec; Sysmex International Reagents; UMA; Wako Pure Chemical Industries; Genzyme; Pointe Scientific; Pacific Biometrics Research Foundation; Warren Grant Magnuson Clinical Center; National Institutes of Health FX Research Funding: G. Miller, principal investigator for the project: Denka Seiken, Kyowa Medex, Sekisui Medical, Serotec, Sysmex International Reagents, UMA, and Wako Pure Chemical Industries donated reagents, calibrators, and controls and contributed financial support to Pacific Biometrics Research Foundation. Genzyme and Pointe Scientific contributed financial support to Pacific Biometrics Research Foundation. Pacific Biometrics Research Foundation provided a grant to Virginia Commonwealth University (funded by the financial contributions noted above). Roche Diagnostics donated reagents, calibrators, controls, and a Hitachi 917 instrument. H. E. van Deventer, Warren Grant Magnuson Clinical Center, Intramural Research Program of the National Institutes of Health. A. T. Remaley, Warren Grant Magnuson Clinical Center, Intramural Research Program of the National Institutes of Health. NR 37 TC 31 Z9 32 U1 0 U2 4 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 MAR PY 2011 VL 57 IS 3 BP 490 EP 501 DI 10.1373/clinchem.2010.154773 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 727ME UT WOS:000287803400022 PM 21228254 ER PT J AU Ravanan, P Harry, GJ Awada, R Hoareau, L Tallet, F Roche, R d'Hellencourt, CL AF Ravanan, Palaniyandi Harry, G. Jean Awada, Rana Hoareau, Laurence Tallet, Frank Roche, Regis d'Hellencourt, Christian Lefebvre TI Exposure to an organometal compound stimulates adipokine and cytokine expression in white adipose tissue SO CYTOKINE LA English DT Article DE White adipose tissue; Adipocytes; Adipokines; Inflammation; Trimethyltin ID NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE; HUMAN ADIPOCYTES; INJURY RESPONSE; MESSENGER-RNA; IN-VITRO; TRIMETHYLTIN; OBESITY; INFLAMMATION; STANNIN AB Objective: White adipose tissue (WAT) is now considered a defined tissue capable of interactions with other organ systems. WAT role in elevating the level of systemic chronic inflammation suggests that alterations in this tissue as the result of disease or environmental factors may influence the development and progression of various obesity-related pathologies. This study investigated WAT cell-specific responses to an organometal compound, trimethyltin (TMT), to determine possible contribution to induced inflammation. Methods: Human primary mature adipocytes and macrophage differentiated THP-1 cells were cultured in TMT presence and relative toxicities and different adipokine levels were determined. The inflammatory response was examined in TMT presence for primary cells from obese ob/ob mice WAT, and after TMT injection in ob/ob mice. Results: Both adipocytes and macrophages were resistant to cell death induced by TMT. However, adipocytes cultured in TMT presence showed increased expression of TNF alpha and IL-6, and modified leptin levels. In macrophage cultures, TMT also increased TNF alpha and IL-6, while MCP-1 and MIP-1 alpha were decreased. In vivo, a single injection of TMT in ob/ob mice, elevated TNF alpha, MIP-1 alpha and adiponectin in WAT. Conclusions: Elevation of the inflammatory related products can be induced by chemical exposure in adipocytes and macrophages, as well as murine WAT. These data suggest that numerous factors, including a systemic chemical exposure, can induce an inflammatory response from the WAT. Furthermore, when characterizing both chemical-induced toxicity and the progression of the chronic inflammation associated with elevated WAT content, such responses in this target tissue should be taken into consideration. (c) 2010 Elsevier Ltd. All rights reserved. C1 [Ravanan, Palaniyandi; Awada, Rana; Hoareau, Laurence; Roche, Regis; d'Hellencourt, Christian Lefebvre] Univ Reunion, Fac Sci, GEICO, Lab Biochim & Genet Mol, F-97490 St Clotilde, Reunion. [Harry, G. Jean] NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP d'Hellencourt, CL (reprint author), Univ Reunion, Fac Sci, GEICO, Lab Biochim & Genet Mol, 15 Ave R Cassin & Plateforme CYROI,2 Rue Maxime R, F-97490 St Clotilde, Reunion. EM Christian.Lefebvre-d-Hellencourt@univ-reunion.fr FU NIEHS/NIH; Conseil Regional de La Reunion; Ministere de L'enseignement Superieur et de la Recherche FX We are grateful to the patients and the reconstructive surgery departments (CHR Felix Guyon, Saint-Denis) for the adipose tissue. We thank the Laboratoire of Biochimie (CHR Felix Guyon, Saint-Denis) for their technical assistance. This work was supported by the Intramural Research Program of NIEHS/NIH and by grants from 'Conseil Regional de La Reunion' and 'Ministere de L'enseignement Superieur et de la Recherche'. P.R. has been funded by a fellowship from 'Conseil Regional de La Reunion'. NR 47 TC 4 Z9 5 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR PY 2011 VL 53 IS 3 BP 355 EP 362 DI 10.1016/j.cyto.2010.11.015 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 727YV UT WOS:000287840200016 PM 21194965 ER PT J AU Jasper, GA Arun, I Venzon, D Kreitman, RJ Wayne, AS Yuan, CM Marti, GE Stetler-Stevenson, M AF Jasper, Gregory A. Arun, Indu Venzon, David Kreitman, Robert J. Wayne, Alan S. Yuan, Constance M. Marti, Gerald E. Stetler-Stevenson, Maryalice TI Variables Affecting the Quantitation of CD22 in Neoplastic B Cells SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD22; quantitative flow cytometry; QuantiBRITE; ABC ID IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; CHRONIC LYMPHOPROLIFERATIVE DISORDERS; CHRONIC LYMPHOCYTIC-LEUKEMIA; FLOW-CYTOMETRY; T-CELLS; EXPRESSION; MALIGNANCIES; TRIAL; STANDARDIZATION; PERFORMANCE AB Background: Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory for diagnosis, prognosis, and assessment of patients receiving antibody-based therapy. ABC values and the, effect of technical variables on CD22 quantitation in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), follicular lymphoma (FCL), hairy cell leukemia (HCL) and normal B cells were studied. Methods: The QuantiBrite System (R) was used to determine the level of CD22 expression (mean antibody bound per cell, ABC) by malignant and normal B cells. The intra-assay variability, number of cells required for precision, effect of delayed processing as well as shipment of peripheral blood specimens (delayed processing and exposure to noncontrolled environments), and the effect of paraformaldehyde fixation on assay results were studied. Results: The QuantiBRITE method of measuring CD22 ABC is precise (median CV 1.6%, 95% confidence interval, 1.2-2.3%) but a threshold of 250 malignant cells is required for reliable CD22 ABC values. Delayed processing and overnight shipment of specimens resulted in significantly different ABC values whereas fixation for up to 12 h had no significant effect. ABC measurements determined that CD22 expression is lower than normal in ALL, CLL, FCL, and MCL but higher than normal in HCL. Conclusions: CD22 expression was atypical in the hematolymphoid malignancies studied and may have diagnostic utility. Technical variables such as cell number analyzed and delayed processing or overnight shipment of specimens impact significantly on the measurement of antigen expression by QFCM in the clinical laboratory. Published 2010 Wiley-Liss, Inc. C1 [Jasper, Gregory A.; Arun, Indu; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Hematol Dis Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Marti, Gerald E.] CBER FDA, Flow & Image Cytometry Sect, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies,Off Cellular Tissues &, Bethesda, MD USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 29 Z9 29 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2011 VL 80B IS 2 BP 83 EP 90 DI 10.1002/cyto.b.20567 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 728RC UT WOS:000287891200003 PM 20872890 ER PT J AU Muniyappa, R AF Muniyappa, Ranganath TI Glucosamine and osteoarthritis: time to quit? SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material AB Glucosamine (2-amino-2-deoxy-D-glucose), an amino monosaccharide derivative of glucose, is a precursor of the glycosaminoglycans and proteoglycans that make up articular cartilage. The notion that augmenting the intake of the precursor molecule, glucosamine, may directly stimulate articular proteoglycan synthesis to modulate osteoarthritis has provided the rationale for its widespread use. Theoretically, exogenous glucosamine may augment glycosaminoglycan synthesis in cartilage. There is a simultaneous theoretical concern that it might also induce insulin resistance in insulin-sensitive tissues. In a previous issue of DMRR, Simon et al. conclude that typical doses of oral glucosamine have no significant effects on glucose metabolism or insulin sensitivity. On the basis of the results from clinical, animal, and cell-based studies they conclude that oral glucosamine neither augments the hexosamine biosynthetic pathway nor reduces insulin-mediated glucose uptake. In recent meta-analyses restricted to well-designed randomized controlled trials that include adequate allocation concealment or to non-industry-funded studies, oral glucosamine fails to show any significant clinical benefit in individuals with osteoarthritis. These data should raise serious questions from patients and their health care providers about its continued use. Published 2011 by John Wiley and Sons, Ltd. C1 NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Muniyappa, R (reprint author), NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM muniyapr@mail.nih.gov NR 6 TC 2 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAR PY 2011 VL 27 IS 3 BP 233 EP 234 DI 10.1002/dmrr.1179 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 730LH UT WOS:000288034300004 PM 21370382 ER PT J AU Birnbaum, LS AF Birnbaum, Linda S. TI SOT at 50: A Proud Legacy, A Vibrant Future SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Birnbaum, LS (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2011 VL 119 IS 3 BP 110 EP 111 DI 10.1289/ehp.1103511 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 729CU UT WOS:000287926700002 PM 21356627 ER PT J AU Freeman, KS AF Freeman, Kris S. TI US Lives: Longer but Sicker? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Freeman, Kris S.] NIH, Bethesda, MD 20892 USA. [Freeman, Kris S.] ABCNews Com, Philadelphia, PA USA. [Freeman, Kris S.] Natl Pk Serv, Washington, DC USA. RP Freeman, KS (reprint author), NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2011 VL 119 IS 3 BP 118 EP 118 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 729CU UT WOS:000287926700007 ER PT J AU Frawley, R White, K Brown, R Musgrove, D Walker, N Germolec, D AF Frawley, Rachel White, Kimber, Jr. Brown, Ronnetta Musgrove, Deborah Walker, Nigel Germolec, Dori TI Gene Expression Alterations in Immune System Pathways in the Thymus after Exposure to Immunosuppressive Chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cyclophosphamide; dexamethasone; diethylstilbestrol; T cell; thymus; toxicogenomics; 2,3,7,8-tetrachlorodibenzo-p-dioxin ID T-CELL DEVELOPMENT; DENDRITIC CELLS; NUCLEAR TRANSLOCATION; THYMOCYTE APOPTOSIS; INDUCED TOXICITY; DOWN-REGULATION; DEFICIENT MICE; FAS LIGAND; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; IMMUNOTOXICITY AB BACKGROUND: Dysregulation of positive and negative selection, antigen presentation, or apoptosis in the thymus can lead to immunosuppression or autoimmunity. Diethylstilbestrol (DES), dexamethasone (DEX), cyclophosphamide (CPS), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are immunosuppressive chemicals that induce similar immunotoxic effects in the thymus, however, the mechanism of toxicity is purported to be different for each compound. OBJECTIVES: We hypothesized that genomic analysis of thymus after chemical-induced atrophy would yield transcriptional profiles that suggest pathways of toxicity associated with reduced function. METHODS: Female B6C3F1 mice were exposed to these immunosuppressive agents and changes in gene expression and immune cell subpopulations were evaluated. RESULTS: All four chemicals induced thymic atrophy and changes in both the relative proportion and absolute number of CD3(+), CD4(+)/CD8(-), CD4(-)/CD8(+), and CD4(+)/CD8(+) thymocytes. The most significant impact of exposure to DEX, DES, and CPS was modulation of gene expression in the T-cell receptor (TCR) complex and TCR and CD28 signaling pathways; this could represent a common mechanism of action and play a pivotal role in lineage commitment and development of T cells. Up-regulation of genes associated with the antigen presentation and dendritic cell maturation pathways was the most distinctive effect of TCDD exposure. These elements, which were also up-regulated by DEX and DES, contribute to positive and negative selection. CONCLUSIONS: Genomic analysis revealed gene expression changes in several pathways that are commonly associated with xenobiotic-induced immune system perturbations, particularly those that contribute to the development and maturation of thymic T cells. C1 [Frawley, Rachel] NIEHS, Toxicol Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [White, Kimber, Jr.; Brown, Ronnetta; Musgrove, Deborah] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA USA. RP Frawley, R (reprint author), NIEHS, Toxicol Branch, Natl Toxicol Program, 530 Davis Dr,MD K2-15, Res Triangle Pk, NC 27709 USA. EM frawleyr@niehs.nih.gov RI Walker, Nigel/D-6583-2012; OI Walker, Nigel/0000-0002-9111-6855; Frawley, Rachel/0000-0001-8490-8240 FU National Institutes of Health (NIH); National Institute of Environmental Health Sciences (NIEHS) [N01-ES-55538] FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS), and NIEHS research and development contract N01-ES-55538. NR 48 TC 23 Z9 23 U1 0 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2011 VL 119 IS 3 BP 371 EP 376 DI 10.1289/ehp.1002358 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 729CU UT WOS:000287926700027 PM 21041162 ER PT J AU Potrykus, K Murphy, H Philippe, N Cashel, M AF Potrykus, Katarzyna Murphy, Helen Philippe, Nadege Cashel, Michael TI ppGpp is the major source of growth rate control in E-coli SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA TRANSCRIPTION; IN-VIVO; RIBONUCLEOPROTEIN PARTICLES; GUANOSINE TETRAPHOSPHATE; SALMONELLA-TYPHIMURIUM; RELAXED PARTICLES; SECONDARY CHANNEL; BALANCED GROWTH; DKSA; PROMOTERS AB P>It is widely accepted that the DNA, RNA and protein content of Enterobacteriaceae is regulated as a function of exponential growth rates; macromolecular content increases with faster growth regardless of specific composition of the growth medium. This phenomenon, called growth rate control, primarily involves regulation of ribosomal RNA and ribosomal protein synthesis. However, it was uncertain whether the global regulator ppGpp is the major determinant for growth rate control. Therefore, here we re-evaluate the effect of ppGpp on macromolecular content for different balanced growth rates in defined media. We find that when ppGpp is absent, RNA/protein and RNA/DNA ratios are equivalent in fast and slow growing cells. Moreover, slow growing ppGpp-deficient cells with increased RNA content, display a normal ribosomal subunit composition although polysome content is reduced when compared with fast growing wild-type cells. From this we conclude that growth rate control does not occur in the absence of ppGpp. Also, artificial elevation of ppGpp or introduction of stringent RNA polymerase mutants in ppGpp-deficient cells restores this control. We believe these findings strongly argue in favour of ppGpp and against redundant regulation of growth rate control by other factors in Escherichia coli and other enteric bacteria. C1 [Potrykus, Katarzyna; Murphy, Helen; Philippe, Nadege; Cashel, Michael] Eunice Kennedy Shriver NICHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA. RP Cashel, M (reprint author), Eunice Kennedy Shriver NICHD, Mol Genet Lab, Program Genom Dev, NIH, Bethesda, MD 20892 USA. EM cashelm@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX We thank Dr R. D'Ari for encouragement and many discussions during the course of this study. We especially acknowledge the constructive exchanges of views with Dr V.J. Hernandez. Dr R. Maraia, A. Crawford, Dr T. E. Dever and Dr B. S. Shin provided help with the polysomes methodology. We also thank Drs D. Vinella, R. Harinarayanan and the Friday Seminar for helpful advice. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural program of the National Institutes of Health. NR 47 TC 56 Z9 59 U1 4 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD MAR PY 2011 VL 13 IS 3 BP 563 EP 575 DI 10.1111/j.1462-2920.2010.02357.x PG 13 WC Microbiology SC Microbiology GA 728CY UT WOS:000287852900002 PM 20946586 ER PT J AU Vianna, NA Goncalves, D Brandao, F de Barros, RP Amado, GM Meire, RO Torres, JPM Malm, O D'Oliveira, A Andrade, LR AF Vianna, Nelzair A. Goncalves, Daniel Brandao, Flavia de Barros, Roberta P. Amado Filho, Gilberto M. Meire, Rodrigo O. Torres, Joao Paulo M. Malm, Olaf D'Oliveira Junior, Argemiro Andrade, Leonardo R. TI Assessment of heavy metals in the particulate matter of two Brazilian metropolitan areas by using Tillandsia usneoides as atmospheric biomonitor SO ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH LA English DT Article DE Air particulate matter; Atmospheric pollution; Biomonitoring; Electron microscopy; Heavy metals; Tillandsia ID RIO-DE-JANEIRO; TRACE-METALS; INDIVIDUAL PARTICLES; AIR; POLLUTION; MERCURY; L.; APPORTIONMENT; CONTAMINATION; ENVIRONMENTS AB The aims of this paper were to quantify the heavy metals (HM) in the air of different sites in Rio de Janeiro (RJ) and Salvador (SA) using Tillandsia usneoides (Bromeliaceae) as a biomonitor, and to study the morphology and elemental composition of the air particulate matter (PM) retained on the Tillandsia surface. Tillandsia samples were collected in a noncontaminated area and exposed to the air of five sites in RJ State and seven in SA for 45 days, in two seasons. Samples were prepared to HM quantification by flame atomic absorption spectrophotometry, while morphological and elemental characterizations were studied by using scanning electron microscopy. HM concentrations were significantly higher when compared to control sites. We found an increasing metal concentration as follows: Cd < Cr < Pb < Cu < Zn. PM exhibited a morphology varying from amorphous- to polygonal-shaped particles. Size measurements indicated that more than 80% of particles were less than 10 mu m. PM contained aluminosilicates iron-rich particles, but Zn, Cu, Cr, and Ba were also detected. HM input in the atmosphere was mainly associated with anthropogenic sources such as vehicle exhaust. Elemental analysis detected HM in the inhalable particles, indicating that those HMs may intensify the toxic effects of PM on human health. Our results indicated T. usneoides as an adequate biomonitor of HM in the PM belonging to the inhalable fraction. C1 [Vianna, Nelzair A.; D'Oliveira Junior, Argemiro] Univ Fed Bahia, Fac Med, Salvador, BA, Brazil. [Amado Filho, Gilberto M.] Inst Pesquisas Jardim Bot Rio de Janeiro, Programa Zona Costeira, Rio De Janeiro, Brazil. [Meire, Rodrigo O.; Torres, Joao Paulo M.; Malm, Olaf] UFRJ, Lab Radioisotopos, Inst Biofis Carlos Chagas Filho, BR-21941590 Rio De Janeiro, Brazil. [Goncalves, Daniel; Brandao, Flavia; de Barros, Roberta P.; Andrade, Leonardo R.] Univ Fed Rio de Janeiro, Inst Ciencias Biomed, Lab Biomineralizacao, BR-21941590 Rio De Janeiro, Brazil. RP Andrade, LR (reprint author), NIDCD, Sect Struct Cell Biol, Lab Cell Struct & Dynam, NIH, 50 South Dr,Rm 4249, Bethesda, MD 20892 USA. EM andrade@histo.ufrj.br RI Andrade, Leonardo/C-9554-2011; Malm, Olaf/H-1724-2012; AMADO FILHO, GILBERTO/I-1324-2012; torres, joao/H-4950-2012; Impetam, INCT/K-2199-2013 OI Andrade, Leonardo/0000-0002-0004-5677; torres, joao/0000-0002-2510-1612; FU SEMA-BA, Superintendencia do Meio Ambiente de Salvador; CNPq [Edital 18] FX We are very grateful to Dr. Juliano Matos (Secretaria de Meio Ambiente do Estado da Bahia), Jose Ricardo Thomaz for the metal analysis, and COPPE-UFRJ for its SEM-EDS analysis. We also express our gratitude to Meggie Meltzer and Nicole Thompson (National Institutes of Health) for the grammar revision; and Alzira Silva and Jose Amado (INEA-RJ) for their field support in Rio de Janeiro. In Salvador, we appreciate the field support of SEMA, Vigilancia Sanitaria, Prefeitura de Salvador, and Dr. Marcos Andre Vannier (Fiocruz-BA). This work received financial support from SEMA-BA, Superintendencia do Meio Ambiente de Salvador, and CNPq (Edital 18). The authors declare no competing financial interests. NR 41 TC 14 Z9 14 U1 2 U2 19 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0944-1344 J9 ENVIRON SCI POLLUT R JI Environ. Sci. Pollut. Res. PD MAR PY 2011 VL 18 IS 3 BP 416 EP 427 DI 10.1007/s11356-010-0387-y PG 12 WC Environmental Sciences SC Environmental Sciences & Ecology GA 723MN UT WOS:000287510800009 PM 20798993 ER PT J AU van Bemmel, DM Li, Y McLean, J Chang, MH Dowling, NF Graubard, B Rajaraman, P AF van Bemmel, Dana M. Li, Yan McLean, Jody Chang, Man-huei Dowling, Nicole F. Graubard, Barry Rajaraman, Preetha TI Blood Lead Levels, ALAD Gene Polymorphisms, and Mortality SO EPIDEMIOLOGY LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; ACUTE INTERMITTENT PORPHYRIA; UNITED-STATES; 5-AMINOLEVULINIC ACID; BRAIN-TUMORS; BONE LEAD; SUSCEPTIBILITY; WORKERS; RISK; ASSOCIATION AB Background: Previous analyses from the National Health and Nutrition Examination Survey (NHANES III) have found that elevated blood lead levels may be associated with cardiovascular mortality, cancer mortality, and all-cause mortality. The 5-aminole-vulinic acid dehydratase (ALAD) G177C genetic polymorphism (rs 1800435) affects lead toxicokinetics and may alter the adverse effects of lead exposure. We examined whether the ALAD G177C single nucleotide polymorphism (SNP) affects the relationship between lead and mortality. Methods: We analyzed a subset of 3349 genotyped NHANES III participants at least 40 years of age. Using Cox proportional hazards regression, we estimated the relative risk of all-cause, cardiovascular disease, and cancer mortality by ALAD genotype, and by blood lead levels (<5 mu g/dL vs. >= 5 mu g/dL). We also tested whether the ALAD genotype modified the relationship between blood lead level and mortality. Results: The adjusted overall relative risk for participants with the variant ALAD(CG/CC) genotype was decreased for all-cause mortality (hazards ratio = 0.68; [95% confidence interval = 0.50-0.93]) compared with persons having the common GG genotype. There was some suggestion that higher lead levels were associated with cancer mortality (1.48 [0.92-2.38]). We observed no convincing interaction effect between ALAD genotype and blood lead level on mortality risk. Conclusion: The ALAD(CG/CC) genotype may be associated with decreased mortality from all causes and from cancer. This association does not seem to be affected by lead exposure. C1 [van Bemmel, Dana M.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Rockville, MD 20852 USA. [van Bemmel, Dana M.; Li, Yan; Graubard, Barry; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA. [McLean, Jody] Ctr Dis Control & Prevent, Northrop Grumman Div Hlth & Nutr Examinat Survey, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Chang, Man-huei; Dowling, Nicole F.] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. RP van Bemmel, DM (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, 6120 Execut Blvd,Suite 150E, Rockville, MD 20852 USA. EM vanbemmeld@mail.nih.gov FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX Supported by intramural funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 51 TC 9 Z9 9 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2011 VL 22 IS 2 BP 273 EP 278 DI 10.1097/EDE.0b013e3182093f75 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 716LR UT WOS:000286970700020 PM 21293208 ER PT J AU Straus, SK Scott, WRP Schwieters, CD Marvin, DA AF Straus, S. K. Scott, W. R. P. Schwieters, C. D. Marvin, D. A. TI Consensus structure of Pf1 filamentous bacteriophage from X-ray fibre diffraction and solid-state NMR SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE alpha-Helix; Fibre diffraction; Solid-state NMR; Xplor-NIH ID MOLECULAR-STRUCTURE DETERMINATION; PROTEIN STRUCTURES; BACTERIAL VIRUSES; ANGLE RESTRAINTS; COAT PROTEIN; STRUCTURE REFINEMENT; ATOMIC REFINEMENT; ELECTRON-DENSITY; XPLOR-NIH; RESOLUTION AB Filamentous bacteriophages (filamentous bacterial viruses or Inovirus) are simple and well-characterised macromolecular assemblies that are widely used in molecular biology and biophysics, both as paradigms for studying basic biological questions and as practical tools in areas as diverse as immunology and solid-state physics. The strains fd, M13 and f1 are virtually identical filamentous phages that infect bacteria expressing F-pili, and are sometimes grouped as the Ff phages. For historical reasons fd has often been used for structural studies, but M13 and f1 are more often used for biological experiments. Many other strains have been identified that are genetically quite distinct from Ff and yet have a similar molecular structure and life cycle. One of these, Pf1, gives the highest resolution X-ray fibre diffraction patterns known for filamentous bacteriophage. These diffraction patterns have been used in the past to derive a molecular model for the structure of the phage. Solid-state NMR experiments have been used in separate studies to derive a significantly different model of Pf1. Here we combine previously published X-ray fibre diffraction data and solid-state NMR data to give a consensus structure model for Pf1 filamentous bacteriophage, and we discuss the implications of this model for assembly of the phage at the bacterial membrane. C1 [Marvin, D. A.] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. [Straus, S. K.; Scott, W. R. P.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. [Schwieters, C. D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Marvin, DA (reprint author), Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. EM d.a.marvin@bioc.cam.ac.uk FU Natural Sciences and Engineering Research Council of Canada; Michael Smith Foundation for Health Research; Center for Information Technology at the NIH; Department of Biochemistry, University of Cambridge FX We thank the many experimentalists whose published work we have cited here and without whom our work would have been impossible. S.K.S. would also like to acknowledge the Natural Sciences and Engineering Research Council of Canada and the Michael Smith Foundation for Health Research for funding. C.D.S. is supported by the intramural program of the Center for Information Technology at the NIH. D.A.M. acknowledges support from the Department of Biochemistry, University of Cambridge. NR 65 TC 10 Z9 10 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD MAR PY 2011 VL 40 IS 3 BP 221 EP 234 DI 10.1007/s00249-010-0640-9 PG 14 WC Biophysics SC Biophysics GA 726UO UT WOS:000287752100001 PM 21082179 ER PT J AU Zhang, Z Lanza, E Ross, AC Albert, PS Colburn, NH Rovine, MJ Bagshaw, D Ulbrecht, JS Hartman, TJ AF Zhang, Z. Lanza, E. Ross, A. C. Albert, P. S. Colburn, N. H. Rovine, M. J. Bagshaw, D. Ulbrecht, J. S. Hartman, T. J. TI A high-legume low-glycemic index diet reduces fasting plasma leptin in middle-aged insulin-resistant and -sensitive men SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ghrelin; insulin resistance; legume-enriched diet; leptin ID OBESE GENE; WEIGHT; FIBER; METABOLISM; GLUCOSE; GHRELIN; PROTEIN; FAT; CARBOHYDRATE; EXPRESSION AB Fasting leptin and ghrelin levels were measured in 36 insulin-sensitive (IS) and 28 insulin-resistant (IR) men who consumed a legume-enriched low-glycemic index (LG) diet or healthy American (HA) diet in a randomly ordered cross-over feeding study consisting of two 4-week periods. Weight remained stable over the entire study. Fasting plasma leptin was significantly reduced from pre-study levels by both the LG (18.8%, P < 0.001) and HA (16.1%, P < 0.001) diets, whereas fasting ghrelin did not change. By subgroup analysis according to prestudy insulin status, leptin was reduced in IR subjects after both the LG (17.1%, P < 0.01) and the HA (33.3%, P < 0.001) diets, whereas IS subjects responded only after the LG diet (23.1%, P < 0.01). Thus, a legume-rich LG index diet may be a beneficial strategy for reducing circulating leptin concentrations, even under conditions of weight maintenance. European Journal of Clinical Nutrition (2011) 65, 415-418; doi:10.1038/ejcn.2010.273; published online 5 January 2011 C1 [Zhang, Z.; Ross, A. C.; Bagshaw, D.; Hartman, T. J.] Penn State Univ, Dept Nutr Sci, Chandlee Lab, University Pk, PA 16802 USA. [Lanza, E.; Albert, P. S.; Colburn, N. H.] NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. [Rovine, M. J.] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. [Ulbrecht, J. S.] Penn State Univ, Dept Biobehav Hlth & Med, University Pk, PA 16802 USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutr Sci, Chandlee Lab 110, University Pk, PA 16802 USA. EM tjh9@psu.edu FU National Cancer Institute [25XS101]; GCRC at Penn State University [NIH M01 RR 10732] FX We acknowledge Amy Ciccarella, Sami Heim and Mary Lou Kiel for their help with menu development and food preparation, and Diane Mitchell and Linda Phelps for their help with the conduct and interpretation of 24-h dietary recalls. Supported by the National Cancer Institute (Subcontract 25XS101) with partial support provided by the GCRC at Penn State University (NIH M01 RR 10732). NR 16 TC 6 Z9 6 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD MAR PY 2011 VL 65 IS 3 BP 415 EP 418 DI 10.1038/ejcn.2010.273 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 728ZA UT WOS:000287911800018 PM 21206508 ER PT J AU Mathew, SJ Vythilingam, M Murrough, JW Zarate, CA Feder, A Luckenbaugh, DA Kinkead, B Parides, MK Trist, DG Bani, MS Bettica, PU Ratti, EM Charney, DS AF Mathew, Sanjay J. Vythilingam, Meena Murrough, James W. Zarate, Carlos A., Jr. Feder, Adriana Luckenbaugh, David A. Kinkead, Becky Parides, Michael K. Trist, David G. Bani, Massimo S. Bettica, Paolo U. Ratti, Emiliangelo M. Charney, Dennis S. TI A selective neurokinin-1 receptor antagonist in chronic PTSD: A randomized, double-blind, placebo-controlled, proof-of-concept trial SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE NK1; Substance P; PTSD; Clinical trial; Randomized ID POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; ELEVATED PLUS-MAZE; SUBSTANCE-P; THERAPEUTIC TARGETS; MAJOR DEPRESSION; ANXIETY; SCALE; SERTRALINE; VETERANS AB The substance P-neurokinin-1 receptor (SP-NK(1)R) system has been extensively studied in experimental models of stress, fear, and reward. Elevated cerebrospinal fluid (CSF) SP levels were reported previously in combat-related PTSD. No medication specifically targeting this system has been tested in PTSD. This proof-of-concept randomized, double-blind, placebo-controlled trial evaluated the selective NK(1)R antagonist GR205171 in predominately civilian PTSD. Following a 2-week placebo lead-in, 39 outpatients with chronic PTSD and a Clinician-Administered PTSD Scale (CAPS) score >= 50 were randomized to a fixed dose of GR205171 (N=20) or placebo (N=19) for 8 weeks. The primary endpoint was mean change from baseline to endpoint in the total CAPS score. Response rate (>= 50% reduction in baseline CAPS) and safety/tolerability were secondary endpoints. CSF SP concentrations were measured in a subgroup of patients prior to randomization. There was significant improvement in the mean CAPS total score across all patients over time, but no significant difference was found between GR205171 and placebo. Likewise, there was no significant effect of drug on the proportion of responders [40% GR205171 versus 21% placebo (p=0.30)]. An exploratory analysis showed that GR205171 treatment was associated with significant improvement compared to placebo on the CAPS hyperarousal symptom cluster. GR205171 was well-tolerated, with no discontinuations due to adverse events. CSF SP concentrations were positively correlated with baseline CAPS severity. The selective Ilk, R antagonist GR205171 had fewer adverse effects but was not significantly superior to placebo in the short-term treatment of chronic PTSD. (ClinicalTrials.gov Identifier: NCT 00211861, NCT 00383786) Published by Elsevier B.V. C1 [Mathew, Sanjay J.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Mathew, Sanjay J.; Murrough, James W.; Feder, Adriana; Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY USA. [Vythilingam, Meena] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Zarate, Carlos A., Jr.; Luckenbaugh, David A.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res, Bethesda, MD 20892 USA. [Kinkead, Becky] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Parides, Michael K.] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY USA. [Trist, David G.; Bani, Massimo S.; Bettica, Paolo U.; Ratti, Emiliangelo M.] GlaxoSmithKline Inc, Neurosci CEDD, Med Res Ctr, Verona, Italy. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY USA. [Charney, Dennis S.] Mt Sinai Sch Med, Off Dean, New York, NY USA. NIMH IRP, Bethesda, MD USA. RP Mathew, SJ (reprint author), Baylor Coll Med, Dept Psychiat & Behav Sci, 1 Baylor Plaza MS BCM 350, Houston, TX 77030 USA. EM sjmathew@bcm.edu RI Murrough, James/J-7129-2013 OI Murrough, James/0000-0001-6286-1242 FU GlaxoSmithKline (GSK) Pharmaceuticals; Roche; AstraZeneca; NIMH [U19 MH69056, K23-MH-069656]; Medicines Research Centre; Neuroscience CEDD; GlaxoSmithKline; National Center for Research Resources (NCRR), NIH [M01-RR-0071] FX Dr. Mathew has received honoraria from AstraZeneca, Cephalon, Merck, and Pfizer, and has received research funding from GlaxoSmithKline (GSK) Pharmaceuticals and Roche. Drs. Bani, Bettica, and Ratti are employees of GSK. Dr. Trist was an employee of GSK during the period of work reported and presently consults for GSK. Dr. Murrough receives salary support through a Mount Sinai School of Medicine Research Fellowship funded by a grant from AstraZeneca. All other authors declare that, except for the income received from their primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 12 months for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.; Funding for this study was provided by NIMH Grant U19 MH69056 and the Intramural Research Program at the National Institute of Mental Health (NIMH). Additional research support and study drug provided by Medicines Research Centre, Neuroscience CEDD, GlaxoSmithKline, NIMH grant K23-MH-069656, and Grant Number M01-RR-0071 from the National Center for Research Resources (NCRR), a component of the NIH. The NIMH and GSK had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 33 TC 24 Z9 25 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2011 VL 21 IS 3 BP 221 EP 229 DI 10.1016/j.euroneuro.2010.11.012 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 728UU UT WOS:000287900800001 PM 21194898 ER PT J AU Pardini, M Guida, S Primavera, A Krueger, F Cocito, L Gialloreti, LE AF Pardini, Matteo Guida, Silvia Primavera, Alberto Krueger, Frank Cocito, Leonardo Gialloreti, Leonardo Emberti TI Amisulpride vs. fluoxetine treatment of Chronic Fatigue Syndrome: A pilot study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Fatigue; Antipsychotic agents ID HEALTH SURVEY; RELIABILITY; VALIDITY; SCALE AB Different pharmacologic agents have been evaluated in the treatment of Chronic Fatigue Syndrome (CFS), albeit with moderate efficacy. Among the compounds thought to present with potential to be efficacious in CFS patients stands out low-dose amisulpride, a substituted benzamide that has been shown to be an useful treatment for conditions which exhibit some overlap with CFS such as dysthymia and somatoform disorders. We thus recruited forty non-depressed CFS patients that were randomized to receive either amisulpride 25 mg bid, or fluoxetine 20 mg uid; all subjects were un-blinded to the treatment regimen. At the time of enrollment in the study and after twelve weeks of treatment, enrolled subjects completed the Krupp Fatigue Severity Scale, the Hospital Anxiety and Depression Scale and a visual analog scale focused on pain and bodily discomfort. Moreover, all subjects were evaluated by a clinician, blinded to the treatment regimen, using the Clinical Global Impression Severity Scale. Our data revealed a significant improvement both in self-report, and observer-based measures for the amisulpride-treated, but not for the fluoxetine-treated patients. Amisulpride-treated subjects also presented with a significant reduction of somatic complaints, while the amisulpride effect on anxiety and mood levels was not significant. Both drugs were equally well tolerated. Summing up, we showed a positive symptomatic effect of amisulpride, compared to SSRI treatment, in a group of non-depressed CSF patients on self-report and on observer-based measures of fatigue and somatic complaints. If confirmed by larger, blinded studies, amisulpride thus could represent an effective approach to this difficult-to-treat condition. (C) 2010 Elsevier B.V. and ECNP. All rights reserved. C1 [Pardini, Matteo; Guida, Silvia; Primavera, Alberto; Cocito, Leonardo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, I-16132 Genoa, Italy. [Pardini, Matteo] Univ Genoa, Magnet Resonance Res Ctr Nervous Syst Dis, I-16132 Genoa, Italy. [Pardini, Matteo; Gialloreti, Leonardo Emberti] Ctr Commun & Neurorehabil Res CNAPP, Rome, Italy. [Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA. [Krueger, Frank] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Gialloreti, Leonardo Emberti] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy. RP Pardini, M (reprint author), Univ Genoa, Dept Neurosci Ophthalmol & Genet DINOG, Via De Toni 5, I-16132 Genoa, Italy. EM matteo.pardini@gmail.com RI Emberti Gialloreti, Leonardo/H-4702-2012; Pardini, Matteo/F-8414-2010; OI Pardini, Matteo/0000-0002-4740-1982; Cocito, Leonardo/0000-0001-7926-3505 NR 18 TC 9 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2011 VL 21 IS 3 BP 282 EP 286 DI 10.1016/j.euroneuro.2010.10.008 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 728UU UT WOS:000287900800008 PM 21112746 ER PT J AU Liou, AP Lu, XP Sei, Y Zhao, XL Pechhold, S Carrero, RJ Raybould, HE Wank, S AF Liou, Alice P. Lu, Xinping Sei, Yoshitatsu Zhao, Xilin Pechhold, Susanne Carrero, Ricardo J. Raybould, Helen E. Wank, Stephen TI The G-Protein-Coupled Receptor GPR40 Directly Mediates Long-Chain Fatty Acid-Induced Secretion of Cholecystokinin SO GASTROENTEROLOGY LA English DT Article DE Fat Metabolism; Hormone Secretion; FACS Analysis; Digestion ID APOLIPOPROTEIN-A-IV; PANCREATIC BETA-CELLS; INSULIN-SECRETION; GASTROINTESTINAL-TRACT; GASTRIC-MOTILITY; LINE STC-1; IN-VIVO; LENGTH; RAT; PATHWAYS AB BACKGROUND & AIMS: Long-chain fatty acid receptors G-protein-coupled receptor 40 (GPR40) (FFAR1) and GPR120 have been implicated in the chemosensation of dietary fats. I cells in the intestine secrete cholecystokinin (CCK), a peptide hormone that stimulates digestion of fat and protein, but these cells are rare and hard to identify. We sought to determine whether dietary fat-induced secretion of CCK is directly mediated by GPR40 expressed on I cells. METHODS: We used fluorescence-activated cell sorting to isolate a pure population of I cells from duodenal mucosa in transgenic mice that expressed green fluorescent protein under the control of the CCK promoter (CCK-enhanced green fluorescent protein [eGFP] bacterial artificial chromosome mice). CCK-eGFP cells were evaluated for GPR40 expression by quantitative reverse transcription polymerase chain reaction and immunostaining. GPR40(-/-) mice were bred with CCK-eGFP mice to evaluate functional relevance of GPR40 on long-chain fatty acid-stimulated increases in [Ca(2+)]i and CCK secretion in isolated CCK-eGFP cells. Plasma levels of CCK after olive oil gavage were compared between GPR40(-/-) and GPR40(-/-) mice. RESULTS: Cells that expressed eGFP also expressed GPR40; expression of GPR40 was 100-fold greater than that of cells that did not express eGFP. In vitro, linoleic, oleic, and linolenic acids increased [Ca(2+)]i; linolenic acid increased CCK secretion by 53% in isolated GPR40(-/-) cells that expressed eGFP. In contrast, in GPR40(-/-) that expressed eGFP, [Ca(2+)] i response to linoleic acid was reduced by 50% and there was no significant CCK secretion in response to linolenic acid. In mice, olive oil gavage significantly increased plasma levels of CCK compared with pregavage levels: 5.7-fold in GPR40(-/-) mice and 3.1-fold in GPR40(-/-) mice. CONCLUSIONS: Long-chain fatty acid receptor GPR40 induces secretion of CCK by I cells in response to dietary fat. C1 [Liou, Alice P.; Lu, Xinping; Sei, Yoshitatsu; Zhao, Xilin; Carrero, Ricardo J.; Wank, Stephen] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. [Pechhold, Susanne] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Liou, Alice P.; Raybould, Helen E.] Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. RP Wank, S (reprint author), NIDDKD, Digest Dis Branch, NIH, 10-9C-101, Bethesda, MD 20892 USA. EM stevew@mail.nih.gov FU University of California, Davis School of Veterinary Medicine; National Institutes of Health DK41004; National Institute of Diabetes, Digestive, and Kidney Diseases Intramural FX Supported by the Veterinary Scientists Training Program, University of California, Davis School of Veterinary Medicine (APL), National Institutes of Health DK41004 (HER), and National Institute of Diabetes, Digestive, and Kidney Diseases Intramural funding. NR 39 TC 111 Z9 115 U1 2 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2011 VL 140 IS 3 BP 903 EP U318 DI 10.1053/j.gastro.2010.10.012 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 730EC UT WOS:000288014700031 PM 20955703 ER PT J AU Geng, XJ Ross, TJ Gu, H Shin, WY Zhan, W Chao, YP Lin, CP Schuff, N Yang, YH AF Geng, Xiujuan Ross, Thomas J. Gu, Hong Shin, Wanyong Zhan, Wang Chao, Yi-Ping Lin, Ching-Po Schuff, Norbert Yang, Yihong TI Diffeomorphic Image Registration of Diffusion MRI Using Spherical Harmonics SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Diffeomorphisms; diffusion magnetic resonance imaging (MRI); orientation distribution function (ODF); ODF reorientation; registration; spherical harmonics ID WEIGHTED MRI; CIRCULAR SPECTRUM; CROSSING FIBERS; TENSOR; ORIENTATION; ARCHITECTURE; INFORMATION; COMPUTATION; ANISOTROPY; TRACKING AB Nonrigid registration of diffusion magnetic resonance imaging (MRI) is crucial for group analyses and building white matter and fiber tract atlases. Most current diffusion MRI registration techniques are limited to the alignment of diffusion tensor imaging (DTI) data. We propose a novel diffeomorphic registration method for high angular resolution diffusion images by mapping their orientation distribution functions (ODFs). ODFs can be reconstructed using q-ball imaging (QBI) techniques and represented by spherical harmonics (SHs) to resolve intra-voxel fiber crossings. The registration is based on optimizing a diffeomorphic demons cost function. Unlike scalar images, deforming ODF maps requires ODF reorientation to maintain its consistency with the local fiber orientations. Our method simultaneously reorients the ODFs by computing a Wigner rotation matrix at each voxel, and applies it to the SH coefficients during registration. Rotation of the coefficients avoids the estimation of principal directions, which has no analytical solution and is time consuming. The proposed method was validated on both simulated and real data sets with various metrics, which include the distance between the estimated and simulated transformation fields, the standard deviation of the general fractional anisotropy and the directional consistency of the deformed and reference images. The registration performance using SHs with different maximum orders were compared using these metrics. Results show that the diffeomorphic registration improved the affine alignment, and registration using SHs with higher order SHs further improved the registration accuracy by reducing the shape difference and improving the directional consistency of the registered and reference ODF maps. C1 [Geng, Xiujuan; Ross, Thomas J.; Gu, Hong; Shin, Wanyong; Yang, Yihong] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Zhan, Wang; Schuff, Norbert] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. [Chao, Yi-Ping] Chung Shan Med Univ, Sch Appl Informat Sci, Taichung 402, Taiwan. [Lin, Ching-Po] Natl Yang Ming Univ, Inst Neurosci, Taipei 112, Taiwan. RP Geng, XJ (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM gengx@nida.nih.gov; tross@intra.nida.nih.gov; hgu@intra.nida.nih.gov; shinwa@nida.nih.gov; wang.zhan@ucsf.edu; catpin@gmail.com; chingpolin@gmail.com; norbert.schuff@ucsf.edu; yihongyang@intra.nida.nih.gov RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012 OI Ross, Thomas/0000-0002-7745-3572; FU National Institute on Drug Abuse (NIDA), National Institute of Health (NIH) FX Manuscript received October 08, 2010; accepted November 07, 2010. Date of publication December 03, 2010; date of current version March 02, 2011. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institute of Health (NIH). Asterisk indicates corresponding author. NR 46 TC 14 Z9 15 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAR PY 2011 VL 30 IS 3 BP 747 EP 758 DI 10.1109/TMI.2010.2095027 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 728GJ UT WOS:000287862300018 PM 21134814 ER PT J AU Le Clerc, S Coulonges, C Delaneau, O Van Manen, D Herbeck, JT Limou, S An, P Martinson, JJ Spadoni, JL Therwath, A Veldink, JH van den Berg, LH Taing, L Labib, T Mellak, S Montes, M Delfraissy, JF Schachter, F Winkler, C Froguel, P Mullins, JI Schuitemaker, H Zagury, JF AF Le Clerc, Sigrid Coulonges, Cedric Delaneau, Olivier Van Manen, Danielle Herbeck, Joshua T. Limou, Sophie An, Ping Martinson, Jeremy J. Spadoni, Jean-Louis Therwath, Amu Veldink, Jan H. van den Berg, Leonard H. Taing, Lieng Labib, Taoufik Mellak, Safa Montes, Matthieu Delfraissy, Jean-Francois Schaechter, Francois Winkler, Cheryl Froguel, Philippe Mullins, James I. Schuitemaker, Hanneke Zagury, Jean-Francois TI Screening Low-Frequency SNPS From Genome-Wide Association Study Reveals a New Risk Allele for Progression to AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; disease progression; genome-wide association study; HIV-1; RICH2; SNP ID HIV-1 DISEASE PROGRESSION; SUSCEPTIBILITY LOCI; GENE-EXPRESSION; COHORT; NONPROGRESSION; DETERMINANTS; ORGANIZATION; RESISTANCE; VARIANTS; COMMON AB Background: Seven genome-wide association studies (GWAS) have been published in AIDS, and only associations in the HLA region on chromosome 6 and CXCR6 have passed genome-wide significance. Methods: We reanalyzed the data from 3 previously published GWAS, targeting specifically low-frequency SNPs (minor allele frequency <5%). Two groups composed of 365 slow progressors and 147 rapid progressors from Europe and the United States were compared with a control group of 1394 seronegative individuals using Eigenstrat corrections. Results: Of the 8584 SNPs with minor allele frequency <5% in cases and controls (Bonferroni threshold = 5.8 x 10(-6)), 4 SNPs showed statistical evidence of association with the slow progressor phenotype. The best result was for HCP5 rs2395029 [P = 8.54 x 10(-15), odds ratio (OR) = 3.41] in the HLA locus, in partial linkage disequilibrium with 2 additional chromosome 6 associations in C6orf48 (P = 3.03 x 10(-10), OR = 2.9) and NOTCH4 (9.08 x 10(-07), OR = 2.32). The fourth association corresponded to rs2072255 located in RICH2 (P = 3.30 x 10(-06), OR = 0.43) in chromosome 17. Using HCP5 rs2395029 as a covariate, the C6orf48 and NOTCH4 signals disappeared, but the RICH2 signal still remained significant. Conclusions: Besides the already known chromosome 6 associations, the analysis of low-frequency SNPs brought up a new association in the RICH2 gene. Interestingly, RICH2 interacts with BST-2 known to be a major restriction factor for HIV-1 infection. Our study has thus identified a new candidate gene for AIDS molecular etiology and confirms the interest of singling out low-frequency SNPs to exploit GWAS data. C1 [Le Clerc, Sigrid; Coulonges, Cedric; Delaneau, Olivier; Limou, Sophie; Spadoni, Jean-Louis; Taing, Lieng; Labib, Taoufik; Mellak, Safa; Montes, Matthieu; Schaechter, Francois; Zagury, Jean-Francois] Conservatoire Natl Arts & Metiers, Chaire Bioinformat, Paris, France. [Le Clerc, Sigrid; Limou, Sophie; Zagury, Jean-Francois] Univ Paris, INSERM, U955, Creteil, France. [Le Clerc, Sigrid; Coulonges, Cedric; Limou, Sophie; Delfraissy, Jean-Francois; Zagury, Jean-Francois] French Agcy Res AIDS & Hepatitis, ANRS Genom Grp, Paris, France. [Van Manen, Danielle; Schuitemaker, Hanneke] Univ Amsterdam, Dept Expt Immunol, Landsteiner Lab, Ctr Infect Dis & Immun,Amsterdam Acad Med Ctr, Amsterdam, Netherlands. [Herbeck, Joshua T.; Mullins, James I.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [Limou, Sophie] Ctr Natl Genotypage, CEA, Inst Genom, Evry, France. [An, Ping; Winkler, Cheryl] NCI, Lab Genom Div, SAIC Frederick Inc, Frederick, MD 21701 USA. [Martinson, Jeremy J.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Therwath, Amu] Univ Paris, Lab Oncol Mol, F-75252 Paris, France. [Veldink, Jan H.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Froguel, Philippe] Inst Pasteur, CNRS, UMR 8090, F-59019 Lille, France. [Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. RP Zagury, JF (reprint author), 292 Rue St Martin, F-75003 Paris, France. EM zagury@cnam.fr OI Martinson, Jeremy/0000-0003-4673-7238; Montes, Matthieu/0000-0001-5921-460X FU Agence Nationale de Recherche sur le SIDA (ANRS); Sidaction; Fondation de France; Conservatoire National des Arts et Metiers (CNAM); AIDS Cancer Vaccine Development Foundation; Neovacs SA; Vaxconsulting; French Ministry of Education, Technology and Research; Netherlands National Institute for Public Health and the Environment; Netherlands Organization for Scientific Research [9120.6046]; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Supported by Agence Nationale de Recherche sur le SIDA (ANRS), Sidaction, Fondation de France, Innovation 2007 program of Conservatoire National des Arts et Metiers (CNAM), AIDS Cancer Vaccine Development Foundation, Neovacs SA, Vaxconsulting. Sophie Limou benefits from a fellowship from the French Ministry of Education, Technology and Research and Sigrid Le Clerc benefits from a fellowship of ANRS. The Amsterdam Cohort Studies on HIV infection and AIDS, a collaboration between the Amsterdam Health Service, the Academic Medical Center of the University of Amsterdam, Sanquin Research, and the University Medical Center Utrecht, are part of the Netherlands HIV Monitoring Foundation and financially supported by the Netherlands National Institute for Public Health and the Environment. The authors acknowledge funding from the Netherlands Organization for Scientific Research (TOP, registration number 9120.6046). The MultiCenter AIDS Cohort Study is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute. UO1-AI-35042, UL1-RR025005 (GCRC), UO1-AI-35043, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041. This project has been funded in part with federal funds from the National Institutes of Health, under contract HHSN261200800001E. This Research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 31 TC 19 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR PY 2011 VL 56 IS 3 BP 279 EP 284 DI 10.1097/QAI.0b013e318204982b PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 728HD UT WOS:000287864300025 PM 21107268 ER PT J AU Rego, ROM Bestor, A Rosa, PA AF Rego, Ryan O. M. Bestor, Aaron Rosa, Patricia A. TI Defining the Plasmid-Borne Restriction-Modification Systems of the Lyme Disease Spirochete Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HELICOBACTER-PYLORI; LINEAR-PLASMID; STRAIN B31; INFECTIOUS CYCLE; TICK VECTOR; TRANSFORMATION; GENOME; DNA; METHYLATION; CULTIVATION AB The restriction-modification (R-M) systems of many bacteria present a barrier to the stable introduction of foreign DNA. The Lyme disease spirochete Borrelia burgdorferi has two plasmid-borne putative R-M genes, bbe02 and bbq67, whose presence limits transformation by shuttle vector DNA from Escherichia coli. We show that both the bbe02 and bbq67 loci in recipient B. burgdorferi limit transformation with shuttle vector DNA from E. coli, irrespective of its dam, dcm, or hsd methylation status. However, plasmid DNA purified from B. burgdorferi transformed naive B. burgdorferi much more efficiently than plasmid DNA from E. coli, particularly when the bbe02 and bbq67 genotypes of the B. burgdorferi DNA source matched those of the recipient. We detected adenine methylation of plasmid DNA prepared from B. burgdorferi that carried bbe02 and bbq67. These results indicate that the bbe02 and bbq67 loci of B. burgdorferi encode distinct R-M enzymes that methylate endogenous DNA and cleave foreign DNA lacking the same sequence-specific modification. Our findings have basic implications for horizontal gene transfer among B. burgdorferi strains with distinct plasmid contents. Further characterization and identification of the nucleotide sequences recognized by BBE02 and BBQ67 will facilitate efficient genetic manipulation of this pathogenic spirochete. C1 [Rego, Ryan O. M.; Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Rego, ROM (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM regor@niaid.nih.gov RI Rego, Ryan/G-9773-2014 OI Rego, Ryan/0000-0001-6932-0940 FU NIH, NIAID FX This research was supported by the Intramural Research Program of the NIH, NIAID. NR 58 TC 31 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2011 VL 193 IS 5 BP 1161 EP 1171 DI 10.1128/JB.01176-10 PG 11 WC Microbiology SC Microbiology GA 718QD UT WOS:000287139200017 PM 21193609 ER PT J AU Wang, Z Bhattacharyya, T AF Wang, Zhong Bhattacharyya, Timothy TI Trends in Incidence of Subtrochanteric Fragility Fractures and Bisphosphonate Use Among the US Elderly, 1996-2007 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE AGING; BONE; POPULATION STUDIES; OSTEOPOROSIS; BISPHOSPHONATES ID SUPPRESSED BONE TURNOVER; LONG-TERM ALENDRONATE; COA REDUCTASE INHIBITORS; FEMORAL-SHAFT FRACTURES; HIP-FRACTURES; DIAPHYSEAL FEMUR; UNITED-STATES; THERAPY; RISK; OSTEOPOROSIS AB Increasing numbers of atypical hip fractures have been reported among patients with bisphosphonate use. However, the nature and extent of the problem are unknown despite recent investigations. To analyze national trends in hip fractures and medication use in the elderly US population, we respectively used the Nationwide Inpatient Sample (NIS) and the Medical Expenditure Panel Survey (MEPS) from 1996 to 2007. In NIS, subtrochanteric fragility fractures were compared with typical hip fractures in femoral neck and intertrochanteric regions. Between 1996 and 2007, age-adjusted rates for typical hip fractures decreased by 31.6% among women (from 1020.5 to 697.4 per 100,000 population) and 20.5% among men (from 424.9 to 337.6 per 100,000 population). In contrast, overall trends in age-adjusted rates for subtrochanteric fragility fractures remained unchanged among men (p = .34) but increased 20.4% among women from 28.4(95% confidence interval [CI] 27.7-29.1) in 1999 to 34.2 (95% CI 33.4-34.9) per 100,000 population in 2007. The annual percentage increase was 2.1% (95% CI 1.3-2.8, p < .001) based on joinpoint regression analysis. In MEPS, bisphosphonate use increased predominantly in women (from 3.5% in 1996 to 16.6% in 2007) compared with men (2.3% in 2007). In the context of declining typical hip fractures among the US elderly, we observed small but significant increases in the incidence of subtrochanteric fragility fractures from 1999 among postmenopausal women. Using age-adjusted rates, we estimated that for every 100 or so reduction in typical femoral neck or intertrochanteric fractures, there was an increase of one subtrochanteric fragility fracture. (c) 2011 American Society for Bone and Mineral Research. C1 [Wang, Zhong; Bhattacharyya, Timothy] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Bhattacharyya, T (reprint author), NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM timothy.bhattacharyya@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) FX We thank Dr Michael Ward from NIAMS, National Institute of Health, for critique and review of the manuscript. This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH). NR 36 TC 77 Z9 79 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2011 VL 26 IS 3 BP 553 EP 560 DI 10.1002/jbmr.233 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 727UG UT WOS:000287827600016 PM 20814954 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Commentary: Are callous unemotional traits all in the eyes? Examining eye contact in youth with conduct problems and callous unemotional traits - reflections on Dadds et al. (2011) SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Editorial Material ID AMYGDALA; EMPATHY; AUTISM C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, NIH, Dept Hlth & Human Serv, 15K N Dr,Rm 115A,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 5 TC 4 Z9 4 U1 8 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD MAR PY 2011 VL 52 IS 3 BP 246 EP 247 DI 10.1111/j.1469-7610.2010.02364.x PG 2 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 716PP UT WOS:000286986200005 PM 21294727 ER PT J AU Strober, W AF Strober, Warren TI Adherent-invasive E. coli in Crohn disease: bacterial "agent provocateur" SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; ILEAL MUCOSA; AUTOPHAGY; REPLICATE AB The role of adherent-invasive E. coli (AIEC) in Crohn disease (CD) has been in debate for decades. AIEC bacteria are found in the small intestine of patients with chronic CD, but it has remained unclear whether this infection is causal or secondary to underlying immune deficiencies in CD patients. In this issue of the JCI, Chassaing and colleagues demonstrate that AIEC bacteria express an adherence factor called long polar fimbriae (LPF) that aids in the binding of these bacteria to M cells overlying Peyer's patches and subsequent entry into lymphoid tissue. These findings provide a mechanism of AIEC penetration but do not prove that AIEC is causing a primary infection in the Peyer's patches that is necessary for the initiation or persistence of CD inflammation. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH,Clin Res Ctr, NIH Campus,9000 Rockville Pike,5 West,Rm 3940, Bethesda, MD 20892 USA. EM Wstrober@niaid.nih.gov NR 20 TC 17 Z9 17 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2011 VL 121 IS 3 BP 841 EP 844 DI 10.1172/JCI46333 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 729YQ UT WOS:000287991000005 PM 21339637 ER PT J AU Vignali, M Armour, CD Chen, JY Morrison, R Castle, JC Biery, MC Bouzek, H Moon, W Babak, T Fried, M Raymond, CK Duffy, PE AF Vignali, Marissa Armour, Christopher D. Chen, Jingyang Morrison, Robert Castle, John C. Biery, Matthew C. Bouzek, Heather Moon, Wonjong Babak, Tomas Fried, Michal Raymond, Christopher K. Duffy, Patrick E. TI NSR-seq transcriptional profiling enables identification of a gene signature of Plasmodium falciparum parasites infecting children SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLYCOPHORIN-BINDING PROTEIN; PREGNANCY-ASSOCIATED MALARIA; CHONDROITIN SULFATE-A; MEMBRANE SKELETON; RNA-SEQ; IN-VIVO; ERYTHROCYTE; REVEALS; VIRULENCE; PLACENTA AB Malaria caused by Plasmodium falciparum results in approximately 1 million annual deaths worldwide, with young children and pregnant mothers at highest risk. Disease severity might be related to parasite virulence factors, but expression profiling studies of parasites to test this hypothesis have been hindered by extensive sequence variation in putative virulence genes and a preponderance of host RNA in clinical samples. We report here the application of RNA sequencing to clinical isolates of P. falciparum, using not-so-random (NSR) primers to successfully exclude human ribosomal RNA and globin transcripts and enrich for parasite transcripts. Using NSR-seq, we confirmed earlier microarray studies showing upregulation of a distinct subset of genes in parasites infecting pregnant women, including that encoding the well-established pregnancy malaria vaccine candidate var2csa. We also describe a subset of parasite transcripts that distinguished parasites infecting children from those infecting pregnant women and confirmed this observation using quantitative real-time PCR and mass spectrometry proteomic analyses. Based on their putative functional properties, we propose that these proteins could have a role in childhood malaria pathogenesis. Our study provides proof of principle that NSR-seq represents an approach that can be used to study clinical isolates of parasites causing severe malaria syndromes as well other blood-borne pathogens and blood-related diseases. C1 [Chen, Jingyang; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. [Vignali, Marissa; Chen, Jingyang; Morrison, Robert; Moon, Wonjong; Fried, Michal; Duffy, Patrick E.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. [Armour, Christopher D.; Castle, John C.; Biery, Matthew C.; Bouzek, Heather; Babak, Tomas; Raymond, Christopher K.] Rosetta Inpharmat LLC, Seattle, WA USA. [Armour, Christopher D.; Castle, John C.; Biery, Matthew C.; Bouzek, Heather; Babak, Tomas; Raymond, Christopher K.] Dept Mol Informat, Seattle, WA USA. [Fried, Michal; Duffy, Patrick E.] Univ Washington, Harborview Med Ctr, Dept Global Hlth, Seattle, WA 98104 USA. RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM patrick.duffy@nih.gov OI Vignali, Marissa/0000-0002-7319-3371 FU Foundation for the NIH through the Grand Challenges in Global Health initiative; Bill and Melinda Gates Foundation [29202]; National Institute of Allergy and Infectious Diseases [R01AI052059] FX Theonest Mutabingwa led the team of MOMS Project clinicians and nurses who collected the clinical samples used in this study. We thank Fenella Raymond for suggesting the collaboration that led to this work; Christopher Mendez, Kathryn Williamson, and Emily Amos for culturing parasites; and Jason Wendler, Cate Speake, and Andrew Oleinikov for helpful discussions. This work was funded in part by a grant from the Foundation for the NIH through the Grand Challenges in Global Health initiative, the Bill and Melinda Gates Foundation (grant 29202), and the National Institute of Allergy and Infectious Diseases (grant R01AI052059 to P.E. Duffy). NR 47 TC 23 Z9 23 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2011 VL 121 IS 3 BP 1119 EP 1129 DI 10.1172/JCI43457 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 729YQ UT WOS:000287991000030 PM 21317536 ER PT J AU Widemann, BC Adamson, PC AF Widemann, Brigitte C. Adamson, Peter C. TI High-Dose Methotrexate-Induced Renal Dysfunction: Is Glucarpidase Necessary for Rescue? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 MAR 1 PY 2011 VL 29 IS 7 BP E181 EP E181 DI 10.1200/JCO.2010.32.8773 PG 1 WC Oncology SC Oncology GA 726NO UT WOS:000287729900012 ER PT J AU Vaisbuch, E Romero, R Gomez, R Kusanovic, JP Mazaki-Tovi, S Chaiworapongsa, T Hassan, SS AF Vaisbuch, Edi Romero, Roberto Gomez, Ricardo Kusanovic, Juan Pedro Mazaki-Tovi, Shali Chaiworapongsa, Tinnakorn Hassan, Sonia S. TI An elevated fetal interleukin-6 concentration can be observed in fetuses with anemia due to Rh alloimmunization: implications for the understanding of the fetal inflammatory response syndrome SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Fetal anemia; FIRS; interleukin-6; pregnancy; Rh hemolytic disease ID PRETERM PREMATURE RUPTURE; UMBILICAL-CORD PLASMA; BRONCHOPULMONARY DYSPLASIA; INTRAAMNIOTIC INFLAMMATION; RHESUS ALLOIMMUNIZATION; THYMIC INVOLUTION; CEREBRAL-PALSY; IMMUNE-SYSTEM; MEMBRANES; CHORIOAMNIONITIS AB Methods. aEuro integral Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n aEuroS== aEuroS16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of > 11 pg/ml. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. Results. aEuro integral(1) The prevalence of an elevated fetal plasma IL-6 was 25%% (4/16); (2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration -- the lower the hematocrit, the higher the fetal IL-6 (r aEuroS== aEuroS--0.68, p aEuroS== aEuroS0.004); (3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18--2.63 vs. 1.46 pg/ml, IQR 1.76--14.7; p aEuroS== aEuroS0.02); (4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. Conclusions. aEuro integral An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization. C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Intramural Div, Detroit, MI 48201 USA. [Vaisbuch, Edi; Romero, Roberto; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Hutzel Womens Hosp, Intramural Div, Perinatol Res Branch, NICHD,NIH,DHHS, Bethesda, MD USA. [Vaisbuch, Edi; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, CEDIP Ctr Perinatal Diag & Res, Dept Obstet & Gynecol, Santiago, Chile. [Gomez, Ricardo] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Intramural Div, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health; Human Development, NIH, DHHS FX This research was supported 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 54 TC 12 Z9 13 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAR PY 2011 VL 24 IS 3 BP 391 EP 396 DI 10.3109/14767058.2010.507294 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 716SE UT WOS:000286993000001 PM 20701435 ER PT J AU Russo, I Barlati, S Bosetti, F AF Russo, Isabella Barlati, Sergio Bosetti, Francesca TI Effects of neuroinflammation on the regenerative capacity of brain stem cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE aging; brain; inflammation; lipopolysaccharide; neurogenesis ID MARROW STROMAL CELLS; ADULT HIPPOCAMPAL NEUROGENESIS; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; NITRIC-OXIDE; NEURODEGENERATIVE DISEASES; STEM/PROGENITOR CELLS; NEUROTROPHIC-FACTOR; NEURAL PROGENITORS; RAT-BRAIN AB P>In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. C1 [Russo, Isabella; Bosetti, Francesca] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. [Russo, Isabella; Barlati, Sergio] Univ Brescia, Natl Inst Neurosci, Dept Biomed Sci & Biotechnol, Div Biol & Genet, Brescia, Italy. RP Bosetti, F (reprint author), NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, 9 Mem Dr,Room 1S126 MSC 0947, Bethesda, MD 20892 USA. EM frances@mail.nih.gov OI Russo, Isabella/0000-0002-6151-2451 FU Intramural NIH HHS [ZIA AG000425-04] NR 121 TC 65 Z9 67 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2011 VL 116 IS 6 BP 947 EP 956 DI 10.1111/j.1471-4159.2010.07168.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 728EE UT WOS:000287856200002 PM 21198642 ER PT J AU Du, XX Chowdhury, SM Manes, NP Wu, S Mayer, MU Adkins, JN Anderson, GA Smith, RD AF Du, Xiuxia Chowdhury, Saiful M. Manes, Nathan P. Wu, Si Mayer, M. Uljana Adkins, Joshua N. Anderson, Gordon A. Smith, Richard D. TI Xlink-Identifier: An Automated Data Analysis Platform for Confident Identifications of Chemically Cross-Linked Peptides Using Tandem Mass Spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE Chemical cross-linking; mass spectrometry; peptide identification; protein-protein interaction; protein structure ID PROTEIN-PROTEIN INTERACTIONS; LINKING REAGENTS; LARGE-SCALE; PHOTOAFFINITY REAGENTS; STRUCTURAL-ANALYSIS; DISULFIDE BONDS; COMPLEXES; SPECTRA; DISSOCIATION; NOMENCLATURE AB Chemical cross-linking combined with mass spectrometry provides a powerful method for identifying protein-protein interactions and probing the structure of protein complexes. A number of strategies have been reported that take advantage of the high sensitivity and high resolution of modern mass spectrometers. Approaches typically include synthesis of novel cross-linking compounds, and/or isotopic labeling of the cross-linking reagent and/or protein, and label-free methods. We report Xlink-Identifier, a comprehensive data analysis Platform that has been developed to support label-free analyses. It can identify interpeptide, intrapeptide, and deadend cross-links as well as underivatized peptides. The software streamlines data preprocessing, peptide scoring, and visualization and provides an overall data analysis strategy for studying protein-protein interactions and protein structure using mass spectrometry. The software has been evaluated using a custom synthesized cross-linking reagent that features an enrichment tag. Xlink-Identifier offers the potential to perform large-scale identifications of protein-protein interactions using tandem mass spectrometry. C1 [Du, Xiuxia] Univ N Carolina, Dept Bioinformat & Genom, Charlotte, NC 28023 USA. [Wu, Si; Mayer, M. Uljana; Adkins, Joshua N.; Anderson, Gordon A.; Smith, Richard D.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Manes, Nathan P.] NIAID, Bethesda, MD 20892 USA. [Chowdhury, Saiful M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Du, XX (reprint author), 500 Laureate Way,Suite 2350, Kannapolis, NC 28081 USA. EM xiuxia.du@uncc.edu RI Manes, Nathan/E-2817-2012; Smith, Richard/J-3664-2012; Adkins, Joshua/B-9881-2013 OI Manes, Nathan/0000-0001-6701-3314; Smith, Richard/0000-0002-2381-2349; Adkins, Joshua/0000-0003-0399-0700 FU University of North Carolina at Charlotte; Pacific Northwest National Laboratory (PNNL); NIH National Center for Research Resources [RR18522]; National Center for Research Resources [RR 018522]; DOE's Office of Biological and Environmental Research; DOE [DE-AC05-76RLO01830] FX This work was supported, in part, by a startup fund from the University of North Carolina at Charlotte, the Laboratory Directed Research and Development program at Pacific Northwest National Laboratory (PNNL), and the NIH National Center for Research Resources (RR18522). This work utilized data generated on instrumentation and capabilities developed under support from the National Center for Research Resources (Grant RR 018522 to RDS) and the DOE's Office of Biological and Environmental Research. Part of this work was performed in the Environmental Molecular Science Laboratory, a U.S. Department of Energy (DOE) national scientific user facility located at PNNL (Richland, WA). Battelle Memorial Institute operates PNNL for the DOE under Contract DE-AC05-76RLO01830. NR 67 TC 19 Z9 19 U1 2 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2011 VL 10 IS 3 BP 923 EP 931 DI 10.1021/pr100848a PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 729JD UT WOS:000287944000001 PM 21175198 ER PT J AU Minasian, LM O'Mara, AM AF Minasian, Lori M. O'Mara, Ann M. TI Accrual to Clinical Trials: Let's Look at the Physicians SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 [Minasian, Lori M.] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Minasian, LM (reprint author), NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, NIH, 6130 Execut Blvd,EPN,MSC-7340, Bethesda, MD 20892 USA. EM minasilo@mail.nih.gov NR 8 TC 9 Z9 9 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 MAR PY 2011 VL 103 IS 5 BP 357 EP U1500 DI 10.1093/jnci/djr018 PG 2 WC Oncology SC Oncology GA 730GC UT WOS:000288020800001 PM 21317381 ER PT J AU Klabunde, CN Keating, NL Potosky, AL Ambs, A He, YL Hornbrook, MC Ganz, PA AF Klabunde, Carrie N. Keating, Nancy L. Potosky, Arnold L. Ambs, Anita He, Yulei Hornbrook, Mark C. Ganz, Patricia A. TI A Population-Based Assessment of Specialty Physician Involvement in Cancer Clinical Trials SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; BREAST-CANCER; PRIMARY-CARE; MEDICAL ONCOLOGISTS; BEHAVIORAL-MODEL; HEALTH-CARE; BARRIERS; PARTICIPATION; SURGEONS; PERSPECTIVES AB Background Clinical trials are critical for evaluating new cancer therapies, but few adult patients participate in them. Physicians have an important role in facilitating patient participation in clinical trials. We examined the characteristics of specialty physicians who participate in clinical trials by enrolling or referring patients, the types of trials in which they participate, and factors associated with physicians who report greater involvement in clinical trials. Methods We analyzed data from the Cancer Care Outcomes Research and Surveillance Consortium. The study included 1533 specialty physicians who cared for colorectal and lung cancer patients (496 medical oncologists, 228 radiation oncologists, and 809 surgeons) and completed a survey conducted during 2005-2006 (response rate = 61.0%). Descriptive statistics were used to characterize physicians' personal and practice characteristics, and regression models were used to examine associations between these characteristics and physician participation in clinical trials. All statistical tests were two-sided. Results A total of 87.8% of medical oncologists, 66.1% of radiation oncologists, and 35.0% of surgeons reported referring or enrolling one or more patients in clinical trials during the previous 12 months. The mean number of patients referred or enrolled by these physicians was 17.2 (95% confidence interval [CI] = 15.5 to 18.9) for medical oncologists, 9.5 (95% CI = 7.7 to 11.3) for radiation oncologists, and 12.2 (95% CI = 9.8 to 14.6) for surgeons (P < .001). Specialty type, involvement in teaching, and affiliation with a Community Clinical Oncology Program (CCOP) and/or a National Cancer Institute-designated cancer center were associated with physician trial participation and enrolling more patients (all Ps < .05). Two-thirds of physicians with a CCOP or National Cancer Institute-designated cancer center affiliation reported participating in trials. Conclusions Features of specialty physicians' practice environments are associated with their trial participation, but many physicians at CCOPs and cancer centers do not participate. C1 [Klabunde, Carrie N.; Ambs, Anita] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.; He, Yulei] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Potosky, Arnold L.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Klabunde, CN (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM Klabundc@mail.nih.gov FU NCI [U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, 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 NCI to the Statistical Coordinating Center (U01 CA093344) PI: David Harrington and the NCI-supported Primary Data Collection and Research Centers (Dana Farber Cancer Institute/Cancer Research Network U01 CA093332 PI: Jane Weeks, Harvard Medical School/Northern California Cancer Center U01 CA093324 PI: John Ayanian, RAND/UCLA U01 CA093348 PI: Katherine Kahn, University of Alabama at Birmingham U01 CA093329 PI: Mona Fouad, University of Iowa U01 CA093339 PI: Robert Wallace, University of North Carolina U01 CA093326, PI: Robert Sandler) and by a Department of Veteran's Affairs grant to the Durham VA Medical Center CRS 02-164 PI: Dawn Provenzale. NR 57 TC 25 Z9 26 U1 0 U2 4 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 MAR PY 2011 VL 103 IS 5 BP 384 EP 397 DI 10.1093/jnci/djq549 PG 14 WC Oncology SC Oncology GA 730GC UT WOS:000288020800008 PM 21317382 ER PT J AU Simon, RM Freidlin, B AF Simon, Richard M. Freidlin, Boris TI Re: Designing a Randomized Clinical Trial to Evaluate Personalized Medicine: A New Approach Based on Risk Prediction SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID ADAPTIVE SIGNATURE DESIGN C1 [Simon, Richard M.; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, RM (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 3 TC 2 Z9 2 U1 1 U2 1 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 MAR PY 2011 VL 103 IS 5 BP 445 EP 445 DI 10.1093/jnci/djq552 PG 1 WC Oncology SC Oncology GA 730GC UT WOS:000288020800013 PM 21228315 ER PT J AU Baker, SG Sargent, DJ AF Baker, Stuart G. Sargent, Daniel J. TI Response and Retraction: Designing a Randomized Clinical Trial to Evaluate Personalized Medicine: A New Approach Based on Risk Prediction SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Baker, Stuart G.