FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Malkin, E Hu, JH Li, Z Chen, ZH Bi, XL Reed, Z Dubovsky, F Liu, J Wang, Q Pan, XG Chen, T Giersing, B Xu, Y Kang, X Gu, J Shen, Q Tucker, K Tierney, E Pan, WQ Long, C Cao, ZF AF Malkin, Elissa Hu, Jinhong Li, Zhen Chen, Zhihui Bi, Xinling Reed, Zarifah Dubovsky, Filip Liu, Jian Wang, Qiang Pan, Xuegong Chen, Tom Giersing, Birgitte Xu, Yu Kang, Xin Gu, Jun Shen, Qian Tucker, Kathryn Tierney, Eveline Pan, Weiqing Long, Carole Cao, Zhifang TI A Phase 1 trial of PfCP2.9: An AMA1/MSP1 chimeric recombinant protein vaccine for Plasmodium falciparum malaria SO VACCINE LA English DT Article DE Malaria vaccine; Clinical trial; Malaria ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; BLOOD-STAGE MALARIA; CARBOXYL-TERMINAL FRAGMENT; MONTANIDE ISA 720; PAPUA-NEW-GUINEA; IMMUNE-RESPONSE; CLINICAL-TRIAL; ANTIBODY TITER; IN-VITRO AB Apical Membrane Antigen 1 (AMA1) and Merozoite Surface Protein 1 (MSP1) were produced as a recombinant fusion protein and formulated with the adjuvant Montanide ISA 720 with the aim of replicating the structure present in the parasite protein. A previous trial with this construct demonstrated the vaccine was safe and immunogenic but was associated with injection site reactogenicity. This Phase I a close-escalating, double blind, randomized, controlled trial of PfCP2.9/Montanide ISA 720 was conducted to evaluate alternative dose levels and vaccination schedules, with a pre-formulated vaccine that had undergone more in-depth and frequent quality control and stability analysis. The trial was conducted in seventy healthy Chinese malaria-naive Volunteers between January 2006 and January 2007. The objective was to assess the safety, reactogenicity and immunogenicity of 5, 20 and 50 mu g of PfCP2.9/ISA 720 under 2 different schedules. The most common adverse event was injection site tenderness (53%). The frequency and severity of adverse events was similar in both vaccination schedules. Antibody responses were induced and remained elevated throughout the study in volunteers receiving vaccine (p < 0.001), Although high antibody titers as measured by ELISA to the PfCP2.9 immunogen were observed, biological function of these antibodies was not reflected by the in vitro inhibition of parasite growth, and there was limited recognition of fixed parasites in in immunofluorescence assay. At all three dose levels and both schedules, this formulation of PfCP2.9/ISA 720 is well tolerated, safe and immunogenic; however no functional activity against the parasite was observed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Malkin, Elissa; Giersing, Birgitte; Tierney, Eveline] PATH Malaria Vaccine Initiat, Bethesda, MD 20814 USA. [Hu, Jinhong; Li, Zhen; Chen, Zhihui; Bi, Xinling; Xu, Yu; Kang, Xin; Gu, Jun; Shen, Qian] Second Mil Med Univ, Shanghai Changhai Hosp, Natl Med Clin Trial Inst, Shanghai, Peoples R China. [Pan, Weiqing] Second Mil Med Univ, Dept Pathogen Biol, Shanghai, Peoples R China. [Reed, Zarifah] WHO, Special Programme Res & Training Trop Dis, Initiat Vaccine Res, CH-1211 Geneva 27, Switzerland. [Dubovsky, Filip] MedImmune, Gaithersburg, MD USA. [Liu, Jian; Wang, Qiang; Pan, Xuegong] Shanghai Wanxing Biopharmaceut, Shanghai, Peoples R China. [Chen, Tom] ProMet Biotherapeut Inc, Rockville, MD USA. [Tucker, Kathryn] Stat Collaborat Inc, Washington, DC USA. [Long, Carole] NIAID, Lab Malaria & Vector Res, NIH, Rockville, ME USA. RP Malkin, E (reprint author), PATH Malaria Vaccine Initiat, 7500 Old Georgetown Rd,12th Floor, Bethesda, MD 20814 USA. EM malkine@medimmune.com FU PATH Malaria Vaccine Initiative; Intramural Program of NIAID/NIH; WHO FX This work was supported by the PATH Malaria Vaccine Initiative and the Intramural Program of NIAID/NIH. The PATH Malaria Vaccine Initiative and WHO reviewed the Study protocol and contributed to its design, the writing of the paper and the decision to submit it for publication. WHO provided Support for on-site training on GCP and ethics, as well as oversight for safety monitoring. NR 39 TC 36 Z9 37 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD DEC 9 PY 2008 VL 26 IS 52 BP 6864 EP 6873 DI 10.1016/j.vaccine.2008.09.081 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 386QT UT WOS:000261898400022 PM 18930094 ER PT J AU Engler, RJM Nelson, MR Klote, MM VanRaden, MJ Huang, CY Cox, NJ Klimov, A Keitel, WA Nichol, KL Carr, WW Treanor, JJ AF Engler, Renata J. M. Nelson, Michael R. Klote, Mary M. VanRaden, Mark J. Huang, Chiung-Yu Cox, Nancy J. Klimov, Alexander Keitel, Wendy A. Nichol, Kristin L. Carr, Warner W. Treanor, John J. CA Walter Reed Hlth Care Syst Influen TI Half- vs Full-Dose Trivalent Inactivated Influenza Vaccine (2004-2005) Age, Dose, and Sex Effects on Immune Responses SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE WORKERS; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM-CARE; ANTIBODY-RESPONSES; COST-EFFECTIVENESS; ELDERLY PERSONS; WORKING ADULTS; VIRUS; SERUM; MORTALITY AB Background: Optimal public health strategies for managing influenza vaccine shortages are not yet defined. Our objective was to determine the effects of age, sex, and dose on the immunogenicity of intramuscular trivalent inactivated vaccine (TIV). Methods: Healthy adults aged 18 to 64 years, stratified by age (18-49 and 50-64 years) and sex, were randomized to receive full- or half-dose TIV. Hemagglutination inhibition titers against vaccine antigens were measured before and 21 days after immunization. A primary outcome of noninferiority was defined as a difference of less than 20% in the upper 95% confidence interval (CI) of the proportion of subjects with strain-specific hemagglutination inhibition antibody titers of 1:40 or higher after vaccination. Secondary outcomes included geometric mean titers, after vaccination side effects, and occurrences of influenza-like illnesses. Results: Among previously immunized subjects (N=1114) receiving half- vs full-dose TIV (age, 18-49 years, n=284 [half] and n=274 [full]; and age 50-64 years, n=276 [half] and n=280 [full]), CIs for proportions of subjects with hemagglutination inhibition antibody titers of 1:40 or higher excluded substantial reduction for all antigens in the 18- to 49-year age group and for B/Shanghai/361/2002 (B) and A/Fujian/411/2002 (A/H3N2) in the 50- to 64-year age group. Geometric mean titer in the female 18- to 49-year age group exceeded male responses for all strains: responses to half- dose TIV that were comparable with male full- dose responses for A/ New Caledonia/20/99 (A/H1N1) antigen, 25.4 (95% CI, 20.9-30.9) vs 25.6 (95% CI, 21.3-30.9); A/H3N2 antigen, 60.8 (95% CI, 50.8-72.7) vs 44.1 (95% CI, 37.6-51.8); and B antigen, 64.4 (95% CI, 53.9-76.9) vs 60.7 (95% CI, 51.4-71.7) (findings were similar for the 50- to 64- year age group). Some injection site and systemic reactions (myalgias and/or arthralgias [P<.05], headache [P<.001], and impact of fatigue [P<.05]) were significantly lower in men. The relative risk of medical visits and hospitalizations for influenza-like illnesses were similar in the half- and full- dose groups regardless of age. Conclusions: Antibody responses to intramuscular half-dose TIV in healthy, previously immunized adults were not substantially inferior to the full- dose vaccine, particularly for ages 18 to 49 years. Significantly higher geometric mean titer responses in women were identified for all ages, regardless of dose or influenza strain. Half-dose vaccination may be an effective strategy for healthy adults younger than 50 years in the setting of an influenza vaccine shortage. Trial Registration: clinicaltrials.gov Identifier: NCT00283283 C1 [Engler, Renata J. M.] Walter Reed Army Med Ctr, Vaccine Healthcare Ctr Network, Allergy Immunol Dept, Washington, DC 20307 USA. [VanRaden, Mark J.; Huang, Chiung-Yu] NIAID, NIH, Bethesda, MD 20892 USA. [Cox, Nancy J.; Klimov, Alexander] Ctr Dis Control & Prevent, Influenza Branch, Atlanta, GA USA. [Keitel, Wendy A.] Baylor Coll Med, Houston, TX 77030 USA. [Nichol, Kristin L.] Univ Minnesota, Sch Med, VA Med Ctr, Minneapolis, MN 55455 USA. [Nichol, Kristin L.] Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. [Treanor, John J.] Univ Rochester, Dept Med, Infect Dis Unit, Rochester, NY USA. RP Engler, RJM (reprint author), Walter Reed Army Med Ctr, Vaccine Healthcare Ctr Network, Allergy Immunol Dept, 6900 Georgia Ave NW,Bldg 41,Ste 21, Washington, DC 20307 USA. EM renata.engler@gmail.com FU Office of the Army Surgeon General in collaboration with Walter Reed Army Medical Center(WRAMC); Healthcare System; North Atlantic Regional Medical Command; US Army Medical Research and Materiel Command; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Influenza Branch of the Centers for Disease Control and Prevention FX This study was supported by the Office of the Army Surgeon General in collaboration with Walter Reed Army Medical Center(WRAMC) and Healthcare System; the North Atlantic Regional Medical Command; the US Army Medical Research and Materiel Command; the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and the Influenza Branch of the Centers for Disease Control and Prevention. NR 34 TC 69 Z9 69 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 8 PY 2008 VL 168 IS 22 BP 2405 EP 2414 DI 10.1001/archinternmed.2008.513 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 380SX UT WOS:000261486600004 PM 19064822 ER PT J AU Kubler-Kielb, J Schneerson, R Mocca, C Vinogradov, E AF Kubler-Kielb, Joanna Schneerson, Rachel Mocca, Chris Vinogradov, Evgeny TI The elucidation of the structure of the core part of the LPS from Plesiomonas shigelloides serotype O17 expressing O-polysaccharide chain identical to the Shigella sonnei O-chain SO CARBOHYDRATE RESEARCH LA English DT Article DE LPS; O-Chain; Plesiomonas shigelloides; Shigella sonnei; Conjugate vaccine; Structure; Core ID ESCHERICHIA-COLI; LIPOPOLYSACCHARIDE; REGION; GENES; FORM AB Plesiomonas shigelloides O17 LPS contains the same O-antigenic polysaccharide chain as a causative agent of dysentery, Shigella sonnei. This polysaccharide can be used as a component of a vaccine against dysentery. Core part of the P. shigelloides O17 LPS was studied using NMR and mass spectrometry and the following structure was proposed: [GRAPHICS] Significant similarity of the P. shigelloides O17 LPS core with the structure of the P. shigelloides O54 core was observed. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Vinogradov, Evgeny] CNR, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. [Kubler-Kielb, Joanna; Schneerson, Rachel; Mocca, Chris] NICHHD, NIH, Bethesda, MD 20892 USA. RP Vinogradov, E (reprint author), CNR, Inst Biol Sci, 100 Sussex Dr, Ottawa, ON K1A 0R6, Canada. EM evguenii.vinogradov@nrc.ca OI Vinogradov, Evgeny/0000-0002-5364-1376 FU Intramural NIH HHS [Z99 HD999999] NR 11 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 8 PY 2008 VL 343 IS 18 BP 3123 EP 3127 DI 10.1016/j.carres.2008.09.017 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 379AE UT WOS:000261365700018 PM 18954864 ER PT J AU Ahmed, ZM Kjellstrom, S Haywood-Watson, RJL Bush, RA Hampton, LL Battey, JF Riazuddin, S Frolenkov, G Sieving, PA Friedman, TB AF Ahmed, Zubair M. Kjellstrom, Sten Haywood-Watson, Ricky J. L., II Bush, Ronald A. Hampton, Lori L. Battey, James F. Riazuddin, Saima Frolenkov, Gregory Sieving, Paul A. Friedman, Thomas B. TI Double homozygous waltzer and Ames waltzer mice provide no evidence of retinal degeneration SO MOLECULAR VISION LA English DT Article ID SENSORY HAIR-CELLS; USHER PROTEIN NETWORK; SYNDROME TYPE 1D; SYNDROME TYPE 1F; MYOSIN-VIIA; PHOTORECEPTOR CELLS; PROTOCADHERIN GENE; ALLELIC MUTATIONS; 1B SYNDROME; DEAFNESS AB Purpose: To determine whether cadherin 23 and protocadherin 15 can substitute for one another in the maintenance of the retina and other tissues in the mouse. Does homozygosity for both v and av mutant alleles (i.e., a double homozygous mouse) cause retinal degeneration or an obvious retinal histopathology? Methods: We generated mice homozygous for both Cdh23(v-6J) and Pcdh15(av-Jfb) alleles. The retinal phenotypes of double heterozygous and double homozygous mutant mice were determined by light microscopy and electroretinography (ERG). Histology on 32 different tissues, scanning electron microscopy of organ of Corti hair cells as well as serum biochemical and hematological examinations were evaluated. Results: ERG waves of double heterozygous and double homozygous mice showed similar shape, growth of the amplitude with intensity, and implicit time for both rod and cone pathway mediated responses. Mice homozygous for both Cdh23(v-6J) and Pcdh15(av-Jfb) mutations showed no sign of retinitis pigmentosa or photoreceptor degeneration but, as expected, were deaf and had disorganized hair cell sensory bundles. Conclusions: The simultaneous presence of homozygous mutant alleles of cadherin 23 and protocadherin 15 results only in deafness, not retinal degeneration or any other additional obvious phenotype of the major organ systems. We conclude that in the mouse cadherin 23 or protocadherin 15 appear not to compensate for one another to maintain the retina. C1 [Friedman, Thomas B.] Natl Inst Deaf & Other Commun Disorders, NIH, Rockville, MD 20850 USA. [Haywood-Watson, Ricky J. L., II] Tulane Univ, Mol & Cellular Biol Program, New Orleans, LA 70118 USA. [Hampton, Lori L.; Battey, James F.] NINDS, Bethesda, MD 20892 USA. [Frolenkov, Gregory] Univ Kentucky, Dept Physiol, Lexington, KY USA. [Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA. RP Friedman, TB (reprint author), Natl Inst Deaf & Other Commun Disorders, NIH, 5 Res Court,Room 2A-15, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov FU Deafness Research Foundation; National Organization for Hearing Research; NIH; NIDCD [1 ZO1 DC000039-11, ZO1DC000065-03]; NINDS [1 Z01 NS00300405] FX We thank Tomoko Makishima, Rob Morell, Julie Schultz, Erich Boger, Dennis Drayna, Susan Sullivan and Doris Wu for their technical help and advice in conducting this study and for their comments in preparing the manuscript. G. F. was supported by grants from the Deafness Research Foundation and the National Organization for Hearing Research. Support to T. B. F., P. A. S., and J. F. B. was provided by NIH intramural funds from the NIDCD ( 1 ZO1 DC000039-11 and ZO1DC000065-03), and from NINDS ( 1 Z01 NS00300405), respectively. NR 52 TC 10 Z9 10 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 8 PY 2008 VL 14 IS 260-62 BP 2227 EP 2236 PG 10 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 413VV UT WOS:000263821500001 PM 19057657 ER PT J AU Donovan, PJ Smith, GT AF Donovan, Paul J. Smith, George T. TI Urethane and N-nitrosodiethylamine are mutagenic for the Syrian hamster fetus SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Urethane; N-nitrosodiethylamine; Mutation; Fetus ID ETHYL CARBAMATE URETHANE; DEVELOPING MOUSE EMBRYO; HUMAN-LIVER-MICROSOMES; TRANSPLACENTAL CARCINOGENESIS; DROSOPHILA-MELANOGASTER; VINYL CARBAMATE; GOLDEN-HAMSTERS; TUMOR-INDUCTION; FUTURE WORK; DNA-DAMAGE AB Urethane and N-nitrosodiethylamine are soluble environmental carcinogens that initiate tumors transplacentally, but have a mixed history of effectiveness in mutagenesis assays in vitro or in vivo with adult rodents. To test for their transplacental mutagenicity, Syrian hamster fetuses at 12 days in gestation were exposed transplacentally to urethane or N-nitrosodiethylamine at 0.5 or 1.0 mM/kg. The fetal cells were isolated on day 13 of gestation and tested for diphtheria toxin resistance as a mutation marker. Both compounds were significantly mutagenic, at both doses, causing 6- to 20-fold increases in mutations compared with controls. Compared with N-nitrosodiethylamine, urethane was somewhat more effective as a mutagen with a more marked dose-response. These results are consistent with mutagenesis as part of the mechanism of transplacental carcinogenicity of urethane and N-nitrosodiethylamine. (c) 2008 Published by Elsevier B.V. C1 [Donovan, Paul J.; Smith, George T.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Donovan, PJ (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205 NCI Frederick, Frederick, MD 21702 USA. EM donovapa@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX The authors thank Dr. Jerry Rice for his support, Dr. Lucy M. Anderson for editorial assistance, Dr. Larry K. Keefer for critical reading of the manuscript, and Kathleen Simon for assistance with manuscript preparation. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 44 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD DEC 8 PY 2008 VL 657 IS 2 BP 160 EP 163 DI 10.1016/j.mrgentox.2008.07.011 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 385ZB UT WOS:000261851000013 PM 18755288 ER PT J AU Woodcock, HL Zheng, WJ Ghysels, A Shao, YH Kong, J Brooks, BR AF Woodcock, H. Lee Zheng, Wenjun Ghysels, An Shao, Yihan Kong, Jing Brooks, Bernard R. TI Vibrational subsystem analysis: A method for probing free energies and correlations in the harmonic limit SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article DE electron correlations; free energy; vibrational states ID NORMAL-MODE ANALYSIS; ELASTIC-NETWORK MODEL; LARGE SYSTEMS; FUNCTIONAL MOTIONS; SINGLE-PARAMETER; PROTEIN DYNAMICS; MYOSIN; FLUCTUATIONS; COORDINATE; PROGRAM AB A new vibrational subsystem analysis (VSA) method is presented for coupling global motion to a local subsystem while including the inertial effects of the environment. The premise of the VSA method is a partitioning of a system into a smaller region of interest and a usually larger part referred to as environment. This method allows the investigation of local-global coupling, a more accurate estimation of vibrational free energy contribution for parts of a large system, and the elimination of the "tip effect" in elastic network model calculations. Additionally, the VSA method can be used as a probe of specific degrees of freedom that may contribute to free energy differences. The VSA approach can be employed in many ways, but it will likely be most useful for estimating activation free energies in QM/MM reaction path calculations. Four examples are presented to demonstrate the utility of this method. C1 [Woodcock, H. Lee; Zheng, Wenjun; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Ghysels, An] Univ Ghent, Ctr Mol Modeling, B-9000 Ghent, Belgium. [Shao, Yihan; Kong, Jing] Q Chem Inc, Design Ctr, Pittsburgh, PA 15213 USA. RP Woodcock, HL (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hlwood@nih.gov RI Woodc, Henry/D-9275-2011; Ghysels, An/M-9095-2015; OI Woodcock, Henry/0000-0003-3539-273X; Zheng, Wenjun/0000-0002-6236-9765 FU NIH; NHLBI; SBIR [GM065617] FX We thank Damian Moran from Macquarie University for helpful insight and fruitful discussions. This research was supported, in part, by the Intramural Research Program of the NIH, NHLBI. Additionally, A. G. was supported by the Fund for Scientific Research-Flanders. Y.S. and J.K. wish to acknowledge the financial support from the National Institutes of Health through SBIR Grant No. GM065617. Use of the LoBoS (www.lobos.nih.gov) supercomputer is also acknowledged and appreciated. NR 38 TC 33 Z9 33 U1 0 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 7 PY 2008 VL 129 IS 21 AR 214109 DI 10.1063/1.3013558 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 379XW UT WOS:000261430900010 PM 19063546 ER PT J AU Clay, JR Paydarfar, D Forger, DB AF Clay, John R. Paydarfar, David Forger, Daniel B. TI A simple modification of the Hodgkin and Huxley equations explains type 3 excitability in squid giant axons SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE nerve; squid axons; ion channel gating; neuronal excitability ID COCHLEAR NUCLEUS NEURONS; POTASSIUM CURRENTS; GATING CURRENTS; SODIUM-CHANNELS; SINGLE-CHANNEL; NERVE FIBRES; KINETICS; INACTIVATION; PERMEABILITY AB The Hodgkin and Huxley (HH) model predicts sustained repetitive. ring of nerve action potentials for a suprathreshold depolarizing current pulse for as long as the pulse is applied (type 2 excitability). Squid giant axons, the preparation for which the model was intended,. re only once at the beginning of the pulse (type 3 behaviour). This discrepancy between the theory and experiments can be removed by modifying a single parameter in the HH equations for the K+ current as determined from the analysis in this paper. K+ currents in general have been described by I-K = g(K) (V - E-K), where g(K) is the membrane's K+ current conductance and E-K is the K+ Nernst potential. However, I-K has a nonlinear dependence on (V - E-K) well described by the Goldman Hodgkin Katz equation that determines the voltage dependence of g(K). This experimental finding is the basis for the modi. cation in the HH equations describing type 3 behaviour. Our analysis may have broad significance given the use of I-K = g(K)(V - E-K) to describe K+ currents in a wide variety of biological preparations. C1 [Clay, John R.] NINDS, NIH, Bethesda, MD 20892 USA. [Paydarfar, David] Univ Massachusetts, Sch Med, Dept Neurol & Physiol, Worcester, MA 01655 USA. [Forger, Daniel B.] Univ Michigan, Ctr Computat Med & Biol, Dept Math, Math Biol Res Grp, Ann Arbor, MI 48109 USA. [Clay, John R.] Marine Biol Lab, Woods Hole, MA 02543 USA. RP Clay, JR (reprint author), NINDS, NIH, Twinbrook Bldg,Rm TN-41,5625 Fishers Lane, Bethesda, MD 20892 USA. EM jrclay@ninds.nih.gov RI Forger, Daniel/C-5552-2015 OI Forger, Daniel/0000-0001-7581-4031 FU Intramural NIH HHS NR 43 TC 24 Z9 25 U1 1 U2 4 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 EI 1742-5662 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD DEC 6 PY 2008 VL 5 IS 29 BP 1421 EP 1428 DI 10.1098/rsif.2008.0166 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 382YY UT WOS:000261642500003 PM 18544505 ER PT J AU Dehghan, A Kottgen, A Yang, Q Hwang, SJ Kao, WHL Rivadeneira, F Boerwinkle, E Levy, D Hofman, A Astor, BC Benjamin, EJ van Duijn, CM Witteman, JC Coresh, J Fox, CS AF Dehghan, Abbas Kottgen, Anna Yang, Qiong Hwang, Shih Jen Kao, W. H. Linda Rivadeneira, Fernando Boerwinkle, Eric Levy, Daniel Hofman, Albert Astor, Brad C. Benjamin, Emelia J. van Duijn, Cornelia M. Witteman, Jacqueline C. Coresh, Josef Fox, Caroline S. TI Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study SO LANCET LA English DT Article ID PRACTICE RESEARCH DATABASE; ATHEROSCLEROSIS RISK; UNIFIED APPROACH; APICAL MEMBRANE; HEART-DISEASE; UNITED-STATES; SERUM URATE; FRAMINGHAM; DESIGN; HYPERURICEMIA AB Background Hyperuricaemia, a highly heritable trait, is a key risk factor for gout. We aimed to identify novel genes associated with serum uric acid concentration and gout. Methods Genome-wide association studies were done for serum uric acid in 7699 participants in the Framingham cohort and in 4148 participants in the Rotterdam cohort. Genome-wide significant single nucleotide polymorphisms (SNPs) were replicated in white (n=11024) and black (n=3843) individuals who took part in the study of Atherosclerosis Risk in Communities (ARIC). The SNPs that reached genome-wide significant association with uric acid in either the Framingham cohort (p<5.0x10(-8)) or the Rotterdam cohort (p<1.0x10(-7)) were evaluated with gout. The results obtained in white participants were combined using meta-analysis. Findings Three loci in the Framingham cohort and two in the Rotterdam cohort showed genome-wide association with uric acid. Top SNPs in each locus were: missense rs16890979 in SLC2A9 (p=7.0x10(-168) and 2.9x10(-18) for white and black participants, respectively); missense rs2231142 in ABCG2 (p=2.5x10(-60) and 9.8x10(-4)), and rs17.65205 in SLC17A3 (p=3.3x10(-26) and 0.33). All SNPs were direction-consistent with gout in white participants: rs16890979 (OR 0.59 per T allele, 95% CI 0.52-0.68, p=7.0x10(-14)), rs2231.142 (1.74, 1.51-1.99, p=3.3x10(-15)), and rs1165205 (0.85, 0.77-0.94, p=0.002). In black participants of the ARIC study, rs2231142 was direction-consistent with gout (1.71, 1.06-2.77, p=0.028). An additive genetic risk score of high-risk alleles at the three loci showed graded associations with uric acid (272-351 mu mol/L in the Framingham cohort, 269-386 mu mol/L in the Rotterdam cohort, and 303-426 mu mol/L in white participants of the ARIC study) and gout (frequency 2-13% in the Framingham cohort, 2-8% in the Rotterdam cohort, and 1-18% in white participants in the ARIC study). Interpretation We identified three genetic loci associated with uric acid concentration and gout. A score based on genes with a putative role in renal urate handling showed a substantial risk for gout. Funding Netherlands Organisation for Scientific Research (NWO); the National Heart, Lung, and Blood Institute. C1 [Hwang, Shih Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Hwang, Shih Jen; Levy, Daniel; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA. [Hwang, Shih Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. [Dehghan, Abbas; Hofman, Albert; van Duijn, Cornelia M.; Witteman, Jacqueline C.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Kottgen, Anna; Kao, W. H. Linda; Astor, Brad C.; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Kottgen, Anna; Kao, W. H. Linda; Astor, Brad C.; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Cardiol, Sch Med, Boston, MA 02215 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Kottgen, Anna/D-2920-2012; Yang, Qiong/G-5438-2014; Rivadeneira, Fernando/O-5385-2015; OI Rivadeneira, Fernando/0000-0001-9435-9441; Benjamin, Emelia/0000-0003-4076-2336; Dehghan, Abbas/0000-0001-6403-016X FU Netherlands organisation for scientific research (NWO) [175.01.2005.011]; National Heart, Lung, and Blood Institute's Framingham heart study [NOI-HC-25195]; Affymetrix genotyping [N02-HL-6-4278]; National Heart, Lung, and Blood Institute [NO1-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, NO1-HC-55021, N01-HC-55022, R01DK076770-01]; National Centre for Research Resources; NIH Roadmap for Medical Research [UL1 RR 025005]; German research foundation fellowship FX We thank the staff and participants in the Framingham cohort study, the Rotterdam study, and the Atherosclerosis Risk in Communities study for their important contributions. We received funding from the Netherlands organisation for scientific research (NWO) (175.01.2005.011); the National Heart, Lung, and Blood Institute's Framingham heart study (NOI-HC-25195). Affymetrix genotyping was supported by contract N02-HL-6-4278. The Atherosclerosis Risk in Communities study was supported by the National Heart, Lung, and Blood Institute (contracts NO1-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, NO1-HC-55021, and N01-HC-55022, with ancillary funding by R01DK076770-01). The project was partly supported by the National Centre for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (grant UL1 RR 025005). AK was supported by a German research foundation fellowship. We acknowledge the individual participating studies and investigators of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGe Consortium). NR 47 TC 291 Z9 320 U1 1 U2 32 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 DEC 6 PY 2008 VL 372 IS 9654 BP 1953 EP 1961 DI 10.1016/S0140-6736(08)61343-4 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 380NE UT WOS:000261471600022 PM 18834626 ER PT J AU Zhou, KX Dempfle, A Arcos-Burgos, M Bakker, SC Banaschewski, T Biederman, J Buitelaar, J Castellanos, FX Doyle, A Ebstein, RP Ekholm, J Forabosco, P Franke, B Freitag, C Friedel, S Gill, M Hebebrand, J Hinney, A Jacob, C Lesch, KP Loo, SK Lopera, F McCracken, JT McGough, JJ Meyer, J Mick, E Miranda, A Muenkel, M Mulas, F Nelson, SF Nguyen, TT Oades, RD Ogdie, MN Palacio, JD Pineda, D Reif, A Renner, TJ Roeyers, H Romanos, M Rothenberger, A Schafer, H Sergeant, J Sinke, RJ Smalley, SL Sonuga-Barke, EJS Steinhausen, HC van der Meulen, E Walitza, S Warnke, A Lewis, CM Faraone, SV Asherson, P AF Zhou, Kaixin Dempfle, Astrid Arcos-Burgos, Mauricio Bakker, Steven C. Banaschewski, Tobias Biederman, Joseph Buitelaar, Jan Castellanos, F. Xavier Doyle, Alysa Ebstein, Richard P. Ekholm, Jenny Forabosco, Paola Franke, Barbara Freitag, Christine Friedel, Susann Gill, Michael Hebebrand, Johannes Hinney, Anke Jacob, Christian Lesch, Klaus Peter Loo, Sandra K. Lopera, Francisco McCracken, James T. McGough, James J. Meyer, Jobst Mick, Eric Miranda, Ana Muenkel, Maximilian Mulas, Fernando Nelson, Stanley F. Nguyen, T. Trang Oades, Robert D. Ogdie, Matthew N. Palacio, Juan David Pineda, David Reif, Andreas Renner, Tobias J. Roeyers, Herbert Romanos, Marcel Rothenberger, Aribert Schaefer, Helmut Sergeant, Joseph Sinke, Richard J. Smalley, Susan L. Sonuga-Barke, Edmund J. S. Steinhausen, Hans-Christoph van der Meulen, Emma Walitza, Susanne Warnke, Andreas Lewis, Cathryn M. Faraone, Stephen V. Asherson, Philip TI Meta-Analysis of Genome-Wide Linkage Scans of Attention Deficit Hyperactivity Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE ADHD; GSMA; linkage ID DEFICIT/HYPERACTIVITY DISORDER; SEARCH METAANALYSIS; SIB-PAIRS; GENETIC-HETEROGENEITY; BIPOLAR DISORDER; ADHD; ASSOCIATION; AUTISM; 17P11; LOCI AB Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, there has been limited replications between the various independent datasets. The current study gathered the results from all seven of the ADHD linkage scans and performed a Genome Scan Meta Analysis (GSMA) to identify the genomic region with most consistent linkage evidence across the studies. Genome-wide significant linkage (P-SR = 0.00034, P-OR = 0.04) was identified on chromosome 16 between 64 and 83 Nth. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes. (c) 2008 Wiley-Liss, Inc. C1 [Asherson, Philip] Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. [Dempfle, Astrid; Nguyen, T. Trang; Schaefer, Helmut] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany. [Arcos-Burgos, Mauricio] Univ Miami, Dept Psychiat & Behav Sci, Leonard M Miller Sch Med, Miami, FL USA. [Arcos-Burgos, Mauricio; Muenkel, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Bakker, Steven C.; Sinke, Richard J.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Banaschewski, Tobias] Heidelberg Univ, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, D-6800 Mannheim, Germany. [Biederman, Joseph; Doyle, Alysa; Mick, Eric; Faraone, Stephen V.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Buitelaar, Jan; Franke, Barbara] Radboud Univ Nijmegen, Dept Psychiat, Donders Ctr Neurosci, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Castellanos, F. Xavier; Sonuga-Barke, Edmund J. S.] NYU, Ctr Child Study, New York, NY USA. [Ebstein, Richard P.] Geha MHC, Petah Tiqwa, Israel. [Ekholm, Jenny; Nelson, Stanley F.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. [Forabosco, Paola; Lewis, Cathryn M.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Forabosco, Paola] CNR, Ist Genet Popolaz, Alghero, Italy. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Freitag, Christine] Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Homburg, Germany. [Friedel, Susann; Hebebrand, Johannes; Hinney, Anke] Univ Duisburg Essen, Dept Child & Adolescent Psychiat, Essen, Germany. [Gill, Michael] St James Hosp, Trinity Ctr Hlth Sci, Dept Psychiat, Dublin 8, Ireland. [Jacob, Christian; Lesch, Klaus Peter; Reif, Andreas] Univ Wurzburg, Dept Psychiat & Psychotherapy, ADHD Clin Res Program, Wurzburg, Germany. [Loo, Sandra K.; McCracken, James T.; McGough, James J.; Smalley, Susan L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Lopera, Francisco; Palacio, Juan David; Pineda, David] Univ Antioquia, Neurosci Grp, Medellin, Colombia. [Meyer, Jobst] Univ Trier, Dept Neurobehav Genet, Trier, Germany. [Miranda, Ana] Univ Valencia, Dept Dev & Educ Psychol, Valencia, Spain. [Mulas, Fernando] La Fe Univ Hosp, Fac Med, Dept Neuropaediat, Valencia, Spain. [Oades, Robert D.] Univ Clin Child & Adolescent Psychiat, Essen, Germany. [Ogdie, Matthew N.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Renner, Tobias J.; Romanos, Marcel; Walitza, Susanne; Warnke, Andreas] Univ Wurzburg, Dept Child & Adolescent Psychiat & Psychotherapy, ADHD Clin Res Program, Wurzburg, Germany. [Roeyers, Herbert] Univ Ghent, B-9000 Ghent, Belgium. [Rothenberger, Aribert] Univ Gottingen, Gottingen, Germany. [Sergeant, Joseph] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Smalley, Susan L.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Sonuga-Barke, Edmund J. S.] Univ Southampton, Sch Psychol, Inst Disorder Impulse & Attent, Southampton, Hants, England. [Steinhausen, Hans-Christoph] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland. [van der Meulen, Emma] Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Asherson, P (reprint author), Kings Coll London, Inst Psychiat, MRC, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. EM p.asherson@iop.kcl.ac.uk RI Franke, Barbara/D-4836-2009; Lewis, Cathryn/A-5225-2010; Nelson, Stanley/D-4771-2009; Sonuga-Barke, Edmund/D-9137-2011; Dempfle, Astrid/D-1513-2012; Hinney, Anke/D-6953-2011; Buitelaar, Jan/E-4584-2012; Renner, Tobias/I-2120-2013; Miranda, Ana/G-8619-2015; Romanos, Marcel/D-7695-2017; Lesch, Klaus-Peter/J-4906-2013 OI Walitza, Susanne/0000-0002-8161-8683; Gill, Michael/0000-0003-0206-5337; Mick, Eric/0000-0001-8505-8145; Castellanos, Francisco/0000-0001-9192-9437; Faraone, Stephen/0000-0002-9217-3982; Franke, Barbara/0000-0003-4375-6572; Lewis, Cathryn/0000-0002-8249-8476; Hinney, Anke/0000-0001-5659-0706; Buitelaar, Jan/0000-0001-8288-7757; Miranda, Ana/0000-0001-6998-5686; Lesch, Klaus-Peter/0000-0001-8348-153X FU NIH [R01HD37694, R01MH62873]; NIMH [MH058277, MH071852]; Deutsche Forschungsgemeinschaft [DFG: KFO 125, SFB 581]; Bundesministerium ftir Bildung und Forschung [BMBF: 01GV0605]; MRC [G0400960] FX The Asherson et al. study is supported by NIH (R01HD37694 and R01MH62873 to S.V.F.). The Ogdie et al. study is supported by NIMH (MH058277 to S.L.S. and MH071852 to S.F.N.), and a fellowship from the Academy of Finland (Ekholm), The Bakker et al. study is supported by the Mammalian Genotyping Service of the Marshfield Medical Research Foundation, and by grants from the Makaria Foundation, the UMC Utrecht's Genvlag program, and the Catharijne Foundation, J.M. and C.F. are supported by the Deutsche Forschungsgemeinschaft (DFG ME 1923/5-1, ME 1923/5-3, GRK 1389/1); M.R., C.J., T.T.N., S.W., T.J.R., A.W., H.S., A.R., and K.P.L. are supported by the Deutsche Forschungsgemeinschaft (DFG: KFO 125, SFB 581) and the Bundesministerium ftir Bildung und Forschung (BMBF: 01GV0605), GSMA methodology development is supported by MRC (G0400960 to C.M.L.). NR 28 TC 98 Z9 99 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD DEC 5 PY 2008 VL 147B IS 8 SI SI BP 1392 EP 1398 DI 10.1002/ajmg.b.30878 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 379SF UT WOS:000261415800010 PM 18988193 ER PT J AU Zhang, LP Zhang, Y Ten Hagen, KG AF Zhang, Liping Zhang, Ying Ten Hagen, Kelly G. TI A Mucin-type O-Glycosyltransferase Modulates Cell Adhesion during Drosophila Development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; UDP-GALNAC; LINKED GLYCOSYLATION; SIGNALING PATHWAY; MEDIATED ADHESION; INTEGRIN SUBUNIT; GENETIC-ANALYSIS; MODIFIES NOTCH; PS2 INTEGRIN; EXPRESSION AB Cell-cell and cell-matrix adhesion are crucial during many stages of eukaryotic development. Here, we provide the first example that mucin-type O-linked glycosylation is involved in a developmentally regulated cell adhesion event in Drosophila melanogaster. Mutations in one member of the evolutionarily conserved family of enzymes that initiates O-linked glycosylation alter epithelial cell adhesion in the Drosophila wing blade. A transposon insertion mutation in pgant3 or RNA interference to pgant3 resulted in blistered wings, a phenotype characteristic of genes involved in integrin-mediated cell interactions. Expression of wild type pgant3 in the mutant background rescued the wing blistering phenotype, whereas expression of another family member (pgant35A) did not, revealing a unique requirement for pgant3. pgant3 mutants displayed reduced O-glycosylation along the basal surface of larval wing imaginal discs, which was restored with wild type pgant3 expression, suggesting that reduced glycosylation of basal proteins is responsible for disruption of adhesion in the adult wing blade. Glycosylation reactions demonstrated that PGANT3 glycosylates certain extracellular matrix (ECM) proteins. Immunoprecipitation experiments revealed that PGANT3 glycosylates tiggrin, an ECM protein known to bind integrin. We propose that this glycosyltransferase is uniquely responsible for glycosylating tiggrin in the wing disc, thus modulating proper cell adhesion through integrin-ECM interactions. This study provides the first evidence for the role of O-glycosylation in a developmentally regulated, integrin-mediated, cell adhesion event and reveals a novel player in wing blade formation during Drosophila development. C1 [Zhang, Liping; Zhang, Ying; Ten Hagen, Kelly G.] NIH, Dev Glycobiol Unit, NIDCR, Bethesda, MD 20892 USA. RP Ten Hagen, KG (reprint author), Bldg 30,Rm 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM Kelly.Tenhagen@nih.gov FU National Institutes of Health FX This work was supported, in whole or in part, by the National Institutes of Health (the Intramural Research Program of the NIDCR). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 49 TC 29 Z9 31 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 DEC 5 PY 2008 VL 283 IS 49 BP 34076 EP 34086 DI 10.1074/jbc.M804267200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 377UY UT WOS:000261277700036 PM 18835818 ER PT J AU Stith, CM Sterling, J Resnick, MA Gordenin, DA Burgers, PM AF Stith, Carrie M. Sterling, Joan Resnick, Michael A. Gordenin, Dmitry A. Burgers, Peter M. TI Flexibility of Eukaryotic Okazaki Fragment Maturation through Regulated Strand Displacement Synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-POLYMERASE-DELTA; REPLICATION PROTEIN-A; CELL NUCLEAR ANTIGEN; ESSENTIAL IN-VIVO; SACCHAROMYCES-CEREVISIAE; FLAP ENDONUCLEASE-1; LIGATABLE NICK; YEAST; SUBUNIT; ROLES AB Okazaki fragment maturation to produce continuous lagging strands in eukaryotic cells requires precise coordination of strand displacement synthesis by DNA polymerase delta (Pol delta) with 5'-flap cutting by FEN1(RAD27) endonuclease. Excessive strand displacement is normally prevented by the 3' -exonuclease activity of Pol delta. This core maturation machinery can be assisted by Dna2 nuclease/helicase that processes long flaps. Our genetic studies show that deletion of the POL32 (third subunit of Pol delta) or PIF1 helicase genes can suppress lethality or growth defects of rad27 Delta pol3-D520V mutants (defective for FEN1RAD27 and the 3' -exonuclease of Pol delta) that produce long flaps and of dna2 Delta mutants that are defective in cutting long flaps. On the contrary, pol32 Delta or pif1 Delta caused lethality of rad27 Delta exo1 Delta double mutants, suggesting that Pol32 and Pif1 are required to generate longer flaps that can be processed by Dna2 in the absence of the short flap processing activities of FEN1(RAD27) and Exo1. The genetic analysis reveals a remarkable flexibility of the Okazaki maturation machinery and is in accord with our biochemical analysis. In vitro, the generation of short flaps by Pol delta is not affected by the presence of Pol32; however, longer flaps only accumulate when Pol32 is present. The presence of FEN1(RAD27) during strand displacement synthesis curtails displacement in favor of flap cutting, thus suggesting an active hand-off mechanism from Pol delta to FEN1(RAD27). Finally, RNA-DNA hybrids are more readily displaced by Pol delta than DNA hybrids, thereby favoring degradation of initiator RNA during Okazaki maturation. C1 [Sterling, Joan; Resnick, Michael A.; Gordenin, Dmitry A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Stith, Carrie M.; Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Gordenin, DA (reprint author), NIEHS, Mol Genet Lab, NIH, D3-01,101 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM gordenin@niehs.nih.gov; burgers@biochem.wustl.edu OI Gordenin, Dmitry/0000-0002-8399-1836 FU National Institutes of Grant [GM32431]; National Institutes of Health [Z01 ES065073]; NIEHS FX This work was supported, in whole or in part, by National Institutes of Grant GM32431 (to P. M. B.) and by the Intramural Research Program of National Institutes of Health, Project 1 Z01 ES065073, of NIEHS (to J. M. A. R., and D. A. G.). The costs of publication of this article were in part by the payment of page charges. This article must therefore hereby marked "advertisement" in accordance with 18 U. S. C. Section solely to indicate this fact. NR 41 TC 66 Z9 66 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 DEC 5 PY 2008 VL 283 IS 49 BP 34129 EP 34140 DI 10.1074/jbc.M806668200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 377UY UT WOS:000261277700041 PM 18927077 ER PT J AU Kovalevsky, AY Louis, JM Aniana, A Ghosh, AK Weber, IT AF Kovalevsky, Andrey Y. Louis, John M. Aniana, Annie Ghosh, Arun K. Weber, Irene T. TI Structural Evidence for Effectiveness of Darunavir and Two Related Antiviral Inhibitors against HIV-2 Protease SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE drug resistance; aspartic protease; darunavir (TMC114) ID IMMUNODEFICIENCY-VIRUS TYPE-2; DRUG-RESISTANCE MUTATIONS; ELECTRON-DENSITY MAPS; ANTIRETROVIRAL THERAPY; CRYSTAL-STRUCTURES; INFECTED-PATIENTS; IN-VITRO; GROUP-O; POTENT; RESOLUTION AB No drug has been targeted specifically for HIV-2 (human immunodeficiency virus type 2) infection despite its increasing prevalence worldwide. The antiviral HIV-1 (human immunodeficiency virus type 1) protease (PR) inhibitor darunavir and the chemically related GRL98065 and GRL06579A were designed with the same chemical scaffold and different substituents at P2 and P2' to optimize polar interactions for HIV-1 PR (PR1). These inhibitors are also effective antiviral agents for HIV2-infected cells. Therefore, crystal structures of HIV-2 PR (PR2) complexes with the three inhibitors have been solved at 1.2-angstrom resolution to analyze the molecular basis for their antiviral potency. Unusually, the crystals were grown in imidazole and zinc acetate buffer, which formed interactions with the PR2 and the inhibitors. Overall, the structures were very similar to the corresponding inhibitor complexes of PR1 with in RMSD of 1.1 angstrom on main-chain atoms. Most hydrogen-bond and weaker C-H... 0 interactions with inhibitors were conserved in the PR2 and PR1 complexes, except for small changes in interactions with water or disordered side chains. Small differences were observed in the hydrophobic contacts for the darunavir complexes, in agreement with relative inhibition of the two PRs. These near-atomic-resolution crystal structures verify the inhibitor potency for PR1 and PR2 and will provide the basis for the development of antiviral inhibitors targeting PR2. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Kovalevsky, Andrey Y.; Weber, Irene T.] Georgia State Univ, Dept Biol, Mol Basis Dis Program, Atlanta, GA 30303 USA. [Louis, John M.; Aniana, Annie] NIDDKD, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Weber, Irene T.] Georgia State Univ, Dept Chem, Mol Basis Dis Program, Atlanta, GA 30303 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, Mol Basis Dis Program, POB 4010, Atlanta, GA 30303 USA. EM iweber@gsu.edu OI Kovalevsky, Andrey/0000-0003-4459-9142 FU Georgia Research Alliance; Georgia Cancer Coalition; National Institutes of Health [GM62920, GM053386]; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; U.S. Department of Energy [DE-AC02-06CH11357] FX The research was supported in part by the Georgia Research Alliance, the Georgia Cancer Coalition, the National Institutes of Health (grants GM62920, ITW and GM053386, AKG), and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. DE-AC02-06CH11357. We thank the staff at the SER-CAT beamline at the Advanced Photon Source, Argonne National Laboratory, for their assistance during X-ray data collection. NR 49 TC 20 Z9 22 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 DEC 5 PY 2008 VL 384 IS 1 BP 178 EP 192 DI 10.1016/j.jmb.2008.09.031 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372WN UT WOS:000260933100014 PM 18834890 ER PT J AU Saneyoshi, H Michel, BY Choi, Y Strazewski, P Marquez, VE AF Saneyoshi, Hisao Michel, Benoit Y. Choi, Yongseok Strazewski, Peter Marquez, Victor E. TI Synthesis of Conformationally Locked Versions of Puromycin Analogues SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID NUCLEOSIDES; MECHANISM AB Conformationally locked North and South versions Of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3'-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3'-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time. C1 [Saneyoshi, Hisao; Choi, Yongseok; Marquez, Victor E.] NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. [Michel, Benoit Y.; Strazewski, Peter] Univ Lyon 1, Lab Synth Biomol, Inst Chim & Biochim Mol & Supramol, UMR 5246, F-69622 Villeurbanne, France. RP Strazewski, P (reprint author), NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. EM strazewski@univ-lyon1.fr; marquev@mail.nih.gov RI Choi, Yongseok/F-8375-2012 OI Choi, Yongseok/0000-0002-3622-3439 FU Intramural Research Program of the NIH; Center for Cancer Research, NCI-Frederick FX This research was Supported in part by the Intramural Research Program of the NIH, Center for Cancer Research, NCI-Frederick. We gratefully acknowledge James A. Kelley, Christopher Lai, D. Bouchu and C. Duchamp for mass spectrometry results; B. Fenet and C. Gilbert for NMR analyses; and Dina M. Sigano for her help during the preparation of this manuscript. B.Y.M. is thankful for the Ministere de la Recherche for his graduate fellowship. NR 15 TC 8 Z9 8 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD DEC 5 PY 2008 VL 73 IS 23 BP 9435 EP 9438 DI 10.1021/jo8016132 PG 4 WC Chemistry, Organic SC Chemistry GA 378JD UT WOS:000261316100030 PM 18991379 ER PT J AU Johnson, CJ Berglin, L Chrenek, MA Redmond, TM Boatright, JH Nickerson, JM AF Johnson, Christiana J. Berglin, Lennart Chrenek, Micah A. Redmond, T. M. Boatright, Jeffrey H. Nickerson, John M. TI Technical Brief: Subretinal injection and electroporation into adult mouse eyes SO MOLECULAR VISION LA English DT Article ID MEDIATED GENE-TRANSFER; LEBERS CONGENITAL AMAUROSIS; DRUG-DELIVERY; IN-VIVO; FLUORESCENT PROTEIN; MAMMALIAN-CELLS; VISUAL FUNCTION; RABBIT RETINA; PLASMID DNA; THERAPY AB Purpose: Our goal was to improve and standardize the procedure for subretinal injection of mouse eyes. Also, we wished to optimize conditions for electroporation of retinal pigment epithelium (RPE) cells in the mouse eye with naked plasmids. Methods: Mouse eyes were injected subretinally with reporter plasmid DNA, nanobeads, or buffer. A blunt needle was introduced across the cornea, through the pupil, into the vitreous, until it made contact with the neural retina. Gentle pressure was applied to the needle, forcing it to puncture the retina and enter the subretinal space. Fluid was injected subretinally, raising large blebs evident on the mouse fundus. Subretinal injection surgery and outcomes were monitored and evaluated by video recording. Vidisic(R) aided in fundus examination of the blebs. Pores in RPE cells, across which the plasmid in the fluid could diffuse, were created by several short electrical bursts. Expression of the delivered gene, tdTomato, in the plasmid was examined under fluorescence microscopy to identify targeted cells. Electroporation conditions were varied from 0 to 200 V, 5 to 10 pulses, 0.1 ms to 100 ms duration of each pulse, and a space of 1.5 to 2 mm between electrodes on the cornea and sclera. Results: A critical sign of surgical success was the appearance and persistence of three large blebs in the mouse eye. This was illustrated by video recordings from two different systems. Application of VidisicR to the cornea made immediate examination of the fundus possible at the end of the surgery. An 80% success rate was readily achieved by following this method. Once a successful subretinal injection technique was established, electroporation conditions were evaluated. Parameters of 50 V, 1 ms pulse duration, 5-10 pulses, 1 s apart and electrodes spaced 1.5-2 mm apart with the anode placed on the sclera in the vicinity of the blebs produced a tight pattern of RPE transfection at approximately 30% efficiency. Conclusions: A standardized surgical method and a fast distinct indicator of successful surgery were essential to establishing a gene delivery system based on subsequent electroporation. With the surgery better controlled, electroporation was adequate to transfect a substantial number of RPE cells in a defined position in the globe. C1 [Johnson, Christiana J.; Berglin, Lennart; Chrenek, Micah A.; Boatright, Jeffrey H.; Nickerson, John M.] Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. [Berglin, Lennart] Karolinska Inst, St Eriks Eye Hosp, Stockholm, Sweden. [Redmond, T. M.] NEI, NIH, Bethesda, MD 20892 USA. RP Nickerson, JM (reprint author), Emory Univ, Dept Ophthalmol, Room B5602,1365B Clifton Rd NE, Atlanta, GA 30322 USA. EM litjn@emory.edu OI Redmond, T. Michael/0000-0002-1813-5291 FU National Eye Institute [R01EY016470, R01EY014026, P30EY006360, R24EY017045, T32EY007092]; Research to Prevent Blindness, Inc.; Foundation Fighting Blindness; Fight for Sight,; Intramural Research Program of the National Eye Institute FX This work was supported by the National Eye Institute (R01EY016470, R01EY014026, P30EY006360, R24EY017045, T32EY007092), an unrestricted grant to the Department of Ophthalmology at Emory University from Research to Prevent Blindness, Inc., the Foundation Fighting Blindness, Fight for Sight, and the Intramural Research Program of the National Eye Institute. We thank Dr. Ton N. M. Schumacher of the Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands, for the kind gift of the pVAX-tdTomato plasmid used in these studies. NR 63 TC 23 Z9 23 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 5 PY 2008 VL 14 IS 258-59 BP 2211 EP 2226 PG 16 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 413VR UT WOS:000263821100002 PM 19057658 ER PT J AU Roder, IV Petersen, Y Choi, KR Witzemann, V Hammer, JA Rudolf, R AF Roeder, Ira Verena Petersen, Yvonne Choi, Kyeong Rok Witzemann, Veit Hammer, John A., III Rudolf, Ruediger TI Role of Myosin Va in the Plasticity of the Vertebrate Neuromuscular Junction In Vivo SO PLOS ONE LA English DT Article AB Background: Myosin Va is a motor protein involved in vesicular transport and its absence leads to movement disorders in humans (Griscelli and Elejalde syndromes) and rodents (e. g. dilute lethal phenotype in mice). We examined the role of myosin Va in the postsynaptic plasticity of the vertebrate neuromuscular junction (NMJ). Methodology/Principal Findings: Dilute lethal mice showed a good correlation between the propensity for seizures, and fragmentation and size reduction of NMJs. In an aneural C2C12 myoblast cell culture, expression of a dominant-negative fragment of myosin Va led to the accumulation of punctate structures containing the NMJ marker protein, rapsyn-GFP, in perinuclear clusters. In mouse hindlimb muscle, endogenous myosin Va co-precipitated with surface-exposed or internalised acetylcholine receptors and was markedly enriched in close proximity to the NMJ upon immunofluorescence. In vivo microscopy of exogenous full length myosin Va as well as a cargo-binding fragment of myosin Va showed localisation to the NMJ in wildtype mouse muscles. Furthermore, local interference with myosin Va function in live wildtype mouse muscles led to fragmentation and size reduction of NMJs, exclusion of rapsyn-GFP from NMJs, reduced persistence of acetylcholine receptors in NMJs and an increased amount of punctate structures bearing internalised NMJ proteins. Conclusions/Significance: In summary, our data show a crucial role of myosin Va for the plasticity of live vertebrate neuromuscular junctions and suggest its involvement in the recycling of internalised acetylcholine receptors back to the postsynaptic membrane. C1 [Roeder, Ira Verena; Petersen, Yvonne; Choi, Kyeong Rok; Rudolf, Ruediger] Res Ctr Karlsruhe, Inst Toxicol & Genet, Eggenstein Leopoldshafen, Germany. [Witzemann, Veit] Max Planck Inst Med Res, D-69120 Heidelberg, Germany. [Hammer, John A., III] NIH, Lab Cell Biol, Bethesda, MD USA. RP Roder, IV (reprint author), Res Ctr Karlsruhe, Inst Toxicol & Genet, Eggenstein Leopoldshafen, Germany. EM ruediger.rudolf@itg.fzk.de RI Rudolf, Ruediger/A-6476-2009 OI Rudolf, Ruediger/0000-0002-0833-1053 FU DFG [RU923/3-1]; AFM [12056] FX RR was supported by grants from the DFG (RU923/3-1) and AFM (# 12056). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 31 Z9 31 U1 0 U2 0 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 DEC 5 PY 2008 VL 3 IS 12 AR e3871 DI 10.1371/journal.pone.0003871 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YP UT WOS:000265452300009 PM 19057648 ER PT J AU Timofeeva, OA Eremeev, AV Goloshchapov, A Kalashnikova, E Ilnitskaya, S Setkov, NA Kobzev, V Buzard, GS Filipenko, ML Kaledin, V Merkulova, TI AF Timofeeva, Olga A. Eremeev, Artem V. Goloshchapov, Andrey Kalashnikova, Eugenia Ilnitskaya, Svetlana Setkov, Nikolai A. Kobzev, Victor Buzard, Gregory S. Filipenko, Maxim L. Kaledin, Vasily . Merkulova, Tatyana I. TI Effects of o-aminoazotoluene on liver regeneration and p53 activation in mice susceptible and resistant to hepatocarcinogenesis SO TOXICOLOGY LA English DT Article DE o-Aminoazotoluene; Hepatocarcinogenesis; Susceptibility; Mitoinhibition; p53 ID HEPATOCELLULAR-CARCINOMA; RAT-LIVER; PARTIAL-HEPATECTOMY; PROTEIN EXPRESSION; GENE-EXPRESSION; CELL-PROLIFERATION; HEPATITIS-B; CARCINOGENESIS; MOUSE; PROMOTION AB The susceptibility to hepatocellular carcinoma (HCC) varies greatly within human populations in response to environmental risk agents. The mechanisms underlying differential susceptibility are still largely unknown and need to be clarified to improve HCC chemoprevention and therapeutic treatment. Inbred rodent strains with established predispositions for hepatocarcinogenesis offer the opportunity to identify intrinsic susceptibility and resistance factors. Previously, we have characterized mouse strains showing differential susceptibility to o-aminoazotoluene (OAT) and established that susceptibility does not result from OAT metabolism or genotoxicity in the livers of resistant and susceptible mice. In this study we have found that OAT differently affects hepatocyte proliferation in mice after partial hepatectomy (PH). OAT inhibited hepatocyte proliferation by 60-80% in the livers of susceptible mice, whereas resistant mice showed less than 15% inhibition. The inhibition resulted in significant delay of hepatic mass recovery in susceptible mice. OAT induced p53 stabilization and transcriptional activation in response to carcinogen treatment to the same degree in both, Susceptible and resistant mice. Taken together, our data support inhibition of hepatocyte proliferation as a major cause for increased mouse susceptibility to hepatocarcinogenesis, and acceleration of functional liver recovery may offer a way to increase resistance to hepatic neoplasms. These results may have relevance to clinical observations of HCCs and implications for HCC chemoprevention and treatment. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Timofeeva, Olga A.; Goloshchapov, Andrey; Kalashnikova, Eugenia; Filipenko, Maxim L.] Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia. [Timofeeva, Olga A.] NCI, Lab Comparat Carcinogenesis, Ctr Canc Res, Frederick, MD 21702 USA. [Eremeev, Artem V.] Federal Agcy Hlth Care & Social Dev, Krasnoyark State Med Acad, Krasnoyarsk 660022, Russia. [Ilnitskaya, Svetlana; Kobzev, Victor; Kaledin, Vasily .; Merkulova, Tatyana I.] Inst Cytol & Genet, Novosibirsk 630090, Russia. [Setkov, Nikolai A.] Krasnoyarsk Sci Ctr, Krasnoyarsk 660036, Russia. [Buzard, Gregory S.] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Timofeeva, OA (reprint author), Georgetown Univ, Med Ctr, 3900 Reservoir Rd,NW, Washington, DC 20057 USA. EM oat@georgetown.edu RI Merkulova, Tatyana/R-9163-2016 FU Russian Foundation for Basic Research [06-04-48575, 07-04-00441]; NIH; National Cancer Institute; Center for Cancer Research FX We thank Professor A. Dritschilo for his helpful comments on the manuscript. This work was supported by Russian Foundation for Basic Research (grants 06-04-48575 and 07-04-00441) and in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 54 TC 3 Z9 5 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 5 PY 2008 VL 254 IS 1-2 BP 91 EP 96 DI 10.1016/j.tox.2008.09.013 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 385TS UT WOS:000261837100011 PM 18852010 ER PT J AU He, PF Borland, MG Zhu, BA Sharma, AK Amin, S El-Bayoumy, K Gonzalez, FJ Peters, JM AF He, Pengfei Borland, Michael G. Zhu, Bokai Sharma, Arun K. Amin, Shantu El-Bayoumy, Karam Gonzalez, Frank J. Peters, Jeffrey M. TI Effect of ligand activation of peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) in human lung cancer cell lines SO TOXICOLOGY LA English DT Article DE Peroxisome proliferator-activated receptor; Lung cancer; Nuclear receptor; Cell proliferation; PTEN ID GROWTH; EXPRESSION; MICE; DIFFERENTIATION; CARCINOGENESIS; KERATINOCYTES; DELTA AB There is compelling evidence that peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) mediates terminal differentiation and is associated with inhibition of cell growth. However, it was recently suggested that growth of two human lung cancer cell lines is enhanced by PPAR beta/delta. The goal of the present study was to provide insight in resolving this controversy. Therefore, the effect of ligand activation of PPAR beta/delta in A549 and H 1838 human lung cancer cell lines was examined using two high affinity PPAR beta/delta ligands. Ligand activation of PPAR beta/delta caused up-regulation of a known PPAR beta/delta target gene, angiopoietin-like 4 (Angptl4) but did not influence expression of phosphatase and tensin homolog (PTEN) or phosphorylation of protein kinase B (Akt), and did not affect cell growth. Results from this study demonstrate that two human lung cancer cell lines respond to ligand activation of PPAR beta/delta by modulation of target gene expression (Angptl4), but fail to exhibit significant modulation of cell proliferation. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [He, Pengfei; Borland, Michael G.; Zhu, Bokai; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Borland, Michael G.; Peters, Jeffrey M.] Penn State Univ, Grad Program Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA. [Sharma, Arun K.; Amin, Shantu] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Hershey, PA 17033 USA. [El-Bayoumy, Karam] Penn State Univ, Milton S Hershey Med Ctr, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU National Institutes of Health [CA124533] FX Funding source: Supported in part by the National Institutes of Health grants CA124533 (J.M.P.). NR 18 TC 18 Z9 18 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 5 PY 2008 VL 254 IS 1-2 BP 112 EP 117 DI 10.1016/j.tox.2008.09.023 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 385TS UT WOS:000261837100014 PM 18950674 ER PT J AU Williams, JP Wu, JQ Johansson, G Rizvi, TA Miller, SC Geiger, H Malik, P Li, WL Mukouyama, YS Cancelas, JA Ratner, N AF Williams, Jon P. Wu, Jianqiang Johansson, Gunnar Rizvi, Tilat A. Miller, Shyra C. Geiger, Hartmut Malik, Punam Li, Wenling Mukouyama, Yoh-suke Cancelas, Jose A. Ratner, Nancy TI Nf1 Mutation Expands an EGFR-Dependent Peripheral Nerve Progenitor that Confers Neurofibroma Tumorigenic Potential SO CELL STEM CELL LA English DT Article ID CREST STEM-CELLS; GROWTH-FACTOR RECEPTOR; MAMMALIAN NEURAL CREST; SCHWANN-CELLS; SELF-RENEWAL; BOUNDARY CAP; GLIAL-CELLS; DIFFERENTIATION; TUMORS; EXPRESSION AB Defining growth factor requirements for progenitors facilitates their characterization and amplification. We characterize a peripheral nervous system embryonic dorsal root ganglion progenitor population using in vitro clonal sphere-formation assays. Cells differentiate into glial cells, smooth muscle/fibroblast (SM/Fb)-like cells, and neurons. Genetic and pharmacologic tools revealed that sphere formation requires signaling from the EGFR tyrosine kinase. Nf1 loss of function amplifies this progenitor pool, which becomes hypersensitive to growth factors and confers tumorigenesis. DhhCre;Nf1(fl/fl) mouse neurofibromas contain a progenitor population with similar growth requirements, potential, and marker expression. In humans, NF1 mutation predisposes to benign neurofibromas, incurable peripheral nerve tumors. Prospective identification of human EGFR(+);P75(+) neurofibroma cells enriched EGF-dependent sphere-forming cells. Neurofibroma spheres contain glial-like progenitors that differentiate into neurons and SM/Fb-like cells in vitro and form benign neurofibroma-like lesions in nude mice. We suggest that expansion of an EGFR-expressing early glial progenitor contributes to neurofibroma formation. C1 [Williams, Jon P.; Wu, Jianqiang; Johansson, Gunnar; Rizvi, Tilat A.; Miller, Shyra C.; Geiger, Hartmut; Malik, Punam; Cancelas, Jose A.; Ratner, Nancy] Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Li, Wenling; Mukouyama, Yoh-suke] NHLBI, Dev Biol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. [Cancelas, Jose A.] Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH 45229 USA. RP Ratner, N (reprint author), Cincinnati Childrens Hosp Med Ctr, Cincinnati Childrens Hosp Res Fdn, Div Expt Hematol & Canc Biol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org FU National Institutes of Health (NIH) [R01-NS 28840] FX We thank M. Nakafuku (Cincinnati Children's Hospital Medical Center) for numerous helpful suggestions, A. Stemmer-Racham imov (Massachusetts General Hospital) and M. Collins (Cincinnati Children's) for assistance with pathology, and B. Ehmer for assistance with confocal microscopy. We also thank the Cooperative Human Tissue Network for assistance in providing human neurofibroma. This work was supported by National Institutes of Health (NIH) R01-NS 28840 to N.R. NR 56 TC 27 Z9 27 U1 1 U2 1 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 DEC 4 PY 2008 VL 3 IS 6 BP 658 EP 669 DI 10.1016/j.stem.2008.10.003 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 383JW UT WOS:000261670900014 PM 19041782 ER PT J AU Ravin, R Hoeppner, DJ Munno, DM Carmel, L Sullivan, J Levitt, DL Miller, JL Athaide, C Panchision, DM Mckay, RDG AF Ravin, Rea Hoeppner, Daniel J. Munno, David M. Carmel, Liran Sullivan, Jim Levitt, David L. Miller, Jennifer L. Athaide, Christopher Panchision, David M. Mckay, Ronald D. G. TI Potency and Fate Specification in CNS Stem Cell Populations In Vitro SO CELL STEM CELL LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; DIFFERENTIATION; NEURONS; PROLIFERATION; NEUROGENESIS; GLIOGENESIS; DIVISIONS; LINEAGES; REVEALS AB To realize the promise of stem cell biology, it is important to identify the precise time in the history of the cell when developmental potential is restricted. To achieve this goal, we developed a real-time imaging system that captures the transitions in fate, generating neurons, astrocytes, and oligodendrocytes from single CNS stem cells in vitro. In the presence of bFGF, tripotent cells normally produce specified progenitors through a bipotent intermediate cell type. Surprisingly, the tripotent state is reset at each passage. The cytokine CNTF is thought to instruct multipotent cells to an astrocytic fate. We demonstrate that CNTF both directs astrogliogenesis from tripotent cells, bypassing two of the three normal bipotent intermediates, and later promotes the expansion of specified astrocytic progenitors. These results show how discrete cell types emerge from a multipotent cell and provide a strong basis for future studies to determine the molecular basis of fate specification. C1 [Ravin, Rea; Hoeppner, Daniel J.; Munno, David M.; Sullivan, Jim; Levitt, David L.; Miller, Jennifer L.; Mckay, Ronald D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Carmel, Liran] Natl Lib Med, NIH, Bethesda, MD 20894 USA. [Athaide, Christopher] EYE Biomachines, Houston, TX 77005 USA. [Panchision, David M.] Childrens Natl Med Ctr, Neurosci Res Ctr, Childrens Res Inst, Washington, DC 20010 USA. RP Mckay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov FU NIH; NINDS FX Several students contributed to the manual annotation of lineages in development of this project, including Daniel Ahmad, Kathleen Bandit, Elizabeth Baumel, Vince Beachley, Pavana Beerelli, Alissa Berliner, Sarah Gan, Brinda Gupta. Daniel Holohan, Josh Lieberman, Reut Mushkat, Christopher Nabel, Meghan Nelson, Emily Prentice, Nicole Ramsey, Jean Suh, and Sahar Zadeh. Professors Ralf Schnabel and Anja-Kristin Schulz provided a script for extracting data from SIMI'BioCell. The authors thank Kang Li and Takeo Kanade (Carnegie Mellon University) for the image stabilizer plugin to ImageJ and Wayne Rasband (NIH) for supporting ImageJ. This research was supported by the Intramural Research Program of the NIH, NINDS. NR 35 TC 67 Z9 67 U1 0 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 DEC 4 PY 2008 VL 3 IS 6 BP 670 EP 680 DI 10.1016/j.stem.2008.09.012 PG 11 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 383JW UT WOS:000261670900015 PM 19041783 ER PT J AU Di Bisceglie, AM Shiffman, ML Everson, GT Lindsay, KL Everhart, JE Wright, EC Lee, WM Lok, AS Bonkovsky, HL Morgan, TR Ghany, MG Morishima, C Snow, KK Dienstag, JL AF Di Bisceglie, Adrian M. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Everhart, James E. Wright, Elizabeth C. Lee, William M. Lok, Anna S. Bonkovsky, Herbert L. Morgan, Timothy R. Ghany, Marc G. Morishima, Chihiro Snow, Kristin K. Dienstag, Jules L. CA HALT-C Trial Investigators TI Prolonged Therapy of Advanced Chronic Hepatitis C with Low-Dose Peginterferon SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEPATOCELLULAR-CARCINOMA; INTERFERON THERAPY; VIRUS-INFECTION; TRIAL; RIBAVIRIN; NONRESPONDERS; INHIBITOR; CIRRHOSIS; ALPHA-2A; RISK AB Background: In patients with chronic hepatitis C who do not have a response to antiviral treatment, the disease may progress to cirrhosis, liver failure, hepatocellular carcinoma, and death. Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain. Methods: We conducted a randomized, controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years, as compared with no treatment, in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified according to stage of fibrosis (622 with noncirrhotic fibrosis and 428 with cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indicated by death, hepatocellular carcinoma, hepatic decompensation, or, for those with bridging fibrosis at baseline, an increase in the Ishak fibrosis score of 2 or more points. Results: We randomly assigned the patients to receive peginterferon (517 patients) or no therapy (533 patients) for 3.5 years. The level of serum aminotransferases, the level of serum hepatitis C virus RNA, and histologic necroinflammatory scores all decreased significantly (P<0.001) with treatment, but there was no significant difference between the groups in the rate of any primary outcome (34.1% in the treatment group and 33.8% in the control group; hazard ratio, 1.01; 95% confidence interval, 0.81 to 1.27; P=0.90). The percentage of patients with at least one serious adverse event was 38.6% in the treatment group and 31.8% in the control group (P=0.07). Conclusions: Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis, with or without cirrhosis, who had not had a response to initial treatment with peginterferon and ribavirin. (ClinicalTrials.gov number, NCT00006164.). C1 [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, Dept Internal Med, St Louis, MO 63110 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Everson, Gregory T.] Univ Colorado, Sch Med, Denver, CO 80202 USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Everhart, James E.; Wright, Elizabeth C.; Ghany, Marc G.] NIDDKD, Bethesda, MD 20892 USA. [Lee, William M.] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Morgan, Timothy R.] Univ Calif Irvine, Irvine, CA USA. [Morgan, Timothy R.] Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. [Morishima, Chihiro] Univ Washington, Seattle, WA 98195 USA. [Snow, Kristin K.] New England Res Inst, Watertown, MA 02172 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, Dept Internal Med, 3635 Vista Ave, St Louis, MO 63110 USA. EM dibiscam@slu.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Cancer Institute,; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institute on Alcohol Abuse and Alcoholism [K24 AA13736]; Hoffmann-La Roche; Idenix Pharmaceuticals; Novartis; Vertex Pharmaceuticals; Bristol- Myers Squibb; Abbott; Schering-Plough; Anadys; GlobeImmune; Pharmasset; SciClone Pharmaceuticals; Clinical Care Options; Gilead; Geneva Foundation; Hoffmann La Roche; Biolex; Valeant Pharmaceuticals; GlaxoSmithKline; Novartis/Human Genome Sciences; King Pharmaceuticals; Peregrine Pharmaceuticals; Roche Diagnostics; ZymoGenetics; Wyeth Pharmaceuticals; Eli Lilly; FibroGen; AstraZeneca; Siemens; Ovation Pharmaceuticals; Boehringer-Ingelheim; Cardax Pharmaceuticals; Achillion Pharmaceuticals; Avant Immunotherapeutics; CombinatoRx; Cubist Pharmaceuticals; Nucleonics; Oxxon; Metabasis; Amgen; Biogen; EnablEd and Clinical Care Options FX Supported by contracts from the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, the National Center for Research Resources, and the National Institute on Alcohol Abuse and Alcoholism (K24 AA13736); and by Hoffmann-La Roche through a Cooperative Research and Development Agreement with the National Institutes of Health.; Dr. Di Bisceglie reports receiving consulting fees from Hoffmann-La Roche, Idenix Pharmaceuticals, Novartis, Vertex Pharmaceuticals, Bristol- Myers Squibb, Abbott, Schering-Plough, Anadys, GlobeImmune, Pharmasset, and SciClone Pharmaceuticals; lecture fees from Novartis and Clinical Care Options; and grant support from Hoffmann- La Roche, Idenix Pharmaceuticals, Vertex Pharmaceuticals, Bristol-Myers Squibb, GlobeImmune, Pharmasset, Gilead, Geneva Foundation, and SciClone Pharmaceuticals; Dr. Shiffman, receiving consulting fees from Hoffmann La Roche, Biolex, Valeant Pharmaceuticals, and GlaxoSmithKline; lecture fees from Hoffmann-La Roche; and grant support from Schering-Plough, Valeant Pharmaceuticals, Vertex Pharmaceuticals, and Hoffmann-La Roche; Dr. Everson, receiving consulting fees from Hoffmann-La Roche and Vertex Pharmaceuticals, lecture fees from Hoffmann-La Roche, and grant support from Hoffmann-La Roche, Schering- Plough, Vertex Pharmaceuticals, Pharmasset, and Novartis/Human Genome Sciences; Dr. Lindsay, receiving consulting fees from Hoffmann-La Roche, Bristol-Myers Squibb, Human Genome Sciences, Idenix Pharmaceuticals, King Pharmaceuticals, Peregrine Pharmaceuticals, Roche Diagnostics, Valeant Pharmaceuticals, and ZymoGenetics; grant support from Hoffmann-La Roche, Idenix Pharmaceuticals, Human Genome Sciences, Schering- Plough, Valeant Pharmaceuticals, Vertex Pharmaceuticals, and Wyeth Pharmaceuticals; and lecture fees from Clinical Care Options; Dr. Lee, receiving consulting fees from Eli Lilly, FibroGen, and AstraZeneca and grant support from Hoffmann-La Roche, Schering-Plough, Vertex Pharmaceuticals, GlaxoSmithKline, Siemens, GlobeImmune, and Bristol- Myers Squibb; Dr. Lok, receiving consulting fees and grant support from Hoffmann-La Roche and Schering-Plough; Dr. Bonkovsky, receiving consulting fees from Novartis, Ovation Pharmaceuticals, and Boehringer- Ingelheim; lecture fees from Ovation Pharmaceuticals; and grant support from Novartis, Vertex Pharmaceuticals, and Hoffmann-La Roche; Dr. Morgan, receiving consulting fees from Hoffmann-La Roche, Vertex Pharmaceuticals, Cardax Pharmaceuticals, and Valeant Pharmaceuticals and lecture fees and grant support from Hoffmann-La Roche and Schering- Plough; and Dr. Dienstag, receiving consulting fees from Achillion Pharmaceuticals, Avant Immunotherapeutics, CombinatoRx, Bristol- Myers Squibb, Cubist Pharmaceuticals, Nucleonics, Pharmasset, SciClone Pharmaceuticals, Human Genome Sciences, Oxxon, Metabasis, Schering- Plough, Amgen, AstraZeneca, Biogen, Vertex Pharmaceuticals, Wyeth Pharmaceuticals, and Gilead; receiving lecture fees from EnablEd and Clinical Care Options; receiving grant support from Vertex Pharmaceuticals; and holding stock options in Metabasis, Achillion Pharmaceuticals, and Nucleonics. No other potential conflict of interest relevant to this article was reported. NR 20 TC 277 Z9 281 U1 1 U2 4 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 DEC 4 PY 2008 VL 359 IS 23 BP 2429 EP 2441 DI 10.1056/NEJMoa0707615 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 378MT UT WOS:000261325900004 PM 19052125 ER PT J AU Jain, R Dey, B Dhar, N Rao, V Singh, R Gupta, UD Katoch, VM Ramanathan, VD Tyagi, AK AF Jain, Ruchi Dey, Bappaditya Dhar, Neeraj Rao, Vivek Singh, Ramandeep Gupta, Umesh D. Katoch, V. M. Ramanathan, V. D. Tyagi, Anil K. TI Enhanced and Enduring Protection against Tuberculosis by Recombinant BCG-Ag85C and Its Association with Modulation of Cytokine Profile in Lung SO PLOS ONE LA English DT Article AB Background: The variable efficacy (0-80%) of Mycobacterium bovis Bacille Calmette Gurein (BCG) vaccine against adult tuberculosis (TB) necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG) over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. Methods/Principal Findings: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immunodominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10), p<0.01) and spleen (2.36 log(10), p<0.001) bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL)-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF)-beta along with up-regulation of inducible nitric oxide synthase (iNOS). In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. Conclusions/Significance: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all likelihood would show enhanced survival of guinea pigs. C1 [Jain, Ruchi; Dey, Bappaditya; Dhar, Neeraj; Rao, Vivek; Singh, Ramandeep; Tyagi, Anil K.] Univ Delhi, Dept Biochem, New Delhi, India. [Gupta, Umesh D.; Katoch, V. M.] Natl JALMA Inst Leprosy & Other Mycobact Dis, Agra, Uttar Pradesh, India. [Ramanathan, V. D.] Tuberculosis Res Ctr, Dept Clin Pathol, Chennai, India. [Dhar, Neeraj] Ecole Polytech Fed Lausanne, Glob Hlth Inst, Lab Bacteriol, Lausanne, Switzerland. [Rao, Vivek] Ridgeweay Mill Hill, Natl Inst Med Res, Div Mycobacter Res, London, England. [Singh, Ramandeep] NIAID, NIH, Lab Clin Infect Dis, Tuberculosis Res Sect, Bethesda, MD USA. RP Jain, R (reprint author), Univ Delhi, Dept Biochem, South Campus, New Delhi, India. EM aniltyagi@south.du.ac.in RI Dhar, Neeraj/K-8171-2013; OI Dhar, Neeraj/0000-0002-5887-8137; Dey, Bappaditya/0000-0003-2728-4683 FU Department of Biotechnology, Ministry of Science and Technology, India; Council of Scientific and Industrial Research, Government of India [research fellowship] FX This work was supported by a research grant to AKT and VDR from the Department of Biotechnology, Ministry of Science and Technology, India. RJ and BD acknowledge Council of Scientific and Industrial Research, Government of India for research fellowship (CSIR JRF/SRF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 32 Z9 34 U1 0 U2 1 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 DEC 4 PY 2008 VL 3 IS 12 AR e3869 DI 10.1371/journal.pone.0003869 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YO UT WOS:000265452200013 PM 19052643 ER PT J AU Srivastava, S Zhang, LX Jin, R Chan, C AF Srivastava, Shireesh Zhang, Linxia Jin, Rong Chan, Christina TI A Novel Method Incorporating Gene Ontology Information for Unsupervised Clustering and Feature Selection SO PLOS ONE LA English DT Article AB Background: Among the primary goals of microarray analysis is the identification of genes that could distinguish between different phenotypes (feature selection). Previous studies indicate that incorporating prior information of the genes' function could help identify physiologically relevant features. However, current methods that incorporate prior functional information do not provide a relative estimate of the effect of different genes on the biological processes of interest. Results: Here, we present a method that integrates gene ontology (GO) information and expression data using Bayesian regression mixture models to perform unsupervised clustering of the samples and identify physiologically relevant discriminating features. As a model application, the method was applied to identify the genes that play a role in the cytotoxic responses of human hepatoblastoma cell line (HepG2) to saturated fatty acid (SFA) and tumor necrosis factor (TNF)-alpha, as compared to the non-toxic response to the unsaturated FFAs (UFA) and TNF-alpha. Incorporation of prior knowledge led to a better discrimination of the toxic phenotypes from the others. The model identified roles of lysosomal ATPases and adenylate cyclase (AC9) in the toxicity of palmitate. To validate the role of AC in palmitate-treated cells, we measured the intracellular levels of cyclic AMP (cAMP). The cAMP levels were found to be significantly reduced by palmitate treatment and not by the other FFAs, in accordance with the model selection of AC9. Conclusions: A framework is presented that incorporates prior ontology information, which helped to (a) perform unsupervised clustering of the phenotypes, and (b) identify the genes relevant to each cluster of phenotypes. We demonstrate the proposed framework by applying it to identify physiologically-relevant feature genes that conferred differential toxicity to saturated vs. unsaturated FFAs. The framework can be applied to other problems to efficiently integrate ontology information and expression data in order to identify feature genes. C1 [Srivastava, Shireesh; Zhang, Linxia; Chan, Christina] Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. [Jin, Rong; Chan, Christina] Michigan State Univ, Dept Comp Sci & Engn, E Lansing, MI 48824 USA. [Chan, Christina] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. RP Srivastava, S (reprint author), NIAAA, Lab Metab Control, Rockville, MD 20852 USA. EM krischan@egr.msu.edu FU National Science Foundation [BES 0425821, IIS-0643494]; National Institute of Health [1R01GM079688-01, 1R21CA126136-01]; Environmental Protection Agency [RD83184701]; MSU Foundation; Center for Systems Biology FX This research was supported by the National Science Foundation (BES 0425821 and IIS-0643494), the National Institute of Health (1R01GM079688-01 and 1R21CA126136-01), the Environmental Protection Agency (RD83184701), and the MSU Foundation and the Center for Systems Biology. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 8 Z9 8 U1 0 U2 4 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 DEC 4 PY 2008 VL 3 IS 12 AR e3860 DI 10.1371/journal.pone.0003860 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YO UT WOS:000265452200010 PM 19052637 ER PT J AU Guo, XA Silva, JC AF Guo, Xiang Silva, Joana C. TI Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva SO BMC GENOMICS LA English DT Article ID NF-KAPPA-B; TRANSFORMING PARASITE THEILERIA; IMMUNODEFICIENCY-VIRUS TYPE-1; HOST-PATHOGEN INTERACTIONS; PLASMODIUM-FALCIPARUM; TRANSCRIPTION FACTORS; GENOME SEQUENCE; SELECTIVE CONSTRAINT; PROKARYOTIC GENOMES; TOXOPLASMA-GONDII AB Background: Parasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species. Results: Intergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know regulatory motifs in other species. These results suggest that these two motifs are likely to represent transcription factor binding sites in Theileria. Conclusion: Theileria genomes are highly compact, with selection seemingly favoring short introns and intergenic regions. Three over-represented sequence motifs were independently identified in intergenic regions of both Theileria species, and the evidence suggests that at least two of them play a role in transcriptional control in T. parva. These are prime candidates for experimental validation of transcription factor binding sites in this single-celled eukaryotic parasite. Sequences similar to two of these Theileria motifs are conserved in Plasmodium hinting at the possibility of common regulatory machinery across the phylum Apicomplexa. C1 [Guo, Xiang; Silva, Joana C.] J Craig Venter Inst, Inst Genom Res, Rockville, MD 20850 USA. [Guo, Xiang] SAIC Frederick Inc, NCI Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Silva, Joana C.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Silva, Joana C.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Guo, XA (reprint author), J Craig Venter Inst, Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. EM guo424@gmail.com; jcsilva@som.umaryland.edu NR 67 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD DEC 3 PY 2008 VL 9 AR 582 DI 10.1186/1471-2164-9-582 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 390WW UT WOS:000262195400001 PM 19055776 ER PT J AU Allen, AM O'Callaghan, EL Hazelwood, L Germain, S Castrop, H Schnermann, J Bassi, JK AF Allen, A. M. O'Callaghan, E. L. Hazelwood, L. Germain, S. Castrop, H. Schnermann, J. Bassi, J. K. TI Distribution of cells expressing human renin-promoter activity in the brain of a transgenic mouse SO BRAIN RESEARCH LA English DT Article DE Brain renin-angiotensin system; Neurochemistry; Brain development ID ANGIOTENSIN CONVERTING ENZYME; II RECEPTOR SUBTYPES; RAT-BRAIN; CRE RECOMBINASE; IMMUNOCYTOCHEMICAL LOCALIZATION; GENE-TRANSCRIPTION; GS-ALPHA; SYSTEM; TISSUE; MICE AB Renin plays a critical role in fluid and electrolyte homeostasis by cleaving angiotensinogen to produce Ang peptides. Whilst it has been demonstrated that renin mRNA is expressed in the brain, the distribution of cells responsible for this expression remains uncertain. We have used a transgenic mouse approach in an attempt to address this question. A transgenic mouse, in which a 12.2 kb fragment of the human renin promoter was used to drive expression of Cre-recombinase, was crossed with the ROSA26-lac Z reporter mouse strain. Cre-recombinase mediated excision of the floxed stop cassette resulted in expression of the reporter protein, beta-galactosidase. This study describes the distribution of beta-galactosidase in the brain of the crossed transgenic mouse. in all cases where it was examined the reporter protein was co-localized with the neuronal marker NeuN. An extensive distribution was observed with numerous cells labeled in the somatosensory, insular, piriform and retrosplenial cortices. The motor cortex was devoid of labeled cells. Several other regions were labeled including the parts of the amygdala, periaqueductal gray, lateral parabrachial nucleus and deep cerebellar nuclei. Overall the distribution shows little overlap with those regions that are known to express receptors for the renin-angiotensin system in the adult brain. This transgenic approach, which demonstrates the distribution of cells which have activated the human renin promoter at any time throughout development, yields a unique and extensive distribution of putative renin-expressing neurons. Our observations suggest that renin may have broader actions in the brain and may indicate a potential for interaction with the (pro)renin receptor or production of a ligand for non-AT(1)/AT(2) receptors. (C) 2008 Elsevier B.V. All rights reserved. C1 [Allen, A. M.; O'Callaghan, E. L.; Hazelwood, L.; Bassi, J. K.] Univ Melbourne, Dept Physiol, Melbourne, Vic 3010, Australia. [Germain, S.] Coll France, INSERM, U833, F-75231 Paris, France. [Castrop, H.; Schnermann, J.] Univ Regensburg, Inst Physiol, Regensburg, Germany. [Castrop, H.] NIDDK, NIH, Bethesda, MD USA. RP Allen, AM (reprint author), Univ Melbourne, Dept Physiol, Melbourne, Vic 3010, Australia. EM a.allen@unimelb.edu.au RI Germain, Stephane/E-2301-2016; OI Germain, Stephane/0000-0001-5992-1275; O'Callaghan, Erin/0000-0003-0602-8779; Allen, Andrew Mark/0000-0002-2183-5360 FU Australian National Heart Foundation; National Health and Medical Research Council of Australia; Deutsche Forschungsgemeinschaft [CA278/4-1] FX This work was supported by project grant funding from the Australian National Heart Foundation, the National Health and Medical Research Council of Australia and the Deutsche Forschungsgemeinschaft (CA278/4-1). NR 46 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 3 PY 2008 VL 1243 BP 78 EP 85 DI 10.1016/j.brainres.2008.09.046 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 384YL UT WOS:000261780000010 PM 18840419 ER PT J AU Wang, NN Yang, GR Jia, ZJ Zhang, H Aoyagi, T Soodvilai, S Symons, JD Schnermann, JB Gonzalez, FJ Litwin, SE Yang, T AF Wang, Ningning Yang, Guangrui Jia, Zhanjun Zhang, Hui Aoyagi, Toshinori Soodvilai, Sunhapas Symons, J. David Schnermann, Jurgen B. Gonzalez, Frank J. Litwin, Sheldon E. Yang, Tianxin TI Vascular PPAR gamma Controls Circadian Variation in Blood Pressure and Heart Rate through Bmal1 SO CELL METABOLISM LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; GENE-EXPRESSION; PERIPHERAL-TISSUES; ENDOTHELIAL-CELLS; SUPRACHIASMATIC NUCLEUS; ESSENTIAL COMPONENTS; METABOLIC SYNDROME; DEFICIENT MICE; MESSENGER-RNA; FEEDBACK LOOP AB Thiazolidinediones (TZDs) are PPAR gamma activators that exhibit vasculoprotective properties. To determine the vascular function of PPAR gamma, we analyzed Tie2-Cre/flox and SM22Cre/flox mice. Unexpectedly, both knockout strains exhibited a significant reduction of circadian variations in blood pressure and heart rate in parallel with diminished variations in urinary norepinephrine/epinephrine excretion and impaired rhythmicity of the canonical clock genes, including Bmal1. PPAR gamma expression in the aorta exhibited a robust rhythmicity with a more than 20-fold change during the light/dark cycle. Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPAR gamma target gene. These studies have uncovered a role for vascular PPAR gamma as a peripheral factor participating in regulation of cardiovascular rhythms. C1 [Wang, Ningning; Yang, Guangrui; Jia, Zhanjun; Zhang, Hui; Aoyagi, Toshinori; Soodvilai, Sunhapas; Litwin, Sheldon E.; Yang, Tianxin] Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. [Wang, Ningning; Yang, Guangrui; Jia, Zhanjun; Zhang, Hui; Aoyagi, Toshinori; Soodvilai, Sunhapas; Litwin, Sheldon E.; Yang, Tianxin] Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA. [Symons, J. David] Univ Utah, Coll Hlth, Salt Lake City, UT 84132 USA. [Symons, J. David] Univ Utah, Div Endocrinol Diabet & Metab, Salt Lake City, UT 84132 USA. [Schnermann, Jurgen B.] NIDDKD, Bethesda, MD 20892 USA. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. [Gonzalez, Frank J.] NIH, Bethesda, MD 20892 USA. RP Yang, T (reprint author), Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. EM tianxin.yang@hsc.utah.edu RI Aoyagi, Toshinori/A-2689-2011; YANG, GUANGRUI/F-9693-2013 OI YANG, GUANGRUI/0000-0002-8310-8257 FU Department of Veterans Affairs; National Institute of Health [RO-1 HL079453] FX This work was supported by Merit Review from the Department of Veterans Affairs as well as RO-1 HL079453 from National Institute of Health (to T.Y.). NR 55 TC 106 Z9 113 U1 2 U2 6 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 DEC 3 PY 2008 VL 8 IS 6 BP 482 EP 491 DI 10.1016/j.cmet.2008.10.009 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 379EN UT WOS:000261379600007 PM 19041764 ER PT J AU Epley, KE Urban, JM Ikenaga, T Ono, F AF Epley, Kimberly E. Urban, Jason M. Ikenaga, Takanori Ono, Fumihito TI A Modified Acetylcholine Receptor delta-Subunit Enables a Null Mutant to Survive Beyond Sexual Maturation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE zebrafish; neuromuscular junction; acetylcholine receptor; synapse; fetal akinesia deformation sequence; fluorescent protein ID GREEN-FLUORESCENT-PROTEIN; NEUROMUSCULAR SYNAPSE; RAPSYN CLUSTERS; MUSCLE-FIBERS; IN-VIVO; ZEBRAFISH; NEURONS; CELLS; IDENTIFICATION; TRAFFICKING AB The contraction of skeletal muscle is dependent on synaptic transmission through acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). The lack of an AChR subunit causes a fetal akinesia in humans, leading to death in the first trimester and characteristic features of Fetal Akinesia Deformation Sequences (FADS). A corresponding null mutation of the delta-subunit in zebrafish (sofa potato; sop) leads to the death of embryos around 5 d postfertilization (dpf). In sop(-/-) mutants, we expressed modified delta-subunits, with one (delta 1YFP) or two yellow fluorescent protein (delta 2YFP) molecules fused at the intracellular loop, under the control of an alpha-actin promoter. AChRs containing these fusion proteins are fluorescent, assemble on the plasma membrane, make clusters under motor neuron endings, and generate synaptic current. We screened for germ-line transmission of the transgene and established a line of sop(-/-) fish stably expressing the delta 2YFP. These delta 2YFP/sop(-/-) embryos can mount escape behavior close to that of their wild-type siblings. Synaptic currents in these embryos had a smaller amplitude, slower rise time, and slower decay when compared with wild-type fish. Remarkably, these embryos grow to adulthood and display complex behaviors such as feeding and breeding. To the best of our knowledge, this is the first case of a mutant animal corresponding to first trimester lethality in human that has been rescued by a transgene and survived to adulthood. In the rescued fish, a foreign promoter drove the transgene expression and the NMJ had altered synaptic strength. The survival of the transgenic animal delineates requirements for gene therapies of NMJ. C1 [Urban, Jason M.; Ikenaga, Takanori; Ono, Fumihito] NIAAA, NIH, Sect Model Synapt Syst, Lab Mol Physiol, Bethesda, MD 20892 USA. [Epley, Kimberly E.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA. RP Ono, F (reprint author), NIAAA, NIH, Sect Model Synapt Syst, Lab Mol Physiol, MSC9411, Bethesda, MD 20892 USA. EM onof@mail.nih.gov RI ono, fumihito/A-6570-2008 FU National Institute of Neurological Disorders and Stroke [1R01NS050388-01A1]; Muscular Dystrophy Association [MDA3818]; National Institute on Alcohol Abuse and Alcoholism-National Institutes of Health FX This work was supported by National Institute of Neurological Disorders and Stroke Grant 1R01NS050388-01A1 to F. O. and K. E. E., Muscular Dystrophy Association Grant MDA3818 to F. O., and the intramural research program of the National Institute on Alcohol Abuse and Alcoholism-National Institutes of Health. We thank Elizabeth Jimenez, Nichole Gebhart, Karen Overstreet, and Anna Mistretta-Bradley for their help in the maintenance of the zebrafish facility. We thank Alison Delargy, Jessica Roberts-Misterly, Rebecca Price, and Jim Netherton for their help in the manuscript editing, clone constructs, setting-up the electrophysiology and the digital imaging of adult fish, respectively. We thank Dr. Stephen Ikeda for critical reading of this manuscript. SV2 antibody, developed by Dr. Kathleen Buckley, was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by the University of Iowa. NR 37 TC 7 Z9 7 U1 0 U2 1 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 DEC 3 PY 2008 VL 28 IS 49 BP 13223 EP 13231 DI 10.1523/JNEUROSCI.2814-08.2008 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 379DZ UT WOS:000261378100022 PM 19052214 ER PT J AU Li, YQ Li, FQ Wang, XY Wu, P Zhao, M Xu, CM Shaham, Y Lu, L AF Li, Yan-Qin Li, Fang-Qiong Wang, Xiao-Yi Wu, Ping Zhao, Mei Xu, Chun-Mei Shaham, Yavin Lu, Lin TI Central Amygdala Extracellular Signal-Regulated Kinase Signaling Pathway Is Critical to Incubation of Opiate Craving SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; morphine; conditioned place preference; incubation; ERK; CREB; relapse ID CONDITIONED PLACE PREFERENCE; ACTIVATED PROTEIN-KINASE; ELEMENT-BINDING PROTEIN; INDUCED COCAINE SEEKING; VENTRAL TEGMENTAL AREA; TIME-DEPENDENT CHANGES; STRESS-INDUCED RELAPSE; NUCLEUS-ACCUMBENS; REINFORCING PROPERTIES; INDUCED REINSTATEMENT AB Cue-induced drug-seeking in rodents progressively increases after withdrawal from operant self-administration of cocaine, heroin, methamphetamine, and alcohol, a phenomenon termed "incubation of drug craving." Here, we used the opiate drug morphine and explored whether incubation of drug craving also occurs in a pavlovian conditioned place preference (CPP) procedure in which rats learn to associate drug effects with a distinct environmental context. We also explored the role of amygdala extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in this incubation. We found that the expression of morphine CPP progressively increases over the first 14 d after the last drug exposure in rats receiving four pairings of low-dose (1 or 3 mg/kg) but not high-dose (10 mg/kg) morphine with a distinct environment. The progressive increase in low-dose (3 mg/kg) morphine CPP was associated with increased ERK phosphorylation (a measure of ERK activity) and CREB( a downstream target of ERK) phosphorylation in central but not basolateral amygdala. Furthermore, inhibition of central but not basolateral amygdala ERK and CREB phosphorylation by U0126 [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene] decreased the enhanced ( incubated) drug CPP after 14 d of withdrawal from morphine. Finally, stimulation of central amygdala ERK and CREB phosphorylation by NMDA enhanced drug CPP after 1 d of withdrawal from morphine, an effect reversed by U0126. These findings indicate that the rat's response to environmental cues previously paired with morphine progressively increases or incubates over the first 14 d of withdrawal from low but not high morphine doses. Additionally, this "incubation of morphine craving" is mediated by acute activation of central amygdala ERK pathway. C1 [Li, Yan-Qin; Li, Fang-Qiong; Wang, Xiao-Yi; Wu, Ping; Zhao, Mei; Xu, Chun-Mei; Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. [Shaham, Yavin] NIDA, NIH, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xue Yuan Rd, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn RI shaham, yavin/G-1306-2014 FU National Basic Research Program of China [2007CB512302, 2009CB522004]; National High Technology Research and Development Program of China 863 Program [2006AA02Z4D1]; Natural Science Foundation of China [30670713, 30725016]; National Institute on Drug Abuse, Intramural Research Program FX This work was supported in part by National Basic Research Program of China Grants 2007CB512302 and 2009CB522004, National High Technology Research and Development Program of China 863 Program/Grant 2006AA02Z4D1, Natural Science Foundation of China Grants 30670713 and 30725016, and the National Institute on Drug Abuse, Intramural Research Program. We thank Drs. Bruce Hope and Eisuke Koya for their helpful comments on previous versions of this manuscript and Drs. Julie Blendy and Bill Carlezon for helpful comments on issues related to CREB role in the behavioral effects of drugs. NR 63 TC 86 Z9 92 U1 2 U2 15 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 DEC 3 PY 2008 VL 28 IS 49 BP 13248 EP 13257 DI 10.1523/JNEUROSCI.3027-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 379DZ UT WOS:000261378100024 PM 19052216 ER PT J AU Ma, JH Goldberg, GI Tjandra, N AF Ma, Junhe Goldberg, Gregory I. Tjandra, Nico TI Weak Alignment of Biomacromolecules in Collagen Gels: An Alternative Way to Yield Residual Dipolar Couplings for NMR Measurements SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID GLUTAMINE-BINDING PROTEIN; LIQUID-CRYSTALLINE MEDIUM; POLYACRYLAMIDE GELS; MEMBRANE-PROTEINS; MACROMOLECULES; RESOLUTION; DYNAMICS; MICELLES; DRIVEN; MEDIA AB Collagen, consisting of glycine, proline, and hydroxyproline, is a fibrous protein that can form a rope-like left-hand triple helix structure. It is demonstrated here that the collagen gels prepared from polymerization in the magnetic field can provide weak alignment for protein. The alignment order induced by collagen gels is quite small when compared to other alignment media, but the magnitude of the dipolar couplings can be easily scaled up by increasing the initial concentration of collagen. The collagen gels showed good pH and detergent tolerance. These advantages of collagen gels make it a promising candidate for the alignment of large biomolecules or membrane protein-detergent complexes in the magnetic field. C1 [Ma, Junhe; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Goldberg, Gregory I.] Washington Univ, Sch Med, Dept Med, Dept Biochem, St Louis, MO 63110 USA. RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU Intramural Research Program of the NIH; National Heart, Lung, and Blood Institute; NCI [R01CA123363]; NIAMS [R01AR040618] FX This work was supported by the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute to N.T. and R01CA123363 from NCI and R01AR040618 from NIAMS to G.I.G. We thank Dr. Chien Ho for providing us with the GlnBP plasmid. NR 32 TC 18 Z9 18 U1 1 U2 9 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 DEC 3 PY 2008 VL 130 IS 48 BP 16148 EP + DI 10.1021/ja807064k PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 406UG UT WOS:000263319800012 PM 18998689 ER PT J AU Kipnis, V Freedman, LS AF Kipnis, Victor Freedman, Laurence S. TI Impact of Exposure Measurement Error in Nutritional Epidemiology SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CONFIDENCE-INTERVALS; QUESTIONNAIRE; CANCER; DIET C1 [Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Freedman, Laurence S.] Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel. RP Kipnis, V (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, 6130 Executive Blvd,Suite 3131, Bethesda, MD 20892 USA. EM kipnisv@mail.nih.gov NR 16 TC 18 Z9 19 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 DEC 3 PY 2008 VL 100 IS 23 BP 1658 EP 1659 DI 10.1093/jnci/djn408 PG 2 WC Oncology SC Oncology GA 380JQ UT WOS:000261462400001 PM 19033567 ER PT J AU Jemal, A Thun, MJ Ries, LAG Howe, HL Weir, HK Center, MM Ward, E Wu, XC Eheman, C Anderson, R Ajani, UA Kohler, B Edwards, BK AF Jemal, Ahmedin Thun, Michael J. Ries, Lynn A. G. Howe, Holly L. Weir, Hannah K. Center, Melissa M. Ward, Elizabeth Wu, Xiao-Cheng Eheman, Christie Anderson, Robert Ajani, Umed A. Kohler, Betsy Edwards, Brenda K. TI Annual Report to the Nation on the Status of Cancer, 1975-2005, Featuring Trends in Lung Cancer, Tobacco Use, and Tobacco Control SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; BREAST-CANCER; COLORECTAL-CANCER; CONTROL PROGRAMS; SMOKING-CESSATION; INCIDENCE RATES; ADULT SMOKERS; SCREENING MAMMOGRAPHY; ENDOMETRIAL CANCER AB The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year's report includes trends in lung cancer incidence and death rates, tobacco use, and tobacco control by state of residence. Information on invasive cancers was obtained from the NCI, CDC, and NAACCR and information on mortality from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term (1975-2005) trends and by least squares linear regression of short-term (1996-2005) trends. All statistical tests were two-sided. Both incidence and death rates from all cancers combined decreased statistically significantly (P < .05) in men and women overall and in most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the three most common cancers in men (lung, colorectum, and prostate) and for two of the three leading cancers in women (breast and colorectum), combined with a leveling off of lung cancer death rates in women. Although the national trend in female lung cancer death rates has stabilized since 2003, after increasing for several decades, there is prominent state and regional variation. Lung cancer incidence and/or death rates among women increased in 18 states, 16 of them in the South or Midwest, where, on average, the prevalence of smoking was higher and the annual percentage decrease in current smoking among adult women was lower than in the West and Northeast. California was the only state with decreasing lung cancer incidence and death rates in women. Although the decrease in overall cancer incidence and death rates is encouraging, large state and regional differences in lung cancer trends among women underscore the need to maintain and strengthen many state tobacco control programs. C1 [Jemal, Ahmedin; Thun, Michael J.; Center, Melissa M.; Ward, Elizabeth] Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30303 USA. [Weir, Hannah K.; Eheman, Christie; Ajani, Umed A.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. [Anderson, Robert] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. [Ries, Lynn A. G.; Edwards, Brenda K.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Howe, Holly L.; Wu, Xiao-Cheng; Kohler, Betsy] N Amer Assoc Cent Canc Registries, Springfield, IL USA. [Wu, Xiao-Cheng] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Kohler, Betsy] Canc Epidemiol Serv, New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. RP Jemal, A (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res Dept, 250 Williams St,NW,6D 206, Atlanta, GA 30303 USA. EM ajemal@cancer.org FU American Cancer Society FX The American Cancer Society, the National Cancer Institute, the centers for Disease control and prevention and the North American Association of Central Cancer registries. Funding to pay for the open Access publication charges for the article - was provided by the American Cancer Society. NR 108 TC 523 Z9 551 U1 4 U2 54 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 DEC 3 PY 2008 VL 100 IS 23 BP 1672 EP 1694 DI 10.1093/jnci/djn389 PG 23 WC Oncology SC Oncology GA 380JQ UT WOS:000261462400008 PM 19033571 ER PT J AU Lee, JE Spiegelman, D Hunter, DJ Albanes, D Bernstein, L van den Brandt, PA Buring, JE Cho, E English, DR Freudenheim, JL Giles, GG Graham, S Horn-Ross, PL Hakansson, N Leitzmann, MF Mannisto, S McCullough, ML Miller, AB Parker, AS Rohan, TE Schatzkin, A Schouten, LJ Sweeney, C Willett, WC Wolk, A Zhang, SM Smith-Warner, SA AF Lee, Jung Eun Spiegelman, Donna Hunter, David J. Albanes, Demetrius Bernstein, Leslie van den Brandt, Piet A. Buring, Julie E. Cho, Eunyoung English, Dallas R. Freudenheim, Jo L. Giles, Graham G. Graham, Saxon Horn-Ross, Pamela L. Hakansson, Niclas Leitzmann, Michael F. Mannisto, Satu McCullough, Marjorie L. Miller, Anthony B. Parker, Alexander S. Rohan, Thomas E. Schatzkin, Arthur Schouten, Leo J. Sweeney, Carol Willett, Walter C. Wolk, Alicja Zhang, Shumin M. Smith-Warner, Stephanie A. TI Fat, Protein, and Meat Consumption and Renal Cell Cancer Risk: A Pooled Analysis of 13 Prospective Studies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MEASUREMENT ERROR-CORRECTION; COVARIANCE STRUCTURE MODELS; HETEROCYCLIC AMINE CONTENT; DIETARY ASSESSMENT; REGRESSION-MODELS; KIDNEY CANCER; CALIFORNIA TEACHERS; COLORECTAL-CANCER; VARYING DEGREES AB Results of several case-control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer. We conducted a pooled analysis of 13 prospective studies that included 530 469 women and 244 483 men and had follow-up times of up to 7-20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer. All participants had completed a validated food frequency questionnaire at study entry. Using the primary data from each study, we calculated the study-specific relative risks (RRs) for renal cell cancer by using Cox proportional hazards models and then pooled these RRs by using a random-effects model. All statistical tests were two-sided. A total of 1478 incident cases of renal cell cancer were identified (709 in women and 769 in men). We observed statistically significant positive associations or trends in pooled age-adjusted models for intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, total protein, and animal protein. However, these associations were attenuated and no longer statistically significant after adjusting for body mass index, fruit and vegetable intake, and alcohol intake. For example, the pooled age-adjusted RR of renal cell cancer for the highest vs the lowest quintile of intake for total fat was 1.30 (95% confidence interval [CI] = 1.08 to 1.56; P(trend) = .001) and for total protein was 1.17 (95% CI = 0.99 to 1.38; P(trend) = .02). By comparison, the pooled multivariable RR for the highest vs the lowest quintile of total fat intake was 1.10 (95% CI = 0.92 to 1.32; P(trend) = .31) and of total protein intake was 1.06 (95% CI = 0.89 to 1.26; P(trend) = .37). Intakes of red meat, processed meat, poultry, or seafood were not associated with the risk of renal cell cancer. Intakes of fat and protein or their subtypes, red meat, processed meat, poultry, and seafood are not associated with risk of renal cell cancer. C1 [Lee, Jung Eun; Hunter, David J.; Cho, Eunyoung; Willett, Walter C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Buring, Julie E.; Zhang, Shumin M.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Spiegelman, Donna; Hunter, David J.; Buring, Julie E.; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hunter, David J.; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Albanes, Demetrius; Leitzmann, Michael F.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Hlth Serv, Bethesda, MD 20892 USA. [Bernstein, Leslie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. [van den Brandt, Piet A.; Schouten, Leo J.] Univ Maastricht, Sch Oncol & Dev Biol, GROW, Dept Epidemiol, Maastricht, Netherlands. [English, Dallas R.; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia. [Freudenheim, Jo L.; Graham, Saxon] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Horn-Ross, Pamela L.] No Calif Canc Ctr, Fremont, CA USA. [Hakansson, Niclas; Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Mannisto, Satu] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [McCullough, Marjorie L.] Amer Canc Soc, Atlanta, GA 30329 USA. [Miller, Anthony B.] Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. [Parker, Alexander S.] Mayo Clin, Coll Med, Dept Urol, Jacksonville, FL 32224 USA. [Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Sweeney, Carol] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT USA. RP Lee, JE (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM jung.lee@channing.harvard.edu RI Schouten, Leo/G-3713-2012; Hakansson, Niclas/L-7913-2013; Albanes, Demetrius/B-9749-2015; OI Hakansson, Niclas/0000-0001-7673-5554; Sweeney, Carol/0000-0003-1113-7160; Mannisto, Satu/0000-0002-8668-3046; Lee, Jung Eun/0000-0003-1141-878X; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU National Cancer Institute [P01CA055075] FX This study was supported by the National Cancer Institute (P01CA055075). NR 59 TC 32 Z9 33 U1 1 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 DEC 3 PY 2008 VL 100 IS 23 BP 1695 EP 1706 DI 10.1093/jnci/djn386 PG 12 WC Oncology SC Oncology GA 380JQ UT WOS:000261462400009 PM 19033572 ER PT J AU Kerlikowske, K Walker, R Miglioretti, DL Desai, A Ballard-Barbash, R Buist, DSM AF Kerlikowske, Karla Walker, Rod Miglioretti, Diana L. Desai, Arati Ballard-Barbash, Rachel Buist, Diana S. M. TI Obesity, Mammography Use and Accuracy, and Advanced Breast Cancer Risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-MASS INDEX; ADULT WEIGHT CHANGE; CARCINOMA IN-SITU; SCREENING MAMMOGRAPHY; UNITED-STATES; POSTMENOPAUSAL WOMEN; COHORT; POPULATION; OVERWEIGHT; GROWTH AB Being overweight or obese is associated with increased breast cancer risk and disease severity among postmenopausal women, but whether extent of mammography use and accuracy modify this association and further contribute to increases in disease severity at diagnosis among overweight and obese women is unclear. We prospectively collected data during 1996-2005 on 287 115 postmenopausal women not using hormone therapy (HT) who underwent 614 562 mammography examinations; 4446 women were diagnosed with breast cancer within 12 months of a mammography examination. We calculated rates per 1000 mammography examinations of large (> 15 mm), advanced-stage (IIb, III, or IV), high-grade (3 or 4), estrogen receptor (ER)-positive and -negative, and screen-detected and non-screen-detected breast cancer across body mass index (BMI, kg/m(2)) groups defined as normal (18.5-24.9), overweight (25.0-29.9), obese class I (30.0-34.9), and obese class II/III (>= 35.0), adjusting for age, race/ethnicity, and mammography registry and use. All statistical tests were two-sided. Adjusted rates per 1000 mammography examinations of overall breast cancer increased across BMI groups (6.6 normal, 7.4 overweight, 7.9 obese I, 8.5 obese II/III; P(trend) < .001), as did rates of advanced disease, including large invasive (2.3 normal, 2.6 overweight, 2.9 obese I, 3.2 obese II/III; P(trend) < .001), advanced-stage (0.8 normal, 0.9 overweight, 1.3 obese I, 1.5 obese II/III; P(trend) < .001), and high nuclear grade (1.5 normal, 1.7 overweight, 1.7 obese I, 1.9 obese II/III; P(trend) = .10) tumors. Rates of ER-positive tumors increased across BMI groups (P(trend) < .001); rates of ER-negative tumors did not. Rates of screen-detected cancers were higher among overweight and obese women than normal and underweight women, but rates of non-screen-detected (false-negative) cancers were similar. Rates of advanced breast cancer increased across BMI groups regardless of extent of mammography use. Patterns of mammography use and mammography accuracy are not the primary reasons for higher rates of advanced breast cancer among overweight and obese postmenopausal women not using HT; thus, biologic differences in breast tumor development and/or progression may be important. C1 [Kerlikowske, Karla] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco Vet Affairs Med Ctr, Dept Vet Affairs, San Francisco, CA 94121 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Walker, Rod; Miglioretti, Diana L.; Buist, Diana S. M.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Miglioretti, Diana L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Desai, Arati] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. [Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Kerlikowske, K (reprint author), Univ Calif San Francisco, Gen Internal Med Sect, San Francisco Vet Affairs Med Ctr, Dept Vet Affairs, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM karla.kerlikowske@ucsf.edu FU NCI [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040] FX NCI-funded Breast Cancer Surveillance Consortium cooperative agreement (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040). The collection of cancer incidence data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see: http://breastscreening.cancer.gov/work/acknowledgement.html. NR 46 TC 41 Z9 43 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 DEC 3 PY 2008 VL 100 IS 23 BP 1724 EP 1733 DI 10.1093/jnci/djn388 PG 10 WC Oncology SC Oncology GA 380JQ UT WOS:000261462400012 PM 19033562 ER PT J AU Francischetti, IMB Meng, ZJ Mans, BJ Gudderra, N Hall, M Veenstra, TD Pham, VM Kotsyfakis, M Ribeiro, JMC AF Francischetti, Ivo M. B. Meng, Zhaojing Mans, Ben J. Gudderra, Nanda Hall, Mark Veenstra, Timothy D. Pham, Van M. Kotsyfakis, Michail Ribeiro, Jose M. C. TI An insight into the salivary transcriptome and proteome of the soft tick and vector of epizootic bovine abortion, Ornithodoros coriaceus SO JOURNAL OF PROTEOMICS LA English DT Article DE Ornithodoros coriaceus; Ixodidae; Argasidae; Sialotranscriptome; Salivary gland transcriptome; Sialome; Tick salivary gland; Ixolaris ID PLATELET-AGGREGATION INHIBITOR; LONE STAR TICK; PHOSPHOLIPASE A(2) ACTIVITY; BUG RHODNIUS-PROLIXUS; ADULT FEMALE MOSQUITO; IXODES-SCAPULARIS; BLOODSUCKING BUG; FACTOR-XA; BOOPHILUS-MICROPLUS; HIGH-AFFINITY AB The salivary glands of blood-sucking arthropods contain a redundant 'magic potion' that counteracts their vertebrate host's hemostasis, inflammation, and immunity. We here describe the salivary transcriptome and proteomics (sialome) of the soft tick Ornithodoros coriaceus. The resulting analysis helps to consolidate the classification of common proteins found in both soft and hard ticks, such as the lipocalins, Kunitz, cystatin, basic tail, hebraein, defensin, TIL domain, metalloprotease, 5'-nucleotidase/apyrase, and phospholipase families, and also to identify protein families uniquely found in the Argasidae, such as the adrenomedullin/CGRP peptides, 7DB, 7 kDa, and the RGD-containing single-Kunitz proteins. Additionally, we found a protein belonging to the cytotoxin protein family that has so far only been identified in hard ticks. Three other unique families common only to the Ornithodoros genus were discovered. Edman degradation, 2D and 1D-PAGE of salivary gland homogenates followed by tryptic digestion and HPLC MS/MS of results confirms, the presence of several proteins. These results indicate that each genus of hematophagous arthropods studied to date evolved unique protein families that assist blood feeding, thus characterizing potentially new pharmacologically active components or antimicrobial agents. Published by Elsevier B.V. C1 [Francischetti, Ivo M. B.; Mans, Ben J.; Pham, Van M.; Kotsyfakis, Michail; Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Meng, Zhaojing; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick Maryland, MD 21702 USA. [Gudderra, Nanda] George Mason Univ, Biomed Res Lab, Manassas, VA 20110 USA. [Hall, Mark] Univ Nevada, Dept Anim Biotechnol, Reno, NV 89557 USA. RP Francischetti, IMB (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 2E-32D, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov RI Kotsyfakis, Michail/G-9525-2014; OI Kotsyfakis, Michail/0000-0002-7526-1876; Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Al lergy and infectious Diseases, National Institutes of Health. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the government of the United States of America. We are grateful to the NIAID Core facility led by Dr. Robert Hohman for their support, and to NIAID intramural editor Brenda Rae Marshall for assistance. NR 90 TC 53 Z9 55 U1 4 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD DEC 2 PY 2008 VL 71 IS 5 BP 493 EP 512 DI 10.1016/j.jprot.2008.07.006 PG 20 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 383FL UT WOS:000261659400001 PM 18725333 ER PT J AU Yiannoutsos, CT An, MW Frangakis, CE Musick, BS Braitstein, P Wools-Kaloustian, K Ochieng, D Martin, JN Bacon, MC Ochieng, V Kimaiyo, S AF Yiannoutsos, Constantin T. An, Ming-Wen Frangakis, Constantine E. Musick, Beverly S. Braitstein, Paula Wools-Kaloustian, Kara Ochieng, Daniel Martin, Jeffrey N. Bacon, Melanie C. Ochieng, Vincent Kimaiyo, Sylvester TI Sampling-Based Approaches to Improve Estimation of Mortality among Patient Dropouts: Experience from a Large PEPFAR-Funded Program in Western Kenya SO PLOS ONE LA English DT Article AB Background: Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices. Methodology/Principal Findings: In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3-4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% Cl 1.3%-2.0%), revised to 2.8% (2.3%-3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%-10.6%) and 9.9% (8.4%-11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%-2.2%), 3.4% (2.9%-4.0%), 10.5% (8.7%-12.3%) and 10.7% (8.9%-12.6%) respectively. Conclusions/Significance Abstract: Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs. C1 [Yiannoutsos, Constantin T.; Musick, Beverly S.] Indiana Univ, Div Biostat, Indianapolis, IN 46204 USA. [An, Ming-Wen] Vassar Coll, Dept Math, Poughkeepsie, NY 12601 USA. [Frangakis, Constantine E.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. [Braitstein, Paula] Indiana Univ, Div Gen Internal Med & Geriat, Indianapolis, IN USA. [Wools-Kaloustian, Kara] Indiana Univ, Div Infect Dis, Indianapolis, IN USA. [Braitstein, Paula; Wools-Kaloustian, Kara; Ochieng, Daniel; Ochieng, Vincent; Kimaiyo, Sylvester] Acad Model Prevent & Treatment HIV AIDS AMPATH, Eldoret, Kenya. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bacon, Melanie C.] Natl Inst Allergies & Infect Dis (NIAID), Bethesda, MD USA. [Braitstein, Paula; Kimaiyo, Sylvester] Moi Univ, Sch Med, Eldoret, Kenya. RP Yiannoutsos, CT (reprint author), Indiana Univ, Div Biostat, Indianapolis, IN 46204 USA. EM cyiannou@iupui.edu FU National Institutes of Health (NIAID) [U01-AI0669911]; President's Emergency Plan for AIDS Relief (PEPFAR); NIDA [R01-DA023879]; National Eye Institute [EY07127]; Clinical Trials Training Program in Vision Research FX This study was funded in part by the National Institutes of Health (NIAID) grant number U01-AI0669911 (East Africa IeDEA Regional Consortium), and a Targeted Evaluation supplement to this grant by the President's Emergency Plan for AIDS Relief (PEPFAR). This research was also supported in part by a grant to the USAID-AMPATH Partnership from PEPFAR. Dr. Frangakis' research was supported by NIDA grant R01-DA023879. Dr. An's research was also supported by the National Eye Institute Training Grant EY07127 and Clinical Trials Training Program in Vision Research. NR 24 TC 52 Z9 52 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 DEC 2 PY 2008 VL 3 IS 12 AR e3843 DI 10.1371/journal.pone.0003843 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YM UT WOS:000265452000010 PM 19048109 ER PT J AU Kubelka, J Henry, ER Cellmer, T Hofrichter, J Eaton, WA AF Kubelka, Jan Henry, Eric R. Cellmer, Troy Hofrichter, James Eaton, William A. TI Chemical, physical, and theoretical kinetics of an ultrafast folding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fluorescence; funneled energy landscape; Ising-like model; laser temperature jump; polypeptide ID VILLIN HEADPIECE SUBDOMAIN; CRYSTAL-STRUCTURES; ENERGY LANDSCAPES; DYNAMICS; MODEL; RATES; SIMULATIONS; COORDINATE; RESOLUTION; FUNNELS AB An extensive set of equilibrium and kinetic data is presented and analyzed for an ultrafast folding protein-the villin subdomain. The equilibrium data consist of the excess heat capacity, tryptophan fluorescence quantum yield, and natural circular-dichroism spectrum as a function of temperature, and the kinetic data consist of time courses of the quantum yield from nanosecond-laser temperature-jump experiments. The data are well fit with three kinds of models-a three-state chemical-kinetics model, a physical-kinetics model, and an Ising-like theoretical model that considers 10(5) possible conformations (microstates). In both the physical-kinetics and theoretical models, folding is described as diffusion on a one-dimensional free-energy surface. In the physical-kinetics model the reaction coordinate is unspecified, whereas in the theoretical model, order parameters, either the fraction of native contacts or the number of native residues, are used as reaction coordinates. The validity of these two reaction coordinates is demonstrated from calculation of the splitting probability from the rate matrix of the master equation for all 10(5) microstates. The analysis of the data on site-directed mutants using the chemical-kinetics model provides information on the structure of the transition-state ensemble; the physical-kinetics model allows an estimate of the height of the free-energy barrier separating the folded and unfolded states; and the theoretical model provides a detailed picture of the free-energy surface and a residue-by-residue description of the evolution of the folded structure, yet contains many fewer adjustable parameters than either the chemical- or physical-kinetics models. C1 [Kubelka, Jan; Henry, Eric R.; Cellmer, Troy; Hofrichter, James; Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Kubelka, Jan] Univ Wyoming, Dept Chem, Laramie, WY 82071 USA. RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 104, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank Attila Szabo, Peter Wolynes, Victor Munoz, and Eugene Shakhnovich for many helpful discussions. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 47 TC 88 Z9 90 U1 4 U2 25 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 DEC 2 PY 2008 VL 105 IS 48 BP 18655 EP 18662 DI 10.1073/pnas.0808600105 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100011 PM 19033473 ER PT J AU Bethea, HN Xu, D Liu, J Pedersen, LC AF Bethea, Heather N. Xu, Ding Liu, Jian Pedersen, Lars C. TI Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE crystal structure; heparin; protein engineering; maltose-binding protein chimera; trimeric proteins ID HERPES-SIMPLEX-VIRUS; CRYSTAL-STRUCTURE; ENTRY RECEPTOR; BINDING; 2-SULFOTRANSFERASE; PROTEIN; TYPE-1; SULFOTRANSFERASES; BIOSYNTHESIS AB Heparan sulfate (HS) is a polysaccharide involved in essential physiological functions from regulating cell growth to blood coagulation. HS biosynthesis involves multiple specialized sulfotransferases such as 2-O-sulfotransferase (2OST) that transfers the sulfo group to the 2-OH position of iduronic acid (IdoA) or glucuronic acid (GlcA) within HS. Here, we report the homotrimeric crystal structure of 2OST from chicken, in complex with 3'-phosphoadenosine 5'-phosphate. Structural based mutational analysis has identified amino acid residues that are responsible for substrate specificity. The mutant R189A only transferred sulfates to GlcA moieties within the polysaccharide whereas mutants Y94A and H106A preferentially transferred sulfates to IdoA units. Our results demonstrate the feasibility for manipulating the substrate specificity of 2OST to synthesize HS with unique sulfation patterns. This work will aid the development of an enzymatic approach to synthesize heparin-based therapeutics. C1 [Bethea, Heather N.; Xu, Ding; Liu, Jian] Univ N Carolina, Eshelman Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. [Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), Univ N Carolina, Eshelman Sch Pharm, Div Med Chem & Nat Prod, Room 309,Beard Hall, Chapel Hill, NC 27599 USA. EM jian_liu@unc.edu RI Xu, Ding/B-2493-2009 OI Xu, Ding/0000-0001-9380-2712 FU National Institutes of Health [AI50050]; National Institute of Environmental Health Sciences, National Institutes of Health; American Heart Association, Mid-Atlantic Affiliate FX We thank H. Kohn, T. Hall, and A. Moon for reviewing the manuscript. This work was supported in part by National Institutes of Health Grant AI50050 (to J.L.) and by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (L.C.P.). D:X. is a recipient of a predoctoral fellowship from the American Heart Association, Mid-Atlantic Affiliate. NR 28 TC 23 Z9 26 U1 2 U2 6 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 DEC 2 PY 2008 VL 105 IS 48 BP 18724 EP 18729 DI 10.1073/pnas.0806975105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100023 PM 19022906 ER PT J AU Rostovtseva, TK Sheldon, KL Hassanzadeh, E Monge, C Saks, V Bezrukov, SM Sackett, DL AF Rostovtseva, Tatiana K. Sheldon, Kely L. Hassanzadeh, Elnaz Monge, Claire Saks, Valdur Bezrukov, Sergey M. Sackett, Dan L. TI Tubulin binding blocks mitochondrial voltage-dependent anion channel and regulates respiration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE evolution; microtubules; oxidative phosphorylation; VDAC; tubulin C-terminal ID OUTER-MEMBRANE; STRUCTURAL BASIS; CELL-DEATH; C-TERMINI; IN-VIVO; VDAC; POLYMERIZATION; CYTOSKELETON; APOPTOSIS; FLUX AB Regulation of mitochondrial outer membrane (MOM) permeability has dual importance: in normal metabolite and energy exchange between mitochondria and cytoplasm and thus in control of respiration, and in apoptosis by release of apoptogenic factors into the cytosol. However, the mechanism of this regulation, dependent on the voltage-dependent anion channel (VDAC), the major channel of MOM, remains controversial. A long-standing puzzle is that in permeabilized cells, adenine nucleotide translocase (ANT) is less accessible to cytosolic ADP than in isolated mitochondria. We solve this puzzle by finding a missing player in the regulation of MOM permeability: the cytoskeletal protein tubulin. We show that nanomolar concentrations of dimeric tubulin induce voltage-sensitive reversible closure of VDAC reconstituted into planar phospholipid membranes. Tubulin strikingly increases VDAC voltage sensitivity and at physiological salt conditions could induce VDAC closure at <10 mV transmembrane potentials. Experiments with isolated mitochondria confirm these findings. Tubulin added to isolated mitochondria decreases ADP availability to ANT, partially restoring the low MOM permeability (high apparent Km for ADP) found in permeabilized cells. Our findings suggest a previously unknown mechanism of regulation of mitochondrial energetics, governed by VDAC and tubulin at the mitochondriacytosol interface. This tubulin-VDAC interaction requires tubulin anionic C-terminal tail (CTT) peptides. The significance of this interaction may be reflected in the evolutionary conservation of length and anionic charge in CTT throughout eukaryotes, despite wide changes in the exact sequence. Additionally, tubulins that have lost significant length or anionic character are only found in cells that do not have mitochondria. C1 [Rostovtseva, Tatiana K.; Sheldon, Kely L.; Hassanzadeh, Elnaz; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. [Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Integrat & Med Biophys, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Monge, Claire; Saks, Valdur] Univ Grenoble 1, Lab Fundamental & Appl Bioenerget, F-38041 Grenoble, France. RP Rostovtseva, TK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, NIH, 9000 Rockville Pike,Bldg 9,Room 1E-106, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov RI SAKS, Valdur/A-8466-2008; Monge, Claire/E-2933-2012 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Agence National de la Recherche Project [BLAN07-2_188128]; Institut National de la Sante et de la Recherche Medicale, France; Estonian Science Foundation [6142, 7117] FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (T.K.R., K.S., E.H., S.M.B., and D.L.S.) and by Agence National de la Recherche Project BLAN07-2_188128, Institut National de la Sante et de la Recherche Medicale, France (to C.M. and V.S.). V.S. was also supported by Estonian Science Foundation Grants 6142 and 7117. NR 42 TC 166 Z9 167 U1 2 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 DEC 2 PY 2008 VL 105 IS 48 BP 18746 EP 18751 DI 10.1073/pnas.0806303105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100027 PM 19033201 ER PT J AU Ortolano, S Di Pasquale, G Crispino, G Anselmi, F Mammano, F Chiorini, JA AF Ortolano, Saida Di Pasquale, Giovanni Crispino, Giulia Anselmi, Fabio Mammano, Fabio Chiorini, John A. TI Coordinated control of connexin 26 and connexin 30 at the regulatory and functional level in the inner ear SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adeno-associated virus; cochlea; gap junctions; gene transfer; hearing loss ID NF-KAPPA-B; GAP-JUNCTION CHANNELS; HEARING IMPAIRMENT; RAT COCHLEA; GENE-EXPRESSION; ULTRASTRUCTURAL ANALYSIS; ADENOASSOCIATED VIRUS; MOLECULAR-CLONING; MUTATIONS; DEAFNESS AB Connexin 26 (Cx26) and connexin 30 (COO) are encoded by two genes (GJB2 and GJa6, respectively) that are found within 50 kb in the same complex deafness locus, DFNB1. Immunocytochemistry and quantitative PCR analysis of Cx30 KO mouse cultures revealed that Cx26 is downregulated at the protein level and at the mRNA level in nonsensory cells located between outer hair cells and the stria vascularis. To explore connexin coregulation, we manipulated gene expression using the bovine adeno-associated virus. Overexpression of Cx30 in the Cx30 KO mouse by transduction with bovine adeno-associated virus restored Cx26 expression, permitted the formation of functional gap junction channels, and rescued propagating Ca(2+) signals. Ablation of Cx26 by transduction of Cx26(loxP/loxP) cultures with a Cre recombinase vector caused concurrent downregulation of Cx30 and impaired intercellular communication. The coordinated regulation of Cx26 and Cx30 expression appears to occur as a result of signaling through PLC and the NF-kappa B pathway, because activation of IP(3)-mediated Ca(2+) responses by stimulation of P2Y receptors for 20 min with 20 nM ATP increased the levels of Cx26 transcripts in Cx30 KO cultures. This effect was inhibited by expressing a stable form of the I kappa B repressor protein that prevents activation/translocation of NF-kappa B. Thus, our data reveal a Ca(2+)-dependent control in the expression of inner ear connexins implicated in hereditary deafness as well as insight into the hitherto unexplained observation that some deafness-associated DFNB1 alleles are characterized by hereditable reduction of both GJB2 and GJB6 expression. C1 [Ortolano, Saida; Crispino, Giulia; Anselmi, Fabio; Mammano, Fabio] Fdn Adv Biomed Res, Venetian Inst Mol Med, I-35129 Padua, Italy. [Ortolano, Saida; Mammano, Fabio] Univ Padua, Dept Phys G Galilei, I-35129 Padua, Italy. [Di Pasquale, Giovanni; Chiorini, John A.] Natl Inst Dental & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mammano, F (reprint author), Fdn Adv Biomed Res, Venetian Inst Mol Med, I-35129 Padua, Italy. EM fabio.mammano@unipd.it; jchiorini@dir.nidcr.nih.gov RI Mammano, Fabio/I-5064-2012; Messier, Claude/A-2322-2008 OI Mammano, Fabio/0000-0003-3751-1691; Messier, Claude/0000-0002-4791-1763 FU Fondazione Cariparo, Padua, Italy; Telethon Italy [GGP05131]; European Commission [LSHG-CT-20054-512063]; National Institutes of Health/National Institute of Dental and Craniofacial Research FX We thank Jinfang Zhu for the CMV-Cre-IRESGFP gene cassette, Klaus Willecke for the Cx26loxP/loxP and Cx30 KO mice, Anke Seydel for mouse genotyping, Tullio Pozzan, Pierluigi Nicotera, Roberto Bruzzone, and the editor of this article, Michael V. L. Bennett, for helpful discussions and constructive criticism. This work was funded by grants from Fondazione Cariparo, Padua, Italy (Progetti di Eccellenza 2006), Telethon Italy Grant GGP05131, and European Commission FP6 Integrated Project EuroHear Grant LSHG-CT-20054-512063 under the Sixth Research Frame Program of The European Union (to F.M.) and by National Institutes of Health/National Institute of Dental and Craniofacial Research intramural support (to J.A.C.). NR 58 TC 37 Z9 37 U1 0 U2 4 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 DEC 2 PY 2008 VL 105 IS 48 BP 18776 EP 18781 DI 10.1073/pnas.0800831105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100032 PM 19047647 ER PT J AU Shen, XY Meza-Carmen, V Puxeddu, E Wang, GH Moss, J Vaughan, M AF Shen, Xiaoyan Meza-Carmen, Victor Puxeddu, Ermanno Wang, Guanghui Moss, Joel Vaughan, Martha TI Interaction of brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 and kinesin motor protein KIF21A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADP-ribosylation factor 1; Golgi; microtubule ID ADP-RIBOSYLATION FACTORS; HEPG2 CELL-NUCLEI; GOLGI-COMPLEX; DISTINCT FUNCTIONS; AXONAL-TRANSPORT; MAMMALIAN-CELLS; MYOSIN-IXB; KINASE-A; ARF; LOCALIZATION AB Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG) 1 activates human ADP-ribosylation factor (ARF) 1 and 3 by accelerating the replacement of ARF-bound GDP with GTP to initiate recruitment of coat proteins for membrane vesicle formation. Liquid chromatography MS/MS analysis of peptides from proteins that co-precipitated with BIG1 antibodies identified "kinesin family member 21A" (KIF21A), a plus-end-directed motor protein that moves cargo on microtubules away from the microtubule-organizing center. Reciprocal immunoprecipitation (IP) of endogenous proteins and microscopically apparent overlap of immunoreactive BIG1 with overexpressed GFP-KIF21A in the perinuclear region were consistent with an interaction of KIF21A-BIG1. Overexpression of full-length KIF21A and BIG1 and their fragments in HEK293 cells followed by reciprocal IP revealed that the C-terminal tail of KIF21A, with seven WD-40 repeats, may interact with structure in the C-terminal region of BIG1. Interfering with cyclic activation and inactivation of ARF1 by overexpressing constitutively active ARF1(Q71L) or dominant inactive ARF1(T31N) altered the distribution of BIG1 as well as its interaction with KIF21A. A requirement for ARF1 was confirmed by its selective depletion with siRNA. Unlike disruption of microtubules with nocodazole, selective inhibition of transport by depletion of KIF21A with specific siRNA altered BIG1 distribution without changing that of intrinsic Golgi membrane proteins. These newly recognized interactions of BIG1 and KIF21A should enable us to understand better the mechanisms through which, acting together, they may integrate local events in membrane trafficking with longer-range transport processes and to relate those processes to the diverse signaling and scaffold functions of BIG1. C1 [Shen, Xiaoyan; Meza-Carmen, Victor; Puxeddu, Ermanno; Moss, Joel; Vaughan, Martha] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Wang, Guanghui] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Vaughan, M (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10,Room 5N307,MSC 1434, Bethesda, MD 20892 USA. EM vaughanm@mail.nih.gov RI Puxeddu, Ermanno/K-8777-2016; OI Puxeddu, Ermanno/0000-0002-5486-7764; MEZA-CARMEN, VICTOR/0000-0003-2838-7211 FU National Institutes of Health, National Heart, Lung, and Blood Institute FX We thank Dr. Christian Combs and Dr. Daniela Malide (National Heart, Lung, and Blood Institute Confocal Microscopy Core Facility) for invaluable help. This research was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. NR 39 TC 19 Z9 20 U1 1 U2 4 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 DEC 2 PY 2008 VL 105 IS 48 BP 18788 EP 18793 DI 10.1073/pnas.0810104105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100034 PM 19020088 ER PT J AU Frei, B Lawson, S Levine, M Chen, Q Espey, MG AF Frei, Balz Lawson, Stephen Levine, Mark Chen, Qi Espey, Michael Graham TI Reply to Borst: Randomized clinical trials of high-dose intravenous vitamin C in cancer patients are warranted SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID TERMINAL HUMAN CANCER; SUPPLEMENTAL ASCORBATE; SUPPORTIVE TREATMENT; SURVIVAL TIMES; PROLONGATION; THERAPY C1 [Frei, Balz; Lawson, Stephen] Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. [Levine, Mark; Chen, Qi; Espey, Michael Graham] NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Frei, B (reprint author), Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. EM balz.frei@oregonstate.edu RI Chen, Qi/D-8278-2015 OI Chen, Qi/0000-0002-7173-8411 NR 10 TC 1 Z9 1 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 DEC 2 PY 2008 VL 105 IS 48 BP E96 EP E96 DI 10.1073/pnas.0810008105 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TW UT WOS:000261489100002 ER PT J AU Honda, H Barrueto, FF Gogusev, J Im, DD Morin, PJ AF Honda, Hiroshi Barrueto, Fermin F. Gogusev, Jean Im, Dwight D. Morin, Patrice J. TI Serial analysis of gene expression reveals differential expression between endometriosis and normal endometrium. Possible roles for AXL and SHC1 in the pathogenesis of endometriosis SO REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY LA English DT Article ID DNA MICROARRAY ANALYSIS; LASER CAPTURE MICRODISSECTION; OVARIAN ENDOMETRIOSIS; EUTOPIC ENDOMETRIUM; ECTOPIC ENDOMETRIUM; CELL MOTILITY; MATRIX METALLOPROTEINASES; ENHANCED EXPRESSION; SUPPRESSOR GENE; P46 SHC AB Background: Endometriosis is a clinical condition that affects up to 10% of the women of reproductive age. Endometriosis is characterized by the presence of endometrial tissues outside the uterine cavity and can lead to chronic pelvic pain, infertility and, in some cases, to ovarian cancer. Methods: In order to better understand the pathogenesis of endometriosis, we have used Serial Analysis of Gene Expression (SAGE) to identify genes differentially in this disease by studying three endometriotic tissues and a normal endometrium sample. Promising candidates (AXL, SHC1, ACTN4, PI3KCA, p-AKT, p-mTOR, and p-ERK) were independently validated by immunohistochemistry in additional normal and endometriotic tissues. Results: We identified several genes differentially expressed between endometriosis and normal endometrium. IGF2, ACTN4, AXL, and SHC1 were among the most upregulated genes. Comparison of the endometriosis gene expression profiles with the gene expression patterns observed in normal human tissues allowed the identification of endometriosis-specific genes, which included several members of the MMP family (MMP1,2,3,10,11,14). Immunohistochemical analysis of several candidates confirmed the SAGE findings, and suggested the involvement of the PI3K-Akt and MAPK signaling pathways in endometriosis. Conclusion: In human endometriosis, the PI3K-Akt and MAPK signaling pathways may be activated via overexpression of AXL and SHC1, respectively. These genes, as well as others identified as differentially expressed in this study, may be useful for the development of novel strategies for the detection and/or therapy of endometriosis. C1 [Honda, Hiroshi; Morin, Patrice J.] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. [Barrueto, Fermin F.; Im, Dwight D.] Mercy Hosp, Gynecol Ctr, Baltimore, MD 21202 USA. [Gogusev, Jean] Hop Necker Enfants Malad, INSERM, U507, Paris, France. [Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. EM h-honda@qg8.so-net.ne.jp; fbarrueto@mdmercy.com; gogusev@necker.fr; dim@mdmercy.com; morinp@grc.nia.nih.gov FU Intramural Research Program of the NIH, National Institute on Aging FX We thank members of our laboratory for useful comments on the manuscript. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 56 TC 31 Z9 35 U1 2 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1477-7827 J9 REPROD BIOL ENDOCRIN JI Reprod. Biol. Endocrinol. PD DEC 2 PY 2008 VL 6 AR 59 DI 10.1186/1477-7827-6-59 PG 13 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 394JD UT WOS:000262442100001 PM 19055724 ER PT J AU De Silva, FS Moss, B AF De Silva, Frank S. Moss, Bernard TI Effects of vaccinia virus uracil DNA glycosylase catalytic site and deoxyuridine triphosphatase deletion mutations individually and together on replication in active and quiescent cells and pathogenesis in mice SO VIROLOGY JOURNAL LA English DT Article ID VIRAL-DNA; IN-VIVO; DUTPASE ACTIVITY; MAMMALIAN-CELLS; A20R PROTEIN; ENCODES; REPAIR; MACROPHAGES; EXPRESSION; IDENTIFICATION AB Background: Low levels of uracil in DNA result from misincorporation of dUMP or cytosine deamination. Vaccinia virus (VACV), the prototype poxvirus, encodes two enzymes that can potentially reduce the amount of uracil in DNA. Deoxyuridine triphosphatase (dUTPase) hydrolyzes dUTP, generating dUMP for biosynthesis of thymidine nucleotides while decreasing the availability of dUTP for misincorporation; uracil DNA glycosylase (UNG) cleaves uracil N-glycosylic bonds in DNA initiating base excision repair. Studies with actively dividing cells showed that the VACV UNG protein is required for DNA replication but the UNG catalytic site is not, whereas the dUTPase gene can be deleted without impairing virus replication. Recombinant VACV with an UNG catalytic site mutation was attenuated in vivo, while a dUTPase deletion mutant was not. However, the importance of the two enzymes for replication in quiescent cells, their possible synergy and roles in virulence have not been fully assessed. Results: VACV mutants lacking the gene encoding dUTPase or with catalytic site mutations in UNG and double UNG/dUTPase mutants were constructed. Replication of UNG and UNG/dUTPase mutants were slightly reduced compared to wild type or the dUTPase mutant in actively dividing cells. Viral DNA replication was reduced about one-third under these conditions. After high multiplicity infection of quiescent fibroblasts, yields of wild type and mutant viruses were decreased by 2-logs with relative differences similar to those observed in active fibroblasts. However, under low multiplicity multi-step growth conditions in quiescent fibroblasts, replication of the dUTPase/UNG mutant was delayed and 5fold lower than that of either single mutant or parental virus. This difference was exacerbated by 1-day serial passages on quiescent fibroblasts, resulting in 2-to 3-logs lower titer of the double mutant compared to the parental and single mutant viruses. Each mutant was more attenuated than a revertant virus upon intranasal infection of mice. Conclusion: VACV UNG and dUTPase activities are more important for replication in quiescent cells, which have low levels of endogenous UNG and dUTPase, than in more metabolically active cells and the loss of both is more detrimental than either alone. Both UNG and dUTPase activities are required for full virulence in mice. C1 [De Silva, Frank S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [De Silva, Frank S.] NIAID, Sci Review Program, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM fdesilva@mail.nih.gov; bmoss@nih.gov FU Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX We thank Norman Cooper for invaluable assistance with cell culture and A. McBride for providing primary cultures of HFFs. The work was funded by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 52 TC 11 Z9 11 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD DEC 2 PY 2008 VL 5 AR 145 DI 10.1186/1743-422X-5-145 PG 12 WC Virology SC Virology GA 414BR UT WOS:000263839400001 PM 19055736 ER PT J AU Waheed, AA Freed, EO AF Waheed, Abdul A. Freed, Eric O. TI Peptide Inhibitors of HIV-1 Egress SO ACS CHEMICAL BIOLOGY LA English DT Article ID VIRUS RELEASE; PROTEIN; TSG101; TRAFFICKING AB HIV-1 release requires a direct interaction between the p6 domain of the Gag protein and Tsg101, a component of the cellular endosomal sorting complex required for transport I (ESCRT-1). Disruption of the binding between Gag and Tsg101 is highly detrimental to particle release, making this viral-host cell interaction a potential target for the development of novel anti-HIV-1 agents. An article in this issue reports on the application of a bacterial reverse two-hybrid strategy to identify a cyclic peptide that disrupts Gag-Tsg101 binding and suppresses HIV-1 particle release. C1 [Waheed, Abdul A.; Freed, Eric O.] NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21702 USA. EM efreed@nih.gov NR 15 TC 10 Z9 11 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD DEC PY 2008 VL 3 IS 12 BP 745 EP 747 DI 10.1021/cb800296j PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 386IS UT WOS:000261877500002 PM 19099395 ER PT J AU Leonov, AP Zheng, JW Clogston, JD Stern, ST Patri, AK Wei, A AF Leonov, Alexei P. Zheng, Jiwen Clogston, Jeffrey D. Stern, Stephan T. Patri, Anil K. Wei, Alexander TI Detoxification of Gold Nanorods by Treatment with Polystyrenesulfonate SO ACS NANO LA English DT Article DE nanorods; nanomedicine; nanobiotechnology; toxicity; dispersion stability ID SURFACE MODIFICATION; CANCER-THERAPY; EXCHANGE RESIN; CYTO-TOXICITY; POLYELECTROLYTE; CELLS; GROWTH; CYTOTOXICITY; ADSORPTION; NANOPARTICLES AB We address an outstanding issue associated with the biocompatibility of gold nanorods (GNRs), a promising agent for biomedical imaging and theragnostics. GNRs are typically prepared in the presence of cetyltrimethylammoniurn bromide (CTAB), a cationic surfactant whose rigorous removal is necessary due to its cytotoxicity and membrane-compromising properties. CTAB-stabilized GNRs can be partially purified by treatment with polystyrenesulfonate (PSS), an anionic polyelectrolyte often used as a surrogate peptizing agent, followed by chloroform extraction and ultrafiltration with minimal loss of dispersion stability. However, in vitro cytotoxicity assays of PSS-coated GNRs revealed IC(50) values in the low to submicromolar range, with subsequent studies indicating the source of toxicity to be associated with a persistent PSS-CTAB complex. Further exchange of CTAB-laden PSS with fresh polyelectrolyte greatly improves biocompatibility, to the extent that 85 mu g/mL of "CTAB-free" GNRs (the highest level evaluated) has comparable toxicity to a standard phosphate buffer solution. Ironically, PSS is not effective by itself at stabilizing GNRs in CTAB-depleted suspensions: while useful as a detergent for GNR detoxification, it should be replaced by more robust coatings for long-term stability under physiological conditions. C1 [Leonov, Alexei P.; Wei, Alexander] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Zheng, Jiwen; Clogston, Jeffrey D.; Stern, Stephan T.; Patri, Anil K.] SAIC Frederick Inc, NCI, Adv Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA. RP Wei, A (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM alexwei@purdue.edu RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Institutes of Health [EB-001777]; NCI [N01-CO-12400] FX The authors gratefully acknowledge financial support from the National Institutes of Health (EB-001777; NCI contract N01-CO-12400). The contents of this publication do 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. Authors declare no competing financial interests. We thank Y. Zhao and Y. Wang (Harbin Institute of Technology) for helpful discussions, A. Oldenburg (Univ, of Illinois) for assistance with ICP-OES analysis, and T. Potter (NCL, SAIC-Frederick) for additional cytotoxicity assays. NR 48 TC 139 Z9 140 U1 3 U2 57 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD DEC PY 2008 VL 2 IS 12 BP 2481 EP 2488 DI 10.1021/nn800466c PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 388MJ UT WOS:000262023600012 PM 19206282 ER PT J AU Collins, CC Lippmann, BM Lo, SJ Moolchan, EI AF Collins, Charles C. Lippmann, Brad M. Lo, Suzanne J. Moolchan, Eric I. TI Time spent with smoking parents and smoking topography in adolescents SO ADDICTIVE BEHAVIORS LA English DT Article DE Tobacco; Adolescent; Nicotine; Smoking topography ID CIGARETTE-SMOKING; NICOTINE; BEHAVIOR; TOBACCO; CESSATION; BLOOD AB Although the relationship between parental and adolescent smoking has been linked to health consequences of smoking, limited study has explored the specific association between exposure to smoking and adolescent smoking topography (the way a cigarette is smoked). As a first step in this line of enquiry, smoking topography measures were collected from 67 adolescent dependent smokers. Participants smoked one cigarette of their own brand while being monitored by a computer-based smoking-topography unit and completed questionnaires about their time spent daily with parents who smoke. Pearson's correlation analysis revealed that time spent daily with parents who smoke was significantly associated with maximum puff velocity (r=0.285, p=.019), a parameter predicting later pulmonary morbidity. ANOVAs, after a median split, were consistent with correlation analyses. There was a significant group effect on puff velocity (F(2,66)=5.197, p=.008); no significant relationship was found with puff volume (F(2,66)=.617) or puff duration (F(2,66)=.776). A post hoc Tukey HSD test indicated puff velocity was higher in the "high time spent" (M=54.37, SD=12.03) than in the "low time spent" group (M=45.59, SD=9.91) and in the group with non-smoking parents (M=44.96, SD=10.17). Future research with a larger non-treatment seeking sample of adolescents aimed at preventing tobacco smoking related diseases should further examine parental influences on adolescent smoking, including potential modeling effects. Published by Elsevier Ltd. C1 [Moolchan, Eric I.] Natl Inst Drug Abuse, Addict Treatment Res Clin, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. RP Moolchan, EI (reprint author), Natl Inst Drug Abuse, Addict Treatment Res Clin, Intramural Res Program, NIH,US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov FU Intramural Research Program; NIH; National Institute on Drug Abuse FX Supported by the Intramural Research Program, NIH, National Institute on Drug Abuse. NR 15 TC 1 Z9 1 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD DEC PY 2008 VL 33 IS 12 BP 1594 EP 1597 DI 10.1016/j.addbeh.2008.07.003 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 367NL UT WOS:000260558600012 PM 18755550 ER PT J AU Nadon, NL Strong, R Miller, RA Nelson, J Javors, M Sharp, ZD Peralba, JM Harrison, DE AF Nadon, N. L. Strong, R. Miller, R. A. Nelson, J. Javors, M. Sharp, Z. D. Peralba, J. M. Harrison, D. E. TI Design of aging intervention studies: the NIA interventions testing program SO AGE LA English DT Article DE Anti-aging; Lifespan; Longevity; Mice ID GENETICALLY HETEROGENEOUS MICE; CONVERTING ENZYME-INHIBITORS; TERT-BUTYL NITRONE; QUANTITATIVE TRAIT LOCI; ACID PHENETHYL ESTER; LIFE-SPAN; BODY-WEIGHT; SPIN-TRAP; ANTIOXIDANT PROPERTIES; CALORIC RESTRICTION AB The field of biogerontology has made great strides towards understanding the biological processes underlying aging, and the time is ripe to look towards applying this knowledge to the pursuit of aging interventions. Identification of safe, inexpensive, and non-invasive interventions that slow the aging process and promote healthy aging could have a significant impact on quality of life and health care expenditures for the aged. While there is a plethora of supplements and interventions on the market that purport to slow aging, the evidence to validate such claims is generally lacking. Here we describe the development of an aging interventions testing program funded by the National Institute on Aging (NIA) to test candidate interventions in a model system. The development of this program highlights the challenges of long-term intervention studies and provides approaches to cope with the stringent requirements of a multi-site testing program. C1 [Nadon, N. L.] NIA, Biol Aging Program, Bethesda, MD 20892 USA. [Strong, R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Nelson, J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Strong, R.; Nelson, J.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Aging Inst, San Antonio, TX 78229 USA. [Miller, R. A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, R. A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Miller, R. A.] VA Med Ctr, Ann Arbor, MI USA. [Javors, M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Sharp, Z. D.; Peralba, J. M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. [Harrison, D. E.] Jackson Labs, Bar Harbor, ME USA. [Strong, R.