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Sargent, Daniel J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, NIH, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov OI Sargent, Daniel/0000-0002-2684-4741 NR 1 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 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR PY 2011 VL 103 IS 5 DI 10.1093/jnci/djq553 PG 2 WC Oncology SC Oncology GA 730GC UT WOS:000288020800014 ER PT J AU Arnold, MM Patton, JT AF Arnold, Michelle M. Patton, John T. TI Diversity of Interferon Antagonist Activities Mediated by NSP1 Proteins of Different Rotavirus Strains SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; MULTIPLE REGULATORY DOMAINS; POSITIVE FEEDBACK; BOVINE ROTAVIRUS; RNA-BINDING; INDUCTION; GENES; IRF-7; ACTIVATION; FACTOR-3 AB Studies involving limited numbers of rotavirus (RV) strains have shown that the viral gene 5 product, NSP1, can antagonize beta interferon (IFN-beta) expression by inducing the degradation of IFN-regulatory factors (IRFs) (IRF3, IRF5, and IRF7) or a component of the E3 ubiquitin ligase complex responsible for activating NF-kappa B (beta-transducin repeat-containing protein [beta-TrCP]). To gain a broader perspective of NSP1 activities, we examined various RV strains for the ability to inhibit IFN-beta expression in human cells. We found that all strains encoding wild-type NSP1 impeded IFN-beta expression but not always through IRF3 degradation. To identify other degradation targets involved in suppressing IFN-beta expression, we used transient expression vectors to test the abilities of a diverse collection of NSP1 proteins to target IRF3, IRF5, IRF7, and beta-TrCP for degradation. The results indicated that human RVs rely predominantly on the NSP1-induced degradation of IRF5 and IRF7 to suppress IFN signaling, whereas NSP1 proteins of animal RVs tended to target IRF3, IRF5, and IRF7, allowing the animal viruses a broader attack on the IFN-beta signaling pathway. The results also suggested that the NSP1-induced degradation of beta-TrCP is an uncommon mechanism of subverting IFN-beta signaling but is one that can be shared with NSP1 proteins that induce IRF degradation. Our analysis reveals that the activities of NSP1 proteins are diverse, with no obvious correlations between degradations of pairs of target proteins. Thus, RVs have evolved functionally distinct approaches for subverting the host antiviral response, a property consistent with the immense sequence variation noted for NSP1 proteins. C1 [Arnold, Michelle M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 50 S Dr,Room 6314, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 38 TC 34 Z9 36 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 1970 EP 1979 DI 10.1128/JVI.01801-10 PG 10 WC Virology SC Virology GA 716MT UT WOS:000286974900006 PM 21177809 ER PT J AU Bowman, JJ Lacayo, JC Burbelo, P Fischer, ER Cohen, JI AF Bowman, J. Jason Lacayo, Juan C. Burbelo, Peter Fischer, Elizabeth R. Cohen, Jeffrey I. TI Rhesus and Human Cytomegalovirus Glycoprotein L Are Required for Infection and Cell-to-Cell Spread of Virus but Cannot Complement Each Other SO JOURNAL OF VIROLOGY LA English DT Article ID VARICELLA-ZOSTER-VIRUS; UL115 GENE-PRODUCT; GH-GL; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; ENVELOPE COMPLEX; FUSION; TYPE-1; GB; EXPRESSION AB Rhesus cytomegalovirus (RhCMV), the homolog of human cytomegalovirus (HCMV), serves as a model for understanding the pathogenesis of HCMV and for developing candidate vaccines. In order to develop a replication-defective virus as a vaccine candidate, we constructed RhCMV with glycoprotein L (gL) deleted. RhCMV gL was essential for viral replication, and virus with gL deleted could only replicate in cells expressing RhCMV gL. Noncomplementing cells infected with RhCMV with gL deleted released intact, noninfectious RhCMV particles that were indistinguishable from wild-type RhCMV by electron microscopy and could be rescued by treatment of cells with polyethylene glycol. In addition, noncomplementing cells infected with RhCMV with gL deleted produced levels of gB, the major target of neutralizing antibodies, at levels similar to those observed in cells infected with wild-type RhCMV. Since RhCMV and HCMV gL share 53% amino acid identity, we determined whether the two proteins could complement the heterologous virus. Cells transfected with an HCMV bacterial artificial chromosome with gL deleted yielded virus that could replicate in human cells expressing HCMV gL. This is the second HCMV mutant with an essential glycoprotein deleted that has been complemented in cell culture. Finally, we found that HCMV gL could not complement the replication of RhCMV with gL deleted and that RhCMV gL could not complement the replication of HCMV with gL deleted. These data indicate that RhCMV and HCMV gL are both essential for replication of their corresponding viruses and, although the two gLs are highly homologous, they are unable to complement each another. C1 [Bowman, J. Jason; Lacayo, Juan C.; Cohen, Jeffrey I.] NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Burbelo, Peter] NIDCR, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Fischer, Elizabeth R.] NIH, Res Technol Sect, Res Technol Branch, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Cohen, JI (reprint author), NIH, Infect Dis Lab, Bldg 50,Room 6134,50 S Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research FX This study was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research. NR 46 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2089 EP 2099 DI 10.1128/JVI.01970-10 PG 11 WC Virology SC Virology GA 716MT UT WOS:000286974900016 PM 21191007 ER PT J AU Johnson, RF Dyall, J Ragland, DR Huzella, L Byrum, R Jett, C St Claire, M Smith, AL Paragas, J Blaney, JE Jahrling, PB AF Johnson, Reed F. Dyall, Julie Ragland, Dan R. Huzella, Louis Byrum, Russell Jett, Catherine St Claire, Marisa Smith, Alvin L. Paragas, Jason Blaney, Joseph E. Jahrling, Peter B. TI Comparative Analysis of Monkeypox Virus Infection of Cynomolgus Macaques by the Intravenous or Intrabronchial Inoculation Route SO JOURNAL OF VIROLOGY LA English DT Article ID MODIFIED VACCINIA VIRUS; NONHUMAN-PRIMATES; SMALLPOX VACCINE; LETHAL MONKEYPOX; ORTHOPOXVIRUS INFECTION; AFRICAN STRAINS; CONGO BASIN; PATHOLOGY; DISEASE; PROTECTION AB Monkeypox virus (MPXV) infection has recently expanded in geographic distribution and can be fatal in up to 10% of cases. The intravenous (i.v.) inoculation of nonhuman primates (NHPs) results in an accelerated fulminant disease course compared to that of naturally occurring MPXV infection in humans. Alternative routes of inoculation are being investigated to define an NHP model of infection that more closely resembles natural disease progression. Our goal was to determine if the intrabronchial (i.b.) exposure of NHPs to MPXV results in a systemic disease that better resembles the progression of human MPXV infection. Here, we compared the disease course following an i.v. or i.b. inoculation of NHPs with 10-fold serial doses of MPXV Zaire. Classical pox-like disease was observed in NHPs administered a high virus dose by either route. Several key events were delayed in the highest doses tested of the i.b. model compared to the timing of the i.v. model, including the onset of fever, lesion appearance, peak viremia, viral shedding in nasal and oral swabs, peak cytokine levels, and time to reach endpoint criteria. Virus distribution across 19 tissues was largely unaffected by the inoculation route at the highest doses tested. The NHPs inoculated by the i.b. route developed a viral pneumonia that likely exacerbated disease progression. Based on the observations of the delayed onset of clinical and virological parameters and endpoint criteria that may more closely resemble those of human MPXV infection, the i.b. MPXV model should be considered for the further investigation of viral pathogenesis and countermeasures. C1 [Johnson, Reed F.] NIAID, Emerging Viral Pathogens Sect, EVPS, NIH, Bethesda, MD 20892 USA. [Dyall, Julie; Ragland, Dan R.; Huzella, Louis; Byrum, Russell; Jett, Catherine; St Claire, Marisa; Paragas, Jason; Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA. RP Johnson, RF (reprint author), NIAID, Emerging Viral Pathogens Sect, EVPS, NIH, Bldg 33,Rm 2E19A,33 N Dr, Bethesda, MD 20892 USA. EM johnsonreed@mail.nih.gov FU NIAID Division of Intramural Research FX This study was supported, in part, by the NIAID Division of Intramural Research. NR 43 TC 26 Z9 26 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2112 EP 2125 DI 10.1128/JVI.01931-10 PG 14 WC Virology SC Virology GA 716MT UT WOS:000286974900018 PM 21147922 ER PT J AU Dussupt, V Sette, P Bello, NF Javid, MP Nagashima, K Bouamr, F AF Dussupt, Vincent Sette, Paola Bello, Nana F. Javid, Melodi P. Nagashima, Kunio Bouamr, Fadila TI Basic Residues in the Nucleocapsid Domain of Gag Are Critical for Late Events of HIV-1 Budding SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ROUS-SARCOMA-VIRUS; ESCRT-III; IN-VITRO; MEMBRANE-BINDING; PLASMA-MEMBRANE; CAPSID PROTEIN; FUNCTIONAL REPLACEMENT; MAMMALIAN-CELLS; CELLULAR RNAS AB The p6 region of HIV-1 Gag contains two late (L) domains, PTAP and LYPXnL, that bind the cellular proteins Tsg101 and Alix, respectively. These interactions are thought to recruit members of the host fission machinery (ESCRT) to facilitate HIV-1 release. Here we report a new role for the p6-adjacent nucleocapsid (NC) domain in HIV-1 release. The mutation of basic residues in NC caused a pronounced decrease in virus release from 293T cells, although NC mutant Gag proteins retained the ability to interact with cellular membranes and RNAs. Remarkably, electron microscopy analyses of these mutants revealed arrested budding particles at the plasma membrane, analogous to those seen following the disruption of the PTAP motif. This result indicated that the basic residues in NC are important for virus budding. When analyzed in physiologically more relevant T-cell lines (Jurkat and CEM), NC mutant viruses remained tethered to the plasma membrane or to each other by a membranous stalk, suggesting membrane fission impairment. Remarkably, NC mutant release defects were alleviated by the coexpression of a Gag protein carrying a wild-type (WT) NC domain but devoid of all L domain motifs and by providing alternative access to the ESCRT pathway, through the in trans expression of the ubiquitin ligase Nedd4.2s. Since NC mutant Gag proteins retained the interaction with Tsg101, we concluded that NC mutant budding arrests might have resulted from the inability of Gag to recruit or utilize members of the host ESCRT machinery that act downstream of Tsg101. Together, these data support a model in which NC plays a critical role in HIV-1 budding. C1 [Dussupt, Vincent; Sette, Paola; Bello, Nana F.; Javid, Melodi P.; Bouamr, Fadila] NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. [Nagashima, Kunio] NCI, SAIC Frederick, Image Anal Lab, Adv Technol Program, Frederick, MD 21702 USA. RP Bouamr, F (reprint author), NIAID, NIH, Mol Microbiol Lab, 4 Ctr Dr, Bethesda, MD 20892 USA. EM bouamrf@mail.nih.gov OI Javid, Melodi/0000-0002-8163-6881 FU NIAID, NIH FX This work was supported by the Intramural Research Program of the NIAID, NIH. NR 77 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2304 EP 2315 DI 10.1128/JVI.01562-10 PG 12 WC Virology SC Virology GA 716MT UT WOS:000286974900035 PM 21159863 ER PT J AU Verweij, MC Lipinska, AD Koppers-Lalic, D Van Leeuwen, WF Cohen, JI Kinchington, PR Messaoudi, I Bienkowska-Szewczyk, K Ressing, ME Rijsewijk, FAM Wiertz, EJHJ AF Verweij, Marieke C. Lipinska, Andrea D. Koppers-Lalic, Danijela Van Leeuwen, Wouter F. Cohen, Jeffrey I. Kinchington, Paul R. Messaoudi, Ilhem Bienkowska-Szewczyk, Krystyna Ressing, Maaike E. Rijsewijk, Frans A. M. Wiertz, Emmanuel J. H. J. TI The Capacity of UL49.5 Proteins To Inhibit TAP Is Widely Distributed among Members of the Genus Varicellovirus SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INFECTIOUS LARYNGOTRACHEITIS VIRUS; CYTOMEGALOVIRUS US6 GLYCOPROTEIN; REGULATES SURFACE EXPRESSION; GREEN FLUORESCENT PROTEIN; ANTIGEN-PROCESSING TAP; TO-CELL SPREAD; CLASS-I; ZOSTER-VIRUS; PEPTIDE TRANSLOCATION AB The lifelong infection by varicelloviruses is characterized by a fine balance between the host immune response and immune evasion strategies used by these viruses. Virus-derived peptides are presented to cytotoxic T lymphocytes by major histocompatibility complex (MHC) class I molecules. The transporter associated with antigen processing (TAP) transports the peptides from the cytosol into the endoplasmic reticulum, where the loading of MHC-I molecules occurs. The varicelloviruses bovine herpesvirus 1 (BoHV-1), pseudorabies virus, and equid herpesviruses 1 and 4 have been found to encode a UL49.5 protein that inhibits TAP-mediated peptide transport. To investigate to what extent UL49.5-mediated TAP inhibition is conserved within the family of Alphaherpesvirinae, the homologs of another five varicelloviruses, one mardivirus, and one iltovirus were studied. The UL49.5 proteins of BoHV-5, bubaline herpesvirus 1, cervid herpesvirus 1, and felid herpesvirus 1 were identified as potent TAP inhibitors. The varicella-zoster virus and simian varicellovirus UL49.5 proteins fail to block TAP; this is not due to the absence of viral cofactors that might assist in this process, since cells infected with these viruses did not show reduced TAP function either. The UL49.5 homologs of the mardivirus Marek's disease virus 1 and the iltovirus infectious laryngotracheitis virus did not block TAP, suggesting that the capacity to inhibit TAP via UL49.5 has been acquired by varicelloviruses only. A phylogenetic analysis of viruses that inhibit TAP through their UL49.5 proteins reveals an interesting hereditary pattern, pointing toward the presence of this capacity in defined clades within the genus Varicellovirus. C1 [Van Leeuwen, Wouter F.; Ressing, Maaike E.; Wiertz, Emmanuel J. H. J.] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands. [Verweij, Marieke C.; Koppers-Lalic, Danijela] Leiden Univ, Med Ctr, Ctr Infect Dis, Dept Med Microbiol, Leiden, Netherlands. [Lipinska, Andrea D.; Bienkowska-Szewczyk, Krystyna] Univ Gdansk, Fac Biotechnol, Dept Mol Virol, PL-80952 Gdansk, Poland. [Cohen, Jeffrey I.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Kinchington, Paul R.] Univ Pittsburgh, Dept Ophthalmol, Pittsburgh, PA 15260 USA. [Messaoudi, Ilhem] Oregon Hlth & Sci Univ, Div Pathobiol & Immunol, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Rijsewijk, Frans A. M.] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Microbiol, Porto Alegre, RS, Brazil. RP Wiertz, EJHJ (reprint author), Univ Med Ctr Utrecht, Dept Med Microbiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM e.wiertz@umcutrecht.nl RI Lipinska, Andrea/K-5649-2014; OI van Leeuwen, Wouter/0000-0002-3874-5441 FU The Macropa Foundation, Leiden, Netherlands; Foundation for Polish Science; National Institute of Allergy and Infectious Diseases; National Institute of Health [NS064022, EY08098]; National Institutes of Health [R01 AG037042-01]; Netherlands Scientific Organization [917.76.330] FX This study was supported by a grant from The Macropa Foundation, Leiden, Netherlands (M.C.V.), the START program of the Foundation for Polish Science (A.D.L.), the intramural research program of the National Institute of Allergy and Infectious Diseases (J.I.C.), grants NS064022 and EY08098 of the National Institute of Health (P.R.K.), grant R01 AG037042-01 from the National Institutes of Health (I.M.), and NWO Vidi grant 917.76.330 from the Netherlands Scientific Organization (M.E.R.). NR 50 TC 10 Z9 13 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2351 EP 2363 DI 10.1128/JVI.01621-10 PG 13 WC Virology SC Virology GA 716MT UT WOS:000286974900040 PM 21159875 ER PT J AU Berkower, I Spadaccini, A Chen, H Al-Awadi, D Muller, J Gao, Y Feigelstock, D Virnik, K Ni, Y AF Berkower, Ira Spadaccini, Angelo Chen, Hong Al-Awadi, Danah Muller, Jacqueline Gao, Yamei Feigelstock, Dino Virnik, Konstantin Ni, Yisheng TI Hepatitis B Virus Surface Antigen Assembly Function Persists when Entire Transmembrane Domains 1 and 3 Are Replaced by a Heterologous Transmembrane Sequence SO JOURNAL OF VIROLOGY LA English DT Article ID PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODY; ENVELOPE GLYCOPROTEINS; GP41 EPITOPE; TYPE-1; MEMBRANE; PARTICLES; VACCINE; HIV-1 AB Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm subviral particles. The particles are lipoprotein micelles, in which HBsAg is believed to span the lipid layer four times. The first two transmembrane domains, TM1 and TM2, are required for particle assembly. We have probed the requirements for particle assembly by replacing the entire first or third TM domain of HBsAg with the transmembrane domain of HIV gp41. We found that either TM domain of HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with the gp41 domain. The results indicate remarkable flexibility in HBsAg particle formation and provide a novel way to express heterologous membrane proteins that are anchored to a lipid surface by their own membrane-spanning domain. The membrane-proximal exposed region (MPER) of gp41 is an important target of broadly reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may provide a good platform for future vaccine development. C1 [Berkower, Ira; Spadaccini, Angelo; Chen, Hong; Al-Awadi, Danah; Muller, Jacqueline; Gao, Yamei; Feigelstock, Dino; Virnik, Konstantin; Ni, Yisheng] US FDA, Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Ctr Biol, Bldg 29,Rm 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov FU NIH FX This research was supported in part by the NIH Intramural AIDS Targeted Research Program. NR 50 TC 7 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2439 EP 2448 DI 10.1128/JVI.02061-10 PG 10 WC Virology SC Virology GA 716MT UT WOS:000286974900048 PM 21177825 ER PT J AU Brown, P AF Brown, Patricia TI A word from OLAW SO LAB ANIMAL LA English DT Editorial Material C1 NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 2011 VL 40 IS 3 BP 66 EP 66 DI 10.1038/laban0311-66a PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 730NB UT WOS:000288039100008 PM 21326183 ER PT J AU Cannon, CZ Kissling, GE Goulding, DR King-Herbert, AP Blankenship-Paris, T AF Cannon, Coralie Zegre Kissling, Grace E. Goulding, David R. King-Herbert, Angela P. Blankenship-Paris, Terry TI Analgesic effects of tramadol, carprofen or multimodal analgesia in rats undergoing ventral laparotomy SO LAB ANIMAL LA English DT Article ID ENCAPSULATED OXYMORPHONE HYDROCHLORIDE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POSTOPERATIVE PAIN; DOGS; BUPRENORPHINE; COMBINATION; PETHIDINE; IBUPROFEN; DURATION; EFFICACY AB In this study, the authors evaluated the analgesic efficacy of tramadol (an opioid-like analgesic), carprofen (a nonsteroidal anti-inflammatory drug) and a combination of both drugs (multimodal therapy) in a rat laparotomy model. The authors randomly assigned rats to undergo either surgery (abdominal laparotomy with visceral manipulation and anesthesia) or anesthesia only. Rats in each group were treated with tramadol (12.5 mg per kg body weight), carprofen (5 mg per kg body weight), a combination of tramadol and carprofen (12.5 mg per kg body weight and 5 mg per kg body weight, respectively) or saline (anesthesia control group only; 5 mg per kg body weight). The authors administered analgesia 10 min before anesthesia, 4 h after surgery or (for the rats that received anesthesia only) anesthesia and 24 h after surgery or anesthesia. They measured locomotor activity, running wheel activity, feed and water consumption, body weight and fecal corticosterone concentration of each animal before and after surgery. Clinical observations were made after surgery or anesthesia to evaluate signs of pain and distress. The authors found that carprofen, tramadol and a combination of carprofen and tramadol were all acceptable analgesia regimens for a rat laparotomy model. C1 [Goulding, David R.; Blankenship-Paris, Terry] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Cannon, Coralie Zegre; King-Herbert, Angela P.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Blankenship-Paris, T (reprint author), NIEHS, Comparat Med Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM blanken1@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences FX We thank Danielle Waxer, James Clark, Page Myers, Sandy Hackney, Joe Hensley and Rodney Chavis for their assistance and support of the research and care of the animals. We thank Dr. Paul Flecknell for his consultation; Dr. Larry Wright for his assistance in literature evaluation; The Brookfield Zoo Endocrinology Lab for carrying out the corticosterone assay; Dr. Mark Cesta for pathology; Eli Ney for imaging; and Dr. Mary Grant, Dr. Mark Hoenerhoff and Dr. Gregory Cannon for manuscript review. This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. This article may be the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), however, the statements, opinions or conclusions contained herein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH or the United States government. NR 37 TC 10 Z9 10 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 2011 VL 40 IS 3 BP 85 EP 93 DI 10.1038/laban0311-85 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 730NB UT WOS:000288039100014 ER PT J AU Furukawa, T Yahiro, K Tsuji, AB Terasaki, Y Morinaga, N Miyazaki, M Fukuda, Y Saga, T Moss, J Noda, M AF Furukawa, Takeshi Yahiro, Kinnosuke Tsuji, Atsushi B. Terasaki, Yasuhiro Morinaga, Naoko Miyazaki, Masaru Fukuda, Yuh Saga, Tsuneo Moss, Joel Noda, Masatoshi TI Fatal hemorrhage induced by subtilase cytotoxin from Shiga-toxigenic Escherichia coli SO MICROBIAL PATHOGENESIS LA English DT Article DE Subtilase cytotoxin; Hemorrhage; Coagulopathy; Inflammation ID ENDOPLASMIC-RETICULUM STRESS; DOWN-REGULATION; FDG PET; COLI; MICE; TOXIN; INFLAMMATION; EXPRESSION; RECEPTORS; INFECTION AB Subtilase cytotoxin (SubAB) is an AB(5) type toxin produced by a subset of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone BiP The B subunit binds to a receptor on the cell surface. Although SubAB is lethal for mice, the cause of death is not clear. In this study, we demonstrate in mice that SubAB induced small bowel hemorrhage and a coagulopathy characterized by thrombocytopenia, prolonged prothrombin time and activated partial thromboplastin time. SubAB also induced inflammatory changes in the small intestine as detected by F-18-fluoro-2-deoxy-D-glucose positron emission tomography imaging and histochemical analysis. Using RT-PCR and ELISA, SubAB was shown to increase interleukin-6 in a time-dependent manner. Thus, our results indicate that death in SubAB-treated mice may be associated with severe inflammatory response and hemorrhage of the small intestine, accompanied by coagulopathy and IL6 production. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Furukawa, Takeshi; Yahiro, Kinnosuke; Morinaga, Naoko; Noda, Masatoshi] Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan. [Furukawa, Takeshi; Miyazaki, Masaru] Chiba Univ, Grad Sch Med, Dept Gen Surg, Chiba 2608670, Japan. [Tsuji, Atsushi B.; Saga, Tsuneo] Natl Inst Radiol Sci, Mol Imaging Ctr, Diagnost Imaging Grp, Inage Ku, Chiba 2638555, Japan. [Terasaki, Yasuhiro; Fukuda, Yuh] Nippon Med Sch, Bunkyo Ku, Tokyo 1130031, Japan. [Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA. RP Yahiro, K (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM yahirok@faculty.chiba-u.jp OI Tsuji, Atsushi/0000-0003-2726-288X FU Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology; Japanese Government; Japan Science and Technology Agency; NIH, NHLBI FX This work was supported by grants-in-aid from Promoting Science and Technology of the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government and for Improvement of Research Environment for Young Researchers from Japan Science and Technology Agency. We thank Dr. Mitsuru Koizumi for comments and discussion. We thank Mr. Hidekatsu Wakizaka for the quality control of the PET scanner. We thank Dr. Akira Shimizu for analysis of kidney sections. Dr. Moss was supported by the Intramural Research Program, NIH, NHLBI. NR 33 TC 10 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD MAR-APR PY 2011 VL 50 IS 3-4 BP 159 EP 167 DI 10.1016/j.micpath.2011.01.002 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA 729NV UT WOS:000287958400004 PM 21232591 ER PT J AU Venkataraman, G Rizzo, KA Chavez, JJ Streubel, B Raffeld, M Jaffe, ES Pittaluga, S AF Venkataraman, Girish Rizzo, Kathryn A. Chavez, Jessica J. Streubel, Berthold Raffeld, Mark Jaffe, Elaine S. Pittaluga, Stefania TI Marginal zone lymphomas involving meningeal dura: possible link to IgG4-related diseases SO MODERN PATHOLOGY LA English DT Article DE dura; IgG4; immunohistochemistry; inflammatory pseudotumor; marginal zone lymphoma; RT-PCR; trisomy 3 ID B-CELL LYMPHOMA; CHRONIC SCLEROSING SIALADENITIS; MALT LYMPHOMA; INFLAMMATORY PSEUDOTUMOR; AUTOIMMUNE PANCREATITIS; CHROMOSOMAL-ABERRATION; VARIABLE FREQUENCIES; SUBDURAL-HEMATOMA; IMMUNOGLOBULIN G4; TISSUE LYMPHOMA AB Dura-based marginal zone lymphomas represent an uncommon group of low-grade B-cell neoplasms, and literature regarding the clinical, histological and genetic profile of these tumors in the context of the newly described IgG4-related entities is lacking. We analyzed 32 dura-based marginal zone lymphomas identified in 27 females and 5 males ranging in age from 33-82 years (median 50). Morphologic examination, immunohistochemical studies and PCR for B-cell clonality were carried out in all cases. In addition, IgG4 immunohistochemistry and cytogenetic studies (either by FISH or RT-PCR) were carried out in 20 (18 primary dural; 2 with associated extradural disease) and 9 cases, respectively. Clinically, most cases presented radiologically as dura-based masses, mimicking meningioma. Histologically, the majority exhibited plasmacytoid differentiation, and were clonal either by PCR or immunohistochemical light chain analysis (28 out of 32). In the subset tested for IgG4, 6 of 18 primary dural marginal zone lymphoma (including one epidural tumor) showed numerous IgG4-positive plasma cells; all 6 were light chain restricted and clonal by PCR in 5 of 6 tested cases. Three IgG4-positive marginal zone lymphomas tested for cytogenetics did not show any cytogenetic aberrations. Across all cases, FISH and RT-PCR identified abnormalities in three out of nine cases (trisomies 3 and 18; trisomies 3 and 1; trisomy 18) without any extranodal marginal zone lymphoma specific translocations. Regardless of the treatment modality, 16 of 17 patients with follow-up are alive without evidence of disease over a period of 4-124 months (median 19.5). The expression of IgG4 in light-chain-restricted clonal plasma cells of a significant subset of dural marginal zone lymphomas, including one in an epidural location, is a novel finding and points to distinctive biology. Cytogenetic aberrations are present only in a minority of dural marginal zone lymphomas. Modern Pathology (2011) 24, 355-366; doi:10.1038/modpathol.2010.206; published online 19 November 2010 C1 [Venkataraman, Girish; Rizzo, Kathryn A.; Chavez, Jessica J.; Raffeld, Mark; Jaffe, Elaine S.; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Streubel, Berthold] Med Univ Vienna, Inst Pathol, Vienna Gen Hosp, Vienna, Austria. RP Pittaluga, S (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 2B 42, Bethesda, MD 20892 USA. EM stefpitt@mail.nih.gov OI Venkataraman, Girish/0000-0002-8674-2608; Jaffe, Elaine/0000-0003-4632-0301 NR 44 TC 32 Z9 34 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD MAR PY 2011 VL 24 IS 3 BP 355 EP 366 DI 10.1038/modpathol.2010.206 PG 12 WC Pathology SC Pathology GA 729XC UT WOS:000287986600003 PM 21102421 ER PT J AU Gallazzini, M Heussler, GE Kunin, M Izumi, Y Burg, MB Ferraris, JD AF Gallazzini, Morgan Heussler, Gary E. Kunin, Margarita Izumi, Yuichiro Burg, Maurice B. Ferraris, Joan D. TI High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID OSMOTIC RESPONSE ELEMENT; ENHANCER-BINDING PROTEIN; TYROSINE KINASE INHIBITOR; CYCLIN-DEPENDENT KINASE-5; DAMAGE-INDUCIBLE KINASE; T-CELL-ACTIVATION; C-ABL; HYPERTONIC STRESS; NUCLEOCYTOPLASMIC TRAFFICKING; PHOSPHOLIPASE C-GAMMA-1 AB When activated by high NaCl, tonicity-responsive enhancer-binding protein/osmotic response element-binding protein (TonEBP/OREBP) increases transcription of osmoprotective genes. High NaCl activates TonEBP/OREBP by increasing its phosphorylation, nuclear localization, and transactivating activity. In HEK293 cells, mass spectrometry shows phosphorylation of TonEBP/OREBP-S120, -S134, -T135, and -S155. When those residues are individually mutated to alanine, nuclear localization is greater for S155A, less for S134A and T135A, and unchanged for S120A. High osmolality increases phosphorylation at T135 in HEK293 cells and in rat renal inner medullas in vivo. In HEK293 cells, high NaCl activates cyclin-dependent kinase 5 (CDK5), which directly phosphorylates TonEBP/OREBP-T135. Inhibition of CDK5 activity reduces the rapid high NaCl-induced nuclear localization of TonEBP/OREBP but does not affect its transactivating activity. High NaCl induces nuclear localization of TonEBP/OREBP faster (<= 2 h) than it increases its overall protein abundance (>= 6 h). Inhibition of CDK5 reduces the increase in TonEBP/OREBP transcriptional activity that has occurred by 4 h after NaCl is raised, associated with less nuclear TonEBP/OREBP at that time, but does not reduce either activity or nuclear TonEBP/OREBP after 16 h. Thus high NaCl-induced increase of the overall abundance of TonEBP/OREBP, by itself, eventually raises its effective level in the nucleus, but its rapid CDK5-dependent nuclear localization accelerates the process, speeding transcription of osmoprotective target genes. C1 [Gallazzini, Morgan; Heussler, Gary E.; Kunin, Margarita; Izumi, Yuichiro; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Lab Kidney & Elect Metab, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), Univ Paris 05, Hop Necker Enfants Malad, Ctr Rech Croissance & Signalisat, INSERM,U845, F-75015 Paris, France. EM maurice_burg@nih.gov RI Gallazzini, Morgan/E-5465-2011 FU National Heart, Lung, and Blood Institute FX This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute. NR 45 TC 14 Z9 16 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR 1 PY 2011 VL 22 IS 5 BP 703 EP 714 DI 10.1091/mbc.E10-08-0681 PG 12 WC Cell Biology SC Cell Biology GA 727NS UT WOS:000287808500015 PM 21209322 ER PT J AU Carrillo-Carrasco, N Sloan, J Manoli, I Hauser, N Zein, WM Gropman, A Tanpaiboon, P Graf, J Baker, E Snow, J Paul, SM Brooks, B Venditti, CP AF Carrillo-Carrasco, N. Sloan, J. Manoli, I. Hauser, N. Zein, W. M. Gropman, A. Tanpaiboon, P. Graf, J. Baker, E. Snow, J. Paul, S. M. Brooks, B. Venditti, C. P. TI Detailed phenotype and long-term outcome of "early-onset" cbIC disease SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Carrillo-Carrasco, N.; Sloan, J.; Manoli, I.; Hauser, N.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD USA. [Zein, W. M.; Brooks, B.] NEI, NIH, Bethesda, MD USA. [Graf, J.; Baker, E.; Snow, J.; Paul, S. M.] NIH, Clin Res Ctr, Bethesda, MD USA. RI Carrillo-Carrasco, Nuria/B-9034-2009 OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 246 EP 247 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800004 ER PT J AU Manoli, I Sysol, JR Li, L Chandler, RJ Senac, J Hoffmann, V Zerfas, P Schnermann, J Venditti, CP AF Manoli, I Sysol, J. R. Li, L. Chandler, R. J. Senac, J. Hoffmann, V Zerfas, P. Schnermann, J. Venditti, C. P. TI Muscle targeted transgene expression rescues the lethal phenotype of Mut knockout mice SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Manoli, I; Sysol, J. R.; Chandler, R. J.; Senac, J.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Li, L.; Schnermann, J.] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD USA. [Hoffmann, V; Zerfas, P.] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 248 EP 248 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800007 ER PT J AU Gahl, WA AF Gahl, William A. TI The NIH Undiagnosed Diseases Program SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Gahl, William A.] NHGRI, Bethesda, MD 20892 USA. [Gahl, William A.] NIH, UDP, Bethesda, MD 20892 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 256 EP 256 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800020 ER PT J AU Mudd, SH AF Mudd, S. Harvey TI The genetic hypermethioninemias SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 259 EP 260 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800029 ER PT J AU Adams, D Tifft, C Wolfe, L Golas, G Markello, T Pierson, T Toro, C Gropman, A Gahl, W AF Adams, D. Tifft, C. Wolfe, L. Golas, G. Markello, T. Pierson, T. Toro, C. Gropman, A. Gahl, W. TI Known-disease diagnoses in the NIH Undiagnosed Diseases Program SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Adams, D.; Tifft, C.; Wolfe, L.; Golas, G.; Markello, T.; Pierson, T.; Toro, C.; Gropman, A.; Gahl, W.] NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Pierson, T.] NINDS, NIH, Bethesda, MD 20892 USA. [Gropman, A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 266 EP 266 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800039 ER PT J AU Berry, SA Brower, AM AF Berry, Susan A. Brower, Amy M. CA Joint Comm NBSTRN Clinical Center NCC RC Long Term Follow Up Workgrp TI Planning for long-term follow-up data collection after newborn screening to advance research and improve service delivery and health outcomes SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Joint Comm NBSTRN Clinical Center] NIH, Newborn Screening Translat Res Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Washington, DC USA. [NCC RC Long Term Follow Up Workgrp] Natl Coordinating Ctr Reg Genet Collaborat, Newborn Screening Serv Collaborat NCC RC, Hlth Resources & Serv Adm, Maternal & Child Hlth Bur,Genet Serv Branchs, Washington, DC USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 269 EP 269 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800045 ER PT J AU Camp, KM Coates, PM Groft, SC AF Camp, K. M. Coates, P. M. Groft, S. C. TI Nutritional therapies for inherited metabolic diseases: Building an infrastructure to guide clinical practice through evidence-based research SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Camp, K. M.; Coates, P. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Groft, S. C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 273 EP 274 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800054 ER PT J AU Chandler, RJ Chandrasekaran, S Carrillo-Carrasco, N Venditti, CP AF Chandler, Randy J. Chandrasekaran, Suma Carrillo-Carrasco, Nuria Venditti, Charles P. TI Effective gene therapy for propionic acidemia SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Chandler, Randy J.; Chandrasekaran, Suma; Carrillo-Carrasco, Nuria; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. RI Carrillo-Carrasco, Nuria/B-9034-2009 OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 274 EP 274 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800055 ER PT J AU Golas, G Wolfe, L Bishop, R Zein, W Gropman, A Markello, T Tifft, C Gahl, W Adams, D AF Golas, G. Wolfe, L. Bishop, R. Zein, W. Gropman, A. Markello, T. Tifft, C. Gahl, W. Adams, D. TI Two siblings diagnosed with adenylosuccinate lyase deficiency in late adolescence SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Golas, G.; Wolfe, L.; Markello, T.; Tifft, C.; Gahl, W.; Adams, D.] NHGRI, Sect Human Biochem Genet, OCD, NIH, Bethesda, MD USA. [Golas, G.; Wolfe, L.; Markello, T.; Tifft, C.; Gahl, W.; Adams, D.] NHGRI, Undiagnosed Dis Program, ORDR, NIH, Bethesda, MD USA. [Bishop, R.; Zein, W.] NEI, NIH, Bethesda, MD USA. [Gropman, A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 284 EP 285 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800075 ER PT J AU Hauser, NS Zein, WM Sloan, JL Manoli, I Bowles, K O'Brien, K Brooks, BP Venditti, CP AF Hauser, N. S. Zein, W. M. Sloan, J. L. Manoli, I. Bowles, K. O'Brien, K. Brooks, B. P. Venditti, C. P. TI Methylmalonic acidemia and optic nerve atrophy: Reversal of sub-acute loss of visual function with anti-oxidant therapy SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Hauser, N. S.] Childrens Hosp Cent Calif, Fresno, CA USA. [Hauser, N. S.; Sloan, J. L.; Manoli, I.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Zein, W. M.; Bowles, K.; Brooks, B. P.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [O'Brien, K.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 288 EP 289 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800081 ER PT J AU O'Brien, K Golas, G Groden, C Wahl, C Nehrebecky, M Davis, J Wolfe, L AF O'Brien, K. Golas, G. Groden, C. Wahl, C. Nehrebecky, M. Davis, J. Wolfe, L. TI The emerging role of Nurse Practitioners in genetics SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [O'Brien, K.; Golas, G.; Groden, C.] NHGRI, Sect Human Biochem Genet, OCD, NIH, Bethesda, MD USA. [Golas, G.; Groden, C.; Wahl, C.; Nehrebecky, M.; Wolfe, L.] NHGRI, Undiagnosed Dis Program, ORDR, NIH, Bethesda, MD USA. [Davis, J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 307 EP 307 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800118 ER PT J AU Parisi, M Urv, T Howell, RR Camp, KM Coates, PM Groft, SC AF Parisi, M. Urv, T. Howell, R. R. Camp, K. M. Coates, P. M. Groft, S. C. TI National institutes of Health phenylketonuria scientific conference SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Parisi, M.; Urv, T.; Howell, R. R.] NICHHD, NIH, Bethesda, MD 20892 USA. [Camp, K. M.; Coates, P. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Groft, S. C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 308 EP 308 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800120 ER PT J AU Wolfe, LA McGrath, JJ Wong, LJ Vladutiu, GD AF Wolfe, L. A. McGrath, J. J. Wong, L. J. Vladutiu, G. D. TI RRM2B mtDNA depletion syndrome presenting with pyruvate dehydrogenase deficiency SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Grove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, Cambrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Wolfe, L. A.; McGrath, J. J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Wolfe, L. A.] NHGRI, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Wong, L. J.] Baylor Coll Med, Houston, TX 77030 USA. [Vladutiu, G. D.] Kaleida Hlth Labs, Robert Guthrie Biochem & Mol Genet Lab, Buffalo, NY USA. [Vladutiu, G. D.] SUNY Buffalo, Buffalo, NY USA. NR 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 321 EP 322 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800148 ER PT J AU Wolfe, LA Golas, GA He, M Xia, B Zhang, W Song, X Cummings, R Adams, DR Yang, S Gropman, A Tifft, CJ AF Wolfe, L. A. Golas, G. A. He, M. Xia, B. Zhang, W. Song, X. Cummings, R. Adams, D. R. Yang, S. Gropman, A. Tifft, C. J. TI Further characterization of congenital disorder of glycosylation IIB in siblings SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 34th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2011) CY FEB 27-MAR 02, 2011 CL Pacific Groove, CA SP Soc Inherited Metabol Disorders, Genzyme, Abbott Metabol, Shire, ARUP Labs, Cytonet LLC, GeneDx, Hyperion Therapeut, Nautricia N Amer, Vitaflo, Ucyclyd Pharma, RDT, BIOMARIN, Applied Nutr Corp, CamBrooke Foods, Hitachi, Mead Johnson, PreventionGenetics, Canadian PKU & Allied Disorders Inc, Transgenomic, Emory Genet Lab, FOD, Kakkis EveryLife Fdn, Natl PKU Alliance, Organ Acidemia Assoc C1 [Wolfe, L. A.; Golas, G. A.; Adams, D. R.; Yang, S.; Gropman, A.; Tifft, C. J.] NHGRI, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [He, M.; Xia, B.; Zhang, W.] Emory Univ, Sch Med, Dept Human Genet, Decatur, GA 30033 USA. [Song, X.; Cummings, R.] Emory Univ, Sch Med, Dept Biochem, Decatur, GA 30033 USA. [Gropman, A.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 321 EP 321 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800147 ER PT J AU Wamelink, MMC Struys, EA Jansen, EEW Blom, HJ Vilboux, T Gahl, WA Komhoff, M Jakobs, C Levtchenko, EN AF Wamelink, M. M. C. Struys, E. A. Jansen, E. E. W. Blom, H. J. Vilboux, T. Gahl, W. A. Komhoff, M. Jakobs, C. Levtchenko, E. N. TI Elevated concentrations of sedoheptulose in bloodspots of patients with cystinosis caused by the 57-kb deletion: Implications for diagnostics and neonatal screening SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Cystinosis; Sedoheptulose; Dried bloodspots; 57-kb deletion; LC-MS/MS ID ORAL CYSTEAMINE THERAPY; NEPHROPATHIC CYSTINOSIS; GENE; CTNS; DEFICIENCY; LEUKOCYTES AB Cystinosis is an autosomal recessive lysosomal storage disease caused by mutations in CTNS. The most prevalent CTNS mutation is a homozygous 57-kb deletion that also includes an adjacent gene named SHPK (CARKL), encoding sedoheptulokinase. Patients with this deletion have elevated urinary concentrations of sedoheptulose. Using derivatisation with pentafluorobenzyl hydroxylamine and liquid chromatography-tandem mass spectrometry (LC-MS/MS), we developed a new sensitive method for the quantification of sedoheptulose in dried blood spots. This method can be utilized as a quick screening test to detect cystinosis patients homozygous for the 57-kb deletion in CTNS; which is the most common mutation of cystinosis. Sedoheptulose concentrations in the deleted patients were 6 to 23 times above the upper limit for controls. The assessment of sedoheptulose in a bloodspot from a known cystinosis patient homozygous for the 57-kb deletion retrieved from the Dutch neonatal screening program showed that sedoheptulose was already elevated in the neonatal period. There was no overlap in sedoheptulose levels between cystinosis patients homozygous for the 57-kb deletion and cystinosis patients not homozygous for this deletion. Our presented method can be used prior to mutation analysis to detect cystinosis patients homozygous for the 57-kb deletion. We feel that the presented method enables fast (pre)-symptomatic detection of cystinosis patients homozygous for the 57-kb deletion, allowing early treatment. (C) 2010 Elsevier Inc. All rights reserved. C1 [Wamelink, M. M. C.; Struys, E. A.; Jansen, E. E. W.; Blom, H. J.; Jakobs, C.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands. [Vilboux, T.; Gahl, W. A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Komhoff, M.] Univ Groningen, Univ Med Ctr Groningen, Dept Pediat Nephrol, NL-9713 AV Groningen, Netherlands. [Levtchenko, E. N.] Univ Hosp Leuven, Dept Pediat Nephrol, Louvain, Belgium. RP Wamelink, MMC (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands. EM m.wamelink@vumc.nl RI Wamelink, Mirjam/A-9007-2015; OI Blom, Henk/0000-0001-5202-9241 NR 14 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 339 EP 342 DI 10.1016/j.ymgme.2010.12.002 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800157 PM 21195649 ER PT J AU Addington, AM Gauthier, J Piton, A Hamdan, FF Raymond, A Gogtay, N Miller, R Tossell, J Bakalar, J Germain, G Gochman, P Long, R Rapoport, JL Rouleau, GA AF Addington, A. M. Gauthier, J. Piton, A. Hamdan, F. F. Raymond, A. Gogtay, N. Miller, R. Tossell, J. Bakalar, J. Germain, G. Gochman, P. Long, R. Rapoport, J. L. Rouleau, G. A. TI A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders SO MOLECULAR PSYCHIATRY LA English DT Letter C1 [Addington, A. M.; Gogtay, N.; Miller, R.; Tossell, J.; Bakalar, J.; Germain, G.; Gochman, P.; Long, R.; Rapoport, J. L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Gauthier, J.; Piton, A.; Raymond, A.; Rouleau, G. A.] Univ Montreal, Ctr Excellence Neur, Ctr Hosp, Montreal, PQ, Canada. [Gauthier, J.; Piton, A.; Raymond, A.; Rouleau, G. A.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Hamdan, F. F.] Univ Montreal, Ctr Excellence Neur, CHU St Justine, Montreal, PQ, Canada. RP Addington, AM (reprint author), NIMH, Child Psychiat Branch, Bldg 10, Bethesda, MD 20892 USA. EM addingta@mail.nih.gov RI Gogtay, Nitin/A-3035-2008; piton, amelie/F-1201-2013 OI piton, amelie/0000-0003-0408-7468 FU Intramural NIH HHS [ZIA MH002581-19] NR 10 TC 33 Z9 33 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2011 VL 16 IS 3 BP 238 EP 239 DI 10.1038/mp.2010.59 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 723AT UT WOS:000287479100001 PM 20479756 ER PT J AU Ayhan, Y Abazyan, B Nomura, J Kim, R Ladenheim, B Krasnova, IN Sawa, A Margolis, RL Cadet, JL Mori, S Vogel, MW Ross, CA Pletnikov, MV AF Ayhan, Y. Abazyan, B. Nomura, J. Kim, R. Ladenheim, B. Krasnova, I. N. Sawa, A. Margolis, R. L. Cadet, J. L. Mori, S. Vogel, M. W. Ross, C. A. Pletnikov, M. V. TI Differential effects of prenatal and postnatal expressions of mutant human DISC1 on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental origin of major psychiatric disorders SO MOLECULAR PSYCHIATRY LA English DT Article DE schizophrenia; mood disorders; DISC1; mouse models; Tet-off system ID DENDRITIC SPINE DENSITY; SCHIZOPHRENIA-RELATED PHENOTYPES; GENE-ENVIRONMENT INTERACTIONS; BIPOLAR DISORDER; ADULT BRAIN; BEHAVIORAL PHENOTYPES; DOPAMINE TRANSPORTER; INDUCIBLE EXPRESSION; NEURAL DEVELOPMENT; PREFRONTAL CORTEX AB Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases. Molecular Psychiatry (2011) 16, 293-306; doi:10.1038/mp.2009.144; published online 5 January 2010 C1 [Ayhan, Y.; Abazyan, B.; Nomura, J.; Kim, R.; Margolis, R. L.; Ross, C. A.; Pletnikov, M. V.] Johns Hopkins Univ, Sch Med, Div Neurobiol, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Ladenheim, B.; Krasnova, I. N.; Cadet, J. L.] NIDA, Mol Neuropsychiatry Branch, NIH, DHHS, Baltimore, MD USA. [Sawa, A.; Ross, C. A.; Pletnikov, M. V.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Sawa, A.; Margolis, R. L.; Ross, C. A.; Pletnikov, M. V.] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21287 USA. [Sawa, A.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Program Mol Psychiat, Baltimore, MD 21287 USA. [Margolis, R. L.; Ross, C. A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Mori, S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. [Vogel, M. W.] Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Ross, C. A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21287 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Div Neurobiol, Dept Psychiat & Behav Sci, 600 N Wolfe St,CMSC 8-121, Baltimore, MD 21287 USA. EM mpletnik@jhmi.edu RI Nomura, Jun/C-2411-2011; Ross, Christopher/H-8395-2013; OI Vogel, Michael/0000-0002-8402-1495; Nomura, Jun/0000-0003-0817-2643 FU NIMH; Autism Speaks; NARSAD; Mortimer W Sackler Foundation FX We thank Chunxia Yang, Krisztina Moldovan, Kimberley Smith, Sandra Birnbaum, Yuan Wang, and Jennifer Tsuan for their excellent technical help. The study was supported by NIMH, Autism Speaks, NARSAD, and the Mortimer W Sackler Foundation (MVP). NR 93 TC 72 Z9 72 U1 3 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAR PY 2011 VL 16 IS 3 BP 293 EP 306 DI 10.1038/mp.2009.144 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 723AT UT WOS:000287479100011 PM 20048751 ER PT J AU Mayer, ML AF Mayer, Mark L. TI Glutamate receptor ion channels: where do all the calories go? SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID LIGAND-BINDING DOMAIN; PARTIAL AGONIST ACTION; ALLOSTERIC MODULATORS; CRYSTAL-STRUCTURES; MECHANISM; DESENSITIZATION; CORE; SELECTIVITY; ANTAGONISTS; COMPLEX C1 NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM mayerm@mail.nih.gov RI Mayer, Mark/H-5500-2013 NR 20 TC 2 Z9 2 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2011 VL 18 IS 3 BP 253 EP 254 DI 10.1038/nsmb0311-253 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 730XZ UT WOS:000288072200002 PM 21372852 ER PT J AU Xu, ZX Wei, G Chepelev, I Zhao, K Felsenfeld, G AF Xu, Zhixiong Wei, Gang Chepelev, Iouri Zhao, Keji Felsenfeld, Gary TI Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID HUMAN INSULIN GENE; IMPRINTING CONTROL REGION; PANCREATIC BETA-CELL; HUMAN CANCER-CELLS; HUMAN ISLETS; SYNAPTOTAGMIN FAMILY; GLUCOSE REGULATION; RECEPTOR-ALPHA; HUMAN GENOME; EXPRESSION AB Insulin (INS) synthesis and secretion from pancreatic beta-cells are tightly regulated; their deregulation causes diabetes. Here we map INS-associated loci in human pancreatic islets by 4C and 3C techniques and show that the INS gene physically interacts with the SYT8 gene, located over 300 kb away. This interaction is elevated by glucose and accompanied by increases in SYT8 expression. Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8 gene expression. SYT8-INS interaction and SYT8 transcription are attenuated by CTCF depletion. Furthermore, SYT8 knockdown decreases insulin secretion in islets. These results reveal a nonredundant role for SYT8 in insulin secretion and indicate that the INS promoter acts from a distance to stimulate SYT8 transcription. This suggests a function for the INS promoter in coordinating insulin transcription and secretion through long-range regulation of SYT8 expression in human islets. C1 [Xu, Zhixiong; Felsenfeld, Gary] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Wei, Gang; Chepelev, Iouri; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov RI Wei, Gang/A-3291-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute (US) FX We thank the Islet Cell Resource Centers Basic Science Islet Distribution Program for providing isolated human pancreatic islets. We thank K. Cui and D. Schones for assistance with the Solexa sequencing and pipeline analysis. This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute (US) Intramural Research Programs. NR 58 TC 24 Z9 24 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2011 VL 18 IS 3 BP 372 EP U166 DI 10.1038/nsmb.1993 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 730XZ UT WOS:000288072200020 PM 21336277 ER PT J AU Wu, T Wang, LA Hallett, M Chen, Y Li, KC Chan, P AF Wu, Tao Wang, Liang Hallett, Mark Chen, Yi Li, Kuncheng Chan, Piu TI Effective connectivity of brain networks during self-initiated movement in Parkinson's disease SO NEUROIMAGE LA English DT Article DE Parkinson's disease; Self-initiated movement; Functional MRI; Motor networks; Basal ganglia; Compensation ID EXTERNALLY TRIGGERED MOVEMENTS; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; DISTINCT STRIATAL REGIONS; EVENT-RELATED FMRI; PREFRONTAL CORTEX; BASAL GANGLIA; FUNCTIONAL CONNECTIVITY; FINGER MOVEMENTS AB Patients with Parkinson's disease (PD) have difficulty in performing self-initiated movements. The neural mechanism of this deficiency remains unclear. In the current study, we used functional MRI (fMRI) and psychophysiological interaction (PPI) methods to investigate the changes in effective connectivity of the brain networks during performance of self-initiated movement in PD patients. Effective connectivity is defined as the influence one neuronal system exerts over another. fMRIs were acquired in 18 PD patients and in 18 age- and sex-matched healthy controls, when performing a self-initiated right hand tapping task. We chose the left primary motor cortex (M1), rostral supplementary motor area (pre-SMA), left premotor cortex (PMC), left putamen, and right cerebellum as index areas for PPI analysis. During the performance of self-initiated movement, connectivity between the putamen and M1, PMC, SMA, and cerebellum was decreased in PD patients compared to controls. In contrast, connections between the M1, pre-SMA, PMC, parietal cortex, and cerebellum were increased in PD patients compared to controls. In addition, the M1, pre-SMA, PMC, and cerebellum also had less connectivity with the dorsal lateral prefrontal cortex in PD. In PD patients, the effective connectivity between the putamen and M1, PMC, SMA, and cerebellum negatively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores; whereas the connectivity between the M1, pre-SMA, PMC, and cerebellum positively correlated with the UPDRS motor scores. Our findings demonstrate that the pattern of interactions of brain networks is disrupted in PD during performance of self-initiated movements. The striatum-cortical and striatum-cerebellar connections are weakened. In contrast, the connections between cortico-cerebellar motor regions are strengthened and may compensate for basal ganglia dysfunction. These altered interregional connections are more deviant when the disorder is more severe, and, therefore, our results give further insight into the explanation for the difficulty in performing self-initiated movements in PD. (c) 2010 Elsevier Inc. All rights reserved. C1 [Wu, Tao; Chen, Yi; Chan, Piu] Capital Med Univ, Beijing Inst Geriatr, Minist Educ, Xuanwu Hosp,Dept Neurobiol,Key Lab Neurodegenerat, Beijing 100053, Peoples R China. [Wang, Liang; Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, T (reprint author), Capital Med Univ, Beijing Inst Geriatr, Minist Educ, Xuanwu Hosp,Dept Neurobiol,Key Lab Neurodegenerat, Beijing 100053, Peoples R China. EM wutao69@gmail.com RI Wang, Liang/E-8652-2011 FU National Science Foundation of China [30870693]; Ministry of Science and Technology [2006AA02A408]; NINDS FX This work was supported by grants from the National Science Foundation of China (30870693), and the Ministry of Science and Technology (2006AA02A408). Dr. Hallett is supported by the Intramural Program of NINDS. The authors wish to thank Ms. Devee Schoenberg for editing the manuscript. NR 89 TC 76 Z9 76 U1 3 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR 1 PY 2011 VL 55 IS 1 BP 204 EP 215 DI 10.1016/j.neuroimage.2010.11.074 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 716YH UT WOS:000287008900018 PM 21126588 ER PT J AU Alvarez, RP Chen, G Bodurka, J Kaplan, R Grillon, C AF Alvarez, Ruben P. Chen, Gang Bodurka, Jerzy Kaplan, Raphael Grillon, Christian TI Phasic and sustained fear in humans elicits distinct patterns of brain activity SO NEUROIMAGE LA English DT Article DE Fear; Anxiety; Dorsal amygdala; BNST; Functional imaging; fMRI ID ANTERIOR CINGULATE CORTEX; EXTENDED AMYGDALA; STRIA TERMINALIS; CENTRAL NUCLEUS; VOXEL VOLUME; BED NUCLEUS; ACTIVATION; RESPONSES; ANXIETY; MRI AB Aversive events are typically more debilitating when they occur unpredictably than predictably. Studies in humans and animals indicate that predictable and unpredictable aversive events can induce phasic and sustained fear, respectively. Research in rodents suggests that anatomically related but distinct neural circuits may mediate phasic and sustained fear. We explored this issue in humans by examining threat predictability in three virtual reality contexts, one in which electric shocks were predictably signaled by a cue, a second in which shocks occurred unpredictably but never paired with a cue, and a third in which no shocks were delivered. Evidence of threat-induced phasic and sustained fear was presented using fear ratings and skin conductance. Utilizing recent advances in functional magnetic resonance imaging (fMRI), we were able to conduct whole-brain fMRI at relatively high spatial resolution and still have enough sensitivity to detect transient and sustained signal changes in the basal forebrain. We found that both predictable and unpredictable threat evoked transient activity in the dorsal amygdala, but that only unpredictable threat produced sustained activity in a forebrain region corresponding to the bed nucleus of the stria terminalis complex. Consistent with animal models hypothesizing a role for the cortex in generating sustained fear, sustained signal increases to unpredictable threat were also found in anterior insula and a frontoparietal cortical network associated with hypervigilance. In addition, unpredictable threat led to transient activity in the ventral amygdala hippocampal area and pregenual anterior cingulate cortex, as well as transient activation and subsequent deactivation of subgenual anterior cingulate cortex, limbic structures that have been implicated in the regulation of emotional behavior and stress responses. In line with basic findings in rodents, these results provide evidence that phasic and sustained fear in humans may manifest similar signs of distress, but appear to be associated with different patterns of neural activity in the human basal forebrain. (C) 2010 Elsevier Inc. All rights reserved. C1 [Alvarez, Ruben P.; Bodurka, Jerzy] Laureate Inst Brain Res, Tulsa, OK 74136 USA. [Alvarez, Ruben P.; Kaplan, Raphael; Grillon, Christian] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Chen, Gang] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. [Bodurka, Jerzy] NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. RP Alvarez, RP (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA. EM ralvarez@laureateinstitute.org FU National Institute of Mental Health FX This study was supported by the Intramural Research Program of the National Institute of Mental Health. NR 64 TC 86 Z9 90 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD MAR 1 PY 2011 VL 55 IS 1 BP 389 EP 400 DI 10.1016/j.neuroimage.2010.11.057 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 716YH UT WOS:000287008900039 PM 21111828 ER PT J AU Mattson, MP AF Mattson, Mark P. TI A Lifetime of Dedication to the Old in His Kentucky Home SO NEUROMOLECULAR MEDICINE LA English DT Biographical-Item DE Alzheimer's disease; Amyloid plaques; 4-hydroxynonenal; Mild cognitive impairment; Neurofibrillary tangles; Oxidative stress AB He spent tens of thousands of hours peering through the oculars of a microscope at stained brain tissue sections from thousands of patients who died with or without a neurodegenerative disorder; most of those patients he had himself cared for and had removed and processed their brain tissues upon their death. His discerning mind, humble demeanor, optimism and patience were fundamental features of his character. Through his research discoveries and advocacy, Dr. William R. Markesbery fought for those millions of elderly Americans with Alzheimer's disease (AD) and their families and friends. For over a decade, my laboratory was located directly above Dr. Markesbery's in the Sanders-Brown Research Center on Aging at the University of Kentucky in Lexington. In this article, I first provide several examples of how he moved research on AD forward on multiple fronts, not only by building one of the best AD Research Centers in the world, but also by providing a helping hand to the tens of thousands of Kentuckian's and their families to ease their suffering as best he could. Also described below are the results of several research projects on which I had the good fortune of collaborating with Dr. Markesbery. 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 FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2011 VL 13 IS 1 BP 6 EP 10 DI 10.1007/s12017-010-8124-8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 726VB UT WOS:000287753400003 PM 20614200 ER PT J AU Harel, A Mattson, MP Yao, PJ AF Harel, Asaff Mattson, Mark P. Yao, Pamela J. TI CALM, A Clathrin Assembly Protein, Influences Cell Surface GluR2 Abundance SO NEUROMOLECULAR MEDICINE LA English DT Article DE CALM; AP180; Clathrin; GluR2; AMPA receptor; Bungarotoxin binding site ID TRAFFICKING; ENDOCYTOSIS; AP180 AB The clathrin assembly protein, CALM, promotes the assembly of clathrin-coated vesicles. In a previous study, we showed that CALM controls the level of the synaptic vesicle protein VAMP2 at the plasma membrane by regulating VAMP2 endocytosis. Here, we provide evidence that CALM also influences the cell surface level of the AMPA receptor subunit GluR2. Although mechanistic details as well as the physiological relevance of CALM and GluR2 in the neuron have yet to be established, CALM-mediated trafficking could function as a component of a dedicated system for controlling postsynaptic abundance of GluR2. C1 [Harel, Asaff; Mattson, Mark P.; Yao, Pamela J.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Yao, PJ (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM yaopa@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging of the NIH FX This work was supported by the Intramural Research Program of the National Institute on Aging of the NIH. NR 18 TC 10 Z9 10 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2011 VL 13 IS 1 BP 88 EP 90 DI 10.1007/s12017-010-8142-6 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 726VB UT WOS:000287753400017 PM 21221849 ER PT J AU Chen, AE Carroll, KC Diener-West, M Ross, T Ordun, J Goldstein, MA Kulkarni, G Cantey, JB Siberry, GK AF Chen, Aaron E. Carroll, Karen C. Diener-West, Marie Ross, Tracy Ordun, Joyce Goldstein, Mitchell A. Kulkarni, Gaurav Cantey, J. B. Siberry, George K. TI Randomized Controlled Trial of Cephalexin Versus Clindamycin for Uncomplicated Pediatric Skin Infections SO PEDIATRICS LA English DT Article DE MRSA; skin infections; abscess; Staphylococcus aureus; clindamycin; cephalexin ID RESISTANT STAPHYLOCOCCUS-AUREUS; ACQUIRED METHICILLIN-RESISTANT; SOFT-TISSUE INFECTIONS; DOUBLE-BLIND; CHILDREN; MANAGEMENT; ABSCESSES; RISK AB OBJECTIVE: To compare clindamycin and cephalexin for treatment of uncomplicated skin and soft tissue infections (SSTIs) caused predominantly by community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that clindamycin would be superior to cephalexin (an antibiotic without MRSA activity) for treatment of these infections. PATIENTS AND METHODS: Patients aged 6 months to 18 years with uncomplicated SSTIs not requiring hospitalization were enrolled September 2006 through May 2009. Eligible patients were randomly assigned to 7 days of cephalexin or clindamycin; primary and secondary outcomes were clinical improvement at 48 to 72 hours and resolution at 7 days. Cultures were obtained and tested for antimicrobial susceptibilities, pulsed-field gel electrophoresis type, and Panton-Valentine leukocidin status. RESULTS: Of 200 enrolled patients, 69% had MRSA cultured from wounds. Most MRSA were USA300 or subtypes, positive for Panton-Valentine leukocidin, and clindamycin susceptible, consistent with CA-MRSA. Spontaneous drainage occurred or a drainage procedure was performed in 97% of subjects. By 48 to 72 hours, 94% of subjects in the cephalexin arm and 97% in the clindamycin arm were improved (P = .50). By 7 days, all subjects were improved, with complete resolution in 97% in the cephalexin arm and 94% in the clindamycin arm (P = .33). Fevers and age less than 1 year, but not initial erythema > 5 cm, were associated with early treatment failures, regardless of antibiotic used. CONCLUSIONS: There is no significant difference between cephalexin and clindamycin for treatment of uncomplicated pediatric SSTIs caused predominantly by CA-MRSA. Close follow-up and fastidious wound care of appropriately drained, uncomplicated SSTIs are likely more important than initial antibiotic choice. Pediatrics 2011;127: e573-e580 C1 [Chen, Aaron E.; Ordun, Joyce; Goldstein, Mitchell A.; Kulkarni, Gaurav; Cantey, J. B.] Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21205 USA. [Carroll, Karen C.; Ross, Tracy] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Diener-West, Marie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. RP Chen, AE (reprint author), Johns Hopkins Univ, Dept Pediat, Div Pediat Emergency Med, CMSC 144,600 N Wolfe St, Baltimore, MD 21287 USA. EM achen33@jhmi.edu FU Thrasher Research Foundation [NR-0001]; National Center for Research Resources/National Institutes of Health [M01-RR0052]; National Institutes of Health (NIH) FX Funded in part by the National Institutes of Health (NIH).; We thank the Thrasher Research Foundation (award NR-0001) and the Johns Hopkins University School of Medicine General Clinical Research Center (grant M01-RR0052, from the National Center for Research Resources/National Institutes of Health) for their generous support of this project; the patients and families who participated; the faculty and staff of the Johns Hopkins ED and Harriet Lane Clinic; and Dr Neal Halsey, Dr Marie Diener-West, and Dr Tim Townsend for serving on the data safety and monitoring board for this study. NR 22 TC 21 Z9 22 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2011 VL 127 IS 3 BP E573 EP E580 DI 10.1542/peds.2010-2053 PG 8 WC Pediatrics SC Pediatrics GA 728AI UT WOS:000287845400005 PM 21339275 ER PT J AU Wadhawan, R Oh, W Vohr, BR Wrage, L Das, A Bell, EF Laptook, AR Shankaran, S Stoll, BJ Walsh, MC Higgins, RD AF Wadhawan, Rajan Oh, William Vohr, Betty R. Wrage, Lisa Das, Abhik Bell, Edward F. Laptook, Abbot R. Shankaran, Seetha Stoll, Barbara J. Walsh, Michele C. Higgins, Rosemary D. CA Eunice Kennedy Shriver Natl Inst C TI Neurodevelopmental Outcomes of Triplets or Higher-Order Extremely Low Birth Weight Infants SO PEDIATRICS LA English DT Article DE extremely low birth weight; triplets; neurodevelopmental outcomes ID REPRODUCTIVE TECHNIQUES; TWIN PREGNANCIES; MULTIPLE BIRTHS; FOLLOW-UP; GESTATIONS; QUADRUPLET; MORTALITY AB BACKGROUND: Extremely low birth weight twins have a higher rate of death or neurodevelopmental impairment than singletons. Higher-order extremely low birth weight multiple births may have an even higher rate of death or neurodevelopmental impairment. METHODS: Extremely low birth weight (birth weight 401-1000 g) multiple births born in participating centers of the Neonatal Research Network between 1996 and 2005 were assessed for death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined by the presence of 1 or more of the following: moderate to severe cerebral palsy; mental developmental index score or psychomotor developmental index score less than 70; severe bilateral deafness; or blindness. Infants who died within 12 hours of birth were excluded. Maternal and infant demographic and clinical variables were compared among singleton, twin, and triplet or higher-order infants. Logistic regression analysis was performed to establish the association between singletons, twins, and triplet or higher-order multiples and death or neurodevelopmental impairment, controlling for confounding variables that may affect death or neurodevelopmental impairment. RESULTS: Our cohort consisted of 8296 singleton, 2164 twin, and 521 triplet or higher-order infants. The risk of death or neurodevelopmental impairment was increased in triplets or higher-order multiples when compared with singletons (adjusted odds ratio: 1.7 [95% confidence interval: 1.29-2.24]), and there was a trend toward an increased risk when compared with twins (adjusted odds ratio: 1.27 [95% confidence: 0.95-1.71]). CONCLUSIONS: Triplet or higher-order births are associated with an increased risk of death or neurodevelopmental impairment at 18 to 22 months' corrected age when compared with extremely low birth weight singleton infants, and there was a trend toward an increased risk when compared with twins. Pediatrics 2011;127:e654-e660 C1 [Wadhawan, Rajan] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Oh, William; Vohr, Betty R.; Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. [Wrage, Lisa] Res Triangle Inst Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA. [Das, Abhik] Res Triangle Inst Int, Stat & Epidemiol Unit, Rockville, MD USA. [Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Wadhawan, R (reprint author), Univ S Florida, All Childrens Hosp, 601 5th St S,OCC 5th Floor, St Petersburg, FL 33701 USA. EM rajan.wadhawan@allkids.org FU NICHD NIH HHS [U10 HD027904, U10 HD027904-21] NR 24 TC 12 Z9 12 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2011 VL 127 IS 3 BP E654 EP E660 DI 10.1542/peds.2010-2646 PG 7 WC Pediatrics SC Pediatrics GA 728AI UT WOS:000287845400015 PM 21357334 ER PT J AU Drozdovitch, V Schonfeld, S Akimzhanov, K Aldyngurov, D Land, CE Luckyanov, N Mabuchi, K Potischman, N Schwerin, MJ Semenova, Y Tokaeva, A Zhumadilov, Z Bouville, A Simon, SL AF Drozdovitch, Vladimir Schonfeld, Sara Akimzhanov, Kuat Aldyngurov, Daulet Land, Charles E. Luckyanov, Nickolas Mabuchi, Kiyohiko Potischman, Nancy Schwerin, Michael J. Semenova, Yulia Tokaeva, Alma Zhumadilov, Zhaxybay Bouville, Andre Simon, Steven L. TI Behavior and food consumption pattern of the population exposed in 1949-1962 to fallout from Semipalatinsk nuclear test site in Kazakhstan SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Article ID RETROSPECTIVE DOSE ASSESSMENT; LOCAL FALLOUT; AREAS AB The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the US National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to deposition of radioactive fallout from nuclear testing conducted by the Soviet Union at the Semipalatinsk Nuclear Test Site in Kazakhstan between 1949 and 1962. The study subjects included individuals of both Kazakh and Russian origin who were exposed during childhood and adolescence. An initial dose reconstruction used for the risk analysis of Land et al. (Radiat Res 169:373-383, 2008) was based on individual information collected from basic questionnaires administered to the study population in 1998. However, because data on several key questions for accurately estimating doses were not obtained from the 1998 questionnaires, it was decided to conduct a second data collection campaign in 2007. Due to the many years elapsed since exposure, a well-developed strategy was necessary to encourage accurate memory recall. In our recent study, a focus group interview data collection methodology was used to collect historical behavioral and food consumption data. The data collection in 2007 involved interviews conducted within four-eight-person focus groups (three groups of women and one group of men) in each of four exposed villages where thyroid disease screening was conducted in 1998. Population-based data on relevant childhood behaviors including time spent in- and outdoors and consumption rates of milk and other dairy products were collected from women's groups. The data were collected for five age groups of children and adolescents ranging from less than 1 year of age to 21 years of age. Dairy products considered included fresh milk and other products from cows, goats, mares, and sheep. Men's focus group interviews pertained to construction materials of houses and schools, and animal grazing patterns and feeding practices. The response data collected are useful for improving estimates of thyroid radiation dose estimates for the subjects of an ongoing epidemiological study. C1 [Drozdovitch, Vladimir; Schonfeld, Sara; Land, Charles E.; Luckyanov, Nickolas; Mabuchi, Kiyohiko; Bouville, Andre; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Akimzhanov, Kuat; Aldyngurov, Daulet; Semenova, Yulia; Tokaeva, Alma; Zhumadilov, Zhaxybay] Semipalatinsk State Med Acad, Semey 400050, Kazakhstan. [Potischman, Nancy] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA. [Schwerin, Michael J.] RTI Int, Res Triangle Pk, NC 27709 USA. RP Drozdovitch, V (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM drozdovv@mail.nih.gov FU National Institute of Allergy and Infectious Diseases (USA); National Cancer Institute [Y3-CO-5117]; NIAID [Y2-Al-5077] FX This study was supported by the Intra-Agency Agreement between the National Institute of Allergy and Infectious Diseases (USA) and the National Cancer Institute, NIAID agreement #Y2-Al-5077 and NCI agreement #Y3-CO-5117. The authors are grateful to the participants of the focus groups and to the key informants for their participation in the study. The authors wish to thank medical authorities and civil officials in Karaul, Kaynar, Dolon, Kanonerka, Sarzhal, Korostely, Novopokrovka, and Bolshaya Vladimirovka who aided in the field study in August-September 2007. Authors also would like to thank Mr. Zhanat Baimaganbet (Semipalatinsk State Medical Academy, Kazakhstan) for his hospitality and valuable assistance during a field trip to Karaul and Kaynar. Special thanks are to Mrs. Norma Kim (RTI, Bethesda, USA) for creating of the database of consumption information. NR 11 TC 1 Z9 2 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD MAR PY 2011 VL 50 IS 1 BP 91 EP 103 DI 10.1007/s00411-010-0334-9 PG 13 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA 723NC UT WOS:000287512400008 PM 20938673 ER PT J AU Zhang, J Mikolajczyk, R Grewal, J Neta, G Klebanoff, M AF Zhang, Jun Mikolajczyk, Rafael Grewal, Jaceteshwar Neta, Gila Klebanoff, Mark TI Prenatal Application of the Individualized Fetal Growth Reference SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE fetal growth retardation; infant; small for gestational age; perinatal mortality ID BIRTH-WEIGHT STANDARDS; POPULATION; RESTRICTION; IMPAIRMENT; MORTALITY; CENTILES; INFANTS; AGE AB The individualized reference for defining small for gestational age (SGA) at birth has gained popularity in recent years. However, its utility on fetal assessment has not been evaluated. The authors compare an individualized with an ultrasound reference in predicting poor perinatal outcomes. Data from a large clinical trial in predominantly white US women (1987-1991) with singleton pregnancies (n = 9,526) were used. The individualized reference classified fewer SGA fetuses than the ultrasound reference, but the risks of adverse outcomes were similar between fetuses classified by both references. The risk increased substantially only when the percentiles fell below the 5th percentile (likelihood ratio positive at birth = 2.68 (95% confidence interval (CI): 2.00, 3.58) and 3.13 (95% CI: 2.34, 4.18) for ultrasound and individualized references, respectively). SGA fetuses defined by either the individualized or ultrasound reference alone had risk ratios of adverse outcomes of 1.91 (95% CI: 0.77, 4.77) and 1.18 (95% CI: 0.37, 3.77), respectively, compared with normal fetuses (the difference between these 2 risk ratios, P = 0.71). The authors conclude that neither the ultrasound-based nor the individualized reference does well in predicting adverse perinatal outcomes. The 5th percentile may be a better cutpoint than the 10th percentile in defining SGA. C1 [Zhang, Jun; Grewal, Jaceteshwar; Neta, Gila; Klebanoff, Mark] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. [Mikolajczyk, Rafael] Univ Bremen, Dept Clin Epidemiol, Bremen Inst Prevent Res & Social Med, Bremen, Germany. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov OI Mikolajczyk, Rafael/0000-0003-1271-7204; Grewal, Jagteshwar/0000-0002-0141-4876 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 25 TC 23 Z9 24 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 MAR 1 PY 2011 VL 173 IS 5 BP 539 EP 543 DI 10.1093/aje/kwq411 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726SK UT WOS:000287746200008 PM 21252054 ER PT J AU Shi, M London, SJ Chiu, GY Hancock, DB Zaykin, D Weinberg, CR AF Shi, Min London, Stephanie J. Chiu, Grace Y. Hancock, Dana B. Zaykin, Dmitri Weinberg, Clarice R. TI Using Imputed Genotypes for Relative Risk Estimation in Case-Parent Studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE epidemiologic methods; genome-wide association study; genotype; imputation; meta-analysis; risk ID LINKAGE; GENES; DISEQUILIBRIUM; ASSOCIATION; IMPUTATION; DISEASE AB Meta-analyses of genome-wide association studies are often based on imputed single nucleotide polymorphism (SNP) data, because component studies were genotyped using different platforms. One would like to include case-parent triad studies along with case-control studies in such meta-analyses. However, there are no published methods for estimating relative risks from imputed data for case-parent triad studies. The authors propose a method for estimating the relative risk for a variant SNP allele based on a log-additive model. Their simulations first confirm that the proposed method performs well with genotyped SNP data. As an empirical test of the method's behavior with imputed SNPs, the authors then apply it to chromosome 22 data from the Mexico City Childhood Asthma Study (1998-2003). For chromosome 22, the authors had data on 7,293 SNPs that were both genotyped and imputed using the software MACH, which relies on linkage disequilibrium with nearby SNPs. Correlation between estimated relative risks based on the actual genotypes and those based on the imputed genotypes was remarkably high (r(2) = 0.95), validating this method of relative risk estimation for the case-parent study design. This method should be useful to investigators who wish to conduct meta-analyses using imputed SNP data from both case-parent triad and case-control studies. C1 [Shi, Min; Zaykin, Dmitri; Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [London, Stephanie J.; Hancock, Dana B.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Chiu, Grace Y.] Westat Corp, Res Triangle Pk, NC USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03 101-A315, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov RI Hancock, Dana/D-8577-2012; OI Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [ZO1 ES040007, ZO1 ES49109, ZO1 ES240245] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS), under project numbers ZO1 ES040007, ZO1 ES49109, and ZO1 ES240245. NR 15 TC 1 Z9 2 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 MAR 1 PY 2011 VL 173 IS 5 BP 553 EP 559 DI 10.1093/aje/kwq363 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726SK UT WOS:000287746200010 PM 21296892 ER PT J AU Abroms, LC Padmanabhan, N Thaweethai, L Phillips, T AF Abroms, Lorien C. Padmanabhan, Nalini Thaweethai, Lalida Phillips, Todd TI iPhone Apps for Smoking Cessation A Content Analysis SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID MOBILE PHONE; TOBACCO-CESSATION; HEALTH; INTERNET; SERVICE; DEMAND AB Background: With the proliferation of smartphones such as the iPhone, mobile phones are being used in novel ways to promote smoking cessation. Purpose: This study set out to examine the content of the 47 iPhone applications (apps) for smoking cessation that were distributed through the online iTunes store, as of June 24, 2009. Methods: Each app was independently coded by two reviewers for its (1) approach to smoking cessation and (2) adherence to the U. S. Public Health Service's 2008 Clinical Practice Guidelines for Treating Tobacco Use and Dependence. Each app was also coded for its (3) frequency of downloads. Results: Apps identified for smoking cessation were found to have low levels of adherence to key guidelines in the index. Few, if any, apps recommended or linked the user to proven treatments such as pharmacotherapy, counseling, and/or a quitline. Conclusions: iPhone apps for smoking cessation rarely adhere to established guidelines for smoking cessation. It is recommended that current apps be revised and future apps be developed around evidence-based practices for smoking cessation. (Am J Prev Med 2011;40(3):279-285) (C) 2011 American Journal of Preventive Medicine C1 [Abroms, Lorien C.; Thaweethai, Lalida] George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. [Phillips, Todd] Acad Educ Dev, Washington, DC USA. [Padmanabhan, Nalini] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. RP Abroms, LC (reprint author), George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, 2175 K St NW,Suite 700, Washington, DC 20037 USA. EM Lorien@gwu.edu FU National Cancer Institute of the NIH [5K07 CA124579-02] FX This research was supported by 5K07 CA124579-02 to Dr. Lorien Abroms, awarded by the National Cancer Institute of the NIH. NR 20 TC 139 Z9 140 U1 6 U2 76 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 MAR PY 2011 VL 40 IS 3 BP 279 EP 285 DI 10.1016/j.amepre.2010.10.032 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 722PB UT WOS:000287445700005 PM 21335258 ER PT J AU Wawer, MJ Gray, RH Serwadda, D Kigozi, G Nalugoda, F Quinn, TC AF Wawer, Maria J. Gray, Ronald H. Serwadda, David Kigozi, Godfrey Nalugoda, Fred Quinn, Thomas C. TI Male Circumcision As a Component of Human Immunodeficiency Virus Prevention SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Letter ID HIV-INFECTION; RISK C1 [Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. [Serwadda, David; Kigozi, Godfrey; Nalugoda, Fred] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Baltimore, MD USA. RP Wawer, MJ (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA. EM mwawer@jhsph.edu NR 11 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAR PY 2011 VL 40 IS 3 BP E7 EP E8 DI 10.1016/j.amepre.2010.12.003 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 722PB UT WOS:000287445700001 PM 21335256 ER PT J AU Mettler, FA Brenner, D Coleman, CN Kaminski, JM Kennedy, AR Wagner, LK AF Mettler, Fred A., Jr. Brenner, David Coleman, C. Norman Kaminski, Joseph M. Kennedy, Ann R. Wagner, Louis K. TI Can Radiation Risks to Patients Be Reduced Without Reducing Radiation Exposure? The Status of Chemical Radioprotectants SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chemical radioprotectants; radiation risk ID VITAMIN-E SUPPLEMENTATION; CANCER-RISKS; CT; AGENTS AB OBJECTIVE. Medical radiation exposure has increased sixfold since 1980 and is the largest controllable source of exposure. Many efforts have been devoted to reducing dose or eliminating unnecessary examinations but with limited success. The concern regarding nuclear terrorism has focused a large amount of attention on radioprotective drugs. The purpose of this article is twofold: to review the current concepts, potential, and limitations of chemical radioprotectants in reducing stochastic and deterministic effects and to assess the potential application to diagnostic and interventional medical radiation procedures. CONCLUSION. There are a wide variety of chemical compounds that have been studied for radioprotective effects. Although there is promising research, chemical radioprotectants have not been shown to be very effective and, with one limited exception, are not the standard of care in medicine. C1 [Mettler, Fred A., Jr.] New Mexico VA Hlth Care Serv, Dept Radiol, Albuquerque, NM 87108 USA. [Mettler, Fred A., Jr.] New Mexico VA Hlth Care Serv, Nucl Med Serv, Albuquerque, NM 87108 USA. [Brenner, David] Columbia Univ, Dept Radiol, New York, NY USA. [Coleman, C. Norman] NCI, Dept Radiol, NIH, Rockville, MD USA. [Kaminski, Joseph M.] US FDA, Div Med Imaging Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Wagner, Louis K.] Univ Texas Houston, Sch Med, Dept Radiol, Houston, TX 77030 USA. RP Mettler, FA (reprint author), New Mexico VA Hlth Care Serv, Dept Radiol, 1501 San Pedro Blvd SE, Albuquerque, NM 87108 USA. EM fmettler@salud.unm.edu NR 20 TC 13 Z9 13 U1 0 U2 6 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 MAR PY 2011 VL 196 IS 3 BP 616 EP 618 DI 10.2214/AJR.10.4959 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 724OC UT WOS:000287585100038 PM 21343505 ER PT J AU Shin, SH Love, DC Hanover, JA AF Shin, Sang-Hoon Love, Dona C. Hanover, John A. TI Elevated O-GlcNAc-dependent signaling through inducible mOGT expression selectively triggers apoptosis SO AMINO ACIDS LA English DT Article DE O-GlcNAc; O-linked N-acetylglucosamine transferase; Apoptosis ID PANCREATIC BETA-CELLS; PROTECTS NEONATAL CARDIOMYOCYTES; N-ACETYLGLUCOSAMINE TRANSFERASE; ISCHEMIA-REPERFUSION INJURY; LINKED GLCNAC; INSULIN-RESISTANCE; TETRATRICOPEPTIDE REPEATS; NUCLEOCYTOPLASMIC PROTEINS; CARDIOVASCULAR-SYSTEM; ATAXIN-10 INTERACTS AB O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling. One differentially spliced isoform of OGT is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed in cells compared with the ncOGT isoform. To understand the basis of this selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP-OGT. Elevated GFP-OGT expression induced a dramatic increase in intracellular O-GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered programmed cell death. Apoptosis was dependent upon the unique N-terminus of mOGT, and its catalytic activity. Induction of mOGT expression triggered programmed cell death in every cell type tested including INS-1, an insulin-secreting cell line. These studies suggest that deregulated activity of the mitochondrially targeted mOGT may play a role in triggering the programmed cell death observed with diseases such as diabetes mellitus and neurodegeneration. C1 [Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Shin, Sang-Hoon] Gyeong Gi Bio Ctr, Suwon, South Korea. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bldg 8 Rm B127,8 Ctr Dr MSC 0850, Bethesda, MD 20892 USA. EM jah@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases in the National Institutes of Health FX We thank Wendy Wu, Bill Lubas for their contributions and stimulating discussions and Nancy Dwyer for assistance with the Zeiss LSM410 confocal microscope. We would also like to thank Brad Fletcher for helpful information and discussions concerning apoptosis and OGT. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases in the National Institutes of Health. NR 52 TC 22 Z9 23 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD MAR PY 2011 VL 40 IS 3 BP 885 EP 893 DI 10.1007/s00726-010-0719-8 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 723HQ UT WOS:000287497800012 PM 20824293 ER PT J AU Sideri, M Minig, L Franchi, D Casadio, C Boveri, S Bocciolone, L AF Sideri, M. Minig, L. Franchi, D. Casadio, C. Boveri, S. Bocciolone, L. TI Reply to Should diagnostic laparoscopy be conducted before hormonal treatment in early-stage endometrial cancer? SO ANNALS OF ONCOLOGY LA English DT Letter C1 [Minig, L.] NCI, Dept Gynecol, NIH, Bethesda, MD 20892 USA. [Sideri, M.; Franchi, D.; Casadio, C.; Boveri, S.; Bocciolone, L.] European Inst Oncol, Dept Gynecol, Milan, Italy. RP Minig, L (reprint author), NCI, Dept Gynecol, NIH, Bethesda, MD 20892 USA. EM lucasminig@yahoo.com NR 2 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2011 VL 22 IS 3 BP 749 EP 749 DI 10.1093/annonc/mdq765 PG 1 WC Oncology SC Oncology GA 726UB UT WOS:000287750700037 ER PT J AU Mazloum, N Stegman, MA Croteau, DL Van Houten, B Kwon, NS Ling, Y Dickinson, C Venugopal, A Towheed, MA Nathan, C AF Mazloum, Nayef Stegman, Melanie A. Croteau, Deborah L. Van Houten, Bennett Kwon, Nyoun Soo Ling, Yan Dickinson, Caitlyn Venugopal, Aditya Towheed, Mohammad Atif Nathan, Carl TI Identification of a Chemical That Inhibits the Mycobacterial UvrABC Complex in Nucleotide Excision Repair SO BIOCHEMISTRY LA English DT Article ID DNA-DAMAGE RECOGNITION; NITRIC-OXIDE; SUBSTRATE-SPECIFICITY; USTILAGO-MAYDIS; BRH2 PROTEIN; FPG PROTEIN; TUBERCULOSIS; SYSTEM; UVRB; GLYCOSYLASE AB Bacterial DNA can be damaged by reactive nitrogen and oxygen intermediates (RNI and ROI) generated by host immunity, as well as by antibiotics that trigger bacterial production of ROI. Thus a pathogen's ability to repair its DNA may be important for persistent infection. A prominent role for nucleotide excision repair (NER) in disease caused by Mycobacterium tuberculosis (Mtb) was suggested by attenuation of uvrB-deficient Mtb in mice. However, it was unknown if Mtb's Uvr proteins could execute NER. Here we report that recombinant UvrA, UvrB, and UvrC from Mtb collectively bound and cleaved plasmid DNA exposed to ultraviolet (UV) irradiation or peroxynitrite. We used the DNA incision assay to test the mechanism of action of compounds identified in a high-throughput screen for their ability to delay recovery of M. smegmatis from UV irradiation. 2-(5-Amino-1,3,4-thiadiazol-2-ylbenzo[f]chromen-3-one) (ATBC) but not several closely related compounds inhibited cleavage of damaged DNA by UvrA, UvrB, and UvrC without intercalating in DNA and impaired recovery of M. smegmatis from UV irradiation. ATBC did not affect bacterial growth in the absence of UV exposure, nor did it exacerbate the growth defect of UV-irradiated mycobacteria that lacked uvrB. Thus, ATBC appears to be a cell-penetrant, selective inhibitor of mycobacterial NER. Chemical inhibitors of NER may facilitate studies of the role of NER in prokaryotic pathobiology. C1 [Mazloum, Nayef; Stegman, Melanie A.; Kwon, Nyoun Soo; Ling, Yan; Dickinson, Caitlyn; Venugopal, Aditya; Nathan, Carl] Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. [Croteau, Deborah L.; Van Houten, Bennett] Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Nathan, C (reprint author), Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA. EM cnathan@med.cornell.edu OI Stegman, Melanie/0000-0003-1505-9497 FU NIH [AI064768, ES 019566]; National Institute of Environmental Health Sciences, NIH; William Randolph Hearst Foundation FX This work was supported by NIH Grant AI064768 (C.N.), the Intramural Research Program at the National Institute of Environmental Health Sciences, NIH (B.V.H.), and NIH Grant ES 019566 (B.V.H.).; We thank W. K. Holloman (Weill Cornell Medical College) for advice; G. Lin, R. Bryk, and J. Roberts (Weill Cornell Medical College) for assistance; and the staff of the High Throughput Screening Resource Center (Rockefeller University). The Department of Microbiology and Immunology is supported by the William Randolph Hearst Foundation. NR 46 TC 12 Z9 12 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 1 PY 2011 VL 50 IS 8 BP 1329 EP 1335 DI 10.1021/bi101674c PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 725EE UT WOS:000287627200005 PM 21235228 ER PT J AU Yang, BY Qin, GS Qin, J AF Yang, Baoying Qin, Gengsheng Qin, Jing TI Empirical likelihood-based inferences for a low income proportion SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Bootstrap; confidence interval; economic policy; empirical likelihood; low income proportion; relative poverty line; survey sampling ID STATISTICAL-INFERENCE; AUXILIARY INFORMATION; POVERTY LINES; SAMPLES AB Low income proportion is an important index in comparisons of poverty in countries around the world. The stability of a society depends heavily on this index. An accurate and reliable estimation of this index plays an important role for government's economic policies. In this paper, the authors study empirical likelihood-based inferences for a low income proportion under the simple random sampling and stratified random sampling designs. It is shown that the limiting distributions of the empirical likelihood ratios for the low income proportion are the scaled chi-square distributions. The authors propose various empirical likelihood-based confidence intervals for the low income proportion. Extensive simulation studies are conducted to evaluate the relative performance of the normal approximation-based interval, bootstrap-based intervals, and the empirical likelihood-based intervals. The proposed methods are also applied to analyzing a real economic survey income dataset. The Canadian Journal of Statistics 39: 1-16; 2011 (C) 2011 Statistical Society of Canada C1 [Yang, Baoying; Qin, Gengsheng] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30302 USA. [Yang, Baoying] Sichuan Univ, Coll Math, Chengdu 610064, Sichuan, Peoples R China. [Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA. RP Qin, GS (reprint author), Georgia State Univ, Dept Math & Stat, Atlanta, GA 30302 USA. EM gqin@gsu.edu FU US National Science Foundation FX We would like to thank the editor and referees for their valuable comments which led to substantial improvements in this article. Dr. Gengsheng Qin's work is supported in part by US National Science Foundation. NR 21 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 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD MAR PY 2011 VL 39 IS 1 BP 1 EP 16 DI 10.1002/cjs.10087 PG 16 WC Statistics & Probability SC Mathematics GA 727GQ UT WOS:000287786500001 ER PT J AU Li, QF Liang, Y Shi, SL Liu, QR Xu, DH Jing, GJ Wang, SY Kong, HY AF Li, Qi-Fu Liang, Ying Shi, Song-Lin Liu, Qing-Rong Xu, Dong-Hui Jing, Guang-Jun Wang, San-Ying Kong, Hai-Yan TI Localization of Prohibitin in the Nuclear Matrix and Alteration of Its Expression During Differentiation of Human Neuroblastoma SK-N-SH Cells Induced by Retinoic Acid SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE Prohibitin; Nuclear matrix; Human neuroblastoma; Cell differentiation ID HEPATOCARCINOMA SMMC-7721 CELLS; OSTEOSARCOMA MG-63 CELLS; PROTEOMIC ANALYSIS; ESCHERICHIA-COLI; EPITHELIAL-CELLS; TANSHINONE IIA; CINNAMIC ACID; IDENTIFICATION; NUCLEOPHOSMIN; REPRESSION AB The nuclear matrix-intermediate filament system of human neuroblastoma SK-N-SH cells before and after retinoic acid (RA) treatment was selectively extracted and the distribution of prohibitin (PHB) in the nuclear matrix, as well as its colocalization with related genes, was observed. Results of two-dimensional gel electrophoresis (2-DE), mass spectrometry (MS) identification, and protein immunoblotting all confirm that PHB was present in the components of SK-N-SH nuclear matrix proteins and was down-regulated after RA treatment. Immunofluorescence microscopy observations show that PHB was localized in the nuclear matrix and its distribution was altered due to RA treatment. Laser confocal microscopy results reveal that PHB colocalized with the expression products of c-myc, c-fos, p53, and Rb, but the colocalization region was altered after RA treatment. Our results prove that PHB is a nuclear matrix protein and is localized in nuclear matrix fibers. The distribution of PHB in SK-N-SH cells and its colocalization with related proto-oncogenes and tumor suppressor genes suggest that PHB plays pivotal roles in the differentiation of SK-N-SH cells and deserves further study. C1 [Li, Qi-Fu; Liang, Ying; Jing, Guang-Jun; Wang, San-Ying; Kong, Hai-Yan] Xiamen Univ, Sch Life Sci, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. [Shi, Song-Lin] Xiamen Univ, Coll Med, Xiamen 361005, Peoples R China. [Liu, Qing-Rong] NIDA IRP, Dept Hlth & Human Serv DHSS, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. [Xu, Dong-Hui] Xiamen Univ, Coll Med, Affiliated Hosp 1, Xiamen 361005, Peoples R China. RP Li, QF (reprint author), Xiamen Univ, Sch Life Sci, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. EM chifulee@xmu.edu.cn RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU National Natural Science Foundation of China [30871241] FX This study was sponsored by National Natural Science Foundation of China (Grant No. 30871241). NR 25 TC 12 Z9 14 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD MAR PY 2011 VL 31 IS 2 BP 203 EP 211 DI 10.1007/s10571-010-9608-7 PG 9 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 726VC UT WOS:000287753500003 PM 21061155 ER PT J AU Karschner, EL Darwin, WD McMahon, RP Liu, F Wright, S Goodwin, RS Huestis, MA AF Karschner, E. L. Darwin, W. D. McMahon, R. P. Liu, F. Wright, S. Goodwin, R. S. Huestis, M. A. TI Subjective and Physiological Effects After Controlled Sativex and Oral THC Administration SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CANNABIS-BASED MEDICINE; MULTIPLE-SCLEROSIS; DELTA-9-TETRAHYDROCANNABINOL; DELTA(9)-TETRAHYDROCANNABINOL; MARIJUANA; SMOKING; PLASMA; PHARMACOLOGY; DELTA-9-THC; DISORDERS AB Sativex is a cannabis- plant extract delivering nearly 1:Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) by oromucosal spray. It has been suggested that CBD attenuates THC-induced tachycardia, anxiety, and euphoria. In this study, pharmacodynamic effects were compared over 10.5 h in nine cannabis smokers randomly assigned to receive placebo, 5 and 15 mg oral synthetic THC, and low (5.4 mg THC, 5.0 mg CBD) and high (16.2 mg THC, 15.0 mg CBD) doses of Sativex. At therapeutic doses, no substantial CBD-induced modulation of THC's effects was evident. Oral THC and Sativex produced similar, clinically insignificant increases in heart rate, anxiety, and "good drug effects" with no serious adverse events. Oral and oromucosal THC have slower absorption, lower rate of THC delivery to the brain, and fewer associated adverse events as compared with smoked cannabis. These results indicate that Sativex has a pharmacodynamic safety profile comparable to that of oral THC at low, therapeutic doses. C1 [Karschner, E. L.; Darwin, W. D.; Goodwin, R. S.; Huestis, M. A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [McMahon, R. P.; Liu, F.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. [Wright, S.] GW Pharma Ltd, Salisbury, Wilts, England. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD USA. EM mhuestis@intra.nida.nih.gov RI McMahon, Robert/C-5462-2009 FU Intramural NIH HHS [ZIA DA000541-05, ZIA DA000541-06] NR 38 TC 28 Z9 28 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2011 VL 89 IS 3 BP 400 EP 407 DI 10.1038/clpt.2010.318 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 722NS UT WOS:000287439600020 PM 21289620 ER PT J AU Barrett, J AF Barrett, John TI Is impact a factor? SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Hematol Branch, 10,CRC Room 3E 5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD MAR PY 2011 VL 13 IS 3 BP 261 EP 261 DI 10.3109/14653249.2010.549684 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 720WK UT WOS:000287313200001 PM 21319938 ER PT J AU Gotherstrom, C Lundqvist, A Duprez, IR Childs, R Berg, L le Blanc, K AF Gotherstrom, Cecilia Lundqvist, Andreas Duprez, Ida Rasmusson Childs, Richard Berg, Louise le Blanc, Katarina TI Fetal and adult multipotent mesenchymal stromal cells are killed by different pathways SO CYTOTHERAPY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC T-LYMPHOCYTES; VERSUS-HOST-DISEASE; STEM-CELLS; BONE-MARROW; MUSCLE REGENERATION; INTERFERON-GAMMA; CYTO-TOXICITY; TUMOR-CELLS; LIVER-CELLS AB Background aims. Multipotent mesenchymal stromal cells, also known as mesenchymal stem cells (MSC), can be isolated from adult and fetal tissues. Recently, there has been considerable interest in MSC because they have features favorable for transplantation, namely their multipotency and non-immunogenic properties. Methods. We analyzed how human MSC derived from first-trimester fetal liver and adult bone marrow interact with naive and activated innate natural killer (NK) cells. NK cell function was studied by measuring killing of MSC, as well as degranulation (CD107a) induced by MSC. To assess the importance of NK cell killing, expression of surface epitopes was analyzed by flow cytometry on MSC before and after stimulation with interferon (IFN)gamma gamma. Results. Fetal and adult MSC express several ligands to activating NK cell receptors as well as low levels of HLA class I, with large inter-individual variation. Naive peripheral blood NK cells did not lyse fetal or adult MSC, whereas interleukin (IL)2 activated allogeneic as well as autologous NK cells did. Pre-incubation of MSC with IFN-gamma gamma increased their levels of HLA class I, protecting them from NK cell recognition. Fetal and adult MSC were preferably killed via the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) pathways, respectively. Blocking NKG2D reduced NK cell degranulation in both fetal and adult MSC. Conclusions. Fetal and adult MSC differ in their interactions with NK cells. Both fetal and adult MSC are susceptible to lysis by activated NK cells, which may have implications for the use of MSC in cell therapy. C1 [Gotherstrom, Cecilia] Karolinska Univ, Huddinge Hosp, Div Clin Immunol & Transfus Med, Hematol Ctr, SE-14186 Stockholm, Sweden. [Lundqvist, Andreas] Karolinska Inst, Dept Pathol & Oncol, Ctr Karolinska, Stockholm, Sweden. [Lundqvist, Andreas; Childs, Richard] NIH, Hematol Branch, Bethesda, MD 20892 USA. [Duprez, Ida Rasmusson] Uppsala Univ, Dept Clin Immunol, Uppsala, Sweden. [Berg, Louise] Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Stockholm, Sweden. [Berg, Louise] Karolinska Inst, Strateg Res Ctr IRIS, Stockholm, Sweden. [Gotherstrom, Cecilia; le Blanc, Katarina] Karolinska Inst, Div Clin Immunol & Transfus Med, Ctr Karolinska, Stockholm, Sweden. RP Gotherstrom, C (reprint author), Karolinska Univ, Huddinge Hosp, Div Clin Immunol & Transfus Med, Hematol Ctr, F79, SE-14186 Stockholm, Sweden. EM Cecilia.Gotherstrom@ki.se OI Lundqvist, Andreas/0000-0002-9709-2970 FU Swedish Society for Medical Research; Magnus Bergvall foundation; Swedish Cancer Society [08 0502]; Children's Cancer Foundation [08/071]; Swedish Research Council [K2006-32X-14716-04-1, K2008-64X-20742-01-3, K2008-64P-15457-04-3]; Tobias Foundation; Cancer Society in Stockholm; Swedish Society of Medicine; Sven and Ebba-Christina Hagbergs Foundation; Stockholm County Council; Karolinska Institutet; National Institutes of Health FX This study was supported by grants from the Swedish Society for Medical Research, Magnus Bergvall foundation, Swedish Cancer Society (08 0502), Children's Cancer Foundation (08/071), Swedish Research Council (K2006-32X-14716-04-1, K2008-64X-20742-01-3, K2008-64P-15457-04-3), Tobias Foundation, Cancer Society in Stockholm, Swedish Society of Medicine, Sven and Ebba-Christina Hagbergs Foundation, Stockholm County Council, Karolinska Institutet and National Institutes of Health. NR 46 TC 30 Z9 32 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD MAR PY 2011 VL 13 IS 3 BP 269 EP 278 DI 10.3109/14653249.2010.523077 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 720WK UT WOS:000287313200003 PM 20942778 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 Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study SO DIABETOLOGIA LA English DT Article DE Fecundability; Pregestational diabetes; Pregnancy; Time-to-pregnancy; Type 1 diabetes; Type 2 diabetes ID PREGNANCY; TIME; MELLITUS; RISK AB We assessed the effects of type 1 diabetes and type 2 diabetes on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large cohort of pregnant women. This study is based on the Norwegian Mother and Child Cohort Study. Members of this large cohort were enrolled early in pregnancy and asked about TTP and other factors. Among the 58,004 women included in the analysis, we identified 221 cases of type 1 diabetes and 88 cases of type 2 diabetes using the Medical Birth Registry of Norway. A logistic analogue of the proportional probability model, a Cox-like discrete-time model, was used to compute fecundability odds ratios (FORs) and 95% CI for type 1 diabetes and type 2 diabetes, adjusted for maternal age and prepregnancy BMI. Compared with non-diabetic women, the adjusted FOR for women with type 1 diabetes was 0.76 (95% CI 0.64-0.89) and the adjusted FOR for women with type 2 diabetes was 0.64 (95% CI 0.48-0.84). These FORs did not change substantively and remained statistically significant after excluding women with irregular menstrual cycles and accounting for cycle length. The results from the present study provide evidence of substantially decreased fecundability for women with type 1 and type 2 diabetes, even among those with a normal menstrual cycle. C1 [Whitworth, K. W.; Baird, D. D.; Longnecker, M. P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Durham, NC 27709 USA. [Stene, L. C.] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway. [Stene, L. C.] Aker & Ulleval Univ Hosp, Diabet Res Ctr, Oslo, Norway. [Skjaerven, R.] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. [Skjaerven, R.] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. RP Whitworth, KW (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop A3-05, Durham, NC 27709 USA. EM whitworthkw@niehs.nih.gov RI Baird, Donna/D-5214-2017; OI Baird, Donna/0000-0002-5544-2653; Longnecker, Matthew/0000-0001-6073-5322 FU National Institutes of Health, National Institute of Environmental Health Sciences [N01-ES-85433]; Norwegian Ministry of Health; NIH/NINDS [1 UO1 NS 047537-01]; Norwegian Research Council/FUGE [151918/S10] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health, NIH/NIEHS (grant no N01-ES-85433), NIH/NINDS (grant no.1 UO1 NS 047537-01), and the Norwegian Research Council/FUGE (grant no. 151918/S10). NR 23 TC 18 Z9 20 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2011 VL 54 IS 3 BP 516 EP 522 DI 10.1007/s00125-010-2003-6 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716PX UT WOS:000286987000007 PM 21170514 ER PT J AU Peckham, EL Lopez, G Shamim, EA Richardson, SP Sanku, S Malkani, R Stacy, M Mahant, P Crawley, A Singleton, A Hallett, M AF Peckham, E. L. Lopez, G. Shamim, E. A. Richardson, S. Pirio Sanku, S. Malkani, R. Stacy, M. Mahant, P. Crawley, A. Singleton, A. Hallett, M. TI Clinical features of patients with blepharospasm: a report of 240 patients SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE blepharospasm; botulinum toxin; dystonia; risk factors ID DYSTONIA; RISK AB Background and purpose: To characterize patients with benign essential blepharospasm (BEB) by diagnosis, environmental risk factors, and family history. Methods: Two hundred and forty patients with BEB were evaluated through a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for the development of blepharospasm and family history of dystonia and other neurological conditions. Results: Benign essential blepharospasm was more commonly found in women (2.8:1) and 93% of the patients were Caucasian. Fifty percent had pure BEB, 31% had BEB/Meige's syndrome, and 4% had BEB and eyelid opening apraxia (+/- Meige's syndrome). A minority of patients reported preceding photophobia (25%) or other eye conditions (22%). The majority were non-smokers, had no exposure to anti-emetic or antipsychotic agents, had a normal birth history, and had no history of head trauma. Seventy-two percent did report a stressful event immediately prior to the development of symptoms. Treatments reported included botulinum toxin (BoNT), oral medications, surgical procedures, and acupuncture. Thirty-two percent of patients reported a family history of focal dystonia, and BEB was the most commonly reported. .Conclusion: This study confirms previous reports of usual age, sex, caffeine and tobacco use, and family history in patients with blepharospasm. New findings include a report on occupation, lower reports of preceding eye conditions and photophobia, and higher reported stressful events. Further, this study shows a change in treatment with an increase in BoNT use and decrease in surgical procedures. C1 [Peckham, E. L.] Neurol Specialists Dallas, Dept Neurol, Dallas, TX 75231 USA. [Shamim, E. A.] Kaiser Permanente, Dept Neurol, Midatlant Permanente Med Grp MAPMG, Suitland, MD USA. [Lopez, G.; Shamim, E. A.; Sanku, S.; Crawley, A.; Hallett, M.] NINDS, NIH, HMCS, Bethesda, MD 20892 USA. [Richardson, S. Pirio] 1 Univ New Mexico, Dept Neurol, Albuquerque, NM USA. [Malkani, R.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Stacy, M.] Duke Univ, Dept Neurol, Durham, NC USA. [Mahant, P.] Movement Disorder Specialists, Dept Neurol, Phoenix, AZ USA. [Singleton, A.] NIA, NIH, Bethesda, MD 20892 USA. RP Peckham, EL (reprint author), Neurol Specialists Dallas, Dept Neurol, 7515 Greenville,Ste 500, Dallas, TX 75231 USA. EM bethulrich@hotmail.com RI Singleton, Andrew/C-3010-2009 FU National Institute of Neurological Disorders and Stroke; National Institute of Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000958-05]; BEBRF; St. Jude Medical; Ortho-McNeill Janssen; Allergan; Novartis; Schering-Plough; Parkinson's Study Group; Ceregene; Impax; US Army; Ariston Pharmaceuticals; Kinetics Foundation; NIH FX This work was supported by the Intramural Research Programs of the National Institute of Neurological Disorders and Stroke and the National Institute of Aging, National Institutes of Health, Department of Health and Human Services; project number Z01 AG000958-05. Dr Mahant received a grant from the BEBRF to help initiate this project. Dr Peckham has received funding from St. Jude Medical and Ortho-McNeill Janssen for clinical trial research in Parkinson's disease and essential tremor. Dr Shamim participated in Allergan speakers bureau training and has participated in research sponsored by Allergan but has not received any personal financial compensation from Allergan. Dr Stacy has received grant/research support from Novartis, Schering-Plough, Parkinson's Study Group, Ceregene and Impax. He has served as a consultant for Allergan, Boeringher-Ingelheim, GE, Novartis, Osmotica, and Synosia. He has been on the speakers' bureau for Allergan, Boeringher-Ingelheim, GlaxoSmithKline, TEVA, and Novartis and has been on the safety monitoring board for Biogen and Neurologix. Dr. Mahant has served as part of the Allergan Speakers bureau. Dr. Hallett reports: Consulting and Advisory Board Membership with honoraria: Neurotoxin Institute; Grants/Research: Funding from NIH, the US Army, Ariston Pharmaceuticals, Kinetics Foundation; Honoraria: University of Navarra, State of New York, University of Wisconsin, Massachusetts Medical Society, Parkinson and Aging Research Society, Columbia University; Intellectual Property Rights: H-coil; Royalties: Wiley-Blackwell, Oxford University Press, Lippincott, Wilkins and Williams, Cambridge University Press, Elsevier Publishers, Springer. NR 15 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD MAR PY 2011 VL 18 IS 3 BP 382 EP 386 DI 10.1111/j.1468-1331.2010.03161.x PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 722RB UT WOS:000287450900006 PM 20649903 ER PT J AU Karp, BI Sinaii, N Nieman, LK Silberstein, SD Stratton, P AF Karp, Barbara Illowsky Sinaii, Ninet Nieman, Lynnette K. Silberstein, Stephen D. Stratton, Pamela TI Migraine in women with chronic pelvic pain with and without endometriosis SO FERTILITY AND STERILITY LA English DT Article DE Chronic pelvic pain; endometriosis; headache; migraine; quality of life; regional pain syndrome ID QUALITY-OF-LIFE; CLINICAL-IMPLICATIONS; CENTRAL SENSITIZATION; UNITED-STATES; PREVALENCE; HEADACHE; HEALTH; EPIDEMIOLOGY; COMORBIDITY; FIBROMYALGIA AB Objective: To examine the prevalence of migraine in women with chronic pelvic pain with and without endometriosis. Design: Prospective study of headache, pelvic pain, and quality of life before laparoscopic surgery for pelvic pain. Endometriosis was diagnosed pathologically. Headaches were classified as migraine or non-migraine using International Headache Society criteria. Setting: Clinical research hospital. Patient(s): 108 women in a clinical trial for chronic pelvic pain (NCT00001848). Intervention(s): Laparoscopy to diagnose endometriosis, assessment by neurologist to assess headaches. Main Outcome Measure(s): Prevalence of migraine and other headaches in women with chronic pelvic pain with or without endometriosis. Headache frequency, severity and relationship to pelvic pain and endometriosis. Result(s): Lifetime prevalence of definite or possible migraine was 67% of women with chronic pelvic pain. An additional 8% met criteria for possible migraine. Migraine was no more likely in women with endometriosis than those without. Women with the most severe headaches had a lower quality of life compared with those with pelvic pain alone. Conclusion(s): Migraine headache is common in women with chronic pelvic pain, regardless of endometriosis, and contributes to disability in those with both conditions. The strong association suggests a common pathophysiology. (Fertil Steril (R) 2011; 95: 895-9. (C) 2011 by American Society for Reproductive Medicine.) C1 [Stratton, Pamela] NICHD, PRAE, NIH, CRC, Bethesda, MD 20892 USA. [Karp, Barbara Illowsky] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Silberstein, Stephen D.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Stratton, P (reprint author), NICHD, PRAE, NIH, CRC, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural Research Programs of the Clinical Center; Program in Reproductive and Adult Endocrinology; Kennedy Shriver National Institute of Child Health and Human Development [NCT00001848]; National Institute of Neurological Disorders and Stroke, Clinical Center, National Institutes of Health FX Supported by the Intramural Research Programs of the Clinical Center, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NCT00001848); and the National Institute of Neurological Disorders and Stroke, Clinical Center, National Institutes of Health. NR 48 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2011 VL 95 IS 3 BP 895 EP 899 DI 10.1016/j.fertnstert.2010.11.037 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 723BD UT WOS:000287480300011 PM 21145540 ER PT J AU Ribases, M Ramos-Quiroga, JA Sanchez-Mora, C Bosch, R Richarte, V Palomar, G Gastaminza, X Bielsa, A Arcos-Burgos, M Muenke, M Castellanos, FX Cormand, B Bayes, M Casas, M AF Ribases, M. Ramos-Quiroga, J. A. Sanchez-Mora, C. Bosch, R. Richarte, V. Palomar, G. Gastaminza, X. Bielsa, A. Arcos-Burgos, M. Muenke, M. Castellanos, F. X. Cormand, B. Bayes, M. Casas, M. TI Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Adult ADHD; attention-deficit; hyperactivity disorder; case-control association study; LPHN3 ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SINGLE-NUCLEOTIDE POLYMORPHISMS; CALCIUM-INDEPENDENT RECEPTOR; ALPHA-LATROTOXIN; LINKAGE DISEQUILIBRIUM; LIFE-SPAN; ASSOCIATION; SUBTYPES; SYMPTOMS AB Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable developmental disorder characterized by a persistent impairing pattern of inattention and/or hyperactivity-impulsivity. Using families from a genetic isolate, the Paisa population from Colombia, and five independent datasets from four different populations (United States, Germany, Norway and Spain), a highly consistent association was recently reported between ADHD and the latrophilin 3 (LPHN3) gene, a brain-specific member of the LPHN subfamily of G-protein-coupled receptors that is expressed in ADHD-related regions, such as amygdala, caudate nucleus, cerebellum and cerebral cortex. To replicate the association between LPHN3 and ADHD in adults, we undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single- and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P = 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P = 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan. C1 [Ribases, M.; Ramos-Quiroga, J. A.; Sanchez-Mora, C.; Bosch, R.; Richarte, V.; Palomar, G.; Gastaminza, X.; Bielsa, A.; Casas, M.] Hosp Univ Vall Hebron, Dept Psychiat, Barcelona 08003, Spain. [Ribases, M.; Sanchez-Mora, C.] Hosp Univ Vall Hebron, Psychiat Genet Unit, Barcelona 08003, Spain. [Ramos-Quiroga, J. A.; Casas, M.] Univ Autonoma Barcelona, Dept Psychiat & Legal Med, E-08193 Barcelona, Catalonia, Spain. [Arcos-Burgos, M.; Muenke, M.; Cormand, B.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Castellanos, F. X.] NYU, Child Study Ctr, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USA. [Castellanos, F. X.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Cormand, B.] Univ Barcelona, Fac Biol, Dept Genet, E-08007 Barcelona, Spain. [Cormand, B.] Univ Barcelona IBUB, Inst Biomed, Barcelona, Spain. [Bayes, M.] CNAG, Barcelona, Catalonia, Spain. RP Ribases, M (reprint author), Hosp Univ Vall Hebron, Dept Psychiat, Passeig Vall Hebron 119-129, Barcelona 08003, Spain. EM mribases@ir.vhebron.net RI Gastaminza, Xavier/C-4183-2014; Cormand, Bru/H-5338-2015; OI Gastaminza, Xavier/0000-0003-0429-1522; Cormand, Bru/0000-0001-5318-4382; Ramos-Quiroga, Josep Antoni/0000-0003-1622-0350; Ribases, Marta/0000-0003-1039-1116; Castellanos, Francisco/0000-0001-9192-9437 FU Instituto de Salud Carlos III; Instituto de Salud Carlos III-FIS [PI041267, PI040524, PI080519]; Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR [2009GR00971]; Department of Health of the Government of Catalonia (Generalitat de Catalunya); Division of Intramural Research, NHGRI, NIH FX We are grateful to patients and controls for their participation in the study, and to M. Dolors Castellar and others from the `Banc de Sang i Teixits' (Hospital Vall d'Hebron) for their collaboration in the recruitment of controls. M.R. is a recipient of a Miguel de Servet contract from `Instituto de Salud Carlos III'. Financial support was received from `Instituto de Salud Carlos III-FIS' (PI041267, PI040524, PI080519), `Agencia de Gestio d'Ajuts Universitaris i de Recerca-AGAUR' (2009GR00971), the Department of Health of the Government of Catalonia (Generalitat de Catalunya) and the Division of Intramural Research, NHGRI, NIH (M.A.-B. and M.M.). SNP genotyping services were provided by the Barcelona node of the Spanish National Genotyping Center (CEGEN; http://www.cegen.org). None of the authors reported any biomedical financial interests or potential conflicts of interest. NR 48 TC 36 Z9 37 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD MAR PY 2011 VL 10 IS 2 BP 149 EP 157 DI 10.1111/j.1601-183X.2010.00649.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 724SB UT WOS:000287595400003 PM 21040458 ER PT J AU Chen, XJ Summers, R Yao, JH AF Chen, Xinjian Summers, Ronald Yao, Jianhua TI FEM-Based 3-D Tumor Growth Prediction for Kidney Tumor SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Finite-element method (FEM); kidney tumor; segmentation; tumor growth prediction ID GLIOMA GROWTH; BRAIN-TUMORS; DIFFUSION; MODEL; DEFORMATION; FRAMEWORK; IMAGES AB It is important to predict the tumor growth so that appropriate treatment can be planned in the early stage. In this letter, we propose a finite-element method (FEM)-based 3-D tumor growth prediction system using longitudinal kidney tumor images. To the best of our knowledge, this is the first kidney tumor growth prediction system. The kidney tissues are classified into three types: renal cortex, renal medulla, and renal pelvis. The reaction-diffusion model is applied as the tumor growth model. Different diffusion properties are considered in the model: the diffusion for renal medulla is considered as anisotropic, while those of renal cortex and renal pelvis are considered as isotropic. The FEM is employed to solve the diffusion model. The model parameters are estimated by the optimization of an objective function of overlap accuracy using a hybrid optimization parallel search package. The proposed method was tested on two longitudinal studies with seven time points on five tumors. The average true positive volume fraction and false positive volume fraction on all tumors is 91.4% and 4.0%, respectively. The experimental results showed the feasibility and efficacy of the proposed method. C1 [Chen, Xinjian; Summers, Ronald; Yao, Jianhua] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. RP Yao, JH (reprint author), NIH, Dept Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA. EM chenx6@mail.nih.gov; rsummers@mail.nih.gov; jyao@mail.nih.gov RI Chen, Xinjian/E-8592-2016 FU Intramural NIH HHS [Z99 CL999999] NR 23 TC 5 Z9 5 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2011 VL 58 IS 3 BP 463 EP 467 DI 10.1109/TBME.2010.2089522 PN 1 PG 5 WC Engineering, Biomedical SC Engineering GA 725QW UT WOS:000287661900001 PM 21342810 ER PT J AU Yan, PK Xu, S Turkbey, B Kruecker, J AF Yan, Pingkun Xu, Sheng Turkbey, Baris Kruecker, Jochen TI Adaptively Learning Local Shape Statistics for Prostate Segmentation in Ultrasound SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Deformable model; prostate; segmentation; shape statistics; transrectal ultrasound (TRUS) ID BOUNDARY SEGMENTATION; IMAGES; POPULATION; TRACKING; MODELS AB Automatic segmentation of the prostate from 2-D transrectal ultrasound (TRUS) is a highly desired tool in many clinical applications. However, it is a very challenging task, especially for segmenting the base and apex of the prostate due to the large shape variations in those areas compared to the midgland, which leads many existing segmentation methods to fail. To address the problem, this paper presents a novel TRUS video segmentation algorithm using both global population-based and patient-specific local shape statistics as shape constraint. By adaptively learning shape statistics in a local neighborhood during the segmentation process, the algorithm can effectively capture the patient-specific shape statistics and quickly adapt to the local shape changes in the base and apex areas. The learned shape statistics is then used as the shape constraint in a deformable model for TRUS video segmentation. The proposed method can robustly segment the entire gland of the prostate with significantly improved performance in the base and apex regions, compared to other previously reported methods. Our method was evaluated using 19 video sequences obtained from different patients and the average mean absolute distance error was 1.65 +/-.0.47 mm. C1 [Yan, Pingkun; Xu, Sheng; Kruecker, Jochen] Philips Res N Amer, Briarcliff Manor, NY 10510 USA. [Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Yan, PK (reprint author), Chinese Acad Sci, State Key Lab Transient Opt & Photon, Xian Inst Opt & Precis Mech, Ctr OPT IMagery Anal & Learning OPTIMAL, Xian 710119, Shaanxi, Peoples R China. EM pingkun.yan@opt.ac.cn; sheng.xu@philips.com; turkbeyi@mail.nih.gov; jochen.kruecker@philips.com NR 27 TC 31 Z9 33 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2011 VL 58 IS 3 BP 633 EP 641 DI 10.1109/TBME.2010.2094195 PN 1 PG 9 WC Engineering, Biomedical SC Engineering GA 725QW UT WOS:000287661900019 PM 21097373 ER PT J AU Wang, X Niu, C Sun, G Dong, DD Villaruz, AE Li, M Wang, DC Wang, JP Otto, M Gao, QA AF Wang, Xing Niu, Chen Sun, Gang Dong, Dandan Villaruz, Amer E. Li, Min Wang, Decheng Wang, Jianping Otto, Michael Gao, Qian TI ygs Is a Novel Gene That Influences Biofilm Formation and the General Stress Response of Staphylococcus epidermidis SO INFECTION AND IMMUNITY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI; QUORUM-SENSING SYSTEM; BACILLUS-SUBTILIS; BACTERIAL BIOFILMS; VIRULENCE FACTORS; INSERTION SITES; AUREUS; EXPRESSION; MODEL AB Infections caused by the nosocomial pathogen Staphylococcus epidermidis frequently develop on implanted medical devices and involve biofilm formation. Biofilms are surface-attached microbial communities that show increased resistance to drug treatment and mechanisms of innate host defense. In this study, a mutant library of the clinical isolate S. epidermidis 1457 was constructed using mariner-based transposon mutagenesis. About a thousand mutants were screened, and 12 mutants were identified as significantly defective in biofilm formation. We focused on a mutant in which the transposon had inserted in a gene with unknown function, SERP0541, which is annotated as a gene encoding a GSP13-like general stress response protein. The gene was named ygs (encoding an unknown general stress protein). Various stresses, including heat, pH, high osmolarity, and ethanol affected the survival of the ygs mutant to a significantly higher degree than the wild-type strain and led to increased expression of ygs. Furthermore, synthesis of polysaccharide intercellular adhesin (PIA) and transcription of the PIA biosynthetic operon were significantly decreased in the ygs mutant. These results are in accordance with the putative involvement of ygs in stress-response gene regulation and indicate that ygs influences biofilm development by controlling PIA-dependent biofilm accumulation. Moreover, ygs had a significant impact on the formation of biofilms and metastatic disease in two catheter-related rat infection models. Our study shows that the ygs gene controls S. epidermidis biofilm accumulation and stress resistance, representing a key regulator of both structural and physiological biofilm characteristics with a significant impact on biofilm-associated infection. C1 [Gao, Qian] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Wang, Xing; Niu, Chen; Sun, Gang; Dong, Dandan; Wang, Decheng; Wang, Jianping; Gao, Qian] Fudan Univ, Inst Med Microbiol, Shanghai 200032, Peoples R China. [Villaruz, Amer E.; Li, Min; Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA. RP Gao, QA (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Inst Biomed Sci, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China. EM qgao99@yahoo.com OI Otto, Michael/0000-0002-2222-4115 FU National Natural Science Foundation of China [30670108, J0730860]; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by National Natural Science Foundation of China grants 30670108 and J0730860 and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 59 TC 6 Z9 6 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2011 VL 79 IS 3 BP 1007 EP 1015 DI 10.1128/IAI.00916-10 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 726DY UT WOS:000287700200003 PM 21173311 ER PT J AU Oakley, MS Anantharaman, V Venancio, TM Zheng, H Mahajan, B Majam, V McCutchan, TF Myers, TG Aravind, L Kumar, S AF Oakley, Miranda S. Anantharaman, Vivek Venancio, Thiago M. Zheng, Hong Mahajan, Babita Majam, Victoria McCutchan, Thomas F. Myers, Timothy G. Aravind, L. Kumar, Sanjai TI Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood SO INFECTION AND IMMUNITY LA English DT Article ID EXPRESSION; CELLS; ERYTHROPOIETIN; ANGIOPOIETIN-1; SEQUESTRATION; ERYTHROCYTES; PATHOGENESIS; PATHWAYS; CHILDREN; IMMUNE AB Cerebral malaria (CM) is a primary cause of deaths caused by Plasmodium falciparum in young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using the Plasmodium berghei ANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, beta-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathione S-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation in P. falciparum-infected young African children as diagnostic markers of CM. C1 [Kumar, Sanjai] FDA, Malaria Res Program, Lab Emerging Pathogens, DETTD,CBER, Rockville, MD 20852 USA. [Oakley, Miranda S.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Anantharaman, Vivek; Venancio, Thiago M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [McCutchan, Thomas F.] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIH, Microarray Res Facil, Res & Technol Branch, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), FDA, Malaria Res Program, Lab Emerging Pathogens, DETTD,CBER, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov RI Venancio, Thiago/B-5003-2011; Entomologiamolecular, Inct/J-8214-2013; OI Anantharaman, Vivek/0000-0001-8395-0009 NR 45 TC 8 Z9 10 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2011 VL 79 IS 3 BP 1244 EP 1253 DI 10.1128/IAI.00964-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 726DY UT WOS:000287700200027 PM 21149594 ER PT J AU Kalil, AC Sun, JF AF Kalil, Andre C. Sun, Junfeng TI Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies SO INTENSIVE CARE MEDICINE LA English DT Review DE Steroids; Sepsis; Shock ID OXIDE SYNTHASE INHIBITOR; DOUBLE-BLIND; HYDROCORTISONE THERAPY; CORTICOSTEROIDS; EFFICACY; METAANALYSIS; MORTALITY; INFUSION; RECOMMENDATIONS; PNEUMONIA AB Low-dose steroids have shown contradictory results in trials and three recent meta-analyses. We aimed to assess the efficacy and safety of low-dose steroids for severe sepsis and septic shock by Bayesian methodology. Randomized trials from three published meta-analyses were reviewed and entered in both classic and Bayesian databases to estimate relative risk reduction (RRR) for 28-day mortality, and relative risk increase (RRI) for shock reversal and side effects. In septic shock trials only (Marik meta-analysis; N = 965), the probability that low-dose steroids decrease mortality by more than 15% (i.e., RRR > 15%) was 0.41 (0.24 for RRR > 20% and 0.14 for RRR > 25%). For severe sepsis and septic shock trials combined, the results were as follows: (1) for the Annane meta-analysis (N = 1,228), the probabilities were 0.57 (RRR > 15%), 0.32 (RRR > 20%), and 0.13 (RRR > 25%); (2) for the Minneci meta-analysis (N = 1,171), the probability was 0.57 to achieve mortality RRR > 15%, 0.32 (RRR > 20%), and 0.14 (RRR > 25%). The removal of the Sprung trial from each analysis did not change the overall results. The probability of achieving shock reversal ranged from 65 to 92%. The probability of developing steroid-induced side effects was as follows: for gastrointestinal bleeding (N = 924), there was a 0.73 probability of steroids causing an RRI > 1%, 0.70 for RRI > 2%, and 0.67 for RRI > 5%; for superinfections (N = 964), probabilities were 0.81 (RRI > 1%), 0.76 (RRI > 2%), and 0.70 (RRI > 5%); and for hyperglycemia (N = 540), 0.99 (RRI > 1%), 0.97 (RRI > 2%), and 0.94 (RRI > 5%). Based on clinically meaningful thresholds (RRR > 15-25%) for mortality reduction in severe sepsis or septic shock, the Bayesian approach to all three meta-analyses consistently showed that low-dose steroids were not associated with survival benefits. The probabilities of developing steroid-induced side effects (superinfections, bleeding, and hyperglycemia) were high for all analyses. C1 [Kalil, Andre C.