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Nadon, NL (reprint author), NIA, Biol Aging Program, 7201 Wisconsin Ave GW 2C231, Bethesda, MD 20892 USA. EM nadonn@nia.nih.gov FU National Institutes of Health [U01-AG-022307, U01-AG-022303, U01-AG-022308] FX This work was support by grants from the National Institutes of Health U01-AG-022307 ( R. S.), U01-AG-022303 ( R. A. M.) and U01-AG-022308 ( D. E. H.). NR 82 TC 58 Z9 60 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD DEC PY 2008 VL 30 IS 4 BP 187 EP 199 DI 10.1007/s11357-008-9048-1 PG 13 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 413LJ UT WOS:000263794300001 PM 19424842 ER PT J AU Messaoudi, I Fischer, M Warner, J Park, B Mattison, J Ingram, DK Totonchy, T Mori, M Nikolich-Zugich, J AF Messaoudi, Ilhem Fischer, Miranda Warner, Jessica Park, Buyng Mattison, Julie Ingram, Donald K. Totonchy, Thomas Mori, Motomi Nikolich-Zugich, Janko TI Optimal window of caloric restriction onset limits its beneficial impact on T-cell senescence in primates SO AGING CELL LA English DT Article DE caloric restriction; immune senescence; monkeys; T cells ID AGE-RELATED DYSREGULATION; MONKEYS MACACA-MULATTA; DIETARY RESTRICTION; RHESUS-MONKEYS; CLONAL EXPANSIONS; REPLICATIVE SENESCENCE; NONHUMAN-PRIMATES; IFN-GAMMA; LIFE-SPAN; ELDERLY HUMANS AB We have recently shown in non-human primates that caloric restriction (CR) initiated during adulthood can delay T-cell aging and preserve naive CD8 and CD4 T cells into advanced age. An important question is whether CR can be initiated at any time in life, and whether age at the time of onset would modulate the beneficial effects of CR. In the current study, we evaluated the impact of CR started before puberty or during advanced age on T-cell senescence and compared it to the effects of CR started in early adulthood. Our data demonstrate that the beneficial effects of adult-onset CR on T-cell aging were lost by both early and late CR onset. In fact, some of our results suggest that inappropriate initiation of CR may be harmful to the maintenance of T-cell function. This suggests that there may be an optimal window during adulthood where CR can delay immune senescence and improve correlates of immunity in primates. C1 [Messaoudi, Ilhem; Fischer, Miranda; Warner, Jessica; Totonchy, Thomas; Nikolich-Zugich, Janko] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Messaoudi, Ilhem; Fischer, Miranda; Warner, Jessica; Totonchy, Thomas; Nikolich-Zugich, Janko] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Park, Buyng; Mori, Motomi] Oregon Hlth & Sci Univ, Oregon Canc Inst, Biostat Shared Resource, Portland, OR 97201 USA. [Mattison, Julie; Nikolich-Zugich, Janko] Univ Arizona, Dept Immunobiol, Tucson, AZ 85724 USA. [Mattison, Julie; Nikolich-Zugich, Janko] Univ Arizona, Arizona Ctr Aging, Coll Med, Tucson, AZ 85724 USA. [Ingram, Donald K.] Natl Inst Aging, Lab Expt Gerontol, NIH, Baltimore, MD USA. [Ingram, Donald K.] Louisiana State Univ, Pennington Biomed Res Inst, Baton Rouge, LA 70803 USA. RP Nikolich-Zugich, J (reprint author), Univ Arizona, Dept Immunobiol, 1656 E Mabel St, Tucson, AZ 85724 USA. EM nikolich@email.arizona.edu OI Nikolich-Zugich, Janko/0000-0001-5830-5323; /0000-0003-3516-7516 FU Intramural NIH HHS [Z01 AG000371-02]; NCRR NIH HHS [K01 RR000163, P51 RR000163, RR0163]; NIA NIH HHS [AG21384, U01 AG021384, U01 AG021384-05]; NIAID NIH HHS [5T32 AI007472-10, T32 AI007472] NR 70 TC 30 Z9 31 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2008 VL 7 IS 6 BP 908 EP 919 DI 10.1111/j.1474-9726.2008.00440.x PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 376LF UT WOS:000261184400012 PM 19032694 ER PT J AU Ptak, RG Fu, W Sanders-Beer, BE Dickerson, JE Pinney, JW Robertson, DL Rozanov, MN Katz, KS Maglott, DR Pruitt, KD Dieffenbach, CW AF Ptak, Roger G. Fu, William Sanders-Beer, Brigitte E. Dickerson, Jonathan E. Pinney, John W. Robertson, David L. Rozanov, Mikhail N. Katz, Kenneth S. Maglott, Donna R. Pruitt, Kim D. Dieffenbach, Carl W. TI Cataloguing the HIV Type 1 Human Protein Interaction Network SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID DATABASE; NCBI; INFORMATION; HOST AB Although many interactions between HIV-1 and human proteins have been reported in the scientific literature, no publicly accessible source for efficiently reviewing this information was available. Therefore, a project was initiated in an attempt to catalogue all published interactions between HIV-1 and human proteins. HIV-related articles in PubMed were used to develop a database containing names, Entrez GeneIDs, and RefSeq protein accession numbers of interacting proteins. Furthermore, brief descriptions of the interactions, PubMed identification numbers of articles describing the interactions, and keywords for searching the interactions were incorporated. Over 100,000 articles were reviewed, resulting in the identification of 1448 human proteins that interact with HIV-1 comprising 2589 unique HIV-1-to-human protein interactions. Preliminary analysis of the extracted data indicates 32% were direct physical interactions ( e. g., binding) and 68% were indirect interactions ( e. g., up-regulation through activation of signaling pathways). Interestingly, 37% of human proteins in the database were found to interact with more than one HIV-1 protein. For example, the signaling protein mitogen-activated protein kinase 1 has a surprising range of interactions with 10 different HIV-1 proteins. Moreover, large numbers of interactions were published for the HIV-1 regulatory protein Tat and envelope proteins: 30% and 33% of total interactions identified, respectively. The database is accessible at http://www.ncbi.nlm.nih.gov/RefSeq/HIVInteractions/ and is cross-linked to other National Center for Biotechnology Information databases and programs via Entrez Gene. This database represents a unique and continuously updated scientific resource for understanding HIV-1 replication and pathogenesis to assist in accelerating the development of effective therapeutic and vaccine interventions. C1 [Ptak, Roger G.] So Res Inst, Dept Infect Dis Res, Frederick, MD 21701 USA. [Dickerson, Jonathan E.; Pinney, John W.; Robertson, David L.] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. [Rozanov, Mikhail N.; Katz, Kenneth S.; Maglott, Donna R.; Pruitt, Kim D.] Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Dieffenbach, Carl W.] NIAID, NIH, Div Aids, Bethesda, MD 20892 USA. RP Ptak, RG (reprint author), So Res Inst, Dept Infect Dis Res, 431 Aviat Way, Frederick, MD 21701 USA. EM ptak@southernresearch.org FU NIH,; NIAID [N01-AI-05415, N01-AI-70042]; BBSRC [BB/C515412/1]; National Library of Medicine FX We thank Joel Gillman for providing database support. R. G. P., W. F., and B. E. S.-B. were funded in whole with federal funds from the NIH, NIAID under Contracts N01-AI-05415 and N01-AI-70042, and wish to thank Dr. Roger Miller, Project Officer, DAIDS. J.E.D. was supported by a Wellcome Trust studentship and J.W.P by a BBSRC project grant ( BB/C515412/1). M.N.R., K. S. K, D. R. M., and K. D. P. were supported by the Intramural Research Program of the NIH, National Library of Medicine. R. G. P. and W. F. catalogued the interactions and curated the database with support from B. E. S.-B.; J.E.D., J.W.P., and D. L. R. carried out the Gene Ontology analysis and visualization of the interactions; M.N.R. and R. G. P. generated the improved NC_001802.1 RefSeq annotation; K. S. K., D. R. M., and K. D. P. generated the open access database resource at NCBI and incorporated the data into Entrez Gene; C. W. D. provided the original concept for the database and support for the project through NIAID/ DAIDS. NR 17 TC 71 Z9 71 U1 0 U2 3 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 DEC PY 2008 VL 24 IS 12 BP 1497 EP 1502 DI 10.1089/aid.2008.0113 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 386UG UT WOS:000261907500003 PM 19025396 ER PT J AU Kunos, G AF Kunos, George TI A Tribute to Dr. Ting-Kai Li SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 NIAAA, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2008 VL 32 IS 12 BP 2030 EP 2030 DI 10.1111/j.1530-0277.2008.00840.x PG 1 WC Substance Abuse SC Substance Abuse GA 379KL UT WOS:000261395000002 PM 18986381 ER PT J AU Taylor, RE Raysor, BR Kwagyan, J Ramchandani, VA Kalu, N Powell-Davis, M Ferguson, CL Carr, L Scott, DM AF Taylor, Robert E. Raysor, Byron R. Kwagyan, John Ramchandani, Vijay A. Kalu, Nnenna Powell-Davis, Monique Ferguson, Clifford L. Carr, Lucinda Scott, Denise M. TI Alterations in Ethyl Alcohol Pharmacokinetics During Oral Consumption of Malt Liquor Beverages in African Americans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Malt Liquor; Pharmacokinetics; Alcohol Dehydrogenase; Aldehyde Dehydrogenase; African-Americans ID TOTAL-BODY WATER; ETHANOL PHARMACOKINETICS; NATIVE-AMERICAN; EFFECTS SCALE; ELIMINATION; BLOOD; DRINKING; INTOXICATION; METABOLISM; CHALLENGE AB Malt liquor (ML) beverages have become increasingly popular among urban minority groups, due partly to their inexpensive price and targeted advertising. We hypothesized that nonfermented by-products contained in ML beverages will alter the pharmacokinetics (PK) and pharmacodynamic (PD) effects of its ethanol content. In addition, we determined the effect of alcohol dehydrogenase (ADH) genotypes on the PK following consumption of ML beverages. The study was conducted in 31 healthy adult African-American social drinkers, mean +/- SD age of 22.3 +/- 1.3 years, and weight of 70.7 +/- 10.9 kg. Participants were administered ethanol, in randomized order, 2-weeks apart, in the form of oral ML beverage (6%v/v), or isocaloric solution of diet soda-ethanol (DS-Etoh) beverage (6%v/v). During each session the beverage was consumed over 4 minutes and breath alcohol concentrations (BrAC) as well as subjective and behavioral effects of ethanol were evaluated over 180 minutes. Pharmacokinetic parameters of ethanol were calculated using Michaelis-Menten elimination kinetics. The effect of ML and ADH genotype on PK was evaluated using the Wilcoxon rank-sum test and the Wilcoxon signed rank test, respectively. Results show a slower mean rate of absorption, K(a), (0.12 vs. 0.15 min(-1), p = 0.03) and a longer time to reach maximum concentration, T(max), (28 vs. 23 minute, p < 0.01) for the ML compared with DS-Etoh beverage. The ML beverage resulted in a larger area under the BrAC-time curve compared with DS-Etoh beverage (8.4 vs. 6.8 min g/dl, p = 0.02). There was no difference in the subjective PD effects between the 2 beverages. Results show that exposure to ethanol following the consumption of ML beverages is different compared to that following nonmalt beverages in African-Americans. These differences may be related to nonfermented by-products present in commercially available ML products. These PK differences do not appear to result in significant perceived alcohol PD changes, nor are they related to ADH genotype. C1 [Taylor, Robert E.; Raysor, Byron R.; Kwagyan, John; Kalu, Nnenna; Powell-Davis, Monique; Ferguson, Clifford L.; Scott, Denise M.] Howard Univ, Alcohol Res Ctr, Washington, DC 20059 USA. [Carr, Lucinda] Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. [Ramchandani, Vijay A.] NIAAA, Bethesda, MD USA. RP Scott, DM (reprint author), Howard Univ, Alcohol Res Ctr, 520 W St NW,Suite 3408, Washington, DC 20059 USA. EM d_m_scott2@howard.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R21AA13531, U24AA11898, AA014643]; General Clinical Research Center (GCRC) [MO1 RR10284] FX The study was supported in part by the following grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), R21AA13531, U24AA11898, AA014643, and General Clinical Research Center (GCRC) grant MO1 RR10284. We would like to thank Dr. T-K Li for his recommendations on the design of this study. NR 36 TC 6 Z9 6 U1 0 U2 3 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 DEC PY 2008 VL 32 IS 12 BP 2074 EP 2080 DI 10.1111/j.1530-0277.2008.00795.x PG 7 WC Substance Abuse SC Substance Abuse GA 379KL UT WOS:000261395000008 PM 18828806 ER PT J AU Dawson, DA Goldstein, RB Chou, SP Ruan, WJ Grant, BF AF Dawson, Deborah A. Goldstein, Rise B. Chou, S. Patricia Ruan, W. June Grant, Bridget F. TI Age at First Drink and the First Incidence of Adult-Onset DSM-IV Alcohol Use Disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Age at First Drink; Incidence of AUD ID GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; FAMILY-HISTORY; DRUG-USE; PREFRONTAL CORTEX; DECISION-MAKING; RISK-FACTORS; FOLLOW-UP; DEPENDENCE AB Existing studies of the association between age at first drink (AFD) and the risk of alcohol use disorders (AUD) suffer from inconsistent levels of control and designs that may inflate associations by failure to control for duration of exposure to risk. This study examined associations between AFD (ages < 15 and 15-17 vs. 18+ years) and first incidence of DSM-IV alcohol dependence, abuse, and specific AUD criteria over a 3-year follow-up in a longitudinal study of U.S. drinkers 18 years of age and older at baseline (n = 22,316), controlling for duration of exposure, family history, and a wide range of baseline and childhood risk factors. After adjusting for all risk factors, the incidence of dependence was increased for AFD < 15 years (OR = 1.38) and for women only with AFD at ages 15 to 17 (OR = 1.54). The incidence of abuse was increased at AFD < 15 and 15 to 17 years (OR = 1.52 and 1.30, respectively). Most dependence criteria showed significant associations with AFD, but hazardous drinking and continued drinking despite interpersonal problems were the only abuse criteria to do so. All associations were nonsignificant after controlling for volume of consumption, except that AFD at all ages < 18 combined was associated with a reduced likelihood of impaired control, and AFD at ages 15 to 17 was associated with lower odds of drinking more/longer than intended among heavy-volume drinkers. In a population of low-risk drinkers that excluded those with positive family histories, personality disorders, and childhood risk factors, there were strong associations between early AFD (< 18) and the incidence of dependence (OR = 3.79) and continued drinking despite physical/psychological problems (OR = 2.71), but no association with incidence of abuse. There is a robust association between AFD and the risk of AUD that appears to reflect willful rather than uncontrolled heavy drinking, consistent with misuse governed by poor decision-making and/or reward-processing skills associated with impaired executive cognitive function (ECF). Additional research is needed to determine causality in the role of impaired ECF, including longitudinal studies with samples of low-risk adolescents. C1 [Dawson, Deborah A.; Goldstein, Rise B.; Chou, S. Patricia; Ruan, W. June; Grant, Bridget F.] NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, Div Intramural Clin & Biol Res, NIH, Room 3071,5635 Fishers Lane,MSC9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [Z99 AA999999] NR 49 TC 157 Z9 158 U1 7 U2 20 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2008 VL 32 IS 12 BP 2149 EP 2160 DI 10.1111/j.1530-0277.2008.00806.x PG 12 WC Substance Abuse SC Substance Abuse GA 379KL UT WOS:000261395000016 PM 18828796 ER PT J AU Hall, KD Jordan, PN AF Hall, Kevin D. Jordan, Peter N. TI Modeling weight-loss maintenance to help prevent body weight regain SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID RESTING ENERGY-EXPENDITURE; FAT-FREE MASS; OBESE WOMEN; ADAPTIVE THERMOGENESIS; PHYSICAL-ACTIVITY; REDUCED-OBESE; FUEL UTILIZATION; METABOLIC-RATE; POST-OBESE; PREDICTION AB Background: Lifestyle intervention can successfully induce weight loss in obese persons, at least temporarily. However, there currently is no way to quantitatively estimate the changes of diet or physical activity required to prevent weight regain. Such a tool would be helpful for goal-setting, because obese patients and their physicians could assess at the outset of an intervention whether long-term adherence to the calculated lifestyle change is realistic. Objective: We aimed to calculate the expected change of steady-state body weight arising from a given change in dietary energy intake and, conversely, to calculate the modification of energy intake required to maintain a particular body-weight change. Design: We developed a mathematical model using data from 8 longitudinal weight-loss studies representing 157 subjects with initial body weights ranging from 68 to 160 kg and stable weight losses between 7 and 54 kg. Results: Model calculations closely matched the change data (R(2) = 0.83, chi(2) = 2.1, P < 0.01 for weight changes; R(2) = 0.91, chi(2) = 0.87, P < 0.0004 for energy intake changes). Our model performed significantly better than the previous models for which chi(2) values were 10-fold those of our model. The model also accurately predicted the proportion of weight change resulting from the loss of body fat (R(2) = 0.90). Conclusions: Our model provides realistic calculations of body-weight change and of the dietary modifications required for weight-loss maintenance. Because the model was implemented by using standard spreadsheet software, it can be widely used by physicians and weight-management professionals. Am J Clin Nutr 2008; 88: 1495-503. C1 [Hall, Kevin D.; Jordan, Peter N.] NIDDK, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Hall, KD (reprint author), NIDDK, NIH, Lab Biol Modeling, 12A South Dr,Room 4007, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX Supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 59 TC 54 Z9 55 U1 0 U2 9 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC 1 PY 2008 VL 88 IS 6 BP 1495 EP 1503 DI 10.3945/ajcn.2008.26333 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 380EO UT WOS:000261449200007 PM 19064508 ER PT J AU Looker, AC Pfeiffer, CM Lacher, DA Schleicher, RL Picciano, MF Yetley, EA AF Looker, Anne C. Pfeiffer, Christine M. Lacher, David A. Schleicher, Rosemary L. Picciano, Mary Frances Yetley, Elizabeth A. TI Serum 25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID VITAMIN-D DEFICIENCY; UNITED-STATES; PREVALENCE; ADOLESCENTS; CHILDREN; INFANTS; OBESITY; FUTURE; CANCER; ADULTS AB Background: Changes in serum 25-hydroxyvitamin D [ 25(OH) D] concentrations in the US population have not been described. Objective: We used data from the National Health and Nutrition Examination Surveys (NHANES) to compare serum 25(OH) D concentrations in the US population in 2000-2004 with those in 1988-1994 and to identify contributing factors. Design: Serum 25(OH) D was measured with a radioimmunoassay kit in 20 289 participants in NHANES 2000-2004 and in 18 158 participants in NHANES III (1988-1994). Body mass index (BMI) was calculated from measured height and weight. Milk intake and sun protection were assessed by questionnaire. Assay differences were assessed by re-analyzing 150 stored serum specimens from NHANES III with the current assay. Results: Age-adjusted mean serum 25(OH) D concentrations were 5-20 nmol/L lower in NHANES 2000-2004 than in NHANES III. After adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 5-9 nmol/L) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH) D concentrations by approximate to 10 nmol/L, and adjustment for changes in the factors likely related to real changes in vitamin D status (ie, BMI, milk intake, and sun protection) changed mean serum 25(OH) D concentrations by 1-1.6 nmol/L. Conclusions: Overall, mean serum 25(OH) D was lower in 2000-2004 than 1988-1994. Assay changes unrelated to changes in vitaminD status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status. Am J Clin Nutr 2008; 88: 1519-27. C1 [Looker, Anne C.; Lacher, David A.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Pfeiffer, Christine M.; Schleicher, Rosemary L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Picciano, Mary Frances; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Looker, AC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Room 4310,3311 Belcrest Rd, Hyattsville, MD 20782 USA. EM acl1@cdc.gov FU NIH HHS [Y01 OD4322-01] NR 22 TC 352 Z9 367 U1 2 U2 13 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 DEC 1 PY 2008 VL 88 IS 6 BP 1519 EP 1527 DI 10.3945/ajcn.2008.26182 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 380EO UT WOS:000261449200010 PM 19064511 ER PT J AU McClelland, RL Bild, DE Burke, GL Mukamal, KJ Lima, JA Kronmal, RA AF McClelland, Robyn L. Bild, Diane E. Burke, Gregory L. Mukamal, Kenneth J. Lima, Joao A. Kronmal, Richard A. TI Alcohol and coronary artery calcium prevalence, incidence, and progression: results from the Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID YOUNG-ADULTS CARDIA; HEART-DISEASE; RISK DEVELOPMENT; CONSUMPTION; CALCIFICATION; METAANALYSIS; POPULATION; DRINKING; HEALTH; CT AB Background: Alcohol use has been consistently found to have a J-shaped association with coronary heart disease, with moderate drinkers exhibiting a decreased risk compared with both heavy drinkers and nondrinkers. However, results of studies of the association between alcohol use and subclinical coronary artery disease are conflicting. Objective: The objective was to determine whether alcohol is associated with the presence, amount, or progression of coronary calcium over a 2- to 4-y period. Design: The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective community-based cohort study of subclinical cardiovascular disease in a multi-ethnic cohort. In 2000-2002, 6814 participants free of clinical cardiovascular disease were enrolled at 6 participating centers. Results: The subjects consisted of 3766 (55.5%) current drinkers, 1635 (24.1%) former drinkers, and 1390 (20.5%) never drinkers. Although light-to-moderate alcohol consumption was associated with lower coronary heart disease risk, we found no evidence of a protective or J-shaped association of alcohol and coronary artery calcium (CAC). In fact, there was evidence that heavy consumption of hard liquor was associated with greater CAC accumulation. Other alcoholic beverages were not associated with CAC prevalence, incidence, or progression. Conclusions: This was the first large study to evaluate the association of alcohol with CAC in 4 racial-ethnic groups and to evaluate the progression of calcification. These results suggest that the cardiovascular benefits that may be derived from light-to-moderate alcohol consumption are not mediated through reduced CAC accumulation. Am J Clin Nutr 2008; 88: 1593-601. C1 [McClelland, Robyn L.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Seattle, WA 98115 USA. [Bild, Diane E.] NIH, Bethesda, MD 20892 USA. [Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Lima, Joao A.] Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. RP McClelland, RL (reprint author), Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Bldg 29,Suite 310,6200 NE 74th St, Seattle, WA 98115 USA. EM rmcclell@u.washington.edu FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX Supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute. NR 21 TC 11 Z9 13 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 DEC 1 PY 2008 VL 88 IS 6 BP 1593 EP 1601 DI 10.3945/ajcn.2008.26420 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 380EO UT WOS:000261449200019 PM 19064520 ER PT J AU Muniyappa, R Hall, G Kolodziej, TL Karne, RJ Crandon, SK Quon, MJ AF Muniyappa, Ranganath Hall, Gail Kolodziej, Terrie L. Karne, Rajaram J. Crandon, Sonja K. Quon, Michael J. TI Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID GREEN TEA POLYPHENOL; CORONARY-HEART-DISEASE; FLAVANOL-RICH COCOA; ENDOTHELIAL DYSFUNCTION; SKELETAL-MUSCLE; DARK CHOCOLATE; DEPENDENT VASODILATION; NITRIC-OXIDE; CARDIOVASCULAR HEALTH; COMBINED THERAPY AB Background: Essential hypertension is characterized by reciprocal relations between endothelial dysfunction and insulin resistance. Cocoa flavanols stimulate production of the vasodilator nitric oxide from vascular endothelium. Objective: The objective was to test the hypothesis that consumption of cocoa may simultaneously lower blood pressure, improve endothelial dysfunction, and ameliorate insulin resistance in subjects with essential hypertension. Design: We conducted a randomized, placebo-controlled, double-blind, crossover trial of a flavanol-rich cocoa drink (150 mL twice a day, approximate to 900 mg flavanols/d) in individuals with essential hypertension (n = 20). Antihypertensive medications were discontinued before study enrollment. After a 7-d cocoa-free run-in period, cocoa or flavanol-poor placebo (approximate to 28 mg flavanols/d) treatment for 2 wk was followed by a 1-wk washout and then crossover to the other treatment arm. Blood pressure was measured thrice weekly. At baseline and after each treatment period, we assessed insulin sensitivity (hyperinsulinemic-isoglycemic glucose clamp) and insulin-stimulated changes in brachial artery diameter and forearm skeletal muscle capillary recruitment (Doppler ultrasound with or without microbubble contrast). Conclusions: Daily consumption of flavanol-rich cocoa for 2 wk is not sufficient to reduce blood pressure or improve insulin resistance in human subjects with essential hypertension. This trial was registered at clinicaltrials. gov as NCT00099476. Am J Clin Nutr 2008; 88: 1685-96. C1 [Muniyappa, Ranganath; Hall, Gail; Kolodziej, Terrie L.; Karne, Rajaram J.; Crandon, Sonja K.; Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NIH, Diabet Unit, NCCAM, 9 Mem Dr,Bldg 9,Room 1N-105 MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural Research Program; NCCAM; NIH FX Supported in part by the Intramural Research Program, NCCAM, NIH, and by the Office of Dietary Supplements, NIH. NR 69 TC 68 Z9 69 U1 6 U2 22 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC 1 PY 2008 VL 88 IS 6 BP 1685 EP 1696 DI 10.3945/ajcn.2008.26457 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 380EO UT WOS:000261449200030 PM 19064532 ER PT J AU Sharp, H Morris, JC Van Waes, C Gius, D Coolely-Zgela, T Singh, AK AF Sharp, Hadley Morris, John C. Van Waes, Carter Gius, David Coolely-Zgela, Theresa Singh, Anurag K. TI High Incidence of Oral Dysesthesias on a Trial of Gefitinib, Paclitaxel, and Concurrent External Beam Radiation for Locally Advanced Head and Neck Cancers SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE gefitinib; paclitaxel; irradiation; oral dysesthesia ID CELL LUNG-CANCER; PHASE-I TRIAL; CLINICAL-EXPERIENCE; NEUROPATHIC PAIN; ONCOLOGY-GROUP; CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; THERAPY; OXALIPLATIN AB Objectives: To report a high incidence of oral mucosal dysesthesia Occurring in patients oil a pilot study of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa) in combination with paclitaxel (Taxol) and external beam radiation therapy for the treatment of locally advanced squamous cell carcinoma of the head and neck. Methods: Nine patients were enrolled on a pilot phase I trial of oral gefitinib 250 mg/d with 6 weekly doses of paclitaxel (36 or 45 mg/m(2)) and Concurrent radiation therapy [66-76 Gray (Gy)]. All had stage III/IVA-B squanious cell carcinoma of the head and neck. Patients were evaluated twice weekly by physicians and daily by nursing For adverse events. Results: Six of 9 patients (67%) developed a grade 3 "burning" quality oral dysesthesia. These patients received at least 50 Gy (range 50-70 Gy) to the oral tongue. The patients without grade 3 oral dysesthesia received less than 50 Gy radiation to the oral tongue. The oral dysesthesia was exacerbated by the ingestion of neutral pH liquids such as water. Of the 6 patients, all eventually developed common toxicity criteria grade 3/4 mucositis; however, symptoms continued after resolution of the mucositis. Gabapentin (Neurontin) was administered to 2 patients as a treatment for painftil mucosal neuropathy, Both patients had near resolution Of Symptoms despite the evolution of oral mucositis. Conclusions: Development of "burning"-type oral dysesthesia occurred in patients treated with the combination of gefitinib, paclitaxel, and external beam radiation of the oral tongue. This dysesthesia was improved by the use of gabapentin. C1 [Singh, Anurag K.] Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. [Sharp, Hadley; Gius, David; Coolely-Zgela, Theresa] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Singh, AK (reprint author), Roswell Pk Canc Inst, Dept Radiat Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM anurag.singh@roswellpark.org FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 40 TC 12 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD DEC PY 2008 VL 31 IS 6 BP 557 EP 560 DI 10.1097/COC.0b013e318172d5de PG 4 WC Oncology SC Oncology GA 382CN UT WOS:000261582700006 PM 19060587 ER PT J AU Queiroga, EM Gualco, G Weiss, LM Dittmer, DP Araujo, I Klumb, CEN Harrington, WJ Bacchi, CE AF Queiroga, Eduardo M. Gualco, Gabriela Weiss, Lawrence M. Dittmer, Dirk P. Araujo, Iguaracyra Klumb, Claudette E. N. Harrington, William J., Jr. Bacchi, Carlos E. TI Burkitt Lymphoma in Brazil Is Characterized by Geographically Distinct Clinicopathologic Features SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Burkitt lymphoma; Brazil; Epstein-Barr virus; Tissue microarray; p53; p63; Immunohistochemistry; Polymerase chain reaction ID EPSTEIN-BARR-VIRUS; P53 PROTEIN EXPRESSION; NON-HODGKIN-LYMPHOMA; B-CELL LYMPHOMA; ENDEMIC AREAS; GENE; ASSOCIATION; P63; MUTATIONS; CHILDREN AB Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma with a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with BL at different frequencies, depending on the clinical variant and geographic regions. This is a large-scale study of BL in Brazil, including 234 patients from 5 geographic regions that are widely disparate socioeconomically, including pediatric (61.1%) and adult (37.6%) populations. EBV was present in 52.6% of all BL cases, varying from 29% (12/42) in the South to 76% (13/17) in the North. Most of the cases were EBV type A. The frequency was higher in the pediatric group, and EBV association within this age range predominated in all regions except the South. Expression of p53 protein was observed inn 16.2%, and only rare cases showed p63 expression. BL in Brazil is regionally distinct and has a low incidence of p53 overexpression and a higher-than-expected association with EBV in sporadic cases. C1 [Queiroga, Eduardo M.; Gualco, Gabriela; Bacchi, Carlos E.] Pathol Reference Lab, Botucatu, SP, Brazil. [Queiroga, Eduardo M.; Bacchi, Carlos E.] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Weiss, Lawrence M.] City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA. [Dittmer, Dirk P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Araujo, Iguaracyra] Prof Edgard Santos Univ Hosp, Salvador, BA, Brazil. [Klumb, Claudette E. N.] Natl Canc Inst, Rio De Janeiro, Brazil. [Harrington, William J., Jr.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Harrington, William J., Jr.] Fogarty Int Ctr AIDS & TB Program, Sylvester Canc Ctr, Miami, FL USA. RP Bacchi, CE (reprint author), Rua Major Leonidas Cardoso 739, BR-18602010 Botucatu, SP, Brazil. RI Klumb, Claudete/L-2682-2015 OI Klumb, Claudete/0000-0002-7672-1088 FU National Cancer Institute (NCI), Bethesda, MD [5R01CA082274, 5R01CA121935, 5R01CA112217, DE018304]; NCI AIDS Malignancy Consortium; University of Miami Fogarty AITRP [D43TW000017] FX Supported in part by grants 5R01CA082274, 5R01CA121935, 5R01CA112217 (to W.J.H.), and DE018304 (to D.P.D.) from the National Cancer Institute (NCI), Bethesda, MD, the NCI AIDS Malignancy Consortium, and the University of Miami Fogarty AITRP grant D43TW000017. NR 55 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2008 VL 130 IS 6 BP 946 EP 956 DI 10.1309/AJCP64YOHAWLUMPK PG 11 WC Pathology SC Pathology GA 373UV UT WOS:000260999900016 PM 19019773 ER PT J AU Kim, S Martin, C Galanko, J Woosley, JT Schroeder, JC Keku, TO Satia, JA Halabi, S Sandler, RS AF Kim, Sangmi Martin, Christopher Galanko, Joseph Woosley, John T. Schroeder, Jane C. Keku, Temitope O. Satia, Jessie A. Halabi, Susan Sandler, Robert S. TI Use of Nonsteroidal Antiinflammatory Drugs and Distal Large Bowel Cancer in Whites and African Americans SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CYTOKINE GENE POLYMORPHISMS; PREVENT COLORECTAL ADENOMAS; LOW-DOSE ASPIRIN; RANDOMIZED-TRIAL; COLON-CANCER; ANTICANCER AGENTS; WOMENS HEALTH; RISK; CYCLOOXYGENASE-2; PRESCRIPTION AB Despite the belief that the etiology of and risk factors for rectal cancer might differ from those for colon cancer, relatively few studies have examined rectal cancer in relation to use of nonsteroidal antiinflammatory drugs (NSAIDs). The authors evaluated the association between NSAIDs and distal large bowel cancer in African Americans and whites, using data from a population-based case-control study of 1,057 incident cases of adenocarcinoma of the sigmoid colon, rectosigmoid junction, and rectum and 1,019 controls from North Carolina (2001-2006). NSAID use was inversely associated with distal large bowel cancer in whites (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.46, 0.79). The inverse association was evident for all types of NSAIDs but was slightly stronger with prescription NSAIDs, particularly selective cyclooxygenase 2 inhibitors (OR = 0.38, 95% CI: 0.25, 0.56). Compared with whites, a relatively weak inverse association was found in African Americans (OR = 0.87, 95% CI: 0.55, 1.40), although odds ratio heterogeneity by race could not be confirmed (P = 0.21). In addition, the strength of the association with NSAIDs varied by tumor location, suggesting more potent effects for rectal and rectosigmoid cancers than for sigmoid cancer. The chemopreventive potential of NSAIDs might differ by population and by tumor characteristics. C1 [Kim, Sangmi; Schroeder, Jane C.; Satia, Jessie A.; Sandler, Robert S.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Martin, Christopher; Galanko, Joseph; Keku, Temitope O.; Sandler, Robert S.] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA. [Woosley, John T.] Univ N Carolina, Sch Med, Dept Pathol, Chapel Hill, NC USA. [Halabi, Susan] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. RP Kim, S (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Kims3@niehs.nih.gov FU National Institutes of Health [R01 CA 66635, P30 DK34987] FX This work was supported in part by grants from the National Institutes of Health (R01 CA 66635 and P30 DK34987). NR 47 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2008 VL 168 IS 11 BP 1292 EP 1300 DI 10.1093/aje/kwn255 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 377VK UT WOS:000261279600009 PM 18945689 ER PT J AU Weiss, JM Lacey, JV Shu, XO Ji, BT Hou, LF Yang, G Li, HL Rothman, N Blair, A Gao, YT Chow, WH Zheng, W AF Weiss, Jocelyn M. Lacey, James V. Jr. Shu, Xiao-Ou Ji, Bu-Tian Hou, Lifang Yang, Gong Li, Honglan Rothman, Nathaniel Blair, Aaron Gao, Yu-Tang Chow, Wong-Ho Zheng, Wei TI Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CHINESE-WOMEN; HORMONE RECEPTORS; C57BL/6J MICE; ESTROGEN; RISK; ADENOCARCINOMA; CARCINOMA; DETERMINANTS; CARDIOLIPIN; ANTIBODIES AB Cigarette smoking is irrefutably the strongest risk factor for lung cancer; however, approximately 25% of cases worldwide occur among nonsmokers. The age-adjusted annual incidence rate of lung cancer in Shanghai, a region where relatively few women smoke cigarettes, is one of the highest in the world. To help further elucidate the etiology of lung cancer among nonsmokers, the authors examined hormonal factors among women who were lifetime nonsmokers. They analyzed data from the prospective Shanghai Women's Health Study, which recruited Chinese women aged 40-70 years between 1996 and 2000 from selected urban communities. The current analysis included 71,314 women (n = 220 cases) who were lifetime nonsmokers and had no history of cancer at baseline. Later age at menopause (>= 51 vs. < 46 years; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.40, 1.00), longer reproductive period (>= 36 vs. < 31 years; HR = 0.60, 95% CI: 0.39, 0.93), higher parity (>= 4 vs. 0 children; HR = 0.42, 95% CI: 0.19, 0.90), and intrauterine device use (HR = 0.59, 95% CI: 0.41, 0.86) were associated with decreased risks of lung cancer. This large prospective study suggests a potential role for hormonal factors in the etiology of lung cancer among nonsmoking women. C1 [Weiss, Jocelyn M.; Lacey, James V. Jr.; Ji, Bu-Tian; Rothman, Nathaniel; Blair, Aaron; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37212 USA. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Li, Honglan; Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Weiss, JM (reprint author), Int Epidemiol Inst, 1455 Res Blvd,Suite 550, Rockville, MD 20850 USA. EM jocelyn@iei.us FU NCI NIH HHS [UM1 CA182910] NR 42 TC 25 Z9 25 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 2008 VL 168 IS 11 BP 1319 EP 1325 DI 10.1093/aje/kwn257 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 377VK UT WOS:000261279600012 PM 18849300 ER PT J AU Anderson, DE McNeely, JD Chesney, MA Windham, BG AF Anderson, David E. McNeely, Jessica D. Chesney, Margaret A. Windham, Beverly G. TI Breathing Variability at Rest is Positively Associated With 24-h Blood Pressure Level SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article ID CHRONIC HEART-FAILURE; SPECTRAL-ANALYSIS; SLEEP-APNEA; HYPERTENSION; SODIUM; CHEMORECEPTORS; RESPIRATION; DISORDERS; SYSTEM AB BACKGROUND Previous research has reported that inhibition of breathing can be observed in hypertensive patients at rest during the daytime, as well as in sleep at night. The present study hypothesized that the variability of breathing and end-tidal CO2 (PetCO(2)) in seated women at rest is positively associated with their 24-h blood pressure level. METHODS Breath-to-breath measures of breathing rate and tidal volume were recorded via inductive plethysmography in each of 54 women during two 20-min sessions of seated rest, and in 32 women during night time sleep. PetCO(2) was also recorded during these sessions via a respiratory gas monitor. Ambulatory blood pressure was recorded for 24 h between the two clinic sessions via oscillometry. RESULTS Breath pauses >10s were observed significantly more often in women in the upper than the lower tertile of 24-h systolic blood pressure. Breath-to-breath variability in breathing rate, tidal volume, and minute ventilation were greater in the higher blood pressure tertile women. Variability in PetCO(2) was also greater in high blood pressure tertile. These associations were independent of age, weight, and body surface area (BSA). Breathing variability was inversely correlated with heart rate variability (HRV). CONCLUSION Greater variability in breathing at rest that is independent of metabolic activity characterizes women with elevoted blood pressure. The linear association of breathing variability with 24-h blood pressure level is consistent with the hypothesis that intermittent breathing inhibition may predispose to the development of some forms of hypertension. C1 [Anderson, David E.; McNeely, Jessica D.; Windham, Beverly G.] NIA, Clin Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Chesney, Margaret A.