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE 68198 USA. [Sun, Junfeng] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Dept Med, 985400 Nebraska Med Ctr, Omaha, NE 68198 USA. EM akalil@unmc.edu FU Eisai; Astra Zeneca FX Andre Kalil has received research grants from Eisai and Astra Zeneca. Junfeng Sun has no conflicts to report. NR 49 TC 23 Z9 25 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD MAR PY 2011 VL 37 IS 3 BP 420 EP 429 DI 10.1007/s00134-010-2121-0 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 723NG UT WOS:000287512900008 PM 21243334 ER PT J AU Fujisawa, T Nakashima, H Nakajima, A Joshi, BH Puri, RK AF Fujisawa, Toshio Nakashima, Hideyuki Nakajima, Atsushi Joshi, Bharat H. Puri, Raj K. TI Targeting IL-13R alpha 2 in human pancreatic ductal adenocarcinoma with combination therapy of IL-13-PE and gemcitabine SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE interleukin-13 cytotoxin; pancreatic ductal adenocarcinoma; IL-13R alpha 2; gemcitabine; orthotopic mice model ID INTERLEUKIN-13 RECEPTOR ALPHA-2; PHASE-III TRIAL; SQUAMOUS-CELL CARCINOMA; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; CANCER-THERAPY; NECK-CANCER; MOUSE MODEL; HUMAN HEAD AB Pancreatic: cancer is an aggressive disease with only limited therapeutic options available. We have identified that 71% pancreatic ductal adenocarcinoma (PDA) express high levels of IL-13R alpha 2, a high-affinity receptor for IL-13. To target IL-13R alpha 2, we have developed a recombinant immunotoxin, which is a fusion of IL-13 and Pseudomonas exotoxin (IL-13-PE). Since IL-13-PE and a commonly used cytotoxic drug gemcitabine act by a different mechanism, we hypothesized that they synergize in mediating antitumor response. Both IL-13-PE and gemcitabine-mediated cytotoxicity to two pancreatic cancer cell lines and when combined synergistic cytotoxicity was observed. This synergism was also demonstrated in vivo in an orthotopic mouse model of human PDA. IL-13-PE and gemcitabine showed complete eradiation of tumors as assessed by whole body imaging of GFP-transfected tumors in 57% of mice in an early cancer model resulting into prolongation of survival. In contrast, monotherapy with either agent did not produce complete eradiation, but tumor volumes were significantly decreased. In advanced PDA model, combination therapy also produced dramatic reduction in tumor growth and enhanced survival compared to animals treated with either agent alone. When IL-13R alpha 2 was knocked-down by RNAi prior to tumor implantation, IL-13-PE and gemcitabine did not synergize indicating that IL-13R alpha 2 is essential. Mechanistically, gemcitabine increased IL-13R alpha 2 expression in vitro and in vivo, which resulted in a synergism of combination therapy. Interestingly, PDA cancer stem cells were resistant to gemcitabine, but not to IL-13-PE. These results suggest that combination therapy with IL-13-PE and gemcitabine may be a useful strategy for PDA therapy. C1 [Fujisawa, Toshio; Nakashima, Hideyuki; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Nakajima, Atsushi] Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20 HFM-735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 38 TC 12 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2011 VL 128 IS 5 BP 1221 EP 1231 DI 10.1002/ijc.25437 PG 11 WC Oncology SC Oncology GA 716HS UT WOS:000286960300022 PM 20473925 ER PT J AU Butan, C Hartnell, LM Fenton, AK Bliss, D Sockett, RE Subramaniam, S Milne, JLS AF Butan, Carmen Hartnell, Lisa M. Fenton, Andrew K. Bliss, Donald Sockett, R. Elizabeth Subramaniam, Sriram Milne, Jacqueline L. S. TI Spiral Architecture of the Nucleoid in Bdellovibrio bacteriovorus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ACTIN HOMOLOG MREB; ESCHERICHIA-COLI; CELL-SHAPE; CAULOBACTER-CRESCENTUS; CHROMOSOME SEGREGATION; BACTERIAL CHROMOSOME; CRYOELECTRON TOMOGRAPHY; SPATIAL-ORGANIZATION; ELECTRON-MICROSCOPY; BACILLUS-SUBTILIS AB We present a cryo-electron tomographic analysis of the three-dimensional architecture of a strain of the Gram-negative bacterium Bdellovibrio bacteriovorus in which endogenous MreB2 was replaced with monomeric teal fluorescent protein (mTFP)-labeled MreB2. In contrast to wild-type Bdellovibrio cells that predominantly displayed a compact nucleoid region, cells expressing mTFP-labeled MreB2 displayed a twisted spiral organization of the nucleoid. The more open structure of the MreB2-mTFP nucleoids enabled clear in situ visualization of ribosomes decorating the periphery of the nucleoid. Ribosomes also bordered the edges of more compact nucleoids from both wild-type cells and mutant cells. Surprisingly, MreB2-mTFP localized to the interface between the spiral nucleoid and the cytoplasm, suggesting an intimate connection between nucleoid architecture and MreB arrangement. Further, in contrast to wild-type cells, where a single tight chemoreceptor cluster localizes close to the single polar flagellum, MreB2-mTFP cells often displayed extended chemoreceptor arrays present at one or both poles and displayed multiple or inaccurately positioned flagella. Our findings provide direct structural evidence for spiral organization of the bacterial nucleoid and suggest a possible role for MreB in regulation of nucleoid architecture and localization of the chemotaxis apparatus. C1 [Butan, Carmen; Hartnell, Lisa M.; Subramaniam, Sriram; Milne, Jacqueline L. S.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Fenton, Andrew K.; Sockett, R. Elizabeth] Univ Nottingham, Sch Biol, Inst Genet, Nottingham NG7 2UH, England. [Bliss, Donald] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Milne, JLS (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 50,Room 4306,50 South Dr, Bethesda, MD 20892 USA. EM jmilne@nih.gov FU Center for Cancer Research at the National Cancer Institute, NIH, Bethesda, MD FX This work was supported by funding to S.S. and to J.L.S.M. from the Center for Cancer Research at the National Cancer Institute, NIH, Bethesda, MD. NR 59 TC 12 Z9 12 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2011 VL 193 IS 6 BP 1341 EP 1350 DI 10.1128/JB.01061-10 PG 10 WC Microbiology SC Microbiology GA 726CL UT WOS:000287696100007 PM 21148724 ER PT J AU Curco, D Zanuy, D Nussinov, R Aleman, C AF Curco, David Zanuy, David Nussinov, Ruth Aleman, Carlos TI A Simulation Strategy for the Atomistic Modeling of Flexible Molecules Covalently Tethered to Rigid Surfaces: Application to Peptides SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE sampling; peptide; simulation; monolayer; surface ID MONTE-CARLO SIMULATIONS; TARGETING IN-VIVO; POTENTIAL FUNCTIONS; TUMOR VASCULATURE; MONOLAYERS; TRANSPORT; POLYMERS; CHAINS AB A computational strategy to model flexible molecules tethered to a rigid inert surface is presented. The strategy is able to provide uncorrelated relaxed microstructures at the atomistic level. It combines an algorithm to generate molecules tethered to the surface without atomic overlaps, a method to insert solvent molecules and ions in the simulation box, and a powerful relaxation procedure. The reliability of the strategy has been investigated by simulating two different systems: (i) mixed monolayers consisting of binary mixtures of long-chain alkyl thiols of different lengths adsorbed on a rigid inert surface and (ii) CREKA (Cys-Arg-Glu-Lys-Ala), a short linear pentapeptide that recognizes clotted plasma proteins and selectively homes to tumors, covalently tethered to a rigid inert surface in aqueous solution. In the first, we examined the segregation of the two species in the monolayers using different lone-chain:short-chain ratios, whereas in the second, we explored the conformational space of CREKA and ions distribution considering densities of peptides per nm2 ranging from 0.03 to 1.67. Results indicate a spontaneous segregation in alkyl thiol monolayers, which enhances when the concentration of longest chains increases. However, the whole conformational profile of CREKA depends on the number of molecules tethered to the surface pointing out the large influence of molecular density on the intermolecular interactions, even though the bioactive conformation was found as the most stable in all cases. (C) 2010 Wiley Periodicals, Inc. J Comput Chem 32: 607-619, 2011 C1 [Curco, David] Univ Barcelona, Fac Quim, Dept Engn Quim, E-08028 Barcelona, Spain. [Zanuy, David; Aleman, Carlos] Univ Politecn Cataluna, ETS Enginyers Ind, Dept Engn Quim, E-08028 Barcelona, Spain. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet Sackler, IL-69978 Tel Aviv, Israel. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Curco, D (reprint author), Univ Barcelona, Fac Quim, Dept Engn Quim, Marti Franques 1, E-08028 Barcelona, Spain. EM curco@angel.qui.ub.es; carlos.aleman@upc.edu RI Zanuy, David/G-3930-2014 OI Zanuy, David/0000-0001-7704-2178 FU National Cancer Institute and National Institutes of Health [HHSN261200800001E]; Ministerio de Educacion y Ciencia: Ramon y Cajal; Generalitat de Catalunya: research group FX Contract/grant sponsor: National Cancer Institute and National Institutes of Health; contract/grant numbers: HHSN261200800001E; Contract/grant sponsor: Ministerio de Educacion y Ciencia: Ramon y Cajal contract to DZ; Contract/grant sponsor: Generalitat de Catalunya: research group 2009 SGR 925, XRQTC and ICREA Academia prize to C.A. NR 30 TC 4 Z9 4 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD MAR PY 2011 VL 32 IS 4 BP 607 EP 619 DI 10.1002/jcc.21647 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 724BM UT WOS:000287551100005 PM 20806264 ER PT J AU Bradford, PT Goldstein, AM Tamura, D Khan, SG Ueda, T Boyle, J Oh, KS Imoto, K Inui, H Moriwaki, SI Emmert, S Pike, KM Raziuddin, A Plona, TM DiGiovanna, JJ Tucker, MA Kraemer, KH AF Bradford, Porcia T. Goldstein, Alisa M. Tamura, Deborah Khan, Sikandar G. Ueda, Takahiro Boyle, Jennifer Oh, Kyu-Seon Imoto, Kyoko Inui, Hiroki Moriwaki, Shin-Ichi Emmert, Steffen Pike, Kristen M. Raziuddin, Arati Plona, Teri M. DiGiovanna, John J. Tucker, Margaret A. Kraemer, Kenneth H. TI Cancer and neurologic degeneration in xeroderma pigmentosum: long term follow-up characterises the role of DNA repair SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID NONMELANOMA SKIN-CANCER; MELANOCORTIN-1 RECEPTOR GENE; SQUAMOUS-CELL CARCINOMA; MESSENGER-RNA LEVELS; COCKAYNE-SYNDROME; XPD GENE; MC1R VARIANTS; UNITED-STATES; GROUP C; MUTATIONS AB Background The frequency of cancer, neurologic degeneration and mortality in xeroderma pigmentosum (XP) patients with defective DNA repair was determined in a four decade natural history study. Methods All 106 XP patients admitted to the National Institutes of Health from 1971 to 2009 were evaluated from clinical records and follow-up. Results In the 65 per cent (n=69) of patients with skin cancer, non-melanoma skin cancer (NMSC) was increased 10 000-fold and melanoma was increased 2000-fold in patients under age 20. The 9 year median age at diagnosis of first non-melanoma skin cancer (NMSC) (n=64) was significantly younger than the 22 year median age at diagnosis of first melanoma (n=38)-a relative age reversal from the general population suggesting different mechanisms of carcinogenesis between NMSC and melanoma. XP patients with pronounced burning on minimal sun exposure (n=65) were less likely to develop skin cancer than those who did not. This may be related to the extreme sun protection they receive from an earlier age, decreasing their total ultraviolet exposure. Progressive neurologic degeneration was present in 24% (n=25) with 16/25 in complementation group XP-D. The most common causes of death were skin cancer (34%, n=10), neurologic degeneration (31%, n=9), and internal cancer (17%, n=5). The median age at death (29 years) in XP patients with neurodegeneration was significantly younger than those XP patients without neurodegeneration (37 years) (p=0.02). Conclusion This 39 year follow-up study of XP patients indicates a major role of DNA repair genes in the aetiology of skin cancer and neurologic degeneration. C1 [Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Bradford, Porcia T.; Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pike, Kristen M.; Raziuddin, Arati; Plona, Teri M.] NCI, Lab Mol Technol, Sci Applicat Int Corp, Bethesda, MD 20892 USA. [DiGiovanna, John J.] Brown Univ, Dept Dermatol, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA. EM kraemerk@nih.gov RI Tucker, Margaret/B-4297-2015 FU National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics; Center for Cancer Research FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics and the Center for Cancer Research. NR 79 TC 114 Z9 116 U1 4 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD MAR PY 2011 VL 48 IS 3 BP 168 EP 176 DI 10.1136/jmg.2010.083022 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 721PI UT WOS:000287366700004 PM 21097776 ER PT J AU Hall, MD Pike, VW AF Hall, Matthew D. Pike, Victor W. TI Avoiding Barriers to PET Radioligand Development: Cellular Assays of Brain Efflux Transporters SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID P-GLYCOPROTEIN FUNCTION; SEROTONIN 5-HT1A RECEPTORS; IN-VIVO; RODENT BRAIN; BLOOD; RADIOTRACERS; BINDING; DESIGN; DRUGS; CNS C1 [Hall, Matthew D.; Pike, Victor W.] NIH, Bethesda, MD 20892 USA. RP Hall, MD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA MH002793-11] NR 22 TC 3 Z9 3 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR 1 PY 2011 VL 52 IS 3 BP 338 EP 340 DI 10.2967/jnumed.110.081125 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 724LR UT WOS:000287578200012 PM 21321273 ER PT J AU Chen, X Li, Y Alawi, F Bouchard, JR Kulkarni, AB Gibson, CW AF Chen, Xu Li, Yong Alawi, Faizan Bouchard, Jessica R. Kulkarni, Ashok B. Gibson, Carolyn W. TI An amelogenin mutation leads to disruption of the odontogenic apparatus and aberrant expression of Notch I SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE abnormal proliferation; amelogenin; dental enamel; Notch1; null and transgenic mice ID TOOTH DEVELOPMENT; ENAMEL PHENOTYPE; MATRIX PROTEINS; GENE-EXPRESSION; MOUSE TOOTH; CELL FATE; MICE; NULL; REGENERATION; IMPERFECTA AB Background: Amelogenins are highly conserved proteins secreted by ameloblasts in the dental organ of developing teeth. These proteins regulate dental enamel thickness and structure in humans and mice. Mice that express an amelogenin transgene with a P70T mutation (TgP70T) develop abnormal epithelial proliferation in an amelogenin null (KO) background. Some of these cellular masses have the appearance of proliferating stratum intermedium, which is the layer adjacent to the ameloblasts in unerupted teeth. As Notch proteins are thought to constitute the developmental switch that separates ameloblasts from stratum intermedium, these signaling proteins were evaluated in normal and proliferating tissues. Methods: Mandibles were dissected for histology and immunohistochemistry using Notch1 antibodies. Molar teeth were dissected for western blotting and RT-PCR for evaluation of Notch levels through imaging and statistical analyses. Results: Notch1 was immunolocalized to ameloblasts of TgP70TKO mice, KO ameloblasts stained, but less strongly, and wild-type teeth had minimal staining. Cells within the proliferating epithelial cell masses were positive for Notch1 and had an appearance reminiscent of calcifying epithelial odontogenic tumor with amyloid-like deposits. Notch1 protein and mRNA were elevated in molar teeth from TgP70TKO mice. Conclusion: Expression of TgP70T leads to abnormal structures in mandibles and maxillae of mice with the KO genetic background and these mice have elevated levels of Notch 1 in developing molars. As cells within the masses also express transgenic amelogenins, development of the abnormal proliferations suggests communication between amelogenin producing cells and the proliferating cells, dependent on the presence of the mutated amelogenin protein. C1 [Chen, Xu] China Med Univ, Dept Pediat Dent, Sch Stomatol, Shenyang 110002, Liaoning Prov, Peoples R China. [Chen, Xu; Li, Yong; Bouchard, Jessica R.; Gibson, Carolyn W.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA. [Alawi, Faizan] Univ Penn, Sch Dent Med, Dept Pathol, Philadelphia, PA 19104 USA. [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. RP Chen, X (reprint author), China Med Univ, Dept Pediat Dent, Sch Stomatol, 117 Nanjing N St, Shenyang 110002, Liaoning Prov, Peoples R China. EM chenxu_cmu@sina.com; cgibson@dental.upenn.edu FU NIDCR of the NIH [DE011089] FX We acknowledge the NIDCR of the NIH for support of this work through grant DE011089. We thank S. Decker, M. Aragon, and G. Hughes for technical assistance, M. Pugach for contributions toward the scientific discussion and A. Kuperstein for microCT analysis. NR 40 TC 3 Z9 3 U1 3 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD MAR PY 2011 VL 40 IS 3 BP 235 EP 242 DI 10.1111/j.1600-0714.2010.00940.x PG 8 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA 725UJ UT WOS:000287671300006 PM 20923441 ER PT J AU Yang, CC Burks, DA Propert, KJ Mayer, RD Peters, KM Nickel, JC Payne, CK FitzGerald, MP Hanno, PM Chai, TC Kreder, KJ Lukacz, ES Foster, HE Cen, LY Landis, JR Kusek, JW Nyberg, LM AF Yang, Claire C. Burks, David A. Propert, Kathleen J. Mayer, Robert D. Peters, Kenneth M. Nickel, J. Curtis Payne, Christopher K. FitzGerald, Mary P. Hanno, Philip M. Chai, Toby C. Kreder, Karl J. Lukacz, Emily S. Foster, Harris E. Cen, Liyi Landis, J. Richard Kusek, John W. Nyberg, Leroy M. CA Interstitial Cystitis Collaborativ TI Early Termination of a Trial of Mycophenolate Mofetil for Treatment of Interstitial Cystitis/Painful Bladder Syndrome: Lessons Learned SO JOURNAL OF UROLOGY LA English DT Article DE urinary bladder; cystitis, interstitial; fetus; drug toxicity; mycophenolate mofetil ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PENTOSAN POLYSULFATE; CYCLOSPORINE-A; ASSOCIATION; ACTIVATION; EFFICACY; DISEASE AB Purpose: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. Materials and Methods: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2: 1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries. Results: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p = 0.67). Secondary outcome measures reflected more improvement in controls. Conclusions: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations. C1 [Yang, Claire C.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Burks, David A.] Henry Ford Hosp, Detroit, MI 48202 USA. [Propert, Kathleen J.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Propert, Kathleen J.; Cen, Liyi; Landis, J. Richard] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Hanno, Philip M.] Univ Penn, Div Urol, Philadelphia, PA 19104 USA. [Mayer, Robert D.] Univ Rochester, Dept Urol, Rochester, NY USA. [Nickel, J. Curtis] Queens Univ, Kingston, ON, Canada. [Payne, Christopher K.] Stanford Univ, Stanford, CA 94305 USA. [Lukacz, Emily S.] Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA. [FitzGerald, Mary P.] Loyola Univ, Dept Obstet & Gynecol, Maywood, IL 60153 USA. [FitzGerald, Mary P.] Loyola Univ, Dept Urol, Maywood, IL 60153 USA. [Chai, Toby C.] Univ Maryland, Div Urol, Baltimore, MD 21201 USA. [Kusek, John W.; Nyberg, Leroy M.] NIDDK, Bethesda, MD USA. [Kreder, Karl J.] Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. [Landis, J. Richard] Yale Univ, Dept Urol Surg, New Haven, CT USA. RP Yang, CC (reprint author), Univ Washington, Dept Urol, Box 356510, Seattle, WA 98195 USA. OI Landis, J Richard/0000-0001-8099-0988 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK65209, U01DK65255, U01DK65213, U01DK65214, U01DK65215, U01DK65178, U01DK65190, U01DK65192, U01DK65267, U01DK65271, U01DK65202]; Astellas; GlaxoSmithKline; Bayer; Bioform; Taris/Lipella; AbbeyMoore; Pfizer; Allergan; Medtronic; Boston Scientific; Uroloplasty; Johnson Johnson; Celgene; Merck; Ortho Women's Health; Farr Labs; Watson; NeurAxon; Genyous Biomed; American Medical Systems; Ortho McNeil; Taris; Afferent; Ferring; Trillium; Tarus; National Institutes of Health; Novartis; Proctor and Gamble; Intuitive Surgical; Elsevier; deCode Genetics FX Supported by National Institute of Diabetes and Digestive and Kidney Diseases Cooperative Agreements U01 DK65209, U01DK65255, U01DK65213, U01DK65214, U01DK65215, U01DK65178, U01DK65190, U01DK65192, U01DK65255, U01DK65267, U01DK65271 and U01DK65202.; Financial interest and/or other relationship with Astellas, GlaxoSmithKline and Bayer.; Financial interest and/or other relationship with Bioform, Taris/Lipella, AbbeyMoore, Pfizer and Allergan.; Financial interest and/or other relationship with Medtronic, Boston Scientific, Uroloplasty, Johnson & Johnson, Celgene, Allergan and Pfizer.; Financial interest and/or other relationship with Merck, GlaxoSmithKline, Pfizer, Ortho Women's Health, Farr Labs, Watson, Medtronic, NeurAxon, Genyous Biomed, Merck, Glaxo-Smith Kline, Allergan, Watson, Pfizer, American Medical Systems, Astellas, Ortho McNeil and Taris.; Financial interest and/or other relationship with Astellas, Allergan, Afferent, Celgene, Pfizer and Medtronic.; Financial interest and/or other relationship with Astellas and Ferring.; Financial interest and/or other relationship with Astellas, Pfizer, Watson, Trillium and Tarus.; Financial interest and/or other relationship with Pfizer, Allergan and National Institutes of Health.; Financial interest and/or other relationship with Pfizer, Astellas and Medtronic.; Financial interest and/or other relationship with Pfizer, Watson, Novartis, Proctor and Gamble, Intuitive Surgical and Elsevier.; Financial interest and/or other relationship with deCode Genetics. NR 28 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2011 VL 185 IS 3 BP 901 EP 906 DI 10.1016/j.juro.2010.10.053 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 718OM UT WOS:000287133900050 PM 21238993 ER PT J AU Vela-Chavez, T Adam, P Kremer, M Bink, K Bacon, CM Menon, G Ferry, JA Fend, F Jaffe, ES Quintanilla-Martinez, L AF Vela-Chavez, Teresa Adam, Patrick Kremer, Marcus Bink, Karin Bacon, Christopher M. Menon, Geetha Ferry, Judith A. Fend, Falko Jaffe, Elaine S. Quintanilla-Martinez, Leticia TI Cyclin D1 positive diffuse large B-cell lymphoma is a post-germinal center-type lymphoma without alterations in the CCND1 gene locus SO LEUKEMIA & LYMPHOMA LA English DT Article ID MULTIPLE-MYELOMA; PROTEIN EXPRESSION; OVEREXPRESSION; PROGRESSION; ACTIVATION; BINDING; G(1); BCL6 AB The aims of this study were to analyze the incidence and morphology of cyclin D1++ DLBCL and cases of Richter transformation (RT), and to elucidate possible molecular mechanisms of cyclin D1 overexpression. Seventy-two cases of de novo DLBCL and 12 cases of RT were included in this study. Cyclin D1 positivity was found in 10/66 (15%%) cases of unselected de novo DLBCL and in 2/11 (18%%) cases of RT. Seven independently identified cases of cyclin D1++ DLBCL, including one RT, were added to the study. Centroblastic morphology was found in 17/19 (89%%) cases of cyclin D1++, most with a post-germinal center phenotype (CD10--, BCL6++, MUM1++). No alterations in the CCND1 gene indicative for a translocation t(11;14) were identified by FISH. Analysis of the MYC locus yielded gene copy alterations in five cases and no disruption of the gene locus in any case, suggesting an alternative mechanism of cyclin D1 deregulation.= 50%), and the remission rate was 45% (final MADRS score of <= 7). Responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders did (P = 0.03). Hot flashes were present in 15 (75%) participants. Among those with hot flashes at baseline, the number of hot flashes per day improved significantly from baseline (P = 0.02) and Hot Flash Related Daily Interference Scale scores decreased significantly (P = 0.006). Conclusions: These data support further study of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition. C1 [Freeman, Marlene P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. [Hibbeln, Joseph R.] NIAAA, Bethesda, MD USA. [Silver, Michael; Hirschberg, April M.; Pascuillo, Erica; Economou, Nicole I.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Freeman, MP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Program, 185 Cambridge St, Boston, MA 02114 USA. EM mfreeman@partners.org FU GlaxoSmithKline (GSK); Forest; Lilly; Astra-Zeneca Pharmaceuticals; Bayer HealthCare Pharmaceuticals; Bristol-Myers Squibb; Forest Laboratories, Inc.; National Institute on Aging, National Institutes of Health, National Institute of Mental Health; Ortho-McNeil Janssen; Pfizer Inc. FX This study was funded by an investigator-initiated grant from GlaxoSmithKline (GSK). GSK had no input on the study implementation, data analysis, or manuscript preparation. This work was completed at Massachusetts General Hospital.; Marlene P. Freeman, MD- research support from investigator-initiated trials: Forest, GSK, and Lilly. CME support of program: Pam Lab. Stipend for medical editing: DSM Nutritionals. Speaking: none. Consulting: none. Stock: none. Hadine Joffe, MD, MSc-research support to the Perinatal and Reproductive Psychiatry Program: Bayer HealthCare Pharmaceuticals, Forest Laboratories, Inc., and GSK. Speaking/honoraria: none. Advisory/consulting: Sanofi-Aventis and Pfizer. Royalty/patent, other income: None. Lee S. Cohen, MD-research support: Astra-Zeneca Pharmaceuticals, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Forest Laboratories, Inc., GSK, National Institute on Aging, National Institutes of Health, National Institute of Mental Health, Ortho-McNeil Janssen, and Pfizer Inc. Advisory/consulting: Eli Lilly & Company and Noven. Honoraria: none. Royalty/patent, other income: None. Michael Silver, Joseph Hibbeln, Amy Yule, April Hirschberg, Betty Wang, Laura Petrillo, Erica Pascuillo, Nicole Economou-nothing to disclose. NR 30 TC 19 Z9 19 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR PY 2011 VL 18 IS 3 BP 279 EP 284 DI 10.1097/gme.0b013e3181f2ea2e PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 725PT UT WOS:000287658600010 PM 21037490 ER PT J AU Chanock, SJ AF Chanock, Stephen J. TI A twist on admixture mapping SO NATURE GENETICS LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; AFRICAN-AMERICANS; PUERTO-RICANS; POPULATIONS; VARIABILITY; VARIANTS; PANEL; MAP AB A new study uses genome-wide SNSNP genotypes to identify a subset of children undergoing therapy for acute lymphoblastic leukemia that are at increased risk for relapse. Borrowing from the classical approach of admixture mapping, the work shows how genome-wide assessment of genetic ancestry can be used as a biomarker for disease outcome. C1 NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Chanock, SJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov NR 15 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2011 VL 43 IS 3 BP 178 EP 179 DI 10.1038/ng0311-178 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 726BR UT WOS:000287693800005 PM 21350496 ER PT J AU Lindstrom, S Vachon, CM Li, JM Varghese, J Thompson, D Warren, R Brown, J Leyland, J Audley, T Wareham, NJ Loos, RJF Paterson, AD Rommens, J Waggott, D Martin, LJ Scott, CG Pankratz, VS Hankinson, SE Hazra, A Hunter, DJ Hopper, JL Southey, MC Chanock, SJ Silva, ID Liu, JJ Eriksson, L Couch, FJ Stone, J Apicella, C Czene, K Kraft, P Hall, P Easton, DF Boyd, NF Tamimi, RM AF Lindstroem, Sara Vachon, Celine M. Li, Jingmei Varghese, Jajini Thompson, Deborah Warren, Ruth Brown, Judith Leyland, Jean Audley, Tina Wareham, Nicholas J. Loos, Ruth J. F. Paterson, Andrew D. Rommens, Johanna Waggott, Darryl Martin, Lisa J. Scott, Christopher G. Pankratz, V. Shane Hankinson, Susan E. Hazra, Aditi Hunter, David J. Hopper, John L. Southey, Melissa C. Chanock, Stephen J. Silva, Isabel dos Santos Liu, JianJun Eriksson, Louise Couch, Fergus J. Stone, Jennifer Apicella, Carmel Czene, Kamila Kraft, Peter Hall, Per Easton, Douglas F. Boyd, Norman F. Tamimi, Rulla M. TI Common variants in ZNF365 are associated with both mammographic density and breast cancer risk SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; RANDOMIZED-TRIAL; MENOPAUSE; FEATURES AB High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 x 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer. C1 [Lindstroem, Sara; Hankinson, Susan E.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Tamimi, Rulla M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lindstroem, Sara; Hazra, Aditi; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Vachon, Celine M.; Scott, Christopher G.; Pankratz, V. Shane] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Li, Jingmei; Eriksson, Louise; Czene, Kamila; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Li, Jingmei; Liu, JianJun] Genome Inst Singapore, Singapore, Singapore. [Varghese, Jajini; Thompson, Deborah; Brown, Judith; Leyland, Jean; Audley, Tina; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Genet Epidemiol, Cambridge, England. [Warren, Ruth] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 2QQ, England. [Wareham, Nicholas J.; Loos, Ruth J. F.] MRC, Epidemiol Unit, Cambridge, England. [Paterson, Andrew D.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Paterson, Andrew D.; Rommens, Johanna] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada. [Waggott, Darryl] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Martin, Lisa J.; Boyd, Norman F.] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada. [Hankinson, Susan E.; Hazra, Aditi; Hunter, David J.; Tamimi, Rulla M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hankinson, Susan E.; Hazra, Aditi; Hunter, David J.; Tamimi, Rulla M.] Harvard Univ, Sch Med, Boston, MA USA. [Hopper, John L.; Stone, Jennifer; Apicella, Carmel] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Silva, Isabel dos Santos] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Tamimi, RM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM rulla.tamimi@channing.harvard.edu RI Li, Jingmei/I-2904-2012; Paterson, Andrew/A-4088-2011 OI Czene, Kamila/0000-0002-3233-5695; Scott, Christopher/0000-0003-1340-0647; dos Santos Silva, Isabel/0000-0002-6596-8798; Li, Jingmei/0000-0001-8587-7511; Paterson, Andrew/0000-0002-9169-118X FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA131332, CA087969, CA049449, CA128931, CA116201, CA075016, CA122340, CA089393]; Breast Cancer Research Fund; National Cancer Institute's Cancer Markers of Susceptibility (CGEMS) initiative; Cancer Research UK; Marit and Hans Rausing's Initiative against Breast Cancer, National Institutes of Health; Susan Komen Foundation; Agency for Science, Technology and Research of Singapore (A*STAR); Campbell Family Institute for Breast Cancer Research; Ontario Ministry of Health and Long Term Care FX This study was supported by Public Health Service Grants CA131332, CA087969, CA049449, CA128931, CA116201, CA075016, CA122340 and CA089393 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services and Breast Cancer Research Fund. The Nurses' Health Study (NHS) breast cancer cases and controls were genotyped with support from the National Cancer Institute's Cancer Markers of Susceptibility (CGEMS) initiative. Data evaluation of mammograms and analysis of the EPIC-Norfolk and SIBS studies was supported by Cancer Research UK. The SASBAC study was supported by Marit and Hans Rausing's Initiative against Breast Cancer, National Institutes of Health, Susan Komen Foundation and Agency for Science, Technology and Research of Singapore (A*STAR). Genotyping in the TORONTO/MELBOURNE subjects was supported by the Campbell Family Institute for Breast Cancer Research. Support was also provided by the Ontario Ministry of Health and Long Term Care. NR 14 TC 70 Z9 70 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2011 VL 43 IS 3 BP 185 EP 187 DI 10.1038/ng.760 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 726BR UT WOS:000287693800007 PM 21278746 ER PT J AU Buonanno, A AF Buonanno, Andres TI Presynaptic NMDA receptors also make the switch SO NATURE NEUROSCIENCE LA English DT Editorial Material ID SOMATOSENSORY CORTEX; GLUTAMATE RELEASE; ENTORHINAL CORTEX; PLASTICITY; EXPRESSION; LTD AB A study shows that NR3A-containing presynaptic NMDA receptors regulate glutamate release, and that a switch in subunit composition underlies the developmental loss of spike timing-dependent LTD at cortical synapses. C1 Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Program Dev Neurobiol, Mol Neurobiol Sect, NIH, Bethesda, MD USA. RP Buonanno, A (reprint author), Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Program Dev Neurobiol, Mol Neurobiol Sect, NIH, Bethesda, MD USA. EM buonanno@mail.nih.gov FU Intramural NIH HHS [ZIA HD000711-22] NR 15 TC 1 Z9 1 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAR PY 2011 VL 14 IS 3 BP 274 EP 276 DI 10.1038/nn0311-274 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 725MW UT WOS:000287650100003 PM 21346744 ER PT J AU Benicky, J Sanchez-Lemus, E Honda, M Pang, T Orecna, M Wang, JA Leng, Y Chuang, DM Saavedra, JM AF Benicky, Julius Sanchez-Lemus, Enrique Honda, Masaru Pang, Tao Orecna, Martina Wang, Juan Leng, Yan Chuang, De-Maw Saavedra, Juan M. TI Angiotensin II AT(1) Receptor Blockade Ameliorates Brain Inflammation SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE innate immune response; lipopolysaccharide; proinflammatory cytokines; microglia activation; sickness behavior ID SPONTANEOUSLY HYPERTENSIVE-RATS; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INNATE IMMUNE-RESPONSE; CENTRAL-NERVOUS-SYSTEM; ANTAGONIST PREVENTS; RENIN-ANGIOTENSIN; LIPOPOLYSACCHARIDE; CANDESARTAN; EXPRESSION AB Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT(1) receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders. Neuropsychopharmacology (2011) 36, 857-870; doi:10.1038/npp.2010.225; published online 8 December 2010 C1 [Benicky, Julius; Sanchez-Lemus, Enrique; Honda, Masaru; Pang, Tao; Orecna, Martina; Wang, Juan; Saavedra, Juan M.] NIMH, Pharmacol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Leng, Yan; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Benicky, J (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, Dept Hlth & Human Serv,NIH, 9000 Rockville Pike,Bldg 10,Room 2D57, Bethesda, MD 20892 USA. EM benickyj@mail.nih.gov FU National Institute of Mental Health, Department of Health and Human Services, USA; Japan Society for the Promotion of Science Research at NIH FX This study was supported by the Division of Intramural Research Programs, National Institute of Mental Health, Department of Health and Human Services, USA. Dr Honda was supported by the Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH. We thank Astra-Zeneca, Molndal, Sweden, for the supply of candesartan, and to Andres Negro Vilar MD, PhD, for his helpful comments and suggestions during the preparation of the manuscript. NR 63 TC 63 Z9 66 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2011 VL 36 IS 4 BP 857 EP 870 DI 10.1038/npp.2010.225 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 719FY UT WOS:000287188200014 PM 21150913 ER PT J AU Sumner, AE Micklesfield, LK Ricks, M Tambay, AV Avila, NA Thomas, F Lambert, EV Levitt, NS Evans, J Rotimi, CN Tulloch-Reid, MK Goedecke, JH AF Sumner, Anne E. Micklesfield, Lisa K. Ricks, Madia Tambay, Anita V. Avila, Nilo A. Thomas, Francine Lambert, Estelle V. Levitt, Naomi S. Evans, Juliet Rotimi, Charles N. Tulloch-Reid, Marshall K. Goedecke, Julia H. TI Waist Circumference, BMI, and Visceral Adipose Tissue in White Women and Women of African Descent SO OBESITY LA English DT Article ID INSULIN-RESISTANCE; METABOLIC SYNDROME; AMERICANS; WEIGHT AB Although waist circumference (WC) is a marker of visceral adipose tissue (VAT), WC cut-points are based on BMI category. We compared WC-BMI and WC-VAT relationships in blacks and whites. Combining data from five studies, BMI and WC were measured in 1,409 premenopausal women (148 white South Africans, 607 African-Americans, 186 black South Africans, 445 West Africans, 23 black Africans living in United States). In three of five studies, participants had VAT measured by computerized tomography (n = 456). Compared to whites, blacks had higher BMI (29.6 +/- 7.6 (mean +/- s.d.) vs. 27.6 +/- 6.6 kg/m(2), P = 0.001), similar WC (92 +/- 16 vs. 90 +/- 15 cm, P = 0.27) and lower VAT (64 +/- 42 vs. 101 +/- 59 cm(2), P < 0.001). The WC-BMI relationship did not differ by race (blacks: beta (s.e.) WC = 0.42 (.01), whites: beta (s.e.) WC = 0.40 (0.01), P = 0.73). The WC-VAT relationship was different in blacks and whites (blacks: beta (s.e.) WC = 1.38 (0.11), whites: beta (s.e.) WC = 3.18 (0.21), P < 0.001). Whites had a greater increase in VAT per unit increase in WC. WC-BMI and WC-VAT relationships did not differ among black populations. As WC-BMI relationship did not differ by race, the same BMI-based WC guidelines may be appropriate for black and white women. However, if WC is defined by VAT, race-specific WC thresholds are required. C1 [Sumner, Anne E.; Ricks, Madia; Tambay, Anita V.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Micklesfield, Lisa K.; Lambert, Estelle V.; Evans, Juliet; Goedecke, Julia H.] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, South Africa. [Micklesfield, Lisa K.] Univ Witwatersrand, Fac Hlth Sci, Dept Pediat, MRC Mineral Metab Res Unit, Johannesburg, South Africa. [Avila, Nilo A.] Washington DC Vet Affairs Med Ctr, Washington, DC USA. [Thomas, Francine] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Levitt, Naomi S.] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa. [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Tulloch-Reid, Marshall K.] Univ W Indies, Epidemiol Res Unit, Kingston 7, Jamaica. [Goedecke, Julia H.] Med Res Council S Africa, Cape Town, South Africa. RP Sumner, AE (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM AnneS@intra.niddk.nih.gov RI Goedecke, Julia/J-8628-2013; Goedecke, Julia/E-1820-2016 OI Goedecke, Julia/0000-0001-6795-4771; Goedecke, Julia/0000-0001-6795-4771 FU NIDDK, NIH; Center for Research in Genomics and Global Health, NHGRI, NIH; NCRR [2M01RR010284]; National Human Genome Center at Howard University; NCMHD; NHGRI; NIDDK; South African Medical Research Council; International Atomic Energy Agency; National Research Foundation of South Africa; University of Cape Town; [S06GM008016-320107] FX A.E.S., A.V.T., and M.R. were supported by the intramural program of NIDDK, NIH. C.N.R. was supported by the Intramural Research Program of the Center for Research in Genomics and Global Health, NHGRI, NIH. The HUFS was supported by grant S06GM008016-320107. African American enrollment was carried out at the General Clinical Research Center supported by NCRR grant 2M01RR010284 and the National Human Genome Center at Howard University. The AADM study was supported by grants obtained from NCMHD, NHGRI, and NIDDK. Symington Radiology is acknowledged for performing the South African scans. The South African study was funded by the South African Medical Research Council, the International Atomic Energy Agency, the National Research Foundation of South Africa, and the University of Cape Town. The authors thank Ms. Ugochi J. Ukegbu for her careful review of the manuscript. NR 16 TC 18 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAR PY 2011 VL 19 IS 3 BP 671 EP 674 DI 10.1038/oby.2010.201 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 725MJ UT WOS:000287648500033 PM 20847732 ER PT J AU Landy, HJ Laughon, SK Bailit, JL Kominiarek, MA Gonzalez-Quintero, VH Ramirez, M Haberman, S Hibbard, J Wilkins, I Branch, DW Burkman, RT Gregory, K Hoffman, MK Learman, LA Hatjis, C VanVeldhuisen, PC Reddy, UM Troendle, J Sun, L Zhang, J AF Landy, Helain J. Laughon, S. Katherine Bailit, Jennifer L. Kominiarek, Michelle A. Gonzalez-Quintero, Victor Hugo Ramirez, Mildred Haberman, Shoshana Hibbard, Judith Wilkins, Isabelle Branch, D. Ware Burkman, Ronald T. Gregory, Kimberly Hoffman, Matthew K. Learman, Lee A. Hatjis, Christos VanVeldhuisen, Paul C. Reddy, Uma M. Troendle, James Sun, Liping Zhang, Jun CA Consortium Safe Labor TI Characteristics Associated With Severe Perineal and Cervical Lacerations During Vaginal Delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ANAL-SPHINCTER DISRUPTION; URINARY-INCONTINENCE; NULLIPAROUS WOMEN; OBSTETRICS UNIT; RISK-FACTORS; STATES AB OBJECTIVE: To characterize potentially modifiable risk factors for third- or fourth-degree perineal lacerations and cervical lacerations in a contemporary U.S. obstetric practice. METHODS: The Consortium on Safe Labor collected electronic medical records from 19 hospitals within 12 institutions (228,668 deliveries from 2002 to 2008). Information on patient characteristics, prenatal complications, labor and delivery data, and maternal and neonatal outcomes were collected. Only women with successful vaginal deliveries of cephalic singletons at 34 weeks of gestation or later were included; we excluded data from sites lacking information about lacerations at delivery and deliveries complicated by shoulder dystocia; 87,267 and 71,170 women were analyzed for third-or fourth-degree and cervical lacerations, respectively. Multivariable logistic regressions were used to adjust for other factors. RESULTS: Third-or fourth-degree lacerations occurred in 2,516 women (2,223 nulliparous [5.8%], 293 [0.6%] multiparous) and cervical lacerations occurred in 536 women (324 nulliparous [1.1%], 212 multiparous [0.5%]). Risks for third-or fourth-degree lacerations included nulliparity (7.2-fold risk), being Asian or Pacific Islander, increasing birth weight, operative vaginal delivery, episiotomy, and longer second stage of labor. Increasing body mass index was associated with fewer lacerations. Risk factors for cervical lacerations included young maternal age, vacuum vaginal delivery, and oxytocin use among multiparous women, and cerclage regardless of parity. CONCLUSION: Our large cohort of women with severe obstetric lacerations reflects contemporary obstetric practices. Nulliparity and episiotomy use are important risk factors for third-or fourth-degree lacerations. Cerclage increases the risk for cervical lacerations. Many identified risk factors may not be modifiable. (Obstet Gynecol 2011;117:627-35) DOI:10.1097/AOG.0b013e31820afaf2 C1 [Landy, Helain J.] Georgetown Univ Hosp, Dept Obstet & Gynecol, MedStar Hlth, Washington, DC 20007 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. Indiana Univ Clarian Hlth, Indianapolis, IN USA. Univ Miami, Miami, FL USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Maimonides Hosp, Brooklyn, NY 11219 USA. Univ Illinois, Chicago, IL USA. Intermt Healthcare, Salt Lake City, UT USA. Tufts Univ, Baystate Med Ctr, Springfield, MA USA. Christiana Care Hlth Syst, Newark, DE USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Akron City Hosp, Summa Hlth Syst, Akron, OH USA. EMMES Corp, Rockville, MD USA. Univ Utah, Salt Lake City, UT USA. RP Landy, HJ (reprint author), Georgetown Univ Hosp, Dept Obstet & Gynecol, MedStar Hlth, 3800 Reservoir Rd,NW 3PHC, Washington, DC 20007 USA. EM landyh@gunet.georgetown.edu OI Grantz, Katherine/0000-0003-0276-8534 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through a contract (number HHSN267200603425C). NR 26 TC 50 Z9 52 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2011 VL 117 IS 3 BP 627 EP 635 DI 10.1097/AOG.0b013e31820afaf2 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 725MR UT WOS:000287649400016 PM 21343766 ER PT J AU Castle, PE Fetterman, B Poitras, N Lorey, T Shaber, R Schiffman, M Demuth, F Kinney, W AF Castle, Philip E. Fetterman, Barbara Poitras, Nancy Lorey, Thomas Shaber, Ruth Schiffman, Mark Demuth, Franklin Kinney, Walter TI Variable Risk of Cervical Precancer and Cancer After a Human Papillomavirus-Positive Test SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NEOPLASIA; CYTOLOGY; TRIAL; WOMEN AB OBJECTIVE: To explore the effect of screening history on the risk of cervical precancer and cancer after an human papillomavirus (HPV)-positive test. METHODS: A large health maintenance organization introduced cytology and HPV cotesting into routine clinical practice in 2003. We selected women aged 30 and older who tested HPV positive, cytology negative between January 2006 and December 2008 who had any clinical follow-up documented before January 2010 (n=26,799). The 1-year and 4-year cumulative incidence rates and rate ratios for cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) with 95% confidence intervals (95% CIs) were calculated as estimates of absolute risk and relative risk, respectively. Results were stratified on immediate past HPV test and Pap results. RESULTS: Without consideration of past screening round, the 1-year and 4-year cumulative incidence rates for CIN 2+ after an HPV-positive, Pap-negative result were 2.83 (95% CI 2.55-3.12) and 7.89 (95% CI 7.00-8.78). However, risks varied substantially by past screening result. For example, the 4-year risk of CIN2+ was greater for women who had a past HPV-positive, Pap-negative result (cumulative incidence rate=11.79, 95% CI 10.22-13.36) compared with those who had HPV-negative, Pap-negative result (cumulative incidence rate=4.56, 95% CI 3.43-5.69; cumulative incidence rate ratio=2.59, 95% CI 2.30-2.87). CONCLUSION: Because cervical precancer is associated with persistent HPV infection, the risk associated with an HPV-positive test can vary significantly depending on the immediate past screening round. Optimizing screening programs will require knowledge of screening history. (Obstet Gynecol 2011;117:650-6) DOI:10.1097/AOG.0b013e318209da59 C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Kaiser Permanente No Calif, Reg Lab, Berkeley, CA USA. Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA. Womens Hlth Res Inst, Oakland, CA USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Room 5026,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU National Institutes of Health (NIH), National Cancer Institute; Women's Health Research Institute at Kaiser Permanente Northern California FX Supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, and Women's Health Research Institute at Kaiser Permanente Northern California. Drs. Castle and Schiffman were supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 21 TC 8 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAR PY 2011 VL 117 IS 3 BP 650 EP 656 DI 10.1097/AOG.0b013e318209da59 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 725MR UT WOS:000287649400019 PM 21343769 ER PT J AU Yauger, B Boggs, NA Dean, J AF Yauger, Belinda Boggs, Nathan A. Dean, Jurrien TI Human ZP4 is not sufficient for taxon-specific sperm recognition of the zona pellucida in transgenic mice SO REPRODUCTION LA English DT Article ID MONOCLONAL-ANTIBODIES; HUMAN SPERMATOZOA; GLYCOPROTEIN-B; MOUSE EGGS; O-GLYCANS; BINDING; FERTILIZATION; MURINE; EXPRESSION; FERTILITY AB The molecular basis of human fertilization remains enigmatic. Mouse models are often used to study sperm-egg recognition, but the mouse zona pellucida surrounding ovulated eggs contains three proteins (ZP1, ZP2, and ZP3) whereas the human zona contains four (ZP1, ZP2, ZP3, and ZP4). Human sperm are fastidious and recognize human but not mouse eggs. Transgenic mouse lines were established to ascertain whether human ZP4 is the sole determinant of human sperm binding. Human ZP4 expressed in transgenic mice had a molecular mass similar to the range of native protein isoforms and was incorporated into the extracellular zona matrix. Transgenic females were fertile with normal litter sizes. Mouse sperm readily recognized transgenic ovulated eggs, but human sperm did not. We conclude that human ZP4 is not sufficient to support human sperm binding to the zona pellucida in transgenic mice and that other zona proteins may be needed for human gamete recognition. Reproduction (2011) 141 313-319 C1 [Boggs, Nathan A.; Dean, Jurrien] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. [Yauger, Belinda] Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD 20892 USA. RP Dean, J (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM jurrien@helix.nih.gov FU Combined Federal Fellowship in Reproductive Endocrinology and Infertility; National Institutes of Health, NIDDK, Bethesda, MD FX Dr B Yauger was supported by the Combined Federal Fellowship in Reproductive Endocrinology and Infertility, and this research was supported by the Intramural Research Program of the National Institutes of Health, NIDDK, Bethesda, MD. NR 38 TC 10 Z9 10 U1 0 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD MAR PY 2011 VL 141 IS 3 BP 313 EP 319 DI 10.1530/REP-10-0241 PG 7 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 724JP UT WOS:000287572200003 PM 21173071 ER PT J AU Giggey, PP Wendell, CR Zonderman, AB Waldstein, SR AF Giggey, Paul P. Wendell, Carrington R. Zonderman, Alan B. Waldstein, Shari R. TI Greater Coffee Intake in Men Is Associated With Steeper Age-Related Increases in Blood Pressure SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; caffeine; coffee; hypertension; pulse pressure ID HABITUAL CAFFEINE CONSUMPTION; HYPERTENSION; RISK; HOMOCYSTEINE; METAANALYSIS; DRINKING; DISEASE; STRESS; MODELS; TRIALS AB BACKGROUND Administration of caffeine or caffeinated coffee in laboratory and ambulatory settings results in small to moderate acute increases in blood pressure (BP). However, habitual coffee intake has not been linked conclusively to long-term increases in basal BP, and findings are inconsistent by sex. This study examined longitudinal relations of habitual coffee use to resting BP and pulse pressure. METHODS In a sample of 2,442 participants from the Baltimore Longitudinal Study of Aging (BLSA), coffee consumption was used to predict resting systolic and diastolic BP and pulse pressure using longitudinal mixed-effects regression models adjusted for age, education, antihypertensive, and antihyperlipidemic use, smoking, and body mass index (BMI). Analyses were stratified by sex (865 women and 1,577 men), and age and BMI were examined as possible effect modifiers. RESULTS In men, we identified a significant three-way interaction among coffee intake (nonlinear), baseline age, and length of follow-up for systolic BP (SBP) and pulse pressure. A significant interaction of coffee intake and BMI (nonlinear) was also noted for SBP in men. There were no significant relations of coffee intake to BP or pulse pressure in women. CONCLUSION Greater coffee intake in men was associated with steeper age-related increases in SBP and pulse pressure, particularly beyond 70 years of age and in overweight to obese men. C1 [Giggey, Paul P.; Wendell, Carrington R.; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. [Wendell, Carrington R.; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Waldstein, Shari R.] Univ Maryland, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Baltimore, MD 21201 USA. [Waldstein, Shari R.] Baltimore VA Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. RP Waldstein, SR (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. EM waldstei@umbc.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 33 TC 5 Z9 6 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0895-7061 EI 1941-7225 J9 AM J HYPERTENS JI Am. J. Hypertens. PD MAR PY 2011 VL 24 IS 3 BP 310 EP 315 DI 10.1038/ajh.2010.225 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 721VW UT WOS:000287386900012 PM 21088672 ER PT J AU Simino, J Shi, G Kume, R Schwander, K Province, MA Gu, CC Kardia, S Chakravarti, A Ehret, G Olshen, RA Turner, ST Ho, LT Zhu, XF Jaquish, C Paltoo, D Cooper, RS Weder, A Curb, JD Boerwinkle, E Hunt, SC Rao, DC AF Simino, Jeannette Shi, Gang Kume, Rezart Schwander, Karen Province, Michael A. Gu, C. Charles Kardia, Sharon Chakravarti, Aravinda Ehret, Georg Olshen, Richard A. Turner, Stephen T. Ho, Low-Tone Zhu, Xiaofeng Jaquish, Cashell Paltoo, Dina Cooper, Richard S. Weder, Alan Curb, J. David Boerwinkle, Eric Hunt, Steven C. Rao, Dabeeru C. TI Five Blood Pressure Loci Identified by an Updated Genome-Wide Linkage Scan: Meta-Analysis of the Family Blood Pressure Program SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; genetics; hypertension; linkage; meta-analysis; QTL ID QUANTITATIVE-TRAIT LOCUS; ANTIHYPERTENSIVE THERAPY; MYOCARDIAL-INFARCTION; HYPERTENSION; MARKERS; GENES; FBPP; CHROMOSOME-6; ASSOCIATION; COMPLEX AB BACKGROUND A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension. METHODS We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups. RESULTS Five quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score >= 3) in at least one meta-analysis and lod scores in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. CONCLUSIONS The new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance. C1 [Simino, Jeannette; Shi, Gang; Kume, Rezart; Schwander, Karen; Gu, C. Charles; Rao, Dabeeru C.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Province, Michael A.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63110 USA. [Kardia, Sharon] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Chakravarti, Aravinda; Ehret, Georg] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Ehret, Georg] Univ Lausanne Hosp, Inst Social & Prevent Med, Geneva, Switzerland. [Ehret, Georg] Univ Hosp Geneva, Ctr Cardiol, Geneva, Switzerland. [Olshen, Richard A.] Stanford Univ, Div Biostat, Stanford, CA 94305 USA. [Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Ho, Low-Tone] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei, Taiwan. [Zhu, Xiaofeng] Case Western Reserve Univ, Dept Biostat & Epidemiol, Cleveland, OH 44106 USA. [Jaquish, Cashell; Paltoo, Dina] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Cooper, Richard S.] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA. [Weder, Alan] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Curb, J. David] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Honolulu, HI 96822 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Hunt, Steven C.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. RP Rao, DC (reprint author), Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. EM rao@wubios.wustl.edu RI EHRET, Georg/A-9532-2009; Shi, Gang/D-3301-2016; Gu, Charles/A-7934-2010 OI EHRET, Georg/0000-0002-5730-0675; Gu, Charles/0000-0002-8527-8145 FU National Heart, Lung, and Blood Institute [T32 HL091823, U01 HL54473, U10 HL054512, R01 HL086694, R21 HL095054] FX We thank all the participants in GenNet, GENOA, HyperGEN, and SAPPHIRe. A complete list of FBPP investigators may be found at: http://www.biostat.wustl.edu/fbpp/Acknowledgments.html. This research was partly supported by grants T32 HL091823, U01 HL54473, U10 HL054512, R01 HL086694, and R21 HL095054 from the National Heart, Lung, and Blood Institute. NR 39 TC 15 Z9 15 U1 0 U2 5 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 MAR PY 2011 VL 24 IS 3 BP 347 EP 354 DI 10.1038/ajh.2010.238 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 721VW UT WOS:000287386900018 PM 21151011 ER PT J AU Barnett, JH Xu, K Heron, J Goldman, D Jones, PB AF Barnett, Jennifer H. Xu, Ke Heron, Jon Goldman, David Jones, Peter B. TI Cognitive Effects of Genetic Variation in Monoamine Neurotransmitter Systems: A Population-Based Study of COMT, MAOA, and 5HTTLPR SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; cognition; serotonin; dopamine ID CATECHOL-O-METHYLTRANSFERASE; SEROTONIN TRANSPORTER GENE; OBSESSIVE-COMPULSIVE DISORDER; ACUTE TRYPTOPHAN DEPLETION; MESSENGER-RNA EXPRESSION; HUMAN PREFRONTAL CORTEX; HUMAN BRAIN; OXIDASE-A; DECISION-MAKING; FUNCTIONAL POLYMORPHISM AB Individual differences in cognitive function are highly heritable and most likely driven by multiple genes of small effect. Well-characterized common functional polymorphisms in the genes MAOA, COMT, and 5HTTLPR each have predictable effects on the availability of the monoamine neurotransmitters dopamine, noradrenaline, and serotonin. We hypothesized that 5HTTLPR genotype would show little association with prefrontal cognitive performance, but that COMT and MAOA would have interacting effects on cognition through their shared influence on prefrontal catecholamine availability. We assessed the individual and epistatic effects of functional polymorphisms in COMT, MAOA, and 5HTTLPR on children's prefrontal cognitive function in nearly 6,000 children from the population-based Avon Longitudinal Study of Parents and Children (ALSPAC). Neither MAOA nor 5HTTLPR polymorphisms showed significant effects on cognitive function. In boys but not girls, there was a modest but statistically significant interaction between MAOA and COMT genotypes such that increased prefrontal catecholamine availability was associated with better working memory. These results suggest that assessment of multiple genes within functionally related systems may improve our understanding of the genetic basis of cognition. (C) 2010 Wiley-Liss, Inc. C1 [Barnett, Jennifer H.; Jones, Peter B.] Univ Cambridge, Dept Psychiat, Cambridge, England. [Barnett, Jennifer H.] Cambridge Cognit Ltd, Cambridge, England. [Xu, Ke] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Heron, Jon] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. [Jones, Peter B.] MRC Wellcome Trust Behav & Clin Neurosci Inst BCN, Cambridge, England. RP Barnett, JH (reprint author), Addenbrookes Hosp, Dept Psychiat, Box 189, Cambridge CB2 2QQ, England. EM jhb32@cam.ac.uk RI Heron, Jon/D-5884-2011; Goldman, David/F-9772-2010 OI Jones, Peter/0000-0002-0387-880X; Heron, Jon/0000-0001-6199-5644; Goldman, David/0000-0002-1724-5405 FU Wellcome Trust [074296/Z/04/Z]; NIHR CLAHRC for Cambridgeshire Peterborough; GlaxoSmithKline; Stanley Medical Research Institute; Parke Davis Exchange Fellowship FX Grant sponsor: Wellcome Trust; Grant Number: 074296/Z/04/Z; Grant sponsor: NIHR CLAHRC for Cambridgeshire & Peterborough.; Dr. Barnett is an employee of Cambridge Cognition Ltd and a co-inventor on patent PCT/GB2005/003279 (methods for assessing psychotic disorders) with Dr. Jones. Dr. Jones has also received research grant support from GlaxoSmithKline and has received a speaker's honorarium from Eli Lilly. Dr. Heron, Dr. Goldman, and Dr. Xu report no competing interests.; The authors thank all of the families who participated in the study, the midwives for their help in recruiting the families, and the entire Avon Longitudinal Study of Parents and Children team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. Core support for the Avon Longitudinal Study of Parents and Children is provided by the UK Medical Research Council, the Wellcome Trust, and the University of Bristol. Dr. Barnett was funded by the Stanley Medical Research Institute and the Parke Davis Exchange Fellowship. Dr. Jones receives funding from the Wellcome Trust (grant number 074296/Z/04/Z); this work forms part of the NIHR CLAHRC for Cambridgeshire & Peterborough. NR 80 TC 18 Z9 19 U1 2 U2 9 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 MAR PY 2011 VL 156B IS 2 BP 158 EP 167 DI 10.1002/ajmg.b.31150 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 718VQ UT WOS:000287154900005 PM 21302344 ER PT J AU Wira, CR Veronese, F AF Wira, Charles R. Veronese, Fulvia TI Mucosal Immunity in the Male and Female Reproductive Tract and Prevention of HIV transmission SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Editorial Material C1 [Wira, Charles R.] Dartmouth Med Sch, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA. [Veronese, Fulvia] NIAID, DAIDS, NIH, DHHS, Bethesda, MD 20892 USA. RP Wira, CR (reprint author), Dartmouth Med Sch, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA. EM Charles.R.Wira@Dartmouth.edu; veronesf@od.nih.gov FU NIAID NIH HHS [R01 AI102838, R13 AI106495] NR 0 TC 4 Z9 4 U1 0 U2 4 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 MAR PY 2011 VL 65 IS 3 BP 182 EP 185 DI 10.1111/j.1600-0897.2010.00976.x PG 4 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 717IP UT WOS:000287037200002 PM 21294802 ER PT J AU Jo, JO Kang, YJ Ock, MS Kleinman, HK Chang, HK Cha, HJ AF Jo, Jin-Ok Kang, Yun-Jeong Ock, Mee Sun Kleinman, Hynda K. Chang, Hee-Kyung Cha, Hee-Jae TI Thymosin beta 4 Expression in Human Tissues and in Tumors Using Tissue Microarrays SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE thymosin beta 4; human cancer; normal tissue; immunohistochemistry; tissue microarray ID ACTIN-SEQUESTERING PROTEIN; INTEGRIN-LINKED KINASE; DIFFERENTIAL EXPRESSION; COLORECTAL-CARCINOMA; CELL-MIGRATION; RAT CEREBELLUM; HUMAN-BRAIN; BETA(4); METASTASIS; GENE AB Thymosin beta 4 has been reported to play the key roles in tumor growth, metastasis, and angiogenesis. Although the importance of thymosin beta 4 in angiogenesis and metastasis is known, few studies to show the expression patterns of thymosin beta 4 in human tissues including tumors have been conducted. The comparisons of the expression of thymosin beta 4 between the normal and tumor tissues are also needed to study the role of thymosin beta 4 in tumor formation. Using tissue microarray analysis, we compared the expression patterns of thymosin beta 4 in the normal human tissues and in the tumors to screen certain tumors and upregulated the expression of thymosin beta 4 by tumorigenesis. Thymosin beta 4 was highly expressed in the hepatic cells in the normal adult liver, duct, and acinar cells in pancreas, and muscle cells in the heart and also expressed highly in certain tumor cells, including osteosarcoma, colon adenocarcinoma, esophageal squamous cell carcinoma, kidney and urinary bladder transitional carcinoma, lung cancer, and liver cancer. Comparing the thymosin beta 4 expression between normal and tumors, thymosin beta 4 was upregulated specifically in osteosarcoma, colorectal carcinoma, and esophageal cancer. To confirm the over-expression of thymosin beta 4 in these tumors, we analyzed expression of thymosin beta 4 with each additional microarray of osteosarcoma, colorectal carcinoma, and esophageal cancer. The significant increased expression of thymosin beta 4 was observed in osteosarcoma and in colorectal cancer. These results suggest that the expression of thymosin beta 4 is highly related with tumorigenesis of certain tumors including the osteosarcoma and colorectal cancers. C1 [Jo, Jin-Ok; Kang, Yun-Jeong; Ock, Mee Sun; Cha, Hee-Jae] Kosin Univ, Coll Med, Dept Parasitol & Genet, Pusan 602703, South Korea. [Chang, Hee-Kyung] Kosin Univ, Coll Med, Dept Pathol, Pusan 602703, South Korea. [Cha, Hee-Jae] Kosin Univ, Coll Med, Inst Med Sci, Pusan 602703, South Korea. [Kleinman, Hynda K.] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Cha, HJ (reprint author), Kosin Univ, Coll Med, Dept Parasitol & Genet, 34 Annam Dong, Pusan 602703, South Korea. EM hcha@kosin.ac.kr FU Korean Government [KRF-20090066740]; Cancer Institute, Kosin University College of Medicine FX This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-20090066740) and the grant of Cancer Institute, Kosin University College of Medicine (2008). NR 42 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 2011 VL 19 IS 2 BP 160 EP 167 DI 10.1097/PAI.0b013e3181f12237 PG 8 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 719GO UT WOS:000287190000012 PM 20975530 ER PT J AU Lo, KS Wilson, JG Lange, LA Folsom, AR Galarneau, G Ganesh, SK Grant, SFA Keating, BJ McCarroll, SA Mohler, ER O'Donnell, CJ Palmas, W Tang, WH Tracy, RP Reiner, AP Lettre, G AF Lo, Ken Sin Wilson, James G. Lange, Leslie A. Folsom, Aaron R. Galarneau, Genevieve Ganesh, Santhi K. Grant, Struan F. A. Keating, Brendan J. McCarroll, Steven A. Mohler, Emile R., III O'Donnell, Christopher J. Palmas, Walter Tang, Weihong Tracy, Russell P. Reiner, Alexander P. Lettre, Guillaume TI Genetic association analysis highlights new loci that modulate hematological trait variation in Caucasians and African Americans SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LINKAGE-DISEQUILIBRIUM; BETA-THALASSEMIA; HEMOGLOBIN; HAPLOTYPE; VARIANTS; METAANALYSIS; POPULATION; DEFICIENCY; CONSORTIUM AB Red blood cell, white blood cell, and platelet measures, including their count, sub-type and volume, are important diagnostic and prognostic clinical parameters for several human diseases. To identify novel loci associated with hematological traits, and compare the architecture of these phenotypes between ethnic groups, the CARe Project genotyped 49,094 single nucleotide polymorphisms (SNPs) that capture variation in similar to 2,100 candidate genes in DNA of 23,439 Caucasians and 7,112 African Americans from five population-based cohorts. We found strong novel associations between erythrocyte phenotypes and the glucose-6 phosphate dehydrogenase (G6PD) A-allele in African Americans (rs1050828, P < 2.0 x 10(-13), T-allele associated with lower red blood cell count, hemoglobin, and hematocrit, and higher mean corpuscular volume), and between platelet count and a SNP at the tropomyosin-4 (TPM4) locus (rs8109288, P = 3.0 x 10(-7) in Caucasians; P = 3.0 x 10(-7) in African Americans, T-allele associated with lower platelet count). We strongly replicated many genetic associations to blood cell phenotypes previously established in Caucasians. A common variant of the alpha-globin (HBA2-HBA1) locus was associated with red blood cell traits in African Americans, but not in Caucasians (rs1211375, P < 7 x 10(-8), A-allele associated with lower hemoglobin, mean corpuscular hemoglobin, and mean corpuscular volume). Our results show similarities but also differences in the genetic regulation of hematological traits in European- and African-derived populations, and highlight the role of natural selection in shaping these differences. C1 [Lo, Ken Sin; Galarneau, Genevieve; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Wilson, James G.] GV Sonny Montgomery VA Med Ctr, Dept Med, Jackson, MS 39216 USA. [Wilson, James G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Folsom, Aaron R.; Tang, Weihong] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA. [Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Grant, Struan F. A.; Keating, Brendan J.] Childrens Hosp Philadelphia, Res Inst, Ctr Appl Genom, Div Human Genet, Philadelphia, PA 19104 USA. [Grant, Struan F. A.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [McCarroll, Steven A.] Seven Cambridge Ctr, Broad Inst, Cambridge, MA 02142 USA. [Mohler, Emile R., III] Univ Penn, Sch Med, Dept Med, Vasc Med Sect,Cardiovasc Div, Philadelphia, PA 19104 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA 01702 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Palmas, Walter] Columbia Univ, Dept Med, New York, NY 10032 USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT 05446 USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT 05446 USA. [Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Lettre, G (reprint author), Montreal Heart Inst, 5000 Belanger St, Montreal, PQ H1T 1C8, Canada. EM apreiner@u.washington.edu; guillaume.lettre@mhi-humangenetics.org FU National Heart, Lung, and Blood Institute FX The authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The grants and contracts that have supported CARe are listed at http://public.nhlbi.nih.gov/GeneticsGenomics/home/care.aspx. Additional support for this work was provided by the Fondation de l'Institut de Cardiologie de Montreal (to G. L.), and by NIH R01 HL71862-06 and ARRA N000949304 (to A. P. R.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 39 Z9 39 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 2011 VL 129 IS 3 BP 307 EP 317 DI 10.1007/s00439-010-0925-1 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 719NJ UT WOS:000287211200008 PM 21153663 ER PT J AU Johnson, L Ousley, A Swarz, J Bingham, RJ Erickson, JB Ellis, S Moody, T AF Johnson, Lenora Ousley, Anita Swarz, Jeffrey Bingham, Raymond J. Erickson, J. Bianca Ellis, Steven Moody, Terra TI The Art and Science of Cancer Education and Evaluation: Toward Facilitating Improved Patient Outcomes SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Cancer education; Educational methodology; Research methodology; Evaluation; Effectiveness; Scientific rigor AB Cancer education is a constantly evolving field, as science continues to advance both our understanding of cancer and its effects on patients, families, and communities. Moving discoveries to practice expeditiously is paramount to impacting cancer outcomes. The continuing education of cancer care professionals throughout their practice life is vital to facilitating the adoption of therapeutic innovations. Meanwhile, more general educational programs serve to keep cancer patients, their families, and the public informed of the latest findings in cancer research. The National Cancer Institute conducted an assessment of the current knowledge base for cancer education which involved two literature reviews, one of the general literature of the evaluation of medical and health education efforts, and the other of the preceding 5 years of the Journal of Cancer Education (JCE). These reviews explored a wide range of educational models and methodologies. In general, those that were most effective used multiple methodologies, interactive techniques, and multiple exposures over time. Less than one third of the articles in the JCE reported on a cancer education or communication product, and of these, only 70% had been evaluated for effectiveness. Recommendations to improve the evaluation of cancer education and the educational focus of the JCE are provided. C1 [Johnson, Lenora; Ousley, Anita; Swarz, Jeffrey] NCI, Off Commun & Educ, NIH, DHHS, Bethesda, MD 20892 USA. [Bingham, Raymond J.] NINR, Off Sci Policy & Publ Liaison, Bethesda, MD 20892 USA. [Erickson, J. Bianca; Ellis, Steven] Univ Massachusetts, Donahue Inst, Amherst, MA 01003 USA. [Moody, Terra] Univ Alabama, Coll Commun & Informat Sci, Tuscaloosa, AL USA. RP Johnson, L (reprint author), NCI, Off Commun & Educ, NIH, DHHS, 6116 Execut Blvd,Suite 407, Bethesda, MD 20892 USA. EM johnslen@mail.nih.gov NR 12 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD MAR PY 2011 VL 26 IS 1 BP 27 EP 35 DI 10.1007/s13187-010-0147-1 PG 9 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 723JN UT WOS:000287502900006 PM 20953858 ER PT J AU Perocchia, RS Hodorowski, JK Williams, LA Kornfeld, J Davis, NL Monroe, M Bright, MA AF Perocchia, Rosemarie Slevin Hodorowski, Julie Keany Williams, Laurie A. Kornfeld, Julie Davis, Nydia Lassalle Monroe, MaryAnn Bright, Mary Anne TI Patient-Centered Communication in Cancer Care: The Role of the NCI's Cancer Information Service SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Patient-centered communication; Health care; NCI; Cancer Information Service (CIS); Patient-centered care; Clinician-patient communication ID CLINICAL COMMUNICATION; DECISION-MAKING; SKILLS; ONCOLOGY; OUTCOMES; FUTURE; TRIAL; MODEL AB While patient-centered care and the reduction of suffering due to cancer are primary goals of the NCI, improvement in the delivery of patient-centered communication has been identified as a key NCI research priority. As research on patient-centered communication evolves, the potential contributions of programs such as the National Cancer Institute's (NCI) Cancer Information Service (CIS) cannot be overlooked. The purpose of this paper is to describe how the six core functions of patient-clinician communication described in the literature (fostering healing relationships, exchanging information, responding to emotions, managing uncertainty, making decisions and enabling patient-self management) are embedded in the work of the CIS. The communication process used by the CIS to extend the patient-centered communication role of the clinician will be discussed. CIS training and quality management systems will be described. Lastly, suggestions for the role of CIS in future health information delivery and research will be explored. C1 [Perocchia, Rosemarie Slevin; Hodorowski, Julie Keany; Williams, Laurie A.; Davis, Nydia Lassalle] Mem Sloan Kettering Canc Ctr, New York Reg Canc Informat Serv, New York, NY 10065 USA. [Monroe, MaryAnn; Bright, Mary Anne] NCI, Canc Informat Serv, NIH, Bethesda, MD 20892 USA. [Kornfeld, Julie] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Coastal Reg Canc Informat Serv, Miami, FL 33136 USA. RP Perocchia, RS (reprint author), Mem Sloan Kettering Canc Ctr, New York Reg Canc Informat Serv, 1275 York Ave,Box 166, New York, NY 10065 USA. EM perocchr@mskcc.org OI Hodorowski, Julie/0000-0003-3587-2135 FU National Cancer Institute [NO2-CO-51101] FX This work has been supported by the National Cancer Institute contract NO2-CO-51101. NR 29 TC 11 Z9 11 U1 3 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD MAR PY 2011 VL 26 IS 1 BP 36 EP 43 DI 10.1007/s13187-010-0121-y PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 723JN UT WOS:000287502900007 PM 20532726 ER PT J AU March, ME Long, EO AF March, Michael E. Long, Eric O. TI beta(2) Integrin Induces TCR zeta-Syk-Phospholipase C-gamma Phosphorylation and Paxillin-Dependent Granule Polarization in Human NK Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MICROTUBULE-ORGANIZING CENTER; PROTEIN-TYROSINE KINASES; RECEPTOR CROSS-LINKING; FC-EPSILON-RI; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; LEUKOCYTE EMIGRATION; CYTOPLASMIC DOMAINS; HUMAN NEUTROPHILS AB Cytotoxic lymphocytes kill target cells through polarized release of the content of lytic granules at the immunological synapse. In human NK cells, signals for granule polarization and for degranulation can be uncoupled: Binding of beta(2) integrin LFA-1 to ICAM is sufficient to induce polarization but not degranulation, whereas CD16 binding to IgG triggers unpolarized degranulation. In this study, we investigated the basis for this difference. IL-2-expanded human NK cells were stimulated by incubation with plate-bound ligands of LFA-1 (ICAM-1) and CD16 (human IgG). Surprisingly, LFA-1 elicited signals similar to those induced by CD16, including tyrosine phosphorylation of the TCR zeta-chain, tyrosine kinase Syk, and phospholipase C-gamma. Whereas CD16 activated Ca2+ mobilization and LAT phosphorylation, LFA-1 did not, but induced strong Pyk2 and paxillin phosphorylation. LFA-1-dependent granule polarization was blocked by inhibition of Syk, phospholipase C-gamma, and protein kinase C, as well as by paxillin knockdown. Therefore, common signals triggered by CD16 and LFA-1 bifurcate to provide independent control of Ca2+-dependent degranulation and paxillin-dependent granule polarization. The Journal of Immunology, 2011, 186: 2998-3005. C1 [March, Michael E.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM eLong@nih.gov RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 76 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2011 VL 186 IS 5 BP 2998 EP 3005 DI 10.4049/jimmunol.1002438 PG 8 WC Immunology SC Immunology GA 721LT UT WOS:000287356900037 PM 21270398 ER PT J AU Gadalla, SM Preiss, LR Eyster, ME Goedert, JJ AF Gadalla, S. M. Preiss, L. R. Eyster, M. E. Goedert, J. J. TI Correlates of high hepatitis C virus RNA load in a cohort of HIV-negative and HIV-positive individuals with haemophilia SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE HCV load; HCV; HIV co-infection; haemophilia ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; LIVER-DISEASE; VIRAL LOAD; HCV RNA; ANTIRETROVIRAL THERAPY; SPONTANEOUS CLEARANCE; COINFECTED PATIENTS; PROTEASE INHIBITOR; BLEEDING DISORDERS AB Hepatitis C virus (HCV) treatment failure and disease progression are more likely with high HCV-RNA load. Correlates of high HCV-RNA load in individuals with haemophilia are largely unknown. Among 1266 interferon naive HCV-infected individuals with haemophilia, we compared those with high (> 2 x 106 HCV-RNA copies/mL) to lower viral load, overall and stratifying on HIV co-infection status using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Overall, high HCV load was independently associated with longer duration of HCV infection (P(trend) = 0.0001), body mass index >= 25 kg/m2 (OR = 1.4, 95% CI = 1.1-1.9), and HIV co-infection (OR = 1.4, 95% CI = 1.0-1.8). Among 795 HIV-negative participants, high HCV-RNA load was associated with older age at HCV acquisition (OR = 1.9 for > 15 years vs < 2 years, P(trend) = 0.008), and lower AST/platelet ratio (P(trend) = 0.01), in addition to longer duration of HCV infection (P(trend) = 0.0008), and body mass index >= 25 kg/m2 (OR = 1.6, P = 0.005). Among 471 HIV-positive individuals, anti-retroviral therapy (ART) was the only variable associated with high HCV-RNA load (OR = 1.8, CI = 1.1-2.9 for combination ART; OR = 1.8, CI = 0.9-3.4, for other ART vs no treatment). High HCV-RNA load with haemophilia is more likely with longer duration of infection, older age at infection, higher body mass index, and antiretroviral therapy. These findings may help identify individuals at increased risk of HCV treatment failure and progression to end-stage liver disease. C1 [Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gadalla, S. M.] NIH, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Preiss, L. R.] RTI Int, Rockville, MD 20852 USA. [Eyster, M. E.] Penn State Univ, Div Hematol & Oncol, Dept Med, Coll Med, Hershey, PA 17033 USA. RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Room 7068, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov FU National Cancer Institute (NCI), National Institutes of Health (NIH) [N01-CP-01004, N02-CP-91027]; RTI International FX The MHCS-II is funded by the Intramural Research Program, National Cancer Institute (NCI), National Institutes of Health (NIH) through contracts N01-CP-01004 and N02-CP-91027 with RTI International, with additional support from the National Heart, Lung and Blood Institute, NIH. NR 40 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAR PY 2011 VL 18 IS 3 BP 161 EP 169 DI 10.1111/j.1365-2893.2010.01289.x PG 9 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 718CB UT WOS:000287096400002 PM 20337924 ER PT J AU Stevens, LA Claybon, MA Schmid, CH Chen, J Horio, M Imai, E Nelson, RG Van Deventer, M Wang, HY Zuo, L Zhang, YP Levey, AS AF Stevens, Lesley A. Claybon, Marcie A. Schmid, Christopher H. Chen, Jing Horio, Masaru Imai, Enyu Nelson, Robert G. Van Deventer, Manuel Wang, Hai-Yan Zuo, Li Zhang, Yaping (Lucy) Levey, Andrew S. TI Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating the glomerular filtration rate in multiple ethnicities SO KIDNEY INTERNATIONAL LA English DT Article DE creatinine; ethnicity; glomerular filtration rate ID GFR-ESTIMATING EQUATIONS; SERUM CREATININE; MUSCLE MASS; CYSTATIN-C; ADULTS; AGE AB An equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) provides more accurate estimates of the glomerular filtration rate (eGFR) than that from the modification of diet in renal disease (MDRD) Study, although both include a two-level variable for race (Black and White and other). Since creatinine generation differs among ethnic groups, it is possible that a multilevel ethnic variable would allow more accurate estimates across all groups. To evaluate this, we developed an equation to calculate eGFR that includes a four-level race variable (Black, Asian, Native American and Hispanic, and White and other) using a database of 8254 patients pooled from 10 studies. This equation was then validated in 4014 patients using 17 additional studies from the United States and Europe (validation database), and in 1022 patients from China (675), Japan (248), and South Africa (99). Coefficients for the Black, Asian, and Native American and Hispanic groups resulted in 15, 5, and 1% higher levels of eGFR, respectively, compared with the White and other group. In the validation database, the two-level race equation had minimal bias in Black, Native American and Hispanic, and White and other cohorts. The four-level ethnicity equation significantly improved bias in Asians of the validation data set and in Chinese. Both equations had a large bias in Japanese and South African patients. Thus, heterogeneity in performance among the ethnic and geographic groups precludes use of the four-level race equation. The CKD-EPI two-level race equation can be used in the United States and Europe across a wide range of ethnicity. Kidney International (2011) 79, 555-562; doi: 10.1038/ki.2010.462; published online 24 November 2010 C1 [Stevens, Lesley A.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Chen, Jing] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Horio, Masaru; Imai, Enyu] Osaka Univ, Grad Sch Med, Osaka, Japan. [Nelson, Robert G.] NIDDK, Phoenix, AZ USA. [Van Deventer, Manuel] Univ Witwatersrand, Dept Chem Pathol, Johannesburg, South Africa. [Van Deventer, Manuel] Univ Witwatersrand, NHLS, Johannesburg, South Africa. [Wang, Hai-Yan; Zuo, Li] Peking Univ, Hosp 1, Beijing 100871, Peoples R China. RP Stevens, LA (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM lstevens1@tuftsmedicalcenter.org RI Nelson, Robert/B-1470-2012; OI Schmid, Christopher/0000-0002-0855-5313 FU [UO1 DK 053869]; [UO1 DK 067651]; [UO1 DK 35073] FX This study was supported by grants UO1 DK 053869, UO1 DK 067651, and UO1 DK 35073. NR 28 TC 99 Z9 103 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2011 VL 79 IS 5 BP 555 EP 562 DI 10.1038/ki.2010.462 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 721KR UT WOS:000287353000011 PM 21107446 ER PT J AU Kuranov, AB Mukhamedyarov, DA Momynaliev, KT AF Kuranov, A. B. Mukhamedyarov, D. A. Momynaliev, K. T. TI Identification of new HLA-DRB1 alleles in Kazakh individuals SO TISSUE ANTIGENS LA English DT Editorial Material DE DNA sequencing; human leukocyte antigen-DRB 1; new allele C1 [Momynaliev, K. T.] Res Inst Physicochem Med, Moscow 119992, Russia. [Kuranov, A. B.; Mukhamedyarov, D. A.; Momynaliev, K. T.] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Momynaliev, KT (reprint author), Res Inst Physicochem Med, Malaya Pirogovskaya 1A, Moscow 119992, Russia. EM dhoroshun@gmail.com NR 5 TC 3 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-2815 EI 1399-0039 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAR PY 2011 VL 77 IS 3 BP 263 EP U4 DI 10.1111/j.1399-0039.2010.01611.x PG 2 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 718AT UT WOS:000287092600019 PM 21299539 ER PT J AU Loomba, R Rivera, MM McBurney, R Park, Y Haynes-Williams, V Rehermann, B Alter, HJ Herrine, SK Liang, TJ Hoofnagle, JH Heller, T AF Loomba, R. Rivera, M. M. McBurney, R. Park, Y. Haynes-Williams, V. Rehermann, B. Alter, H. J. Herrine, S. K. Liang, T. J. Hoofnagle, J. H. Heller, T. TI The natural history of acute hepatitis C: clinical presentation, laboratory findings and treatment outcomes SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INTERFERON-ALPHA THERAPY; VIRUS-INFECTION; UNITED-STATES AB P>Background Acute hepatitis C has variable modes of presentation and frequently results in chronic infection. Its optimal management has yet to be defined. Aim To establish natural history and complications of treatment of acute hepatitis C. Methods Data from all patients presenting with acute hepatitis C to the National Institutes of Health between 1994 and 2007 were reviewed. Results Twenty-five patients were identified. Symptoms were reported by 80% and jaundice by 40%. Aminotransferase levels and hepatitis C virus (HCV) RNA levels fluctuated greatly; 18% of patients were intermittently negative for HCV RNA. Five patients recovered spontaneously whereas 20 developed chronicity or received interferon-based therapy during the acute phase. Among 15 patients treated during the acute phase with peginterferon with or without ribavirin for 24 weeks, all became HCV RNA negative within 4-8 weeks, and all except two (HIV-positive) achieved a sustained virological response. Side effects (particularly psychiatric) were common and limited treatment in 30%. Conclusions Among 25 patients with acute HCV infection, fluctuating illness was common and spontaneous recovery occurred in only 20%. Anti-viral treatment with a 24-week course of peginterferon and ribavirin was highly effective, but marked by frequent and severe side effects. C1 [Loomba, R.; Rivera, M. M.; Park, Y.; Haynes-Williams, V.; Rehermann, B.; Liang, T. J.; Hoofnagle, J. H.; Heller, T.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Alter, H. J.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. [Herrine, S. K.] Thomas Jefferson Univ Hosp, Dept Med, Philadelphia, PA 19107 USA. RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10-9B-16,MSC 1800,10 Ctr Dr, Bethesda, MD 20892 USA. EM theller@nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases [Z01 DK054514-02 LDB]; Clinical Center, National Institutes of Health, Bethesda, MD FX We thank the patients for participating in the study. The assistance of the staff in the department of transfusion medicine, in particular June Germain, is much appreciated. We also thank Theresa Kennedy for expert blood drawing and shipping. Declaration of personal interests: None. Declaration of funding interests: This research was supported by the intramural research programme of the National Institute of Diabetes and Digestive and Kidney Diseases (Z01 DK054514-02 LDB) and the Clinical Center, National Institutes of Health, Bethesda, MD. NR 19 TC 30 Z9 31 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD MAR PY 2011 VL 33 IS 5 BP 559 EP 565 DI 10.1111/j.1365-2036.2010.04549.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 710KS UT WOS:000286511100006 PM 21198704 ER PT J AU Gawron, AJ Fought, AJ Lissowska, J Ye, WM Zhang, XA Chow, WH Freeman, LEB Hou, LF AF Gawron, Andrew J. Fought, Angela J. Lissowska, Jolanta Ye, Weimin Zhang, Xiao Chow, Wong-Ho Freeman, Laura E. Beane Hou, Lifang TI Polymorphisms in chemokine and receptor genes and gastric cancer risk and survival in a high risk Polish population SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Chemokine; gastric cancer; single nucleotide polymorphisms; survival ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HELICOBACTER-PYLORI INFECTION; STOMACH-CANCER; CARDIA ADENOCARCINOMA; OVARIAN-CANCER; UP-REGULATION; CARCINOMA; CELL; SUSCEPTIBILITY; EXPRESSION AB Objective. To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival. Methods. The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994--1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models. Results. Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1++151 G > T (rs2734648), IVS2++80 C > T (rs1800024) and minor allele of IVS1++246 A > G (rs1799987) was associated with a borderline significantly increased risk (OR == 1.5, 95% CI: 1.0--2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2++241 G > A (rs1799864) (HR == 1.5, 95% CI: 1.1--2.1) and CCR5 IVS2++80 C > T (rs1800024) (HR == 1.5, 95% CI: 1.1--2.1). Carriers of the CCR5 minor allele of IVS1++151 G > T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR == 0.8, 95% CI: 0.6--1.0). Conclusions. Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies. C1 [Gawron, Andrew J.; Fought, Angela J.; Zhang, Xiao; Hou, Lifang] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Gawron, Andrew J.] Northwestern Univ, Div Gastroenterol, Feinberg Sch Med, Chicago, IL 60611 USA. [Fought, Angela J.; Hou, Lifang] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Chow, Wong-Ho; Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. RP Gawron, AJ (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM agawron@northwestern.edu RI zhang, xiao/B-3947-2010; Gawron, Andrew/H-4479-2013; Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Lissowska, Jolanta/0000-0003-2695-5799 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; Feinberg School of Medicine, Northwestern University FX This study was supported, in part, by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. Salary support (AJG) was provided by the Physician Scientist Training Program of the Feinberg School of Medicine, Northwestern University. We would also like to thank Jason Sinnwell (Mayo Clinic, Rochester, MN) for his assistance with Haplo Stats. NR 52 TC 12 Z9 13 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD MAR PY 2011 VL 46 IS 3 BP 333 EP 340 DI 10.3109/00365521.2010.537679 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 717JI UT WOS:000287039100013 PM 21091093 ER PT J AU Yao, JH Dwyer, A Summers, RM Mollura, DJ AF Yao, Jianhua Dwyer, Andrew Summers, Ronald M. Mollura, Daniel J. TI Computer-aided Diagnosis of Pulmonary Infections Using Texture Analysis and Support Vector Machine Classification SO ACADEMIC RADIOLOGY LA English DT Article DE Computer-aided diagnosis; pulmonary infection; texture analysis ID INFLUENZA-A H1N1; CT FINDINGS; PNEUMONIA; LUNG; VIRUS AB Rationale and Objectives: The purpose of this study was to develop and test a computer-assisted detection method for the identification and measurement of pulmonary abnormalities on chest computed tomographic (CT) imaging in cases of infection, such as novel H1N1 influenza. The method developed could be a potentially useful tool for classifying and quantifying pulmonary infectious disease on CT imaging. Materials and Methods: Forty chest CT examinations were studied using texture analysis and support vector machine classification to differentiate normal from abnormal lung regions on CT imaging, including 10 patients with immunohistochemistry-proven infection, 10 normal controls, and 20 patients with fibrosis. Results: Statistically significant differences in the receiver-operating characteristic curves for detecting abnormal regions in H1N1 infection were obtained between normal lung and regions of fibrosis, with significant differences in texture features of different infections. These differences enabled the quantification of abnormal lung volumes on CT imaging. Conclusion: Texture analysis and support vector machine classification can distinguish between areas of abnormality in acute infection and areas of chronic fibrosis, differentiate lesions having consolidative and ground-glass appearances, and quantify those texture features to increase the precision of CT scoring as a potential tool for measuring disease progression and severity. C1 [Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging CIDI, Bethesda, MD 20892 USA. NIH, Dept Radiol & Image Sci, Ctr Clin, Bethesda, MD 20892 USA. RP Mollura, DJ (reprint author), NIH, Ctr Infect Dis Imaging CIDI, 10 Ctr Dr, Bethesda, MD 20892 USA. EM molluradj@mail.nih.gov FU National Institutes of Health, Clinical Center FX From the Center for Infectious Disease Imaging (CIDI) and Department of Radiology and Image Sciences, Clinical Center, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892. Received August 11, 2010; accepted November 9, 2010. This research was supported by the Intramural Research Program of the National Institutes of Health, Clinical Center. Address correspondence to: D.J.M. e-mail: molluradj@mail.nih.gov NR 21 TC 27 Z9 28 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2011 VL 18 IS 3 BP 306 EP 314 DI 10.1016/j.acra.2010.11.013 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 725BR UT WOS:000287620700007 PM 21295734 ER PT J AU Cao, XG Shen, DF Callanan, DG Mochizuki, M Chan, CC AF Cao, Xiaoguang Shen, Defen Callanan, David G. Mochizuki, Manabu Chan, Chi-Chao TI Diagnosis of systemic metastatic retinal lymphoma SO ACTA OPHTHALMOLOGICA LA English DT Article DE cytokine; IgH gene rearrangement; intraocular lymphoma; systemic metastatic retinal lymphoma; TCR gene rearrangement ID PRIMARY INTRAOCULAR LYMPHOMA; NON-HODGKINS-LYMPHOMA; T-CELL LYMPHOMA; OF-THE-LITERATURE; CLINICAL-FEATURES; INTERLEUKIN-10 IL-10; OCULAR INVOLVEMENT; MALIGNANT-LYMPHOMA; IMMUNE PRIVILEGE; AQUEOUS-HUMOR AB Purpose: Systemic metastatic retinal lymphoma (SMRL) is exceptionally rare, as systemic lymphomas most often metastasize to the uvea. We have evaluated a series of SMRL cases to elucidate the clinical and pathological features of SMRL. Methods: The pathological specimens of intraocular lymphomas (IOLs) at the National Eye Institute from 1991 to 2009 were retrospectively reviewed. These cases were diagnosed by cytology, cytokine measurement (ELISA for interleukin (IL)-10 and IL-6 levels) and Immunoglobulin-Heavy (IgH) and T-cell-receptor (TCR) gene analyses. Results: There were nine B-cell SMRLs (B-SMRL) among 96 B-cell retinal lymphomas (9.4%) and three T-cell SMRLs (T-SMRL) among five T-cell retinal lymphomas (60%) from a total of 116 IOLs, in which 101 were retinal lymphoma. The original sites were nasopharynx (3), testis (2), skin (2), breast (1), blood (1), retroperitoneum (1), ileo-caecum (1) and stomach (1). Cytology of vitreous samples illustrated atypical lymphoma cells with either B- or T-monoclonality. More B-SMRLs had a high ratio of vitreal IL-10 to IL-6 than T-SMRLs. Molecular pathology demonstrated lymphoma cells with gene rearrangements of IgH in all B-SMRLs and TCR in all T-SMRLs. Conclusions: SMRL and primary retinal lymphoma present with similar clinical manifestations. Systemic T-cell lymphoma invades the retina and vitreous more aggressively than systemic B-cell lymphoma. A diagnosis of SMRL is made when there is a clinical history of systemic lymphoma (particularly from nasopharynx, testis and skin), and lymphoma cells are identified in the vitreous or retina. Molecular analysis is more useful than vitreal cytokine measurement for SMRL diagnosis. C1 [Cao, Xiaoguang; Shen, Defen; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cao, Xiaoguang] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. [Callanan, David G.] Texas Retina Associates, Arlington, TX USA. [Mochizuki, Manabu] Tokyo Med & Dent Univ, Sch Med, Dept Ophthalmol, Tokyo 113, Japan. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU NEI Intramural Research program FX The NEI Intramural Research program supported the study. We thank Hema Ramkumar for her assistance in editing. NR 67 TC 13 Z9 13 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-375X J9 ACTA OPHTHALMOL JI Acta Ophthalmol. PD MAR PY 2011 VL 89 IS 2 BP E149 EP E154 DI 10.1111/j.1755-3768.2009.01797.x PG 6 WC Ophthalmology SC Ophthalmology GA 725RV UT WOS:000287664700008 PM 19958292 ER PT J AU Lopez-Quintero, C Hasin, DS de los Cobos, JP Pines, A Wang, SA Grant, BF Blanco, C AF Lopez-Quintero, Catalina Hasin, Deborah S. Perez de los Cobos, Jose Pines, Abigail Wang, Shuai Grant, Bridget F. Blanco, Carlos TI Probability and predictors of remission from life-time nicotine, alcohol, cannabis or cocaine dependence: results from the National Epidemiologic Survey on Alcohol and Related Conditions SO ADDICTION LA English DT Article DE Alcohol; cannabis; cocaine; dependence; nicotine; remission ID PSYCHIATRIC DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; UNITED-STATES; USE-DISORDER; DRUG-USE; SMOKING-CESSATION; PERSONALITY-DISORDERS; NATURAL COURSE; FOLLOW-UP AB Aim To estimate the general and racial/ethnic specific cumulative probability of remission from nicotine alcohol cannabis or cocaine dependence, and to identify predictors of remission across substances. Design Data were collected from structured diagnostic interviews using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. Setting The 2001-2002 National Epidemiological Survey of Alcohol and Related Conditions (NESARC) surveyed a nationally representative sample from US adults (n = 43 093) selected in a three-stage sampling design. Participants The subsamples of individuals with life-time DSM-IV diagnosis of dependence on nicotine (n = 6937), alcohol (n = 4781), cannabis (n = 530) and cocaine (n = 408). Measurements Cumulative probability estimates of dependence remission for the general population and across racial/ethnic groups. Hazard ratios for remission from dependence. Findings Life-time cumulative probability estimates of dependence remission were 83.7% for nicotine, 90.6% for alcohol, 97.2% for cannabis and 99.2% for cocaine. Half of the cases of nicotine, alcohol, cannabis and cocaine dependence remitted approximately 26, 14, 6 and 5 years after dependence onset, respectively. Males, Blacks and individuals with diagnosis of personality disorders and history of substance use comorbidity exhibited lower hazards of remission for at least two substances. Conclusions A significant proportion of individuals with dependence on nicotine, alcohol, cannabis or cocaine achieve remission at some point in their life-time, although the probability and time to remission varies by substance and racial/ethnic group. Several predictors of remission are shared by at least two substances, suggesting that the processes of remission overlap. The lower rates of remission of individuals with comorbid personality or substance use disorders highlight the need for providing coordinated psychiatric and substance abuse interventions. C1 [Lopez-Quintero, Catalina; Hasin, Deborah S.; Wang, Shuai; Blanco, Carlos] Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [Hasin, Deborah S.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Perez de los Cobos, Jose] Hosp Santa Creu & Sant Pau, Addict Behav Unit, Dept Psychiat, Barcelona, Spain. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Blanco, C (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Psychiat, Coll Phys & Surg, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA. EM cb255@columbia.edu RI Lopez-Quintero, Catalina/A-2294-2013; Blanco, Carlos/I-4906-2013; Perez de los Cobos, Jose/Q-2734-2016 OI Lopez-Quintero, Catalina/0000-0002-6579-6180; Blanco, Carlos/0000-0001-6187-3057; Perez de los Cobos, Jose/0000-0002-9796-5823 FU National Institute on Alcohol Abuse and Alcoholism; NIH [DA019606, DA020783, DA023200, DA023973, MH076051, MH082773, CA133050, AA014223, DA018652, AA018111]; New York State Psychiatric Institute; American Foundation for Suicide Prevention FX The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism with supplemental support from the National Institute on Drug Abuse. Work on this manuscript was supported by NIH grants DA019606, DA020783, DA023200, DA023973, MH076051, MH082773 and CA133050 (Dr Blanco) and AA014223, DA018652, and AA018111 (Dr Hasin), a grant from the American Foundation for Suicide Prevention (Dr Blanco), and the New York State Psychiatric Institute (Drs Blanco and Hasin). The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies or the US government. NR 57 TC 53 Z9 54 U1 4 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2011 VL 106 IS 3 BP 657 EP 669 DI 10.1111/j.1360-0443.2010.03194.x PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 717GV UT WOS:000287032500032 PM 21077975 ER PT J AU Levine, M Padayatty, SJ Espey, MG AF Levine, Mark Padayatty, Sebastian J. Espey, Michael Graham TI Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries SO ADVANCES IN NUTRITION LA English DT Review AB A concentration-function approach to vitamin C (ascorbate) has yielded new physiology and pharmacology discoveries. To determine the range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted. They showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal reabsorption. A 4th mechanism, rate of utilization, may be important in disease. With ingested amounts found in foods, vitamin C plasma concentrations do not exceed 100 mu mol/L. Even with supplementation approaching maximally tolerated doses, ascorbate plasma concentrations are always <250 mu mol/L and frequently <150 mu mol/L. By contrast, when ascorbate is iv. injected, tight control is bypassed until excess ascorbate is eliminated by glomerular filtration and renal excretion. With i.v. infusion, pharmacologic ascorbate concentrations of 25-30 mmol/L are safely achieved. Pharmacologic ascorbate can act as a pro-drug for hydrogen peroxide (H2O2) formation, which can lead to extracellular fluid at concentrations as high as 200 mu mol/L. Pharmacologic ascorbate can elicit cytotoxicity toward cancer cells and slow the growth of tumors in experimental murine models. The effects of pharmacologic ascorbate should be further studied in diseases, such as cancer and infections, which may respond to generation of reactive oxygen species via H2O2. Adv. Nutr. 2: 78-88, 2011. C1 [Levine, Mark; Padayatty, Sebastian J.; Espey, Michael Graham] NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. EM MarkL@mail.nih.gov RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 FU Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX Supported by the Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 84 TC 79 Z9 82 U1 0 U2 15 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 J9 ADV NUTR JI Adv. Nutr. PD MAR PY 2011 VL 2 IS 2 BP 78 EP 88 DI 10.3945/an.110.000109 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V27BR UT WOS:000208589200002 PM 22332036 ER PT J AU Turanov, AA Xu, XM Carlson, BA Yoo, MH Gladyshev, VN Hatfield, DL AF Turanov, Anton A. Xu, Xue-Ming Carlson, Bradley A. Yoo, Min-Hyuk Gladyshev, Vadim N. Hatfield, Dolph L. TI Biosynthesis of Selenocysteine, the 21st Amino Acid in the Genetic Code, and a Novel Pathway for Cysteine Biosynthesis SO ADVANCES IN NUTRITION LA English DT Review AB The biosynthetic pathway for selenocysteine (Sec), the 21st amino acid in the genetic code whose codeword is UGA, was recently determined in eukaryotes and archaea. Sec tRNA, designated tRNA([Ser]Sec), is initially aminoacylated with serine by seryl-tRNA synthetase and the resulting seryl moiety is converted to phosphoserine by O-phosphoseryl-tRNA kinase to form O-phosphoseryl-tRNA([Ser]Sec). Sec synthase (SecS) then uses O-phosphoseryl-tRNA([Ser]Sec) and the active donor of selenium, selenophosphate, to form Sec-tRNA([Ser]Sec). Selenophosphate is synthesized from selenide and ATP by selenophosphate synthetase 2 (SPS2). Sec was the last protein amino acid in eukaryotes whose biosynthesis had not been established and the only known amino acid in eukaryotes whose biosynthesis occurs on its tRNA. Interestingly, sulfide can replace selenide to form thiophosphate in the SPS2-catalyzed reaction that can then react with O-phosphoseryl-tRNA([Ser]Sec) in the presence of SecS to form cysteine-(Cys-)tRNA([Ser]Sec). This novel pathway of Cys biosynthesis results in Cys being decoded by UGA and replacing Sec in normally selenium-containing proteins (selenoproteins). The selenoprotein, thioredoxin reductase 1 (TR1), was isolated from cells in culture and from mouse liver for analysis of Cys/Sec replacement by MS. The level of Cys/Sec replacement in TR1 was proportional to the level of selenium in the diet of the mice. Elucidation of the biosynthesis of Sec and Sec/Cys replacement provides novel ways of regulating selenoprotein functions and ultimately better understanding of the biological roles of dietary selenium. Adv. Nutr. 2: 122-128, 2011. C1 [Turanov, Anton A.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Turanov, Anton A.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Xu, Xue-Ming; Carlson, Bradley A.; Yoo, Min-Hyuk; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu; hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; NIH FX Supported by the Intramural Research Program of the NIH, National Cancer Institute, and Center for Cancer Research (to D.L.H.) and by NIH grants awarded to V.N.G. NR 48 TC 43 Z9 44 U1 2 U2 24 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 J9 ADV NUTR JI Adv. Nutr. PD MAR PY 2011 VL 2 IS 2 BP 122 EP 128 DI 10.3945/an.110.000265 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA V27BR UT WOS:000208589200007 PM 22332041 ER PT J AU Maggio, M Ceda, GP Lauretani, F Bandinelli, S Metter, EJ Guralnik, JM Basaria, S Cattabiani, C Luci, M Dall'Aglio, E Vignali, A Volpi, R Valenti, G Ferrucci, L AF Maggio, Marcello Ceda, Gian Paolo Lauretani, Fulvio Bandinelli, Stefania Metter, Earl Jeffrey Guralnik, Jack M. Basaria, Shehzad Cattabiani, Chiara Luci, Michele Dall'Aglio, Elisabetta Vignali, Alessandro Volpi, Riccardo Valenti, Giorgio Ferrucci, Luigi TI Gonadal status and physical performance in older men SO AGING MALE LA English DT Article DE Testosterone; physical performance; older men ID ANDROGEN-DEPRIVATION THERAPY; TESTOSTERONE LEVELS; PROSTATE-CANCER; ELDERLY-MEN; SKELETAL-MUSCLE; ASSOCIATION; INCHIANTI; MORTALITY; DECLINE; ANEMIA AB Methods. aEuro integral The study included 455 aEuroS >= a parts per thousand yen aEuroS65 year older men of InCHIANTI study, Italy, with complete data on testosterone levels, hand grip strength, cross-sectional muscle area (CSMA), short physical performance battery (SPPB). Linear models were used to test the relationship between gonadal status and determinants of physical performance. Results. aEuro integral Three different groups of older men were created: (1) severely hypogonadal (N aEuroS== aEuroS23), total testosterone levels < a parts per thousand currency sign230 ng /dl; (2) moderately hypogonadal (N aEuroS== aEuroS88), total testosterone > 230 and aEuroS < aEuroS350 ng/dl) and (3) eugonadal (N aEuroS== aEuroS344), testosterone levels >= a parts per thousand yen350 ng/dl. With increased severity of hypogonadal status, participants were significantly older while their BMI was substantially similar. In the age and BMI adjusted analysis, there was a significant difference in haemoglobin levels, hand grip strength and SPPB score (p for trend aEuroS < aEuroS0.001) among three groups, with severely hypogonadal men having lower values of haemoglobin, muscle strength and physical performance. We found no association between testosterone group assignment and calf muscle mass and 4 m walking speed. In the multivariate analysis grip strength (p for trend aEuroS== aEuroS0.004) and haemoglobin (p for trend aEuroS < aEuroS0.0001) but not SPPB and other determinants of physical performance were significantly different between the three groups. Conclusions. aEuro integral In older men, gonadal status is independently associated with some determinants (haemoglobin and muscle strength) of physical performance. C1 [Maggio, Marcello; Ceda, Gian Paolo; Cattabiani, Chiara; Luci, Michele; Dall'Aglio, Elisabetta; Vignali, Alessandro; Volpi, Riccardo; Valenti, Giorgio] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. [Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Metter, Earl Jeffrey; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Basaria, Shehzad] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. RP Maggio, M (reprint author), Harbor Hosp, NIA, NIH, NIA ASTRA Unit, 3001 S Hanover St, Baltimore, MD 21225 USA. EM marcellomaggio2001@yahoo.it RI Lauretani, Fulvio/K-5115-2016 OI Ceda, Gian Paolo/0000-0002-9648-8295; Lauretani, Fulvio/0000-0002-5287-9972 FU Italian Ministry of Health [ICS 110.1/RS97.71]; US National Institute on Aging [N01-AG-916413, N01-AG821336, 263 MD 9164 13, 263 MD 821336] FX The InCHIANTI Study was supported as a 'targeted project' (ICS 110.1/RS97.71) by the Italian Ministry of Health and in part by the US National Institute on Aging (Contracts N01-AG-916413 and N01-AG821336), and by the Intramural Research Program of the US National Institute on Aging (Contracts 263 MD 9164 13 and 263 MD 821336). None of the sponsoring institutions interfered with the collection, analysis, presentation, or interpretation of the data reported here. NR 27 TC 16 Z9 17 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1368-5538 J9 AGING MALE JI Aging Male PD MAR PY 2011 VL 14 IS 1 BP 42 EP 47 DI 10.3109/13685538.2010.518179 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 716SK UT WOS:000286993600009 PM 20937007 ER PT J AU Wira, CR Veronese, F AF Wira, Charles R. Veronese, Fulvia TI 2010 Workshop: Mucosal Immunity in the Male and Female Reproductive Tract and Prevention of HIV Transmission SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter C1 [Veronese, Fulvia] NIAID, Div Aids, NIH, DHHS, Bethesda, MD 20892 USA. [Wira, Charles R.] Dartmouth Med Sch, Lebanon, NH USA. RP Veronese, F (reprint author), NIAID, Div Aids, NIH, DHHS, 6700 Rockledge Dr,Room 5122, Bethesda, MD 20892 USA. EM veronesf@niaid.nih.gov FU NIAID NIH HHS [R01 AI071761] NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2011 VL 27 IS 3 BP 249 EP 249 DI 10.1089/aid.2011.0014 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 733DO UT WOS:000288241600004 PM 21235350 ER PT J AU Grant, BF Dawson, DA Moss, HB AF Grant, Bridget F. Dawson, Deborah A. Moss, Howard B. TI Disaggregating the Burden of Substance Dependence in the United States SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID ALCOHOL C1 [Grant, Bridget F.; Dawson, Deborah A.] NIAAA, LEB, Lab Epidemiol, Div Intramural Clin & Biol Res,NIH, Bethesda, MD 20892 USA. [Moss, Howard B.] NIAAA, Off Director, NIH, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, LEB, Lab Epidemiol, Div Intramural Clin & Biol Res,NIH, Room 3083,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM bgrant@mail.nih.gov FU Intramural NIH HHS [Z01 AA000449-04] NR 5 TC 6 Z9 6 U1 0 U2 2 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 MAR PY 2011 VL 35 IS 3 BP 387 EP 388 DI 10.1111/j.1530-0277.2011.01433.x PG 2 WC Substance Abuse SC Substance Abuse GA 731XF UT WOS:000288143100001 PM 22132830 ER PT J AU Jung, MK Callaci, JJ Lauing, KL Otis, JS Radek, KA Jones, MK Kovacs, EJ AF Jung, M. Katherine Callaci, John J. Lauing, Kristen L. Otis, Jeffrey S. Radek, Katherine A. Jones, Michael K. Kovacs, Elizabeth J. TI Alcohol Exposure and Mechanisms of Tissue Injury and Repair SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Acute Alcohol; Alcoholic Myopathy; Angiogenesis; Antioxidant; Binge Alcohol; Bone Fracture Repair; Canonical Wnt Signaling; Chronic Alcohol; Cytoprotection; Extracellular Matrix; Fracture Non Union; Gastric Mucosa; Glutathione; Inflammation; Myopathy; Orthopedic Trauma; p34(cdc2) Kinase; Oxidative Stress; Survivin; Tissue Injury; Wound Healing ID ACUTE ETHANOL EXPOSURE; SURVIVIN EXPRESSION; INFLAMMATORY RESPONSE; ANTIOXIDANT STATUS; ENDOTHELIAL-CELLS; ALPHA-TOCOPHEROL; RAT HEPATOCYTES; VASCULAR INJURY; BINGE ALCOHOL; LIPID RAFTS AB Tissue injury owing to acute and chronic alcohol consumption has extensive medical consequences, with the level and duration of alcohol exposure affecting both the magnitude of injury and the time frame to recovery. While the understanding of many of the molecular processes disrupted by alcohol has advanced, mechanisms of alcohol-induced tissue injury remain a subject of intensive research. Alcohol has multiple targets, as it affects diverse cellular and molecular processes. Some mechanisms of tissue damage as a result of alcohol may be common to many tissue types, while others are likely to be tissue specific. Here, we present a discussion of the alcohol-induced molecular and cellular disruptions associated with injury or recovery from injury in bone, muscle, skin, and gastric mucosa. In every case, the goal of characterizing the sites of alcohol action is to devise potential measures for protection, prevention, or therapeutic intervention. C1 [Jung, M. Katherine] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. [Callaci, John J.; Lauing, Kristen L.] Loyola Univ, Stritch Sch Med, Alcohol Res Program, Burn & Shock Trauma Inst,Dept Orthopaed Surg, Maywood, IL 60153 USA. [Kovacs, Elizabeth J.] Loyola Univ, Stritch Sch Med, Alcohol Res Program, Burn & Shock Trauma Inst,Dept Surg, Maywood, IL 60153 USA. [Otis, Jeffrey S.] Emory Univ, Sch Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA USA. [Radek, Katherine A.] Univ Calif San Diego, VA San Diego Healthcare Syst, San Diego, CA 92103 USA. [Radek, Katherine A.] Univ Calif San Diego, Dept Med, Div Dermatol, San Diego, CA 92103 USA. [Jones, Michael K.] VA Long Beach Healthcare Syst, Res Healthcare Grp, Long Beach, CA USA. [Jones, Michael K.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. RP Jung, MK (reprint author), NIAAA, Div Metab & Hlth Effects, 5635 Fishers Lane, Bethesda, MD 20892 USA. EM jungma@mail.nih.gov FU NIH [R01AA016138, T32AA013527, K01AA017190, R01AA 014946, P30AA019373, R01AA012034]; Ralph and Marian C Falk Medical Research Trust; Margaret A. Baima Endowment Fund for Alcohol Research; VA Biomedical Laboratory Research & Development Service FX This research was supported by NIH grants R01AA016138 (JJC), T32AA013527 (KLL), K01AA017190 (JS0), R01AA 014946 (MKJ), P30AA019373 (EJK, KAR), R01AA012034 (EJK), the Ralph and Marian C Falk Medical Research Trust (EJK), the Margaret A. Baima Endowment Fund for Alcohol Research (EJK), and the VA Biomedical Laboratory Research & Development Service (MKJ). NR 48 TC 13 Z9 14 U1 3 U2 13 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 MAR PY 2011 VL 35 IS 3 BP 392 EP 399 DI 10.1111/j.1530-0277.2010.01356.x PG 8 WC Substance Abuse SC Substance Abuse GA 731XF UT WOS:000288143100003 PM 21118273 ER PT J AU Weinstein, SJ Yu, K Horst, RL Ashby, J Virtamo, J Albanes, D AF Weinstein, Stephanie J. Yu, Kai Horst, Ronald L. Ashby, Jason Virtamo, Jarmo Albanes, Demetrius TI Serum 25-Hydroxyvitamin D and Risks of Colon and Rectal Cancer in Finnish Men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; colorectal neoplasms; prospective studies; vitamin D ID VITAMIN-D STATUS; COLORECTAL-CANCER; PANCREATIC-CANCER; SCREENING TRIAL; PROSTATE-CANCER; SUBSEQUENT RISK; OVARIAN-CANCER; UNITED-STATES; PLASMA; SUPPLEMENTATION AB Prospective investigations of circulating vitamin D concentrations suggest inverse associations with colorectal cancer risk, although inconsistencies remain and few studies have examined the impact of season. The authors conducted a prospective case-control study of 239 colon cancer cases and 192 rectal cancer cases (diagnosed in 1993-2005) and 428 controls matched on age and blood collection date within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort study of Finnish male smokers. Baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations were categorized using a priori defined cutpoints of < 25, 25-< 37.5, 37.5-< 50, 50-< 75, and >= 75 nmol/L and by season-specific and season-standardized 25(OH)D quartiles. Conditional logistic regression models yielded multivariate-adjusted odds ratios for the predefined cutpoints of 0.63, 0.91, 0.73, 1.00 (referent), and 1.44 for colon cancer and 0.64, 0.58, 0.84, 1.00, and 0.76 for rectal cancer, respectively (all 95% confidence intervals included 1.00). Colon cancer risks were significantly elevated for the highest season-specific and season-standardized quartiles versus the lowest quartiles (OR = 2.11 (95% CI: 1.20, 3.69) and OR = 1.88 (95% CI: 1.07, 3.28), respectively), while rectal cancer risk estimates were null. These results provide no evidence to support an inverse association between vitamin D status and colon or rectal cancer risk; instead, they suggest a positive association for colon cancer. C1 [Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA. [Ashby, Jason] Informat Management Serv Inc, Silver Spring, MD USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Weinstein, SJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20892 USA. EM weinstes@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU US National Institutes of Health; National Cancer Institute; US Public Health Service, National Cancer Institute [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C] FX This work was supported in part by the Intramural Research Program of the US National Institutes of Health and the National Cancer Institute. Additionally, this research was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the National Cancer Institute. NR 52 TC 21 Z9 23 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2011 VL 173 IS 5 BP 499 EP 508 DI 10.1093/aje/kwq398 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726SK UT WOS:000287746200004 PM 21248311 ER PT J AU Schonfeld, SJ Pfeiffer, RM Lacey, JV de Gonzalez, AB Doody, MM Greenlee, RT Park, Y Schairer, C Schatzkin, A Sigurdson, AJ Hartge, P Visvanathan, K AF Schonfeld, Sara J. Pfeiffer, Ruth M. Lacey, James V., Jr. de Gonzalez, Amy Berrington Doody, Michele M. Greenlee, Robert T. Park, Yikyung Schairer, Catherine Schatzkin, Arthur Sigurdson, Alice J. Hartge, Patricia Visvanathan, Kala TI Hormone-related Risk Factors and Postmenopausal Breast Cancer Among Nulliparous Versus Parous Women: An Aggregated Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; body mass index; breast neoplasms; hormone replacement therapy; parity; prospective studies; risk factors ID COLLABORATIVE REANALYSIS; REPLACEMENT THERAPY; INDIVIDUAL DATA; NURSES HEALTH; MAMMARY-GLAND; COHORT; AGE; PREGNANCY; ESTROGEN; MENOPAUSAL AB Nulliparity is an established breast cancer risk factor, particularly when compared with parity at young ages. The authors aggregated data from 4 US prospective studies (1979-2006) including 32,641 nulliparous (1,612 breast cancers) and 204,270 parous (8,180 breast cancers) women to examine the hypothesis that nulliparity may increase susceptibility to established postmenopausal breast cancer risk factors. The aggregated hazard ratio for nulliparous versus all parous women = 1.27 (95% confidence interval: 1.21, 1.34), and that for nulliparous versus women < 25 years of age at first birth = 1.38 (95% confidence interval: 1.30, 1.46). Among nulliparous women, the hazard ratios for current menopausal hormone therapy use (vs. never use), body mass index >= 30 kg/m(2) (vs. < 25 kg/m(2)), and weekly consumption of >= 7 alcoholic drinks (vs. none) ranged from 1.3 to 1.6. The hazard ratios did not differ by parity. In a model including all women, the joint association for each of these factors and nulliparity combined compared with first birth before age 25 years was an approximately 2-fold increased breast cancer risk. Although the baseline risk is higher for nulliparous women compared with parous women, these results suggest that the associations between hormone-related factors and breast cancer do not differ by parity. C1 [Schonfeld, Sara J.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schonfeld, Sara J.; Visvanathan, Kala] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lacey, James V., Jr.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Greenlee, Robert T.] Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI USA. [Visvanathan, Kala] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Schonfeld, SJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM schonfes@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; OI Park, Yikyung/0000-0002-6281-489X FU NIH; National Cancer Institute; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the NIH and the National Cancer Institute. PLCO research was supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 40 TC 9 Z9 9 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 MAR 1 PY 2011 VL 173 IS 5 BP 509 EP 517 DI 10.1093/aje/kwq404 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726SK UT WOS:000287746200005 PM 21266505 ER PT J AU Anuradha, S Healy, GN Dunstan, DW Klein, R Klein, BE Cotch, MF Wong, TY Owen, N AF Anuradha, Satyamurthy Healy, Genevieve N. Dunstan, David W. Klein, Ronald Klein, Barbara E. Cotch, Mary Frances Wong, Tien Y. Owen, Neville TI Physical Activity, Television Viewing Time, and Retinal Microvascular Caliber SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arterioles; microvessels; motor activity; retina; sedentary lifestyle; venules ID 4 RACIAL/ETHNIC GROUPS; CHRONIC HEART-FAILURE; VASCULAR CALIBER; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS RISK; UNITED-STATES; EXERCISE; MARKERS; MESA; ASSOCIATIONS AB Physical activities and sedentary behaviors are 2 broad classes of behavior that may be clearly distinguished from each other and have different patterns of determinants. The authors examined the associations of physical activity and television viewing time with retinal vascular caliber among US adults (n = 5,893) from 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (2002-2004) that included non-Hispanic whites, blacks, Hispanics, and Chinese. Physical activity and television viewing time were assessed by using a questionnaire, and vascular calibers (arteriolar and venular) were measured from digital retinal photographs. Those in the lowest quartile of physical activity had wider retinal venular caliber compared with those in the highest quartile in multivariate models adjusted for demographic, cardiovascular, behavioral, and inflammatory risk factors. This was noted in non-Hispanic whites and Hispanics but not in blacks or Chinese. For television viewing time, non-Hispanic whites (but not the other racial/ethnic groups) who were in the highest quartile of television viewing time had wider retinal venular caliber compared with those in the lowest quartile. No associations were noted with arteriolar caliber. Lower levels of physical activity (among non-Hispanic whites and Hispanics) and higher levels of television viewing time (among whites) are associated with wider retinal venules. C1 [Anuradha, Satyamurthy] Univ Queensland, Canc Prevent Res Ctr, Sch Populat Hlth, Herston, Qld 4006, Australia. [Healy, Genevieve N.; Dunstan, David W.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia. [Klein, Ronald; Klein, Barbara E.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. RP Anuradha, S (reprint author), Univ Queensland, Canc Prevent Res Ctr, Sch Populat Hlth, Level 3,Publ Hlth Bldg,Herston Rd, Herston, Qld 4006, Australia. EM s.anuradha@sph.uq.edu.au RI Healy, Genevieve/A-7408-2008; Owen, Neville/K-5986-2012; Dunstan, David/E-8473-2010; OI Healy, Genevieve/0000-0001-7093-7892; Dunstan, David/0000-0003-2629-9568; Cotch, Mary Frances/0000-0002-2046-4350; Owen, Neville/0000-0003-2784-4820 FU National Heart, Lung, and Blood Institute [HL69979-03]; National Health and Medical Research Council (NHMRC) [569764, 569861, 301200]; Victorian Health Promotion Foundation; National Heart Foundation of Australia [PH 08B 3905]; Queensland Health Core Research Infrastructure grant; [N01-HC-95159]; [N01-HC-95165]; [N01-HC-95169] FX This study was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 and by grant HL69979-03 from the National Heart, Lung, and Blood Institute. S. A. is supported by National Health and Medical Research Council (NHMRC) Public Health Postgraduate Scholarship 569764. D. W. D. is supported by a Victorian Health Promotion Foundation Public Health Research Fellowship. G. N. H. is supported by NHMRC Scholarship 569861 and by National Heart Foundation of Australia Fellowship PH 08B 3905. N. O. is supported by a Queensland Health Core Research Infrastructure grant and by NHMRC Program Grant 301200. NR 44 TC 11 Z9 11 U1 2 U2 8 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 MAR 1 PY 2011 VL 173 IS 5 BP 518 EP 525 DI 10.1093/aje/kwq412 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 726SK UT WOS:000287746200006 PM 21300854 ER EF