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. RP Anderson, DE (reprint author), NIA, Clin Res Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM Andersod@grc.nia.nih.gov FU National Institute on Aging Intramural Research Program; National Institutes of Health FX This work was supported by the National Institute on Aging Intramural Research Program, National Institutes of Health. We hereby thank Beverly Parsons for her expert assistance with subject recruitment and testing, Denis Muller for help with statistical analysis of data, and S. Morteza "Mo" Farasat for his careful reading of the manuscript. NR 27 TC 4 Z9 4 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD DEC PY 2008 VL 21 IS 12 BP 1324 EP 1329 DI 10.1038/ajh.2008.292 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 374JL UT WOS:000261039500014 PM 18820654 ER PT J AU Contopoulos-Ioannidis, D Evangeliou, A ter Laak, H de Vries, B Pfundt, R Schewer, H Smeitink, J Tzoufi, M Makis, A Marinos, E Hess, R Adams, D Huizing, M Morava, E AF Contopoulos-Ioannidis, Despina Evangeliou, Athanasios ter Laak, Henk de Vries, Bert Pfundt, Rolph Schewer, Hans Smeitink, Jan Tzoufi, Meropi Makis, Alexandros Marinos, Evangelos Hess, Richard Adams, David Huizing, Marjan Morava, Eva TI Recurrent Rhabdomyolysis in a Patient With Oculocutaneous Albinism Type 1 and Platelet Storage-Pool Deficiency SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID HERMANSKY-PUDLAK-SYNDROME; LYSOSOME-RELATED ORGANELLES; CENTRAL CORE DISEASE; MALIGNANT HYPERTHERMIA; GENE-MUTATIONS; DYSBINDIN; BIOGENESIS; SUBUNIT; PROTEIN; VARIANT C1 [Contopoulos-Ioannidis, Despina; Tzoufi, Meropi; Makis, Alexandros] Univ Ioannina, Dept Pediat, Sch Med, GR-45110 Ioannina, Greece. [Contopoulos-Ioannidis, Despina] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA. [Evangeliou, Athanasios] Aristotle Univ Thessaloniki, Sch Med, Dept Neurol, GR-54006 Thessaloniki, Greece. [ter Laak, Henk] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [de Vries, Bert; Pfundt, Rolph; Schewer, Hans] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands. [Smeitink, Jan; Morava, Eva] Radboud Univ Nijmegen, Med Ctr, Nijmegen Ctr Mitochondrial Disorders, Dept Pediat, NL-6525 ED Nijmegen, Netherlands. [Marinos, Evangelos] Univ Athens, Sch Med, Lab Histol & Embryol, GR-11527 Athens, Greece. [Hess, Richard; Adams, David; Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Contopoulos-Ioannidis, D (reprint author), Univ Ioannina, Dept Pediat, Sch Med, GR-45110 Ioannina, Greece. EM dcontop@cc.uoi.gr RI Smeitink, Jan/C-1351-2013; Pfundt, Rolph/L-4576-2015; Morava, E./L-4529-2015 FU Intramural NIH HHS [Z01 HG200322-03] NR 20 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2008 VL 146A IS 23 BP 3100 EP 3103 DI 10.1002/ajmg.a.32569 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 382WM UT WOS:000261636100020 PM 19006216 ER PT J AU Taub, DD Ershler, WB Janowski, M Artz, A Key, ML McKelvey, J Muller, D Moss, B Ferrucci, L Duffey, PL Longo, DL AF Taub, Dennis D. Ershler, William B. Janowski, Mark Artz, Andrew Key, Michael L. McKelvey, Julie Muller, Denis Moss, Bernard Ferrucci, Luigi Duffey, Patricia L. Longo, Dan L. TI Immunity from Smallpox Vaccine Persists for Decades: A Longitudinal Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aging; BLSA; Biodefense; Smallpox; Vaccination; Vaccinia ID IMMUNOLOGICAL MEMORY; RESPONSES; VIRUS; REVACCINATION; BIOTERRORISM; PROTECTION; ANTIBODIES AB PURPOSE: The threat of smallpox resulting from bioterrorist action has prompted a reassessment of the level of immunity in current populations. METHODS: We have examined the magnitude and duration of antiviral antibody immunity conferred by smallpox vaccination in 246 participants of the Baltimore Longitudinal Study of Aging. Of this population, 209 subjects were vaccinated one or more times 13 to 88 years before this evaluation, and stored serum samples were available at various intervals after vaccination. An additional 8 subjects who had documented childhood smallpox infection and 29 subjects with no history of infection or vaccination were included. We quantified the total vaccinia IgG and neutralizing antibody titers in each of these subgroups of participants over time. RESULTS: Vaccinated participants maintained antivaccinia IgG and neutralizing antibody titers above 3 natural logs essentially indefinitely. The absolute titer of antivaccinia antibody was only slightly higher after multiple vaccinations. In 97% of the participants, no decrease in vaccinia-specific antibody titers was noted with age over a follow-up period of up to 88 years. Moreover, Baltimore Longitudinal Study of Aging participants who survived active smallpox infections in their youth retained antivaccinia antibody titers that were similar to the levels detected in vaccinated subjects. CONCLUSION: These data suggest that multiple or recent vaccinations are not essential to maintain vaccinia-specific antibody responses in human subjects. Scarce vaccine supplies should be applied first to individuals who have not previously been vaccinated. (C) 2008 Published by Elsevier Inc. The American Journal of Medicine (2008) 121, 1058- 1064 C1 [Taub, Dennis D.; Ershler, William B.; Janowski, Mark; Artz, Andrew; Key, Michael L.; McKelvey, Julie; Muller, Denis; Ferrucci, Luigi; Duffey, Patricia L.; Longo, Dan L.] NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Taub, Dennis D.; Ershler, William B.; Janowski, Mark; Artz, Andrew; Key, Michael L.; McKelvey, Julie; Muller, Denis; Ferrucci, Luigi; Duffey, Patricia L.; Longo, Dan L.] NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Moss, Bernard] NIAID, Viral Dis Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Longo, DL (reprint author), NIA, Immunol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000015-50] NR 31 TC 42 Z9 42 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC PY 2008 VL 121 IS 12 BP 1058 EP 1064 DI 10.1016/j.amjmed.2008.08.019 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 387XO UT WOS:000261985100025 PM 19028201 ER PT J AU Ananth, C Basso, O AF Ananth, Cande Basso, Olga TI IMPACT OF PREGNANCY-INDUCED HYPERTENSION ON PERINATAL SURVIVAL IN FIRST AND HIGHER ORDER BIRTHS: A POPULATION-BASED STUDY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Ananth, Cande] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Obstet Gynecol & Reprod Sci, New Brunswick, NJ USA. [Basso, Olga] Natl Inst Environm Hlth Sci, NIH, DHHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 819 BP S231 EP S231 DI 10.1016/j.ajog.2008.09.850 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700812 ER PT J AU Atrash, H Jack, BW Johnson, K Coonrod, DV Moos, MK Stubblefield, PG Cefalo, R Damus, K Reddy, UM AF Atrash, Hani Jack, Brian W. Johnson, Kay Coonrod, Dean V. Moos, Merry-K Stubblefield, Phillip G. Cefalo, Robert Damus, Karla Reddy, Uma M. TI Where is the "W"oman in MCH? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE maternal and child health; preconception; woman ID PRECONCEPTIONAL HEALTH-PROMOTION; UNITED-STATES; EISENMENGER-SYNDROME; FOLIC-ACID; CARE; PREGNANCY; WOMEN; PROVIDER; MANAGEMENT; WELLNESS AB Scientific evidence indicates that improving a woman's health before pregnancy will improve pregnancy outcomes. However, for many years, our efforts have focused primarily on prenatal care and on caring for infants after birth. The concept of preconception care has been identified repeatedly as a priority for improving maternal and infant health. Preconception care is not something new that is being added to the already overburdened healthcare provider, but it is a part of routine primary care for women of reproductive age. Many opportunities exist for preconception intervention, and much of preconception care involves merely the provider reframing his or her thinking, counseling, and decisions in light of the reproductive plans and sexual and contraceptive practices of the patient. With existing scientific evidence that improving the health of "W"omen will improve the health of mothers and children, we must focus on improving the health of "W"omen before pregnancy and put the "W" in Maternal and Child Health. C1 [Atrash, Hani] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. [Jack, Brian W.] Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. [Stubblefield, Phillip G.] Boston Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02118 USA. [Johnson, Kay] Dartmouth Med Sch, Dept Pediat, Lebanon, NH USA. [Coonrod, Dean V.] Maricopa Cty Gen Hosp, Dept Obstet & Gynecol, Phoenix, AZ USA. [Moos, Merry-K; Cefalo, Robert] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Damus, Karla] Albert Einstein Coll Med & Natl March Dimes, Dept Obstet & Gynecol & Womens Hlth, White Plains, NY USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Atrash, H (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. OI Jack, Brian/0000-0002-6497-2437 FU CMS [# 1HOCMS030207 101] FX Hani Atrash, MD, MPH; Brian W. Jack, MD; Kay Johnson, MPH, EdM; Merry- K Moos, BSN, FNP, MPH; Phillip G. Stubblefield, MD; Robert Cefalo, MD, PhD; Karla Damus, MSPH, PhD, RN; and Uma M. Reddy, MD, MPH have no conflict of interest including grants, honoraria, advisory board membership, or share holdings. Dean V. Coonrod, MD, MPH is a Grant Recipient from the March of Dimes Arizona Chapter to develop an internatal Care Clinic and has funding from CMS (# 1HOCMS030207 101) working on compliance with the 6 week postpartum visit as a strategy to improve preconception care. NR 64 TC 25 Z9 27 U1 2 U2 8 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 DEC PY 2008 VL 199 IS 6 SU 2 BP S259 EP S265 DI 10.1016/j.ajog.2008.08.059 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 382BP UT WOS:000261580200002 PM 19081420 ER PT J AU Clark, E AF Clark, Erin TI INFLAMMATION PATHWAY GENE POLYMORPHISMS ARE ASSOCIATED WITH NEURODEVELOPMENTAL DELAY AT AGE 2 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Clark, Erin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 63 BP S29 EP S29 DI 10.1016/j.ajog.2008.09.087 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700064 ER PT J AU Dunlop, AL Jack, BW Bottalico, JN Lu, MC James, A Shellhaas, CS Hallstrom, LHK Solomon, BD Feero, G Menard, MK Prasad, MR AF Dunlop, Anne L. Jack, Brian W. Bottalico, Joseph N. Lu, Michael C. James, Andra Shellhaas, Cynthia S. Hallstrom, Lynne Haygood-Kane Solomon, Benjamin D. Feero, Gregory Menard, M. Kathryn Prasad, Mona R. TI The clinical content of preconception care: women with chronic medical conditions SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE chronic; medical condition; preconception ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GESTATIONAL DIABETES-MELLITUS; CONGENITAL HEART-DISEASE; TRANSPLANTATION PREGNANCY REGISTRY; MATERNAL THYROID-DEFICIENCY; MILD CHRONIC HYPERTENSION; COLLEGE-OF-CARDIOLOGY; CHRONIC RENAL-DISEASE; HIGH BLOOD-PRESSURE; RHEUMATOID-ARTHRITIS AB This article reviews the medical conditions that are associated with adverse pregnancy outcomes for women and their offspring. We also present the degree to which specific preconception interventions and treatments can impact the effects of the condition on birth outcomes. Because avoiding, delaying, or achieving optimal timing of a pregnancy is often an important component of the preconception care of women with medical conditions, contraceptive considerations particular to the medical conditions are also presented. C1 [Dunlop, Anne L.] Emory Univ, Sch Med, Dept Family & Prevent Med, Atlanta, GA 30322 USA. [Jack, Brian W.] Boston Univ, Med Ctr, Dept Family Med, Boston, MA USA. [Bottalico, Joseph N.] Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Stratford, NJ 08084 USA. [Lu, Michael C.] Univ Calif Los Angeles, Dept Obstet & Gynecol, Sch Publ Med, Los Angeles, CA 90024 USA. [Lu, Michael C.] Univ Calif Los Angeles, Dept Obstet & Gynecol, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Lu, Michael C.] Univ Calif Los Angeles, Dept Community Hlth Sci, Sch Publ Med, Los Angeles, CA USA. [Lu, Michael C.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. [James, Andra] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Shellhaas, Cynthia S.; Prasad, Mona R.] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Columbus, OH 43210 USA. [Shellhaas, Cynthia S.] Bur Child & Family Hlth Serv, Columbus, OH USA. [Hallstrom, Lynne Haygood-Kane] Tulane Univ, Dept Obstet & Gynecol, New Orleans, LA 70118 USA. [Solomon, Benjamin D.; Feero, Gregory] NIH, Natl Human Genome Project Res Inst, Bethesda, MD USA. [Menard, M. Kathryn] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. RP Dunlop, AL (reprint author), Emory Univ, Sch Med, Dept Family & Prevent Med, 1256 Briarcliff Rd,Bldg A,Suite 238, Atlanta, GA 30322 USA. EM amlang@emory.edu RI Shellhaas, Cynthia/E-4077-2011; OI Jack, Brian/0000-0002-6497-2437 FU March of Dimes FX Anne L. Dunlop, MD, MPH; Brian W. Jack, MD; Michael C. Lu, MD, MS, MPH; Andra James, MD, MPH; Cynthia S. Shellhaas, MD, MPH; Lynne Haygood-Kane Hallstrom, DO, CNM, MS; Benjamin D. Solomon, MD; W. Gregory Feero, MD, PhD; and M. Kathryn Menard, MD, MPH have no conflict of interest including grants, honoraria, advisory board membership, or share holdings. Joseph N. Bottalico, DO, is a member of the CDC Select Panel on Preconception Care, a voluntary unpaid position in which he represents the American College of Osteopathic Ob-Gyn and the American Osteopathic Assn (no known conflict). He is also an (appointed, unpaid) volunteer member of the NJ DHSS Diabetes Advisory Council, also without conflict. With the New Jersey Chapter of the March of Dimes, he is a member of the annual conference planning committee (no known conflict) and has received one honorarium from the March of Dimes jointly with the Johnson and Johnson foundation (New Brunswick, NJ) for a grand rounds presentation on preconception care presented to the OB-Gyn Dept at UMDNJ-SOM in December 2007. He sits on the regional MCH consortium's BOD (Southern NJ Perinatal Cooperative) and chairs their Clinical/QA committee which also presents no known conflicts. Mona R. Prasad, DO, MPH is the recipient of a $25,000 service grant from the March of Dimes for the year 2008. NR 203 TC 32 Z9 35 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 SU 2 BP S310 EP S327 DI 10.1016/j.ajog.2008.08.031 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 382BP UT WOS:000261580200007 PM 19081425 ER PT J AU Durnwald, C AF Durnwald, Celeste TI THE IMPACT OF CERVICAL LENGTH ON RISK OF PRETERM BIRTH IN TWIN GESTATIONS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Durnwald, Celeste] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 19 BP S10 EP S10 DI 10.1016/j.ajog.2008.09.047 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700020 ER PT J AU Gyamfi, C AF Gyamfi, Cynthia TI THE EFFECT OF BMI AND OBESITY ON MATERNAL AND CORD BLOOD BETAMETHASONE CONCENTRATIONS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Gyamfi, Cynthia] NICHHD, MFMU Network, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 615 BP S177 EP S177 DI 10.1016/j.ajog.2008.09.645 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700610 ER PT J AU Gyamfi, C AF Gyamfi, Cynthia TI MATERNAL AND CORD BLOOD BETAMETHASONE CONCENTRATIONS IN SINGLETON AND TWIN GESTATIONS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Gyamfi, Cynthia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 550 BP S161 EP S161 DI 10.1016/j.ajog.2008.09.580 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700546 ER PT J AU Gyamfi, C AF Gyamfi, Cynthia TI NEONATAL AND DEVELOPMENTAL OUTCOMES IN CHILDREN BORN IN THE LATE PRETERM PERIOD VERSUS TERM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Gyamfi, Cynthia] Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 113 BP S45 EP S45 DI 10.1016/j.ajog.2008.09.140 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700114 ER PT J AU Harper, M AF Harper, Margaret TI EFFECT OF OMEGA-3 SUPPLEMENTATION ON PLASMA FATTY ACID LEVELS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Harper, Margaret] MFMU Network, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 178 BP S62 EP S62 DI 10.1016/j.ajog.2008.09.205 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700178 ER PT J AU Harper, M AF Harper, Margaret TI CYTOKINE GENE SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) AND LENGTH OF GESTATION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Harper, Margaret] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 32 BP S15 EP S15 DI 10.1016/j.ajog.2008.09.886 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700033 ER PT J AU Hashima, J AF Hashima, Jason TI THE EFFECT OF MATERNAL OBESITY ON NEONATAL OUTCOME IN WOMEN RECEIVING A SINGLE COURSE OF ANTENATAL CORTICOSTEROIDS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Hashima, Jason] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Networl, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 812 BP S229 EP S229 DI 10.1016/j.ajog.2008.09.843 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700805 ER PT J AU Hickman, MA AF Hickman, M. Ashley TI THE MFMU CESAREAN REGISTRY: RISK OF UTERINE RUPTURE IN WOMEN ATTEMPTING VBAC WITH AN UNKNOWN UTERINE SCAR SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Hickman, M. Ashley] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 81 BP S36 EP S36 DI 10.1016/j.ajog.2008.09.107 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700082 ER PT J AU Horton, A Gyamfi, C AF Horton, Amanda Gyamfi, Cynthia TI 17-ALPHA HYDROXYPROGESTERONE CAPROATE DOES NOT INCREASE THE RISK OF GESTATIONAL DIABETES IN SINGLETON AND TWIN PREGNANCIES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Horton, Amanda; Gyamfi, Cynthia] Eunice Kennedy Shriver Natl Inst Child Hlth, Bethesda, MD USA. [Horton, Amanda; Gyamfi, Cynthia] Human Dev MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 689 BP S197 EP S197 DI 10.1016/j.ajog.2008.09.720 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700683 ER PT J AU Incerti, M Roberson, R Vink, J Abebe, D Spong, C AF Incerti, Maddalena Roberson, Robin Vink, Joy Abebe, Daniel Spong, Catherine TI VIP, ADNP AND GFAP EXPRESSION IN ADULT OFFSPRING BRAIN IN A MODEL OF FETAL ALCOHOL SYNDROME SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Incerti, Maddalena; Roberson, Robin; Abebe, Daniel; Spong, Catherine] NICHD, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. [Vink, Joy] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 538 BP S158 EP S158 DI 10.1016/j.ajog.2008.09.568 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700534 ER PT J AU Incerti, M Roberson, R Vink, J Abebe, D Spong, C AF Incerti, Maddalena Roberson, Robin Vink, Joy Abebe, Daniel Spong, Catherine TI ADULT TREATMENT WITH NEUROPEPTIDES ATTENUATES C-FOS EXPRESSION IN FETAL ALCOHOL SYNDROME SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Incerti, Maddalena; Roberson, Robin; Abebe, Daniel; Spong, Catherine] NICHD, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. [Vink, Joy] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 244 BP S80 EP S80 DI 10.1016/j.ajog.2008.09.272 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700244 ER PT J AU Incerti, M Vink, J Roberson, R Abebe, D Spong, C AF Incerti, Maddalena Vink, Joy Roberson, Robin Abebe, Daniel Spong, Catherine TI ADULT TREATMENT WITH NEUROPEPTIDES: DELINEATING THE MECHANISM OF LEARNING DEFICITS PREVENTION IN FETAL ALCOHOL SYNDROME SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Incerti, Maddalena; Roberson, Robin; Abebe, Daniel; Spong, Catherine] NICHD, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD USA. [Vink, Joy] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 62 BP S29 EP S29 DI 10.1016/j.ajog.2008.09.086 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700063 ER PT J AU Landon, MB AF Landon, Mark B. TI A PROSPECTIVE MULTICENTER RANDOMIZED TREATMENT TRIAL OF MILD GESTATIONAL DIABETES (GDM) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Landon, Mark B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 2 BP S2 EP S2 DI 10.1016/j.ajog.2008.09.028 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700003 ER PT J AU Levine, R Horowitz, G Qian, C Yu, K Epstein, F Vatten, L AF Levine, Richard Horowitz, Gary Qian, Cong Yu, Kai Epstein, Franklin Vatten, Lars CA S Ananth Karumanchi CPEP TI SOLUBLE FLT-1 (SFLT1), PREECLAMPSIA, AND HYPOTHYROIDISM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Levine, Richard; Yu, Kai] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Horowitz, Gary] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Qian, Cong] Allied Technol Grp, Rockville, MD USA. [Epstein, Franklin] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Vatten, Lars] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway. [S Ananth Karumanchi CPEP] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 245 BP S80 EP S80 DI 10.1016/j.ajog.2008.09.273 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700245 ER PT J AU Manuck, T AF Manuck, Tracy TI DO ANTIPHOSPHOLIPID ANTIBODIES AFFECT PREGNANCY OUTCOMES IN WOMEN HETEROZYGOUS FOR FACTOR V LEIDEN? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Manuck, Tracy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 519 BP S152 EP S152 DI 10.1016/j.ajog.2008.09.548 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700515 ER PT J AU Manuck, T AF Manuck, Tracy CA Eunice Kennedy Shriver TI THE RELATIONSHIP BETWEEN POLYMORPHISMS IN THE HUMAN PROGESTERONE RECEPTOR AND CLINICAL RESPONSE TO 17 ALPHA- HYDROXYPROGESTERONE CAPROATE FOR THE PREVENTION OF RECURRENT SPONTANEOUS PRETERM BIRTH SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Manuck, Tracy] NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 38 BP S18 EP S18 DI 10.1016/j.ajog.2008.09.059 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700039 ER PT J AU Mercer, B AF Mercer, Brian TI FETAL THYROID FUNCTION AND NEURO-DEVELOPMENTAL OUTCOMES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Mercer, Brian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 545 BP S160 EP S160 DI 10.1016/j.ajog.2008.09.575 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700541 ER PT J AU Mikolajczyk, R Zhang, J Chan, L Grewal, J AF Mikolajczyk, Rafael Zhang, Jun Chan, Linda Grewal, Jagteshwar TI EARLY VERSUS LATE ADMISSION TO LABOR/DELIVERY, LABOR PROGRESS AND RISK OF CAESAREAN SECTION IN NULLIPAROUS WOMEN SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Mikolajczyk, Rafael] Univ Bielefeld Germany, Sch Publ Hlth, Rockville, MD USA. [Mikolajczyk, Rafael] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Zhang, Jun; Grewal, Jagteshwar] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 129 BP S49 EP S49 DI 10.1016/j.ajog.2008.09.156 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700130 ER PT J AU Picconi, J Hanif, F Egerman, R Meyer, N Giancarlo, M AF Picconi, Jason Hanif, Farhan Egerman, Robert Meyer, Norman Giancarlo, Mari TI AORTIC ISTHMUS DOPPLER TRANSITIONAL PHASE IN IUGR FETUSES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Picconi, Jason] Wayne State Univ, Detroit Med Ctr, Detroit, MI USA. [Hanif, Farhan] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Egerman, Robert; Meyer, Norman; Giancarlo, Mari] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 BP S95 EP S95 DI 10.1016/j.ajog.2008.09.332 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700304 ER PT J AU Refuerzo, J AF Refuerzo, Jerrie TI COMPARISON OF NEONATAL MORBIDITY AND MORTALITY IN TWIN PREGNANCIES BORN AT MODERATELY PRETERM, LATE PRETERM, AND TERM GESTATION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Refuerzo, Jerrie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 381 BP S115 EP S115 DI 10.1016/j.ajog.2008.09.409 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700380 ER PT J AU Roberts, JM AF Roberts, James M. TI A RANDOMIZED CONTROLLED TRIAL OF ANTIOXIDANT VITAMINS TO PREVENT SERIOUS COMPLICATIONS ASSOCIATED WITH PREGNANCY RELATED HYPERTENSION IN LOW RISK, NULLIPAROUS WOMEN SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Roberts, James M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 7 Z9 7 U1 0 U2 3 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 DEC PY 2008 VL 199 IS 6 MA 8 BP S4 EP S4 DI 10.1016/j.ajog.2008.09.034 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700009 ER PT J AU Rouse, D AF Rouse, Dwight TI MAGNESIUM SULFATE (MGSO4) DOSE AND TIMING, AND UMBILICAL CORD MG plus plus CONCENTRATION: RELATIONSHIP TO CEREBRAL PALSY (CP) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Rouse, Dwight] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 117 BP S46 EP S46 DI 10.1016/j.ajog.2008.09.144 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700118 ER PT J AU Rouse, D AF Rouse, Dwight TI SECOND STAGE LABOR DURATION: RELATIONSHIP TO MATERNAL AND PERINATAL OUTCOMES SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Rouse, Dwight] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 86 BP S37 EP S37 DI 10.1016/j.ajog.2008.09.112 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700087 ER PT J AU Silver, R AF Silver, Robert TI PROTHROMBIN GENE G20210A MUTATION AND OBSTETRIC COMPLICATIONS: A PROPSECTIVE COHORT SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Silver, Robert] Eunice Kennedy Shriver NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 436 BP S131 EP S131 DI 10.1016/j.ajog.2008.09.465 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700433 ER PT J AU Simhan, H Caritis, S AF Simhan, Hyagriv Caritis, Steve TI 17-ALPHA HYDROXYPROGESTERONE CAPROATE (17-OHPC) AND CORTICOTROPIN RELEASING HORMONE (CRH) AMONG WOMEN WITH TWINS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Simhan, Hyagriv; Caritis, Steve] Eunice Kennedy Shriver NICHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 726 BP S207 EP S207 DI 10.1016/j.ajog.2008.09.757 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700720 ER PT J AU Solomon, BD Jack, BW Feero, G AF Solomon, Benjamin D. Jack, Brian W. Feero, Gregory TI The clinical content of preconception care: genetics and genomics SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE family history; genetics; preconception ID NEURAL-TUBE DEFECTS; FRAGILE-X-SYNDROME; CONGENITAL-ANOMALIES; FAMILY-HISTORY; PREGNANCY; DIAGNOSIS; DISEASE; RISK; TRANSLOCATIONS; MODEL AB The prevalence of paternal and maternal genetic conditions that affect pregnancy varies according to many factors that include parental age, medical history, and family history. Although some genetic conditions that affect pregnancy are identified easily early in life, other conditions are not and may require additional diagnostic testing. A complete 3-generation family medical history that includes ethnicity information about both sides of the family is arguably the single best genetic "test" that is applicable to preconception care. Assessment of genetic risk by an experienced professional has been shown to improve the detection rate of identifiable risk factors. Learning about possible genetic issues in the preconception period is ideal, because knowledge permits patients to make informed reproductive decisions. Options that are available to couples before conception include adoption, surrogacy, use of donor sperm, in vitro fertilization after preimplantation genetic diagnosis, and avoidance of pregnancy. Future technologic advances will increase the choices that are available to couples. C1 [Feero, Gregory] NHGRI, Genom Healthcare Branch, NIH, Bethesda, MD 20892 USA. [Jack, Brian W.] Boston Univ, Med Ctr, Dept Family Med, Boston, MA USA. RP Feero, G (reprint author), NHGRI, Genom Healthcare Branch, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM feerow@mail.nih.gov OI Jack, Brian/0000-0002-6497-2437 FU Intramural NIH HHS [Z99 HG999999] NR 36 TC 12 Z9 13 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 SU 2 BP S340 EP S344 DI 10.1016/j.ajog.2008.09.870 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 382BP UT WOS:000261580200010 PM 19081428 ER PT J AU Stubblefield, PG Coonrod, DV Reddy, UM Sayegh, R Nicholson, W Rychlik, DF Jack, BW AF Stubblefield, Phillip G. Coonrod, Dean V. Reddy, Uma M. Sayegh, Raja Nicholson, Wanda Rychlik, Daniel F. Jack, Brian W. TI The clinical content of preconception care: reproductive history SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE low birthweight; preconception; preterm birth; reproductive history ID PRIOR CESAREAN DELIVERY; SYMPTOMATIC UTERINE RUPTURE; SPONTANEOUS PRETERM BIRTH; FETAL-GROWTH RESTRICTION; DOUBLE-LAYER CLOSURE; GESTATIONAL-AGE; SINGLE-LAYER; INTERDELIVERY INTERVAL; RECURRENT STILLBIRTH; PLACENTA PREVIA AB A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories. C1 [Stubblefield, Phillip G.; Sayegh, Raja] Boston Univ, Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Coonrod, Dean V.] Maricopa Cty Gen Hosp, Dept Obstet & Gynecol, Phoenix, AZ USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Nicholson, Wanda] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD USA. [Rychlik, Daniel F.] Fertil Treatment Ctr, Tempe, AZ USA. [Jack, Brian W.] Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. RP Stubblefield, PG (reprint author), Boston Med Ctr, DOB 720 Harrison Ave,Suite 1105, Boston, MA 02118 USA. EM phillip.stubblefield@bmc.org OI Sayegh, Raja/0000-0003-4687-3037; Jack, Brian/0000-0002-6497-2437 FU CMS [#1HOCMS030207 101] FX Phillip G. Stubblefield, MD; Uma M. Reddy, MD, MPH; Raja Sayegh, MD; Wanda Nicholson, MD, MPH, MBA; Daniel F. Rychlik, MD; and Brian W. Jack, MD have no conflict of interest including grants, honoraria, advisory board membership, or share holdings. Dean V. Coonrod, MD, MPH is a Grant Recipient from the March of Dimes Arizona Chapter to develop an internatal Care Clinic and has funding from CMS (#1HOCMS030207 101) working on compliance with the 6 week postpartum visit as a strategy to improve preconception care. NR 91 TC 6 Z9 7 U1 0 U2 3 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 DEC PY 2008 VL 199 IS 6 SU 2 BP S373 EP S383 DI 10.1016/j.ajog.2008.10.048 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 382BP UT WOS:000261580200015 PM 19081433 ER PT J AU Vink, J Incerti, M Toso, L Roberson, R Abebe, D Spong, C AF Vink, Joy Incerti, Maddalena Toso, Laura Roberson, Robin Abebe, Daniel Spong, Catherine TI PRENATAL NAP plus SAL PREVENTS DEVELOPMENTAL DELAY IN A DOWN SYNDROME MOUSE MODEL BY ALTERING NMDA AND GABA RECEPTOR SUBUNITS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Vink, Joy] Georgetown Univ, Washington, DC USA. [Incerti, Maddalena; Toso, Laura; Roberson, Robin; Spong, Catherine] NIH, Bethesda, MD 20892 USA. [Abebe, Daniel] NICHD, SDMP, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 27 BP S14 EP S14 DI 10.1016/j.ajog.2008.09.881 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700028 ER PT J AU Zhang, J Troendle, J Mikolajczyk, R Trumble, A AF Zhang, Jun Troendle, James Mikolajczyk, Rafael Trumble, Ann TI NATURAL HISTORY OF LABOR PROGRESSION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Trumble, Ann] NICHD, NIH, Bethesda, MD USA. [Mikolajczyk, Rafael] NIH, Rockville, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 134 BP S51 EP S51 DI 10.1016/j.ajog.2008.09.161 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700135 ER PT J AU Zhang, J Vanveldhuisen, P Troendle, J Reddy, U Branch, W Bailit, J Kominiarek, M Ramirez, M Quintero, VHG Hoffman, M Hibbard, J Fanning, J Burkman, R Haberman, S Landy, H Gregory, K AF Zhang, Jun Vanveldhuisen, Paul Troendle, James Reddy, Uma Branch, Ware Bailit, Jennifer Kominiarek, Michelle Ramirez, Mildred Quintero, Victor Hugo Gonzalez Hoffman, Matthew Hibbard, Judith Fanning, James Burkman, Ronald Haberman, Shoshana Landy, Helain Gregory, Kimberly TI NORMAL LABOR PATTERNS IN US WOMEN SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Mat Fetal Med C1 [Zhang, Jun; Troendle, James] NIH, Bethesda, MD 20892 USA. [Vanveldhuisen, Paul] EMMES Corp, Rockville, MD USA. [Reddy, Uma] Univ Maryland Baltimore Cty, Bethesda, MD USA. [Bailit, Jennifer] MetroHlth, Cleveland, OH USA. [Kominiarek, Michelle] Indiana Univ, Indianapolis, IN 46204 USA. [Ramirez, Mildred] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Quintero, Victor Hugo Gonzalez] Univ Miami, Dept Ob Gyn, MFM Div, Miami, FL USA. [Hoffman, Matthew] Christiana Hosp, Newark, DE USA. [Hibbard, Judith] Univ Illinois, Chicago, IL USA. [Fanning, James] Summa Hlth Syst, Toledo, OH USA. [Burkman, Ronald] Tufts Univ, Springfield, MA USA. [Haberman, Shoshana] Maimonides Hosp, Brooklyn, NY 11219 USA. [Landy, Helain] Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2008 VL 199 IS 6 MA 80 BP S36 EP S36 DI 10.1016/j.ajog.2008.09.106 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 391AV UT WOS:000262205700081 ER PT J AU Holland, GN Belfort, R Dernouchamps, JP Franklin, R Martenet, AC Nozik, RA Nussenblatt, RB Ohno, S Palimeris, G Saari, KM Schwab, IR Secchi, AG Smith, RE Tabbara, KF Tessler, HH AF Holland, Gary N. Belfort, Rubens, Jr. Dernouchamps, Jean-Paul Franklin, Rudolph Martenet, Anne-Catherine Nozik, Robert A. Nussenblatt, Robert B. Ohno, Shigeaka Palimeris, Gerassimos Saari, K. Matti Schwab, Ivan R. Secchi, Antonio G. Smith, Ronald E. Tabbara, Khalid F. Tessler, Howard H. TI Uveitis in 2008: a Festschrift for G. Richard O'Connor, MD SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Biographical-Item C1 [Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Holland, Gary N.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Belfort, Rubens, Jr.] Univ Fed Sao Paulo, Vis Inst, Sao Paulo, Brazil. [Dernouchamps, Jean-Paul] Baron Lambert Eye Clin, Brussels, Belgium. [Martenet, Anne-Catherine] Univ Zurich, Zurich, Switzerland. [Nozik, Robert A.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. [Nozik, Robert A.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA. [Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Ohno, Shigeaka] Hokkaido Univ, Dept Ophthalmol & Visual Sci, Sapporo, Hokkaido, Japan. [Palimeris, Gerassimos] Univ Athens, Dept Ophthalmol, Athens, Greece. [Saari, K. Matti] Univ Turku, Dept Ophthalmol, Tampere, Finland. [Schwab, Ivan R.] Univ Calif Davis, Dept Ophthalmol, Sacramento, CA 95817 USA. [Secchi, Antonio G.] Univ Padua, Italy Sch Med, Dept Ophthalmol, I-35100 Padua, Italy. [Smith, Ronald E.] USC Keck Sch Med, Doheny Eye Inst, Los Angeles, CA USA. [Smith, Ronald E.] USC Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA. [Tabbara, Khalid F.] King Faisal Specialist Hosp & Res Ctr, Ctr Eye, Riyadh 11211, Saudi Arabia. [Tabbara, Khalid F.] King Faisal Specialist Hosp & Res Ctr, Eye Fdn Res Ophthalmol, Riyadh 11211, Saudi Arabia. [Tessler, Howard H.] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. RP Holland, GN (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM uveitis@jsei.ucla.edu RI Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2008 VL 146 IS 6 BP 795 EP 798 DI 10.1016/j.ajo.2008.10.001 PG 4 WC Ophthalmology SC Ophthalmology GA 378UH UT WOS:000261349200001 PM 19027418 ER PT J AU Kempen, JH Gangaputra, S Daniel, E Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Jabs, DA Helzlsouer, KJ AF Kempen, John H. Gangaputra, Sapna Daniel, Ebenezer Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Helzlsouer, Kathy J. TI Long-term Risk of Malignancy Among Patients Treated With Immunosuppressive Agents for Ocular Inflammation: A Critical Assessment of the Evidence SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; RENAL-TRANSPLANT RECIPIENTS; NECROSIS-FACTOR ANTAGONISTS; NON-HODGKINS-LYMPHOMA; RHEUMATOID-ARTHRITIS; MYCOPHENOLATE-MOFETIL; SKIN-CANCER; FOLLOW-UP; LIVER-TRANSPLANTATION; ORGAN-TRANSPLANTATION C1 [Kempen, John H.] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, Scheie Eye Inst,Ocular Inflammat Serv, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Gangaputra, Sapna; Daniel, Ebenezer; Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.; Jabs, Douglas A.; Helzlsouer, Kathy J.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Ctr Prevent & Res, Baltimore, MD USA. RP Kempen, JH (reprint author), Univ Penn, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, Scheie Eye Inst,Ocular Inflammat Serv, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU NEI NIH HHS [EY014943, R01 EY014943, R01 EY014943-05, R56 EY014943] NR 96 TC 49 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2008 VL 146 IS 6 BP 802 EP 812 DI 10.1016/j.ajo.2008.04.035 PG 11 WC Ophthalmology SC Ophthalmology GA 378UH UT WOS:000261349200003 PM 18579112 ER PT J AU Kacmaz, RO Kempen, JH Newcomb, C Gangaputra, S Daniel, E Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Jabs, DA Foster, CS AF Kacmaz, R. Oktay Kempen, John H. Newcomb, Craig Gangaputra, Sapna Daniel, Ebenezer Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Jabs, Douglas A. Foster, C. Stephen CA Systemic Immunosuppressive Therapy TI Ocular Inflammation in Behcet Disease: Incidence of Ocular Complications and of Loss of Visual Acuity SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INFLIXIMAB TREATMENT; PROGNOSTIC-FACTORS; RISK; EPIDEMIOLOGY; INVOLVEMENT; UVEITIS; VISION; TRIAL AB PURPOSE: To estimate the risk of structural ocular complications and loss of visual acuity (VA) in cases of Behcet disease (BD) and to evaluate potential risk and protective factors for these events. 0 DESIGN: Retrospective cohort study. METHODS: A total of 168 consecutive patients with 1313,associated ocular inflammation treated at five academic center ocular inflammation subspecialty practices were included. Clinical data for these patients were ascertained by standardized chart review. Main outcome measures included VA, structural ocular complications of inflammation, and intraocular pressure (lop). RESULTS: Over a median follow-up of 1.05 years, the incidence of specific structural complications and IOP disturbances were common: the incidence rate of any ocular complication was 0.45 per eye-year (EY). Rates of loss of VA to 20/50 or worse and to 20/200 or worse were 0.12 per EY and 0.09 per EY, respectively. Risk factors for loss of VA during follow-up were persistent inflammatory activity, presence of posterior synechiae, presence of hypotony, and presence of elevated IOP. In a time-dependent analysis, current activity of ocular in, flammation was associated with an increased risk of loss of VA to 20/50 or worse (relative risk [RR], 2.45; 95% confidence interval [CI], 1.1 to 5.5; P =.03) and to 20/200 or worse (RR, 2.67; 95% CI, 1.2 to 5.8; P= .01). CONCLUSIONS: Loss of VA and occurrence of ocular complications were common in patients with ocular inflammation associated with BD, even with aggressive therapy. Ongoing inflammation during follow-up, presence or occurrence of posterior synechiae, hypotony, and elevated IOP were associated with an increased risk of loss of VA. (Am J Ophthalmol 2008;146:828-836. (C) 2008 by Elsevier Inc. All rights reserved.) C1 [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA 02142 USA. [Kempen, John H.; Newcomb, Craig] Univ Penn, Ocular Inflammat Serv, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Ctr Prevent Ophthalmol & Biostat, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Kempen, John H.; Newcomb, Craig] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Gangaputra, Sapna; Daniel, Ebenezer; Rosenbaum, James T.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, 5 Cambridge Ctr,8th Floor, Cambridge, MA 02142 USA. EM sfoster@mersi.us OI Daniel, Ebenezer/0000-0002-2027-2316 FU NATIONAL EYE INSTITUTE, NATIONAL INSTITUTES of Health, Bethesda, Maryland [EY014943]; Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania; Research to Prevent Blindness Inc (RPB), New York, New York FX THIS STUDY WAS SUPPORTED PRIMARILY BY GRANT EY014943 FROM THE NATIONAL EYE INSTITUTE, NATIONAL INSTITUTES of Health, Bethesda, Maryland (Dr Kempen). Additional support was provided by the Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania, and Research to Prevent Blindness Inc (RPB), New York, New York. Dr Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Dr Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Drs Jabs and Rosenbaum are a Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr Levy-Clarke was previously and Dr Nussenblatt continues to be supported by intramural funds of the National Eye Institute. The authors indicate no financial conflict of interest. Involved in conception and design (R.O.K., J.H.K., C.N., S.G., E.D., G.A.L.-C., R.B.N., J.T.R., E.B.S., J.E.T., D.A.J., C.S.F.); analysis and interpretation (R.O.K., J.H.K., C.W.N.); writing the article (R.O.K., J.H.K.); critical review of the article (R.O.K., J.H.K., C.N., S.G., E.D., G.A.L.-C., R.B.N., J.T.R., E.B.S., J.E.T., D.A.J., C.S.F.); final approval of the article (R.O.K., J.H.K., C.N., S.G., E.D., G.A.L.,C., R.B.N., J.T.R., E.B.S., J.E.T., D.A.J., C.S.F.); data collection (R.O.K., J.H.K., S.G., E.D.); provision of resources (R.O.K., J.H.K., C.N., S.G., E.D., G.A.L.-C., R.B.N., J.T.R., E.B.S., J.E.T., D.A.J., C.S.F.); statistical expertise (J.H.K., C.W.N.); obtaining funding (J.H.K.); literature search (R.O.K., J.H.K.); and administrative, technical, or logistic support (R.O.K., J.H.K., C.N., S.G., E.D., G.A.L.-C., R.B.N., J.T.R., E.B.S., J.E.T., D.A.J., C.S.F.). The SITE Cohort Study was conducted with the approval of the following institutional review boards: University of Pennsylvania Office of Regulatory Affairs (PENN); Johns Hopkins School of Medicine Institutional Review Board no. 3 (Wilmer/JHU); New England Institutional Review Board (MERSI); Massachusetts Eye & Ear Infirmary Institutional Review Board (MEEI); Oregon Health & Sciences University Institutional Review Board (Casey/OHSU); Combined Neurosciences (CNS) Institutional Review Board of the Clinical Center (CC), National Eye Institute. The study was conducted in accordance with the precepts of the Declaration of Helsinki. NR 28 TC 43 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2008 VL 146 IS 6 BP 828 EP 836 DI 10.1016/j.ajo.2008.06.019 PG 9 WC Ophthalmology SC Ophthalmology GA 378UH UT WOS:000261349200006 PM 18708181 ER PT J AU Ahanchi, SS Varu, VN Tsihlis, ND Martinez, J Pearce, CG Kapadia, MR Jiang, Q Saavedra, JE Keefer, LK Hrabie, JA Kibbe, MR AF Ahanchi, Sadaf S. Varu, Vinit N. Tsihlis, Nick D. Martinez, Janet Pearce, Charles G. Kapadia, Muneera R. Jiang, Qun Saavedra, Joseph E. Keefer, Larry K. Hrabie, Joseph A. Kibbe, Melina R. TI Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE proliferation; neointimal hyperplasia; cell cycle; reactive oxygen species; vascular smooth muscle cells ID SMOOTH-MUSCLE-CELLS; CORONARY-HEART-DISEASE; RAT CAROTID-ARTERY; NEOINTIMAL HYPERPLASIA; INTIMAL HYPERPLASIA; NAD(P)H OXIDASE; ENDOTHELIAL DYSFUNCTION; GUANOSINE-MONOPHOSPHATE; PERIVASCULAR DELIVERY; SUPEROXIDE-PRODUCTION AB Ahanchi SS, Varu VN, Tsihlis ND, Martinez J, Pearce CG, Kapadia MR, Jiang Q, Saavedra JE, Keefer LK, Hrabie JA, Kibbe MR. Heightened efficacy of nitric oxide-based therapies in type II diabetes mellitus and metabolic syndrome. Am J Physiol Heart Circ Physiol 295: H2388-H2398, 2008. First published October 17, 2008; doi: 10.1152/ajpheart. 00185.2008.-Type II diabetes mellitus (DM) and metabolic syndrome are associated with accelerated restenosis following vascular interventions due to neointimal hyperplasia. The efficacy of nitric oxide (NO)-based therapies is unknown in these environments. Therefore, the aim of this study is to examine the efficacy of NO in preventing neointimal hyperplasia in animal models of type II DM and metabolic syndrome and examine possible mechanisms for differences in outcomes. Aortic vascular smooth muscle cells (VSMC) were harvested from rodent models of type II DM (Zucker diabetic fatty), metabolic syndrome (obese Zucker), and their genetic control (lean Zucker). Interestingly, NO inhibited proliferation and induced G(0)/G(1) cell cycle arrest to the greatest extent in VSMC from rodent models of metabolic syndrome and type II DM compared with controls. This heightened efficacy was associated with increased expression of cyclin-dependent kinase inhibitor p21, but not p27. Using the rat carotid artery injury model to assess the efficacy of NO in vivo, we found that the NO donor PROLI/NO inhibited neointimal hyperplasia to the greatest extent in type II DM rodents, followed by metabolic syndrome, then controls. Increased neointimal hyperplasia correlated with increased reactive oxygen species (ROS) production, as demonstrated by dihydroethidium staining, and NO inhibited this increase most in metabolic syndrome and DM. In conclusion, NO was surprisingly a more effective inhibitor of neointimal hyperplasia following arterial injury in type II DM and metabolic syndrome vs. control. This heightened efficacy may be secondary to greater inhibition of VSMC proliferation through cell cycle arrest and regulation of ROS expression, in addition to other possible unidentified mechanisms that deserve further exploration. C1 [Ahanchi, Sadaf S.; Varu, Vinit N.; Tsihlis, Nick D.; Martinez, Janet; Pearce, Charles G.; Kapadia, Muneera R.; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. [Ahanchi, Sadaf S.; Varu, Vinit N.; Tsihlis, Nick D.; Martinez, Janet; Pearce, Charles G.; Kapadia, Muneera R.; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA. [Saavedra, Joseph E.; Hrabie, Joseph A.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD USA. RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, 201 E Huron St,Galter 10-105, Chicago, IL 60611 USA. EM mkibbe@nmh.org RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Tsihlis, Nick/0000-0002-0410-0143 FU NIH [1K08HL084203]; American Vascular Association; the Department of Veterans Affairs; the American Medical Association Foundation; National Cancer Institute, NIH [NO1-CO-12400]; Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research FX This work was supported in part by funding from the NIH (1K08HL084203 to M. Kibbe); the American Vascular Association, the Department of Veterans Affairs (VA Merit Review Grant to M. Kibbe); the American Medical Association Foundation (2007 Seed Grant to S. S. Ahanchi); and through the generosity of Hilda Rosenbloom and Eleanor Baldwin. In addition, part of this research was supported with federal funds from the National Cancer Institute, NIH under contract NO1-CO-12400 with SAIC-Frederick, Inc. (L. K. Keefer), and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (L. K. Keefer). NR 57 TC 24 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 2008 VL 295 IS 6 BP H2388 EP H2398 DI 10.1152/ajpheart.00185.2008 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 379MH UT WOS:000261399900022 PM 18931034 ER PT J AU Laposky, AD Bradley, MA Williams, DL Bass, J Turek, FW AF Laposky, A. D. Bradley, M. A. Williams, D. L. Bass, J. Turek, F. W. TI Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE sleep fragmentation; metabolic syndrome; energy metabolism; sleep homeostasis; sleep deprivation ID DAYTIME SLEEPINESS; METABOLIC SYNDROME; CIRCADIAN-RHYTHMS; REM-SLEEP; RECEPTOR; MOUSE; DEPRIVATION; PATTERNS; MUTATION; DELTA AB Laposky AD, Bradley MA, Williams DL, Bass J, Turek FW. Sleep-wake regulation is altered in leptin-resistant (db/db) genetically obese and diabetic mice. Am J Physiol Regul Integr Comp Physiol 295: R2059-R2066, 2008. First published October 8, 2008; doi:10.1152/ajpregu.00026.2008. -Recent epidemiological and clinical studies indicate that the control of sleep-wake states may be an important factor in the regulation of energy metabolism. Leptin is a peripherally synthesized hormone that has critical signaling properties in the brain for the control of long-term energy homeostasis. In this study, we examined the hypothesis that leptin signaling exerts a role in sleep-wake regulation and that leptin may represent an important mechanistic link in the coordination of sleep-wake states and metabolism. Sleep-wake patterns were recorded in a genetic mouse model of obesity and diabetes, the db/db mouse, which harbors a mutation in a particular isoform of the leptin receptor (long form, LRb). We found that db/db mice exhibit a variety of alterations in sleep regulation, including an increase in overall sleep time, a dramatic increase in sleep fragmentation, attenuated diurnal rhythmicity in rapid eye movement sleep and non-rapid eye movement EEG delta power ( a measure of sleep homeostatic drive), and a decrease in the compensatory response to acute (i.e., 6 h) sleep deprivation. The db/db mice also generated low amounts of locomotor activity and a reduction in the diurnal rhythm of activity. These results indicate that impaired leptin signaling has deleterious effects on the regulation of sleep amount, sleep architecture, and temporal consolidation of these arousal states. In summary, leptin may represent an important molecular component in the integration of sleep, circadian rhythms, and energy metabolism. C1 [Laposky, A. D.; Bradley, M. A.; Williams, D. L.; Turek, F. W.] Northwestern Univ, Dept Neurobiol & Physiol, Ctr Sleep & Circadian Biol, Evanston, IL 60208 USA. [Laposky, A. D.; Bass, J.; Turek, F. W.] Evanston NW Healthcare & Res Inst, Evanston, IL USA. [Bass, J.] Evanston Hosp Corp, Dept Med, Evanston, IL 60201 USA. RP Laposky, AD (reprint author), NHLBI, NIH, Div Lung Dis, Natl Ctr Sleep Disorders Res, 6701 Rockledge Dr,Ste 10042, Bethesda, MD 20892 USA. EM laposkya@nhlbi.nih.gov FU National Institutes of Health [P01AG11412, R01HL075020] FX This work was supported by National Institutes of Health Grants P01AG11412 (to F. W. Turek and J. Bass) and R01HL075020 (to J. Bass). NR 40 TC 59 Z9 60 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC PY 2008 VL 295 IS 6 BP R2059 EP R2066 DI 10.1152/ajpregu.00026.2008 PG 8 WC Physiology SC Physiology GA 381TV UT WOS:000261559700040 PM 18843095 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI Analysis of DNA breaks, DNA damage response, and apoptosis produced by high NaCl SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE DNA damage; hypertonicity; osmotic stress; HeLa cells; mIMCD3 cells ID LASER-SCANNING CYTOMETRY; MEDULLARY EPITHELIAL-CELLS; CELLULAR SENESCENCE; MRE11 COMPLEX; STRAND BREAKS; HISTONE H2AX; IN-VIVO; REPAIR; STRESS; ACTIVATION AB We previously reported that, both in cell culture and in the renal inner medulla in vivo, elevating NaCl increased the number of DNA breaks, which persisted as long as NaCl remained high but were rapidly repaired when NaCl was lowered. Furthermore, those breaks did not induce the DNA repair protein gamma H2AX or cause activation of the MRN (Mre11, Rad50, Nbs1) complex. In contrast, others recently reported that high NaCl does induce gamma H2AX and MRN complex formation and concluded that these activities are associated with repair of the DNA (Sheen MR, Kim SW, Jung JY, Ahn JY, Rhee JG, Kwon HM, Woo SK. Am J Physiol Renal Physiol 291: F1014-F1020, 2006). The purpose of the present studies was to resolve the disparity. The important difference is that HeLa cells, which were the main subject of the later report, are much less tolerant of high NaCl than are the mIMCD3 cells, which were our main subject. mIMCD3 cells survive levels of NaCl that kill HeLa cells by apoptosis. Here we demonstrate that in both cell types raising NaCl to a level that the cells survive (higher for mIMCD3 than HeLa) increases DNA breaks without inducing gamma H2AX or activating the MRN complex and that the DNA breaks persist as long as NaCl remains elevated, but are rapidly repaired when it is lowered. Importantly, in both cell types, raising NaCl further to cause apoptosis activates these DNA damage response proteins and greatly fragments DNA, associated with cell death. We conclude that gamma H2AX induction and MRN activation in response to high NaCl are associated with apoptosis, not DNA repair. C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Dmitrieva, NI (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 FU National Heart, Lung, and Blood Institute; National Institutes of Health FX This research was supported by the Intramural Research Programs of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 44 TC 14 Z9 14 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2008 VL 295 IS 6 BP F1678 EP F1688 DI 10.1152/ajprenal.90424.2008 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 379GQ UT WOS:000261385100010 PM 18829739 ER PT J AU Leelahavanichkul, A Yasuda, H Doi, K Hu, XZ Zhou, H Yuen, PST Star, RA AF Leelahavanichkul, Asada Yasuda, Hideo Doi, Kent Hu, Xuzhen Zhou, Hua Yuen, Peter S. T. Star, Robert A. TI Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cecal ligation-puncture; spleen; apoptosis; nuclear factor-kappa B; chloroquine ID ACUTE-RENAL-FAILURE; NF-KAPPA-B; APOPTOTIC CELL-DEATH; HEMORRHAGIC-SHOCK; POLYMICROBIAL SEPSIS; IMPROVES SURVIVAL; INDUCED IMMUNOSUPPRESSION; SYSTEMIC INFLAMMATION; ORGAN DYSFUNCTION; CECAL LIGATION AB We tested the anti-inflammatory agent methyl-2-acetamidoacrylate (M2AA), an ethyl pyruvate analog, in a cecal ligation-and-puncture (CLP) model of sepsis in CD-1 mice. M2AA administration at the time of CLP improved survival, renal function, kidney histology, liver injury, and splenocyte apoptosis, and lowered cytokine levels (TNF-alpha, IL-6, IFN-gamma, and IL-10). When M2AA treatment was delayed 6 h ( but not 12 h), M2AA still significantly reduced kidney dysfunction, liver injury, splenocyte apoptosis, and cytokine levels. NF-kappa B, a M2AA target, was transiently activated in spleen, peaking at 6 h; kidney and liver NF-kappa B increased steadily with a plateau at 12-24 h. M2AA reduced NF-kappa B activation in spleen at 6 h and in kidney and liver at 24 h. Splenectomy diminished the ability of M2AA to reduce cytokines, especially IL-6, but M2AA still decreased kidney and liver dysfunction, suggesting that splenic NF-kappa B is not central to M2AA action. In contrast, beneficial effects of chloroquine on cytokines and organ damage were neutralized by splenectomy, demonstrating a spleen-specific chloroquine target. Because M2AA and chloroquine act differently, we tested this combination. Survival at 96 h was highest with combination therapy (57%) vs. chloroquine (38%), M2AA (47.6%), or vehicle (5%). The benefit of combination therapy over chloroquine or M2AA alone did not reach statistical significance, indicating potential mechanistic overlap. We conclude that the transient target(s) for M2AA responsible for the narrow 6-h therapeutic window is not splenic NF-kappa B. Identifying this new target and downstream signaling pathways could lengthen the therapeutic window and improve combination therapy with chloroquine. C1 [Leelahavanichkul, Asada; Yasuda, Hideo; Doi, Kent; Hu, Xuzhen; Zhou, Hua; Yuen, Peter S. T.; Star, Robert A.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Yuen, PST (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bldg 10,Rm 3N108,10 Ctr Dr,MSC 1268, Bethesda, MD 20892 USA. EM py@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 58 TC 41 Z9 45 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2008 VL 295 IS 6 BP F1825 EP F1835 DI 10.1152/ajprenal.90442.2008 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 379GQ UT WOS:000261385100025 PM 18922884 ER PT J AU Sachs, AN Pisitkun, T Hoffert, JD Yu, MJ Knepper, MA AF Sachs, Aaron N. Pisitkun, Trairak Hoffert, Jason D. Yu, Ming-Jiun Knepper, Mark A. TI LC-MS/MS analysis of differential centrifugation fractions from native inner medullary collecting duct of rat SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin-2; phosphorylation; vasopressin; membrane trafficking ID AQUAPORIN-2 WATER CHANNELS; UREA TRANSPORTER UT-A1; PLASMA-MEMBRANE; VASOPRESSIN; PHOSPHORYLATION; KIDNEY; CELLS; IDENTIFICATION; TRAFFICKING; PROTEINS AB We carried out LC-MS/MS based proteomic profiling of differential centrifugation fractions from rat inner medullary collecting duct (IMCD): 1) to provide baseline knowledge of the IMCD proteome and 2) to evaluate the utility of differential centrifugation in assessing trafficking of the water channel aquaporin-2 (AQP2). IMCD suspensions were freshly prepared from rat kidneys using standard methods. Homogenized samples were subjected to sequential centrifugations at 1,000, 4,000, 17,000, and 200,000 g. These samples, as well as the final supernatant, were subjected to LC-MS/MS analysis. Preliminary immunoblotting confirmed that the ratio of AQP2 in the 17,000-g fraction to the 200,000-g fraction underwent an increase in response to the vasopressin analog dDAVP, largely due to a reduction in the 200,000-g fraction. Immunoblotting for the major phosphorylated forms of AQP2 revealed that phosphorylated AQP2 was present in both the 17,000- and 200,000- g fractions. LC-MS/MS analysis showed that markers of "intracellular vesicles," chiefly endosomal markers, were present in both the 17,000- and the 200,000- g fractions. In contrast, plasma membrane proteins were predominantly present in the 4,000- and 17,000- g fractions. Proteins associated with several multiprotein complexes (e. g., actin-related protein 2/3 complex and proteasome complex) were virtually exclusively present in the 200,000- g fraction. Overall, we identified 656 proteins, including 189 not previously present in the IMCD database. The data show that both the 17,000- and 200,000- g fractions are highly heterogeneous and cannot be equated with " plasma membrane" and "intracellular vesicle" fractions, respectively, leading us to propose an alternative approach for use of differential centrifugation to assess vesicular trafficking to the plasma membrane. C1 [Sachs, Aaron N.; Pisitkun, Trairak; Hoffert, Jason D.; Yu, Ming-Jiun; Knepper, Mark A.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU National Heart, Lung, and Blood Institute [Z01-HL-01285-KE] FX This work was supported by the intramural budget of the National Heart, Lung, and Blood Institute (Project number Z01-HL-01285-KE). NR 22 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2008 VL 295 IS 6 BP F1799 EP F1806 DI 10.1152/ajprenal.90510.2008 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 379GQ UT WOS:000261385100022 PM 18922883 ER PT J AU Leibenluft, E AF Leibenluft, Ellen TI The Rhythm of the Blues SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID SLEEP-WAKE CYCLE; DEPRESSION; MELATONIN C1 NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Mood Anxiety Program,NIH,HHS, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Mood Anxiety Program,NIH,HHS, Bldg 15K,Rm 203,MSC-2670, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 MH002778-08] NR 16 TC 1 Z9 2 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2008 VL 165 IS 12 BP 1501 EP 1504 DI 10.1176/appi.ajp.2008.08081286 PG 4 WC Psychiatry SC Psychiatry GA 377QP UT WOS:000261266000001 PM 19047326 ER PT J AU Blum, N Fee, E AF Blum, Nava Fee, Elizabeth TI Critical Shortcomings at Walter Reed Army Medical Center Create Doubt SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Blum, Nava] Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci, IL-31905 Haifa, Israel. [Blum, Nava] Max Stern Acad, Coll Emek Yezreel, Dept Hlth Syst Adm, Yezreel Valley, Israel. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Blum, N (reprint author), Univ Haifa, Sch Publ Hlth, Fac Social Welf & Hlth Sci, IL-31905 Haifa, Israel. EM navablum@hotmail.com NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2008 VL 98 IS 12 BP 2159 EP 2160 DI 10.2105/AJPH.2007.127407 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 378GP UT WOS:000261309500013 PM 18923122 ER PT J AU Amis, ES Baker, SR Becker, GJ Colletti, PM Dunnick, NR Davis, LP Forman, HP Koss, SA Resnik, CS Berquist, TH AF Amis, E. Stephen, Jr. Baker, Stephen R. Becker, Gary J. Colletti, Patrick M. Dunnick, N. Reed Davis, Lawrence P. Forman, Howard P. Koss, Scott A. Resnik, Charles S. Berquist, Thomas H. TI Panel Discussions in Radiology: Changes in Radiology Training and New Examination Format SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE CAQs; certification; maintenance of certification; radiology examinations; radiology training C1 [Baker, Stephen R.] Univ Med & Dent New Jersey, Newark, NJ 07101 USA. [Becker, Gary J.] Miami Cardiac & Vasc Inst, Miami, FL 33176 USA. [Becker, Gary J.] NIH, Bethesda, MD 20892 USA. [Becker, Gary J.] Univ Arizona, Coll Med, Tucson, AZ 85004 USA. [Colletti, Patrick M.] Univ So Calif, Los Angeles, CA 90089 USA. [Dunnick, N. Reed] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Davis, Lawrence P.] Albert Einstein Coll Med, N Shore Univ Hosp, Bronx, NY 10467 USA. [Resnik, Charles S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. EM Berquist.Thomas@mayo.edu NR 0 TC 8 Z9 8 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2008 VL 191 IS 6 BP W217 EP W230 DI 10.2214/AJR.08.1936 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 374HZ UT WOS:000261035700041 PM 19020208 ER PT J AU O'Kane, P Shelkovoy, E McConnell, RJ Shpak, V Parker, L Bogdanova, TI Brenner, A Naida, Y Frangos, A Zablotska, L Robbins, J Greenebaum, E Zurnadzhy, LY Tronko, M Hatch, M AF O'Kane, Patrick Shelkovoy, Evgeniy McConnell, Robert J. Shpak, Victor Parker, Laurence Bogdanova, Tatiana I. Brenner, Alina Naida, Yuri Frangos, Andrea Zablotska, Lydia Robbins, Jacob Greenebaum, Ellen Zurnadzhy, Lydia Y. Tronko, Mykolo Hatch, Maureen TI Differences in Sonographic Conspicuity According to Papillary Thyroid Cancer Subtype: Results of the Ukrainian-American Cohort Study After the Chornobyl Accident SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE Chernobyl accident; Chornobyl accident; papillary thyroid cancer; radiation exposure; sonography ID CARCINOMA; MALIGNANCY; FEATURES; DISEASES; RELIABILITY; CRITERIA; NODULES AB OBJECTIVE. Over time, the histology of papillary thyroid cancers detected in a repeatedly screened population exposed to radiation at Chornobyl (Chernobyl) has shifted from a more aggressive subtype toward less aggressive subtypes. This change may reflect biologic behavior but could also be influenced by the detectability of different subtypes. The study objective was to identify whether there is any relationship between the conspicuity of sonographically detected papillary cancers and histologic subtype. MATERIALS AND METHODS. Sonographic images of 84 papillary cancers occurring in young people exposed to radiation at Chornobyl were each given a conspicuity score using a subjective 1-5 scale by four independent expert readers blinded to histologic subtype. The effects of tumor subtype, tumor encapsulation, reader, machine type, and nodule size on sonographic conspicuity were determined using analysis of variance and Spearman correlations. RESULTS. Cancer subtype was related to sonographic conspicuity (p < 0.01). The relatively aggressive solid subtype of papillary carcinoma was more conspicuous than the papillary, follicular, and mixed subtypes (p < 0.05). The other subtypes did not differ significantly from each other in conspicuity. Conspicuity was not significantly related to nodule size, degree of encapsulation, age and sex of the subject, or machine type. Although the mean conspicuity score for each reader differed significantly, reliability of conspicuity judgments across readers was fair. CONCLUSION. In subjects exposed to radiation from the Chornobyl accident, the solid subtype of papillary carcinoma appears to be more conspicuous on sonography than the other subtypes. Therefore, the change in subtype observed over time in this repeatedly screened population may be influenced by differences in nodule conspicuity. C1 [O'Kane, Patrick; Parker, Laurence; Frangos, Andrea] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. [Shelkovoy, Evgeniy; Shpak, Victor; Bogdanova, Tatiana I.; Naida, Yuri; Zurnadzhy, Lydia Y.; Tronko, Mykolo] Inst Endocrinol & Metab, Kiev, Ukraine. [McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Dept Med, Thyroid Clin, New York, NY USA. [Brenner, Alina] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zablotska, Lydia] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Robbins, Jacob] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. [Greenebaum, Ellen] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. RP O'Kane, P (reprint author), Thomas Jefferson Univ Hosp, Dept Radiol, 10th St & Walnut St,796 Main Bldg, Philadelphia, PA 19107 USA. EM patrick.okane@jefferson.edu FU Intramural NIH HHS [Z01 CP010132-12] NR 19 TC 4 Z9 5 U1 0 U2 0 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 DEC PY 2008 VL 191 IS 6 BP W293 EP W298 DI 10.2214/AJR.07.3812 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 374HZ UT WOS:000261035700051 PM 19020218 ER PT J AU Bucuvalas, JC Alonso, E Magee, JC Talwalkar, J Hanto, D Doo, E AF Bucuvalas, J. C. Alonso, E. Magee, J. C. Talwalkar, J. Hanto, D. Doo, E. TI Improving Long-Term Outcomes After Liver Transplantation in Children SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Children; liver transplantation; outcomes ID CARDIOVASCULAR RISK-FACTORS; REGULATORY T-CELLS; EPSTEIN-BARR-VIRUS; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDERS; HEALTH-INSURANCE CONSIDERATIONS; DONOR-SPECIFIC ALLOREACTIVITY; CHRONIC RENAL DYSFUNCTION; QUALITY-OF-LIFE; CALCINEURIN INHIBITORS; HISTONE ACETYLATION AB The objective was to review the current state of knowledge and recommend future research directions related to long-term outcomes for pediatric liver transplant recipients. A 1-day Clinical Research Workshop on Improving Long-Term Outcomes for Pediatric Liver Transplant Recipients was held on February 12, 2007, in Washington, DC. The speaker topics were germane to research priorities delineated in the chapters on Pediatric Liver Diseases and on Liver Transplantation in the Trans-NIH Action Plan for Liver Disease Research. Issues that compromise long-term well-being and survival but are amenable to existing and new research efforts were presented and discussed. Areas of research that further enhanced the research priorities in the Action Plan for Liver Disease Research included collection of longitudinal data to define emerging trends of clinical challenges; identification of risk factors associated with long-term immunosuppression complications; development of tolerance-inducing regimens; definition of biomarkers that reflect the level of clinical immunosuppression; development of instruments for the measurement of health wellness; identification of risk factors that impede growth and intellectual development before and after liver transplantation and identification of barriers and facilitators that impact nonadherence and transition of care for adolescents. C1 [Bucuvalas, J. C.] Cincinnati Childrens Hosp, Pediat Liver Care Ctr, Cincinnati, OH USA. [Alonso, E.] Childrens Mem Hosp, Siragusa Transplant Ctr, Chicago, IL 60614 USA. [Alonso, E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Magee, J. C.] Univ Michigan Hlth Syst, Sect Gen Surg, Div Transplantat, Ann Arbor, MI USA. [Talwalkar, J.] Mayo Clin, Transplant Ctr, Rochester, MN USA. [Hanto, D.] Beth Israel Deaconess Med Ctr, Div Transplantat, Boston, MA 02215 USA. [Doo, E.] NIDDK, Liver Dis Res Branch, Natl Inst Hlth, Bethesda, MD USA. RP Bucuvalas, JC (reprint author), Cincinnati Childrens Hosp, Pediat Liver Care Ctr, Cincinnati, OH USA. EM john.bucuvalas@cchmc.org FU Liver Diseases Research Branch; Division of Digestive Diseases and Nutrition; National Institute of Diabetes; Digestive and Kidney Diseases; National Institutes of Health FX The workshop was sponsored by the Liver Diseases Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) in collaboration with the Office of Rare Diseases (ORD), National Institutes of Health. NR 79 TC 29 Z9 29 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2008 VL 8 IS 12 BP 2506 EP 2513 DI 10.1111/j.1600-6143.2008.02432.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 374OM UT WOS:000261053600010 PM 18853949 ER PT J AU Freise, CE Gillespie, BW Koffron, AJ Lok, ASF Pruett, TL Emond, JC Fair, JH Fisher, RA Olthoff, KM Trotter, JF Ghobrial, RM Everhart, JE AF Freise, C. E. Gillespie, B. W. Koffron, A. J. Lok, A. S. F. Pruett, T. L. Emond, J. C. Fair, J. H. Fisher, R. A. Olthoff, K. M. Trotter, J. F. Ghobrial, R. M. Everhart, J. E. CA A2ALL Study Grp TI Recipient Morbidity After Living and Deceased Donor Liver Transplantation: Findings from the A2ALL Retrospective Cohort Study(dagger) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE A2ALL; complications; learning curve; liver transplant; living donor; outcomes ID DUCT BILIARY RECONSTRUCTION; HEPATIC-ARTERY; SINGLE-CENTER; RISK-FACTORS; BILE-DUCT; LOBE; COMPLICATIONS; EXPERIENCE; OUTCOMES; CHOLECYSTECTOMY AB Patients considering living donor liver transplantation (LDLT) need to know the risk and severity of complications compared to deceased donor liver transplantation (DDLT). One aim of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) was to examine recipient complications following these procedures. Medical records of DDLT or LDLT recipients who had a living donor evaluated at the nine A2ALL centers between 1998 and 2003 were reviewed. Among 384 LDLT and 216 DDLT, at least one complication occurred after 82.8% of LDLT and 78.2% of DDLT (p = 0.17). There was a median of two complications after DDLT and three after LDLT. Complications that occurred at a higher rate (p < 0.05) after LDLT included biliary leak (31.8% vs. 10.2%), unplanned reexploration (26.2% vs. 17.1%), hepatic artery thrombosis (6.5% vs. 2.3%) and portal vein thrombosis (2.9% vs. 0.0%). There were more complications leading to retransplantation or death (Clavien grade 4) after LDLT versus DDLT (15.9% vs. 9.3%, p = 0.023). Many complications occurred more commonly during early center experience; the odds of grade 4 complications were more than two-fold higher when centers had performed <= 20 LDLT (vs. > 40). In summary, complication rates were higher after LDLT versus DDLT, but declined with center experience to levels comparable to DDLT. C1 [Freise, C. E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Gillespie, B. W.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Koffron, A. J.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Lok, A. S. F.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Pruett, T. L.] Univ Virginia, Dept Surg, Charlottesville, VA USA. [Emond, J. C.] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA. [Fair, J. H.] Univ N Carolina, Dept Surg, Chapel Hill, NC USA. [Fisher, R. A.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA USA. [Olthoff, K. M.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Trotter, J. F.] Univ Colorado, Dept Surg, Denver, CO 80202 USA. [Ghobrial, R. M.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Everhart, J. E.] NIDDK, Div Digest Dis & Nutr, Natl Inst Hlth, Bethesda, MD USA. RP Freise, CE (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM freisec@surgery.ucsf.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531]; U. S. Department of Health Resources and Services Administration; American Society of Transplant Surgeons FX This study was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK grant numbers U01-DK62536, U01-DK62444, U01-DK62467, U01-DK62483, U01-DK62484, U01-DK62494, U01-DK62496, U01-DK62498, U01-DK62505, U01-DK62531) through cooperative agreements ( listed below). Additional support was provided by the U. S. Department of Health Resources and Services Administration (HRSA) and the American Society of Transplant Surgeons (ASTS). This study was presented in part at the 57th annual meeting of the American Association for the Study of Liver Diseases, Boston, MA, October 2006. NR 33 TC 110 Z9 113 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2008 VL 8 IS 12 BP 2569 EP 2579 DI 10.1111/j.1600-6143.2008.02440.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 374OM UT WOS:000261053600017 PM 18976306 ER PT J AU Plassmeyer, ML MacDonald, N Reiter, K Shimp, R Zhang, YL House, B Lebowitz, J Kotova, S Jin, A Hickman, M Herrera, R Uchime, O Nguyen, V Glen, J Miller, L Wu, YM Narum, D AF Plassmeyer, Matthew Lee MacDonald, Nick Reiter, Karine Shimp, Richard Zhang, Yanling House, Brent Lebowitz, Jack Kotova, Svetlana Jin, Albert Hickman, Merrit Herrera, Raul Uchime, Onyinyechukwu Nguyen, Vu Glen, Jacqueline Miller, Louis Wu, Yimin Narum, David TI THE BIOCHEMICAL AND BIOPHYSICAL CHARACTERIZATION OF AN ESCHERICHIA COLI EXPRESSED PLASMODIUM FALCIPARUM CIRCUMSPOROZOITE PROTEIN (CSP), A LEADING MALARIA VACCINE CANDIDATE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Plassmeyer, Matthew Lee; MacDonald, Nick; Reiter, Karine; Shimp, Richard; Zhang, Yanling; Hickman, Merrit; Herrera, Raul; Uchime, Onyinyechukwu; Nguyen, Vu; Glen, Jacqueline; Miller, Louis; Wu, Yimin; Narum, David] NIH, Rockville, MD USA. [House, Brent] USN, Silver Spring, MD USA. [Lebowitz, Jack; Kotova, Svetlana; Jin, Albert] NIH, Bethesda, MD 20892 USA. OI Jin, Albert/0000-0003-3826-1081 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 3 BP 1 EP 1 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600004 ER PT J AU Bruder, JT Chen, P Stefaniak, ME Semenova, E Limbach, K Patterson, NB Konovalova, S Thomas, C Campo, JJ Ettyreddy, D McVey, D Long, CA Li, S Locke, E Richie, TL King, CR Doolan, DL AF Bruder, Joseph T. Chen, Ping Stefaniak, Maureen E. Semenova, Elena Limbach, Keith Patterson, Noelle B. Konovalova, Svetlana Thomas, Charlie Campo, Joseph J. Ettyreddy, Damodar McVey, Duncan Long, Carole A. Li, Sheng Locke, Emily Richie, Thomas L. King, C. Richter Doolan, Denise L. TI DEVELOPMENT OF A MULTI-ANTIGEN MULTI-STAGE ADENOVECTOR-BASED MALARIA VACCINE THAT INDUCES ROBUST T-CELL AND ANTIBODY RESPONSES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Bruder, Joseph T.; Chen, Ping; Semenova, Elena; Konovalova, Svetlana; Thomas, Charlie; Ettyreddy, Damodar; McVey, Duncan; King, C. Richter] GenVec, Gaithersburg, MD USA. [Limbach, Keith; Patterson, Noelle B.; Campo, Joseph J.; Richie, Thomas L.; Doolan, Denise L.] Naval Med Res Ctr, Silver Spring, MD USA. [Long, Carole A.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Li, Sheng; Locke, Emily] PATH Malaria Vaccine Initiat, Bethesda, MD USA. RI Doolan, Denise/F-1969-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 6 BP 2 EP 3 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600007 ER PT J AU Murray, SA Zhou, H Aebig, J Lambert, L Martin, LB Miller, L Long, C Miura, K AF Murray, Sara A. Zhou, Hong Aebig, Joan Lambert, Lynn Martin, Laura B. Miller, Louis Long, Carole Miura, Kazutoyo TI CHARACTERIZATION OF ANTI-AMA1 ANTIBODIES INDUCED BY AMA1-C2, A THREE-ALLELE COMBINATION VACCINE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Murray, Sara A.; Aebig, Joan; Lambert, Lynn; Martin, Laura B.; Miller, Louis; Miura, Kazutoyo] NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. [Zhou, Hong; Long, Carole] NIAID, Lab Malaria & Vector Res, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 4 BP 2 EP 2 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600005 ER PT J AU Patterson, NB Bruder, JT Limbach, K Moretz, SE Zhou, H Diouf, A King, CR Gowda, K Chen, P Konovalova, S Bergmann-Leitner, ES Locke, E Soisson, L Diggs, C Angov, E Long, CA Richie, TL Doolan, DL AF Patterson, Noelle B. Bruder, Joseph T. Limbach, Keith Moretz, Samuel E. Zhou, Hong Diouf, Ababacar King, C. Richter Gowda, Kalpana Chen, Ping Konovalova, Svetlana Bergmann-Leitner, Elke S. Locke, Emily Soisson, Lorraine Diggs, Carter Angov, Evelina Long, Carole A. Richie, Thomas L. Doolan, Denise L. TI THE FIRST GENERATION PLASMODIUM FALCIPARUM AMA-1 BASED MONOVALENT ADENOVECTOR VACCINE AND THE SECOND GENERATION BIVALENT ADENOVECTOR VACCINE EXPRESSING PLASMODIUM FALCIPARUM AMA-1 AND MSP1-42 ELICIT ROBUST FUNCTIONAL ANTIBODIES IN NZW RABBIT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Patterson, Noelle B.; Limbach, Keith; Gowda, Kalpana; Bergmann-Leitner, Elke S.; Angov, Evelina; Richie, Thomas L.; Doolan, Denise L.] Naval Med Res Ctr, US Mil Malaria Vaccine Program, Silver Spring, MD USA. [Patterson, Noelle B.; Limbach, Keith; Gowda, Kalpana; Bergmann-Leitner, Elke S.; Angov, Evelina; Richie, Thomas L.; Doolan, Denise L.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Bruder, Joseph T.; King, C. Richter; Chen, Ping; Konovalova, Svetlana] GenVec Inc, Gaithersburg, MD USA. [Moretz, Samuel E.; Zhou, Hong; Diouf, Ababacar; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Locke, Emily] PATH Malaria Vaccine Initiat, Bethesda, MD USA. [Soisson, Lorraine; Diggs, Carter] US Agcy Int Dev, Malaria Vaccine Dev Program, Washington, DC 20523 USA. RI Bergmann-Leitner, Elke/B-3548-2011; Doolan, Denise/F-1969-2015 OI Bergmann-Leitner, Elke/0000-0002-8571-8956; NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 5 BP 2 EP 2 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600006 ER PT J AU Ellis, RD Wu, YM Shaffer, D Fontes, E Malkin, E Mahanty, S Fay, MP Narum, D Rausch, K Miles, AP Aebig, J Orcutt, A Muratova, O Song, GH Lambert, L Zhu, DM Miura, K Long, C Saul, A Miller, LH Durbin, AP AF Ellis, Ruth D. Wu, Yimin Shaffer, Donna Fontes, Erica Malkin, Elissa Mahanty, Siddhartha Fay, Michael P. Narum, David Rausch, Kelly Miles, Aaron P. Aebig, Joan Orcutt, Andrew Muratova, Olga Song, Guanhong Lambert, Lynn Zhu, Daming Miura, Kazutoyo Long, Carole Saul, Allan Miller, Louis H. Durbin, Anna P. TI A PHASE 1 TRIAL OF THE MALARIA TRANSMISSION BLOCKING VACCINE CANDIDATES PFS25 AND PVS25 FORMULATED WITH MONTANIDE ISA 51 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ellis, Ruth D.; Wu, Yimin; Malkin, Elissa; Mahanty, Siddhartha; Fay, Michael P.; Narum, David; Rausch, Kelly; Miles, Aaron P.; Aebig, Joan; Orcutt, Andrew; Muratova, Olga; Song, Guanhong; Lambert, Lynn; Zhu, Daming; Miura, Kazutoyo; Long, Carole; Saul, Allan; Miller, Louis H.] NIH, Rockville, MD USA. [Shaffer, Donna; Fontes, Erica; Durbin, Anna P.] Johns Hopkins Ctr Immunizat Res, Washington, DC USA. OI Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2008 VL 79 IS 6 MA 22 BP 7 EP 7 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600023 ER PT J AU Sagara, I Ellis, R Dicko, A Niambele, MB Kamate, B Guindo, O Pierce, M Fay, M Sissoko, MS Guindo, MA Kante, O Saye, R Dolo, A Miura, K Diallo, DA Miller, L Doumbo, OK AF Sagara, Issaka Ellis, Ruth Dicko, Alassane Niambele, Mohamed Balla Kamate, Beh Guindo, Ousmane Pierce, Mark Fay, Michael Sissoko, Mahamadou S. Guindo, Merepen A. Kante, Ousmane Saye, Renion Dolo, Amagana Miura, Kazutoyo Diallo, Dapa A. Miller, Louis Doumbo, Ogobara K. TI RANDOMIZED, CONTROLLED, PHASE 1 STUDY OF THE SAFETY AND IMMUNOGENICITY OF THE AMA1-C1/ALHYDROGEL (R) + CPG 7909 VACCINE FOR PLASMODIUM FALCIPARUM MALARIA, IN SEMI-IMMUNE MALIAN ADULTS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Sagara, Issaka; Dicko, Alassane; Niambele, Mohamed Balla; Kamate, Beh; Guindo, Ousmane; Sissoko, Mahamadou S.; Guindo, Merepen A.; Kante, Ousmane; Saye, Renion; Dolo, Amagana; Diallo, Dapa A.; Doumbo, Ogobara K.] Univ Bamako, MRTC FMPOS, Bamako, Mali. [Ellis, Ruth; Pierce, Mark; Fay, Michael; Miura, Kazutoyo; Miller, Louis] NIAIDI, MVDB, NIH, Twinbrook, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 24 BP 8 EP 8 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600025 ER PT J AU Scott, E Kabat, J Schwartz, O Nash, TE Mahanty, S AF Scott, Erick Kabat, Juraj Schwartz, Owen Nash, Theodore E. Mahanty, Siddhartha TI IN VITRO ASSESSMENT OF TAENIA CRASSICEPS MOTILITY AND ITS APPLICATION TO THE STUDY OF ANTHELMINTIC TREATMENT IN NEUROCYSTICERCOSIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Scott, Erick] NIH, Rockville, MD USA. [Kabat, Juraj; Schwartz, Owen; Nash, Theodore E.; Mahanty, Siddhartha] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 36 BP 11 EP 12 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600037 ER PT J AU Moore, C Jacob, S Pinkerton, R Banura, P Meya, D Reynolds, S Kenya-Mugisha, N Mayanja-Kizza, H Scheld, WM AF Moore, Christopher Jacob, Shevin Pinkerton, Relana Banura, Patrick Meya, David Reynolds, Steven Kenya-Mugisha, Nathan Mayanja-Kizza, Harriet Scheld, W. Michael TI TREATMENT OF SEVERE SEPSIS WITH ARTEMETHER-LUMEFANTRINE IS ASSOCIATED WITH DECREASED MORTALITY IN UGANDAN PATIENTS WITHOUT MALARIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Moore, Christopher; Jacob, Shevin; Pinkerton, Relana; Scheld, W. Michael] Univ Virginia, Charlottesville, VA USA. [Banura, Patrick; Kenya-Mugisha, Nathan] Masaka Reg Referral Hosp, Masaka, Uganda. [Meya, David; Mayanja-Kizza, Harriet] Makerere Univ, Kampala, Uganda. [Reynolds, Steven] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 73 BP 22 EP 22 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600074 ER PT J AU Coulibaly, SY Dembele, B Sanogo, D Coulibaly, ME Doumbia, SS Soumarou, L Konate, S Dolo, H Diallo, AA Traore, S Nutman, TB Klion, AD Coulibaly, YI Keita, AD AF Coulibaly, Siaka Y. Dembele, Benoit Sanogo, Dramane Coulibaly, Michel E. Doumbia, Salif S. Soumarou, Lamine Konate, Siaka Dolo, Housseini Diallo, Abdallah A. Traore, Sekou Nutman, Thomas B. Klion, Amy D. Coulibaly, Yaya I. Keita, Adama D. TI INCREASED PREVALENCE OF HYDROCELE, LYMPHATIC DILATATION AND TESTICULAR CALCIFICATION IN MEN WITH MANSONELLA PERSTANS INFECTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Coulibaly, Siaka Y.; Dembele, Benoit; Sanogo, Dramane; Coulibaly, Michel E.; Doumbia, Salif S.; Soumarou, Lamine; Konate, Siaka; Dolo, Housseini; Diallo, Abdallah A.; Traore, Sekou; Coulibaly, Yaya I.] Univ Bamako, Fac Med Pharm & Dent, Bamako, Mali. [Nutman, Thomas B.; Klion, Amy D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Keita, Adama D.] Hosp Point G, Dept Radiol, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 128 BP 38 EP 38 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600129 ER PT J AU Dembele, B Coulibaly, YI Konate, S Dolo, H Coulibal, SY Sanogo, D Soumaoro, L Coulibaly, ME Doumbia, SS Diallo, AA Traore, SF Keita, AD Nutman, TB Klion, AD AF Dembele, Benoit Coulibaly, Yaya I. Konate, Siaka Dolo, Housseini Coulibal, Siaka Y. Sanogo, Dramane Soumaoro, Lamine Coulibaly, Michel E. Doumbia, Salif S. Diallo, Abdallah A. Traore, Sekou F. Keita, Adama D. Nutman, Thomas B. Klion, Amy D. TI EFFECT OF ALBENDAZOLE AND IVERMECTIN DOSE ON WUCHERERIA BANCROFTI MICROFILARIAL CLEARANCE IN MALI: A RANDOMIZED, OPEN LABEL STUDY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Dembele, Benoit; Coulibaly, Yaya I.; Konate, Siaka; Dolo, Housseini; Coulibal, Siaka Y.; Sanogo, Dramane; Soumaoro, Lamine; Coulibaly, Michel E.; Doumbia, Salif S.; Diallo, Abdallah A.; Traore, Sekou F.] Univ Bamako, Fac Med Pharm & Dent, Bamako, Mali. [Keita, Adama D.] Hosp Point G, Dept Radiol, Bamako, Mali. [Nutman, Thomas B.; Klion, Amy D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 129 BP 38 EP 38 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600130 ER PT J AU Steel, C Myers, TG Su, Q Nutman, TB AF Steel, Cathy Myers, Timothy G. Su, Qin Nutman, Thomas B. TI DIFFERENCES IN EXPOSURE AND CHRONICITY IN HUMAN FILARIAL INFECTION LEADS TO VARIABLE GENE EXPRESSION PROFILES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Steel, Cathy; Myers, Timothy G.; Su, Qin; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 143 BP 43 EP 43 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600144 ER PT J AU Shakarian, AM McGugan, G Dwyer, D AF Shakarian, Alison M. McGugan, Glen Dwyer, Dennis TI LDLIP3 ENCODES A SECRETED LIPASE IN THE HUMAN PATHOGEN LEISHMANIA DONOVANI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Shakarian, Alison M.] Salve Regina Univ, Newport, RI USA. [McGugan, Glen; Dwyer, Dennis] Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 157 BP 46 EP 47 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600158 ER PT J AU Kayentao, K Ongoiba, A Traore, B Doumbo, S Doumtabe, D Kone, Y Traore, A Weiss, G Diakite, SA Krause, MA Doumbia, S Guindo, A Fairhurst, RM Miller, LH Pierce, SK Crompton, PD Doumbo, OK AF Kayentao, Kassoum Ongoiba, Aissata Traore, Boubacar Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Traore, Abdrahamane Weiss, Greta Diakite, Seidina A. Krause, Michael A. Doumbia, Seydou Guindo, Aldiouma Fairhurst, Rick M. Miller, Louis H. Pierce, Susan K. Crompton, Peter D. Doumbo, Ogobara K. TI CHARACTERIZATION OF THE KAMBILA, MALI COHORT FOR LONGITUDINAL STUDIES OF THE ACQUISITION AND MAINTENANCE OF NATURALLY-ACQUIRED MALARIA IMMUNITY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Kayentao, Kassoum; Ongoiba, Aissata; Traore, Boubacar; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Traore, Abdrahamane; Diakite, Seidina A.; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. [Weiss, Greta; Pierce, Susan K.; Crompton, Peter D.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Krause, Michael A.; Fairhurst, Rick M.] NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Miller, Louis H.] NIAID, NIH, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA. RI Crompton, Peter/N-1130-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 220 BP 65 EP 65 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600221 ER PT J AU Rayavara, K Desai, SA AF Rayavara, Kempaiah Desai, Sanjay A. TI GENETIC DISRUPTION OF A MECHANOSENSITIVE ION CHANNEL IN PLASMODIUM FALCIPARUM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Rayavara, Kempaiah; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RI Desai, Sanjay/B-7110-2009 NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 221 BP 65 EP 66 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600222 ER PT J AU Murray, CK Pimentel, G Parker, T Beckius, ML Samir, A Rhman, BA Mende, K Galloway, RL Hospenthal, DR AF Murray, Clinton K. Pimentel, Guillermo Parker, Tina Beckius, Miriam L. Samir, Ahmed Rhman, Bassern Abdel Mende, Katrin Galloway, Renee L. Hospenthal, Duane R. TI ANTIMICROBIAL SUSCEPTIBILITIES OF CLINICAL HUMAN ISOLATES OF LEPTOSPIRA FROM EGYPT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Murray, Clinton K.; Beckius, Miriam L.; Hospenthal, Duane R.] Brooke Army Med Ctr, Ft Sam Houston, TX 78234 USA. [Pimentel, Guillermo; Rhman, Bassern Abdel] US NAMRU3, Cairo, Egypt. [Parker, Tina] NIH, Bethesda, MD 20892 USA. [Samir, Ahmed] Cairo Univ, Cairo, Egypt. [Mende, Katrin] Infect Dis Clin Res Program, Ft Sam Houston, TX USA. [Galloway, Renee L.] Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 266 BP 78 EP 78 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600267 ER PT J AU Weiss, G Traore, B Doumbo, S Doumtabe, D Kone, Y Mircetic, M Ongoiba, A Kayentao, K Doumbo, OK Pierce, SK Crompton, PD AF Weiss, Greta Traore, Boubacar Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Mircetic, Marko Ongoiba, Aissata Kayentao, Kassoum Doumbo, Ogobara K. Pierce, Susan K. Crompton, Peter D. TI A LONGITUDINAL STUDY OF THE ACQUISITION AND MAINTENANCE OF PLASMODIUM FALCIPARUM-SPECIFIC MEMORY B CELLS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Weiss, Greta; Mircetic, Marko; Pierce, Susan K.; Crompton, Peter D.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Traore, Boubacar; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Ongoiba, Aissata; Kayentao, Kassoum; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. RI Crompton, Peter/N-1130-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 325 BP 95 EP 95 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600325 ER PT J AU Babu, S Bhat, S Kumar, P Kolappan, C Kumaraswami, V Nutman, TB AF Babu, Subash Bhat, Sajid Kumar, Pavan Kolappan, C. Kumaraswami, V. Nutman, Thomas B. TI FILARIAL LYMPHATIC PATHOLOGY IS CHARACTERIZED BY AUGMENTED PRO-INFLAMMATORY CYTOKINE PRODUCTION IN RESPONSE TO TLR2 AND TLR9 LIGANDS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Babu, Subash; Bhat, Sajid; Kumar, Pavan] NIH TRC Int Ctr Excellence Res, Madras, Tamil Nadu, India. [Kolappan, C.; Kumaraswami, V.] TB Res Ctr, Madras, Tamil Nadu, India. [Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 381 BP 112 EP 112 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600381 ER PT J AU Bennuru, S Maldarelli, G Kumaraswanni, V Nutman, TB AF Bennuru, Sasisekhar Maldarelli, Grace Kumaraswanni, V Nutman, Thomas B. TI ELEVATED PLASMA ANGIOGENIC AND LYMPHANGIOGENIC FACTORS ARE ASSOCIATED WITH INFECTION PER SE RATHER THAN CLINICALLY APPARENT DISEASE IN HUMAN FILARIAL INFECTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Bennuru, Sasisekhar; Maldarelli, Grace; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. [Kumaraswanni, V] TB Res Ctr, Madras, Tamil Nadu, India. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 382 BP 112 EP 113 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600382 ER PT J AU Semnani, RT Venugopal, PG Mahapatra, L Skinner, J Meylan, F Chaussabel, D Siegel, RM Nutman, TB AF Semnani, Roshanalk Tolouei Venugopal, Priyanka Goel Mahapatra, Lily Skinner, Jason Meylan, Francoise Chaussabel, Damien Siegel, Richard M. Nutman, Thomas B. TI INDUCTION OF TRAIL- AND TNF-alpha-DEPENDENT APOPTOTIC CELL DEATH IN HUMAN MONOCYTE-DERIVED DENDRITIC CELLS BY BRUGIA MALAYI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Semnani, Roshanalk Tolouei; Venugopal, Priyanka Goel; Mahapatra, Lily; Meylan, Francoise; Siegel, Richard M.; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. [Skinner, Jason; Chaussabel, Damien] Baylor Inst Immunol Res, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 379 BP 112 EP 112 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600379 ER PT J AU Ramanathan, R Talaat, K Fedorko, D Mahanty, S Nash, T AF Ramanathan, Roshan Talaat, Kawsar Fedorko, Daniel Mahanty, Siddhartha Nash, Theodore TI MOLECULAR DIAGNOSTICS AND SPECIATION GUIDE CHOICE OF ALTERNATIVE, SHORT-COURSE TREATMENT REGIMENS FOR CUTANEOUS LEISHMANIASIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ramanathan, Roshan; Fedorko, Daniel; Mahanty, Siddhartha; Nash, Theodore] Natl Inst Hlth, Bethesda, MD USA. [Talaat, Kawsar] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 420 BP 124 EP 124 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600420 ER PT J AU O'Meara, WP Noor, A Tsofa, B McKenzie, FE Marsh, K AF O'Meara, Wendy P. Noor, Abdisalan Tsofa, Benjamin McKenzie, F. Ellis Marsh, Kevin TI THE IMPACT OF ACCESS TO PRIMARY HEALTH CARE ON THE INCIDENCE OF CLINICAL MALARIA IN CHILDREN SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [O'Meara, Wendy P.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Noor, Abdisalan] KEMRI Wellcome Trust Collaborat Program, Nairobi, Kenya. [Tsofa, Benjamin] Minist Hlth, Kilifi, Kenya. [Marsh, Kevin] CGMRC Wellcome Trust Collaborat Program, Kenya Med Res Inst, Kilifi, Kenya. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 617 BP 182 EP 183 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600616 ER PT J AU Crompton, PD Miura, K Traore, B Kayentao, K Ongoiba, A Weiss, G Doumbo, S Doumtabe, D Kone, Y Huang, CY Doumbo, OK Miller, LH Long, CA Pierce, SK AF Crompton, Peter D. Miura, Kazutoyo Traore, Boubacar Kayentao, Kassoum Ongoiba, Aissata Weiss, Greta Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Huang, Chiung-Yu Doumbo, Ogobara K. Miller, Louis H. Long, Carole A. Pierce, Susan K. TI ASSESSING THE CORRELATION BETWEEN GROWTH INHIBITION ACTIVITY AND MALARIA RISK IN A LONGITUDINAL STUDY IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Crompton, Peter D.; Weiss, Greta; Pierce, Susan K.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Miura, Kazutoyo; Miller, Louis H.] NIAID, NIH, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA. [Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. [Huang, Chiung-Yu] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. [Long, Carole A.] NIAID, NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RI Crompton, Peter/N-1130-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 620 BP 183 EP 184 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600619 ER PT J AU Crompton, PD Kayala, M Traore, B Weiss, G Burk, C Kayentao, K Ongoiba, A Doumbo, S Miller, LH Doumbo, OK Doolan, DL Baldi, P Felgner, PL Pierce, SK AF Crompton, Peter D. Kayala, Matt Traore, Boubacar Weiss, Greta Burk, Chad Kayentao, Kassoum Ongoiba, Aissata Doumbo, Safiatou Miller, Louis H. Doumbo, Ogobara K. Doolan, Denise L. Baldi, Pierre Felgner, Philip L. Pierce, Susan K. TI PROFILING PROTECTIVE HUMORAL IMMUNE RESPONSES TO PLASMODIUM FALCIPARUM BY PROTEIN MICROARRAY IN A LONGITUDINAL STUDY IN MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Crompton, Peter D.; Weiss, Greta; Pierce, Susan K.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Kayala, Matt; Baldi, Pierre] Univ Calif Irvine, Inst Genom & Bioinformat, Sch Informat & Comp Sci, Irvine, CA USA. [Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. [Burk, Chad; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA. [Miller, Louis H.] NIAID, NIH, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA. [Doolan, Denise L.] Queensland Inst Med Res, Vaccine Immunol Lab, Brisbane, Qld 4006, Australia. RI Doolan, Denise/F-1969-2015; Crompton, Peter/N-1130-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 621 BP 184 EP 184 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600620 ER PT J AU Mircetic, M Weiss, G Mullen, GE Martin, LB Miller, LH Pierce, SK Crompton, PD AF Mircetic, Marko Weiss, Greta Mullen, Gregory E. Martin, Laura B. Miller, Louis H. Pierce, Susan K. Crompton, Peter D. TI VACCINATION WITH MSP142-C1/ALHYDROGEL (R) GENERATES ANTIGEN-SPECIFIC MEMORY B CELLS IN MALARIA-NAIVE US ADULTS AND THE CPG 7909 OLIGODEOXYNUCLEOTIDE ADJUVANT ENHANCES THIS RESPONSE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Mircetic, Marko; Weiss, Greta; Pierce, Susan K.; Crompton, Peter D.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Mullen, Gregory E.; Martin, Laura B.; Miller, Louis H.] NIAID, NIH, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA. RI Martin, Laura/N-1789-2013; Crompton, Peter/N-1130-2016 OI Martin, Laura/0000-0002-4431-4381; NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 623 BP 184 EP 185 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600622 ER PT J AU Traore, B Doumbo, S Doumtabe, D Kone, Y Traore, A Mircetic, M Ellis, RD Martin, LB Miller, LH Crompton, PD Pierce, SK Doumbo, OK AF Traore, Boubacar Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Traore, Abdrahamane Mircetic, Marko Ellis, Ruth D. Martin, Laura B. Miller, Louis H. Crompton, Peter D. Pierce, Susan K. Doumbo, Ogobara K. TI THE MEMORY B CELL RESPONSE TO AMA1-C1/ALHYDROGEL (R) VACCINATION IN SEMI-IMMUNE ADULTS IN MALI, WITH OR WITHOUT THE CPG 7909 OLIGODEOXYNUCLEOTIDE ADJUVANT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Traore, Boubacar; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Traore, Abdrahamane; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. [Mircetic, Marko; Crompton, Peter D.; Pierce, Susan K.] NIAID, NIH, Immunogenet Lab, Bethesda, MD 20892 USA. [Ellis, Ruth D.; Martin, Laura B.; Miller, Louis H.] NIAID, NIH, Malaria Vaccine Dev Branch, Bethesda, MD 20892 USA. RI Martin, Laura/N-1789-2013; Crompton, Peter/N-1130-2016 OI Martin, Laura/0000-0002-4431-4381; NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 622 BP 184 EP 184 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644600621 ER PT J AU Ellis, RD Martin, LB Pierce, M Miura, K Mullen, GE Fay, MP Long, CA Shaffer, D Saul, A Miller, LH Durbin, AP AF Ellis, Ruth D. Martin, Laura B. Pierce, Mark Miura, Kazutoyo Mullen, Gregory E. Fay, Michael P. Long, Carole A. Shaffer, Donna Saul, Allan Miller, Louis H. Durbin, Anna P. TI A PHASE 1 STUDY OF THE BLOOD STAGE MALARIA VACCINE CANDIDATE AMA1-C1/ALHYDROGEL WITH CPG 7909, USING TWO DIFFERENT FORMULATIONS AND DOSING INTERVALS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ellis, Ruth D.; Martin, Laura B.; Pierce, Mark; Miura, Kazutoyo; Fay, Michael P.; Long, Carole A.; Saul, Allan; Miller, Louis H.] NIH, Rockville, MD USA. [Shaffer, Donna; Durbin, Anna P.] Johns Hopkins Ctr Immunizat Res, Washington, DC USA. RI Martin, Laura/N-1789-2013; OI Martin, Laura/0000-0002-4431-4381; Saul, Allan/0000-0003-0665-4091 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 642 BP 190 EP 190 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601007 ER PT J AU Rausch, KM Ramineni, B Lambert, L Miura, K Barnafo, EK Long, CA Miller, LH Martin, LB AF Rausch, Kelly M. Ramineni, Bhanumati Lambert, Lynn Miura, Kazutoyo Barnafo, Emma K. Long, Carole A. Miller, Louis H. Martin, Laura B. TI COMPARATIVE ANALYSIS OF MALARIA VACCINE CANDIDATE AMA1-C1/ALHYDROGEL WITH THE ADDITION OF UNIQUE CPG SEQUENCES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Rausch, Kelly M.; Ramineni, Bhanumati; Lambert, Lynn; Miura, Kazutoyo; Barnafo, Emma K.; Long, Carole A.; Miller, Louis H.; Martin, Laura B.] NIH, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2008 VL 79 IS 6 MA 645 BP 191 EP 191 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601010 ER PT J AU Miura, K Zhou, H Diouf, A Moretz, SE Miller, LH Martin, LB Mullen, GE Long, CA AF Miura, Kazutoyo Zhou, Hong Diouf, Ababacar Moretz, Samuel E. Miller, Louis H. Martin, Laura B. Mullen, Gregory E. Long, Carole A. TI ANTI-APICAL MEMBRANE ANTIGEN 1 IGG IS MORE EFFECTIVE IN INHIBITING PLASMODIUM FALCIPARUM GROWTH AS MEASURED BY IN VITRO GROWTH INHIBITION ASSAY THAN ANTI-MEROZOITE SURFACE PROTEIN 1 42 IGG SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Miura, Kazutoyo; Miller, Louis H.; Martin, Laura B.; Mullen, Gregory E.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Zhou, Hong; Diouf, Ababacar; Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 652 BP 193 EP 193 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601017 ER PT J AU Rodrigues, J Abban, E Ortega, C Molina-Cruz, A Mury, CB AF Rodrigues, Janneth Abban, Ekua Ortega, Corrie Molina-Cruz, Alvaro Mury, Carolina Barillas TI ROLE OF A SERINE PROTEASE FROM ANOPHELES GAMBIAE IN PLASMODIUM DEVELOPMENT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Rodrigues, Janneth; Abban, Ekua; Ortega, Corrie; Molina-Cruz, Alvaro; Mury, Carolina Barillas] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 691 BP 203 EP 203 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601056 ER PT J AU Hume, J Lehmann, T AF Hume, Jen Lehmann, Tovi TI IDENTIFICATION OF THE BARRIERS PREVENTING SUCCESSFUL DEVELOPMENT OF PLASMODIUM FALCIPARUM IN CULEX MOSQUITOES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Hume, Jen; Lehmann, Tovi] NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 748 BP 221 EP 221 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601113 ER PT J AU Mzayek, F Deng, H Mave, V Hadi, A Lertora, JJ Krogstad, DJ AF Mzayek, Fawaz Deng, Haiyan Mave, Vidya Hadi, Azam Lertora, Juan J. Krogstad, Donald J. TI RANDOMIZED CROSSOVER TRIAL TO EXAMINE THE SAFETY AND PHARMACOKINETICS OF 2100 MG DOSE OF AQ-13 AND THE FOOD EFFECT ON ITS BIOAVAILABILITY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Mzayek, Fawaz; Deng, Haiyan; Mave, Vidya; Hadi, Azam; Krogstad, Donald J.] Tulane Univ, New Orleans, LA 70118 USA. [Lertora, Juan J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 761 BP 224 EP 224 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601126 ER PT J AU Levy, MZ Malaga, F del Carpio, JGC McKenzie, E Plotkin, JB AF Levy, Michael Z. Malaga, Fernando Cornejo del Carpio, Juan G. McKenzie, Ellis Plotkin, Joshua B. TI SPATIO-TEMPORAL ORDERING OF A CHAGAS DISEASE VECTOR ELIMINATION CAMPAIGN SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Levy, Michael Z.; McKenzie, Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Malaga, Fernando; Cornejo del Carpio, Juan G.] Reg Salud, Arequipa, Peru. [Plotkin, Joshua B.] Univ Penn, Philadelphia, PA 19104 USA. RI Plotkin, Joshua/E-6947-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 767 BP 226 EP 226 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601132 ER PT J AU Sa, JM Twu, O Hayton, K Ringwald, P Wellems, TE AF Sa, Juliana M. Twu, Olivia Hayton, Karen Ringwald, Pascal Wellems, Thomas E. TI ANALYSIS OF DRUG RESISTANCE USING PLASMODIUM FALCIPARUM GENETIC CROSSES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Sa, Juliana M.; Twu, Olivia; Hayton, Karen; Ringwald, Pascal; Wellems, Thomas E.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 774 BP 228 EP 228 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601139 ER PT J AU Bosio, CF Jarrett, CO Hinnebusch, BJ AF Bosio, Christopher F. Jarrett, Clayton O. Hinnebusch, B. Joseph TI EARLY INNATE IMMUNE EVENTS IN THE SKIN AFTER TRANSMISSION OF YERSINIA PESTIS BY FLEAS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Bosio, Christopher F.; Jarrett, Clayton O.; Hinnebusch, B. Joseph] NIH, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 782 BP 230 EP 231 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601147 ER PT J AU Dembele, B Konate, S Dolo, H Sanogo, D Coulibaly, SY Coulibaly, ME Soumaoro, L Metenou, S Doumbia, SS Diallo, A Coulibaly, YI Traore, SF Klion, A Nutman, TB Mahanty, S AF Dembele, Benoit Konate, Siaka Dolo, Housseini Sanogo, Dramane Coulibaly, Siaka Y. Coulibaly, Michel E. Soumaoro, Lamine Metenou, Simon Doumbia, Salif S. Diallo, Abdallah Coulibaly, Yaya I. Traore, Sekou F. Klion, Amy Nutman, Thomas B. Mahanty, Siddhartha TI WUCHERERIA BANCROFTI AND MANSONELLA PERSTANS INFECTIONS MAY PROTECT AGAINST PLASMODIUM FALCIPARUM INDUCED ANEMIA IN FILARIA/MALARIA CO-INFECTED POPULATIONS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Sanogo, Dramane; Coulibaly, Siaka Y.; Coulibaly, Michel E.; Soumaoro, Lamine; Doumbia, Salif S.; Diallo, Abdallah; Coulibaly, Yaya I.; Traore, Sekou F.] Univ Bamako, FMPOS, Filariasis Unit, Bamako, Mali. [Metenou, Simon; Klion, Amy; Nutman, Thomas B.; Mahanty, Siddhartha] NIAID, LPD, NIH, Bethesda, MD 20892 USA. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 SU S MA 789 BP 232 EP 233 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601154 ER PT J AU Dembele, B Dolo, H Konate, S Coulibaly, SY Sanogo, D Metenou, S Mahanty, S Coulibaly, ME Soumaoro, L Doumbia, SS Wagner, M Guindo, B Diallo, AA Guindo, A Diakite, S Guindo, MA Saye, R Kante, O Diallo, DA Traore, SF Nutman, TB Coulibaly, YI Klion, AD AF Dembele, Benoit Dolo, Housseini Konate, Siaka Coulibaly, Siaka Y. Sanogo, Dramane Metenou, Simon Mahanty, Siddhartha Coulibaly, Michel E. Soumaoro, Lamine Doumbia, Salif S. Wagner, Marissa Guindo, Boubacar Diallo, Abdallah A. Guindo, Aldiouma Diakite, Seidina Guindo, Merepin A. Saye, Renion Kante, Ousmane Diallo, Dapa A. Traore, Sekou F. Nutman, Thomas B. Coulibaly, Yaya I. Klion, Amy D. TI INFLUENCE OF PRE-EXISTING FILARIAL INFECTION ON THE INCIDENCE AND SEVERITY OF CLINICAL MALARIA IN CHILDREN AND YOUNG ADULTS IN A COENDEMIC REGION OF MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Dembele, Benoit; Dolo, Housseini; Konate, Siaka; Coulibaly, Siaka Y.; Sanogo, Dramane; Coulibaly, Michel E.; Soumaoro, Lamine; Doumbia, Salif S.; Guindo, Boubacar; Diallo, Abdallah A.; Guindo, Aldiouma; Diakite, Seidina; Guindo, Merepin A.; Saye, Renion; Kante, Ousmane; Diallo, Dapa A.; Traore, Sekou F.; Coulibaly, Yaya I.] Univ Bamako, Fac Med Pharm & Dent, Bamako, Mali. [Wagner, Marissa] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Metenou, Simon; Mahanty, Siddhartha; Nutman, Thomas B.; Klion, Amy D.] NIH, Bethesda, MD 20892 USA. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 SU S MA 787 BP 232 EP 232 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601152 ER PT J AU Nelson, S Mehlhop, E Jost, CA Johnson, S Fremont, DH Diamond, MS Pierson, TC AF Nelson, Steevenson Mehlhop, Erin Jost, Christiane A. Johnson, Syd Fremont, Daved H. Diamond, Michael S. Pierson, Theodore C. TI THE STOICHIOMETRY OF ANTIBODY-MEDIATED NEUTRALIZATION OF WEST NILE VIRUS INFECTION: FACTORS THAT GOVERN ANTIBODY POTENCY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Nelson, Steevenson; Jost, Christiane A.; Pierson, Theodore C.] NIH, Bethesda, MD 20892 USA. [Mehlhop, Erin; Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, St Louis, MO USA. [Johnson, Syd] Macrogenics Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 804 BP 237 EP 238 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601169 ER PT J AU Nagarkatti, R Jani, D Beatty, W Angel, R Slebodnick, C Andersen, J Kumar, S Rathore, D AF Nagarkatti, Rana Jani, Dewal Beatty, Wandy Angel, Ross Slebodnick, Carla Andersen, John Kumar, Sanjai Rathore, Dharmendar TI HDP- A NOVEL HEME DETOXIFICATION PROTEIN IN THE MALARIA PARASITE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Nagarkatti, Rana; Jani, Dewal; Rathore, Dharmendar] Virginia Bioinformat Inst, Blacksburg, VA USA. [Beatty, Wandy] Washington Univ, Sch Med, St Louis, MO USA. [Beatty, Wandy] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [Andersen, John] NIH, Lab Malaria & Vector Res, Rockville, MD USA. [Kumar, Sanjai] US FDA, Bethesda, MD 20014 USA. RI Angel, Ross/K-9924-2015 OI Angel, Ross/0000-0003-0861-398X NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 811 BP 239 EP 240 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601176 ER PT J AU O'Meara, WP Mwangi, T Williams, T McKenzie, FE Snow, R Marsh, K AF O'Meara, Wendy P. Mwangi, Tabitha Williams, Thomas McKenzie, F. Ellis Snow, Robert Marsh, Kevin TI THE RELATIONSHIP BETWEEN MALARIA TRANSMISSION INTENSITY, CLINICAL DISEASE AND MORTALITY IN AN AREA OF DECLINING TRANSMISSION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [O'Meara, Wendy P.; McKenzie, F. Ellis] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Mwangi, Tabitha; Williams, Thomas; Marsh, Kevin] Kenya Govt Med Res Ctr, CGMRC Wellcome Trust Collaborat Program, Kilifi, Kenya. [Snow, Robert] KEMRI Wellcome Trust Collaborat Program, Nairobi, Kenya. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 817 BP 241 EP 241 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601182 ER PT J AU Narum, DL Haynes, JD Moch, JK Dutta, S AF Narum, David L. Haynes, J. David Moch, J. Kathleen Dutta, Sheetij TI ISOLATION OF INVASIVE LONG LIVED PLASMODIUM FALCIPARUM MEROZOITES BY CELL SIEVING SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Narum, David L.] Natl Inst Hlth, Rockville, MD USA. [Haynes, J. David; Moch, J. Kathleen; Dutta, Sheetij] Walter Reed Army Inst Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 839 BP 247 EP 248 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601204 ER PT J AU Srinivasan, P Coppens, I Jacobs-Lorena, M AF Srinivasan, Prakash Coppens, Isabelle Jacobs-Lorena, Marcelo TI DISTINCT ROLES OF PLASMODIUM RHOMBOID 1 IN PARASITE DEVELOPMENT AND MALARIA PATHOGENESIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Srinivasan, Prakash] NIAID, Natl Inst Hlth, Rockville, MD USA. [Coppens, Isabelle; Jacobs-Lorena, Marcelo] Johns Hopkins Sch Publ Hlth, Malaria Res Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2008 VL 79 IS 6 MA 838 BP 247 EP 247 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601203 ER PT J AU Jochim, RC Valenzuela, JG AF Jochim, Ryan C. Valenzuela, Jesus G. TI SEARCHING FOR MOLECULAR DETERMINANTS OF SPECIES SPECIFICITY IN SAND FLIES COLONIZED BY LEISHMANIA PARASITES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Jochim, Ryan C.; Valenzuela, Jesus G.] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 848 BP 250 EP 250 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601213 ER PT J AU Oliveira, F Gomes, R Teixeira, C Faye, O Traore, P Diarra, SS Anderson, JM Dia-Eldin, EA Samake, S Traore, B Coulibaly, CA Rick, F Keita, S Doumbia, S Kamhawi, S Valenzuela, JG AF Oliveira, Fabiano Gomes, Regis Teixeira, Clarissa Faye, Ousmane Traore, Pierre Diarra, Souleymane S. Anderson, Jeniffer M. Dia-Eldin, Elnaiem A. Samake, Sibiry Traore, Bourama Coulibaly, Cheick A. Rick, Fairhurst Keita, Somita Doumbia, Seydou Kamhawi, Shaden Valenzuela, Jesus G. TI HUMANS FROM AN ENDEMIC AREA OF CUTANEOUS LEISHMANIASIS IN MALI PRODUCE IFN-gamma TO SAND FLY SALIVARY PROTEINS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Oliveira, Fabiano; Gomes, Regis; Teixeira, Clarissa; Faye, Ousmane; Traore, Pierre; Diarra, Souleymane S.; Anderson, Jeniffer M.; Dia-Eldin, Elnaiem A.; Samake, Sibiry; Traore, Bourama; Coulibaly, Cheick A.; Rick, Fairhurst; Keita, Somita; Doumbia, Seydou; Kamhawi, Shaden; Valenzuela, Jesus G.] NIH, Rockville, MD USA. RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2008 VL 79 IS 6 SU S MA 866 BP 255 EP 255 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601231 ER PT J AU Gomes, RB Oliveira, F Teixeira, C Elnaiem, DE Kamhawi, S Valenzuela, JG AF Gomes, Regis B. Oliveira, Fabiano Teixeira, Clarissa Elnaiem, Dia-Eldin Kamhawi, Shaden Valenzuela, Jesus G. TI LUTZOMYIA LONGIPALPIS RECOMBINANT SALIVARY YELLOW-RELATED PROTEIN (LJM11) CONFERS PROTECTION AGAINST LEISHMANIA INFECTED SAND FLIES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Gomes, Regis B.; Oliveira, Fabiano; Teixeira, Clarissa; Elnaiem, Dia-Eldin; Kamhawi, Shaden; Valenzuela, Jesus G.] NIH, Rockville, MD USA. RI Oliveira, Fabiano/B-4251-2009 OI Oliveira, Fabiano/0000-0002-7924-8038 NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2008 VL 79 IS 6 MA 918 BP 270 EP 270 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601283 ER PT J AU Teixeira, CR Oliveira, LF Gomes, RB Elnaiem, D Kamhawi, S Valenzuela, JG AF Teixeira, Clarissa R. Oliveira, Luis F. Gomes, Regis B. Elnaiem, Dia Kamhawi, Shaden Valenzuela, Jesus G. TI CHARACTERIZATION OF THE EARLY INFLAMMATORY RESPONSE TO BITES OF LEISHMANIA MAJOR INFECTED PHLEBOTOMUS DUBOSCQI SAND FLIES IN NAIVE AND PRE-EXPOSED MICE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Teixeira, Clarissa R.; Oliveira, Luis F.; Gomes, Regis B.; Elnaiem, Dia; Kamhawi, Shaden; Valenzuela, Jesus G.] NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 921 BP 271 EP 271 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601286 ER PT J AU Ostera, GR Ribeiro, J Hume, J Tokumasu, F AF Ostera, Graciela R. Ribeiro, Jose Hume, Jennifer Tokumasu, Fuyuki TI TYROSINE NITRATION OF PROTEINS BY A PUTATIVE NITRATE REDUCTASE IN SEXUAL AND ASEXUAL PLASMODIUM FALCIPARUM PARASITES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ostera, Graciela R.; Ribeiro, Jose; Hume, Jennifer; Tokumasu, Fuyuki] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 DEC PY 2008 VL 79 IS 6 MA 941 BP 276 EP 277 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601306 ER PT J AU Tozan, Y Breman, JG AF Tozan, Yesim Breman, Joel G. TI THE COST-EFFECTIVENESS OF RECTAL ARTESUNATE FOR TREATING SEVERE CHILDHOOD MALARIA AT THE COMMUNITY LEVEL SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Tozan, Yesim] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 945 BP 277 EP 278 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601310 ER PT J AU Sissoko, MS Assadou, MH Kone, M Diallo, A Guindo, A Sagara, I Guindo, MA Saye, R Ellis, RD Dicko, A Diallo, D Doumbo, O Miller, LH Pierce, MA AF Sissoko, Mahamadou S. Assadou, Mahamadoun H. Kone, Mamady Diallo, A. Guindo, Aldiouma Sagara, Issaka Guindo, Merapen A. Saye, Renion Ellis, Ruth D. Dicko, Alassane Diallo, Dapa Doumbo, Ogobara Miller, Louis H. Pierce, Mark A. TI MALARIA INCIDENCE IN INFANTS IN BANCOUMANA, MALI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ellis, Ruth D.; Miller, Louis H.; Pierce, Mark A.] NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD USA. [Sissoko, Mahamadou S.; Assadou, Mahamadoun H.; Kone, Mamady; Diallo, A.; Guindo, Aldiouma; Sagara, Issaka; Guindo, Merapen A.; Saye, Renion; Dicko, Alassane; Diallo, Dapa; Doumbo, Ogobara] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1005 BP 295 EP 295 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601369 ER PT J AU Sedegah, M McGrath, S Regis, D Chuang, I Ganeshan, H Abot, S Banania, G Manohar, N Doolan, D Limbach, K House, B Aguiarl, J Long, C Bruder, J King, C Patterson, N Tamminga, C Epstein, J Mendoza-Silveiras, J Williams, F Soisson, L Diggs, C Ockenhouse, C Richie, T AF Sedegah, Martha McGrath, Shannon Regis, David Chuang, Ilin Ganeshan, Harini Abot, Stephen Banania, Glena Manohar, Nalini Doolan, Denise Limbach, Keith House, Brent Aguiarl, Joao Long, Carole Bruder, Joseph King, Christopher Patterson, Noelle Tamminga, Cindy Epstein, Judith Mendoza-Silveiras, Jose Williams, Frank Soisson, Lorraine Diggs, Carter Ockenhouse, Christopher Richie, Thomas TI IMMUNOGENICITY OF TWO DOSES OF A MULTI-STAGE, MULTI-ANTIGEN ADENOVIRUS-VECTORED PLASMODIUM FALCIPARUM MALARIA VACCINE IN A PHASE 1 TRIAL SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Sedegah, Martha; Regis, David; Chuang, Ilin; Ganeshan, Harini; Abot, Stephen; Banania, Glena; Manohar, Nalini; Doolan, Denise; Limbach, Keith; House, Brent; Aguiarl, Joao; Patterson, Noelle; Tamminga, Cindy; Epstein, Judith; Richie, Thomas] USN, Med Res Ctr, Silver Spring, MD USA. [McGrath, Shannon; Ockenhouse, Christopher] Walter Reed Army Inst Res, Silver Spring, MD USA. [Long, Carole] NIH, Bethesda, MD 20892 USA. [Bruder, Joseph; King, Christopher] GenVec, Gaithersburg, MD USA. [Williams, Frank] Natl Naval Med Ctr, Bethesda, MD USA. [Soisson, Lorraine; Diggs, Carter] US Agcy Int Dev, Washington, DC 20523 USA. RI Doolan, Denise/F-1969-2015 NR 0 TC 0 Z9 0 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 DEC PY 2008 VL 79 IS 6 MA 1034 BP 304 EP 304 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601398 ER PT J AU Pierce, MA Ellis, RD Malkin, E Miura, K Marjason, J Mullen, GE Long, CA Miller, LH Martin, LB AF Pierce, Mark Arden Ellis, Ruth D. Malkin, Elissa Miura, Kazutoyo Marjason, Joanne Mullen, Gregory E. Long, Carole A. Miller, Louis H. Martin, Laura B. TI PHASE 1 SAFETY AND IMMUNOGENICITY TRIAL OF A BLOOD-STAGE MALARIA VACCINE AMA1-C1/ISA 720 IN AUSTRALIAN ADULTS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Pierce, Mark Arden; Ellis, Ruth D.; Miura, Kazutoyo; Miller, Louis H.; Martin, Laura B.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. [Malkin, Elissa] Malaria Vaccine Initiat, Bethesda, MD USA. [Marjason, Joanne] Q Pharm Pty Ltd, Brisbane, Qld, Australia. [Mullen, Gregory E.] Kings Coll London, London WC2R 2LS, England. [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RI Martin, Laura/N-1789-2013 OI Martin, Laura/0000-0002-4431-4381 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1039 BP 305 EP 306 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601403 ER PT J AU Uchime, O Reiter, K Nguyen, V Glen, J Miller, L Narum, DL Plassmeyer, ML AF Uchime, Onyinyechukwu Reiter, Karine Nguyen, Vu Glen, Jacqueline Miller, Louis Narum, David L. Plassmeyer, Matthew L. TI PRODUCTION, CHARACTERIZATION AND IMMUNOLOGICAL EVALUATION OF AN ESCHERICHIA COLI EXPRESSED PLASMODIUM FALCIPARUM THROMBOSPONDIN RELATED APICAL MEROZOITE PROTEIN (PTRAMP), A PUTATIVE MALARIA VACCINE CANDIDATE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Uchime, Onyinyechukwu; Reiter, Karine; Nguyen, Vu; Glen, Jacqueline; Miller, Louis; Narum, David L.; Plassmeyer, Matthew L.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1038 BP 305 EP 305 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601402 ER PT J AU Tachibana, M Iriko, H Muratova, O Song, G Wu, Y Sattabongkot, J Takeo, S Otsuki, H Torii, M Tsuboi, T AF Tachibana, Mayumi Iriko, Hideyuki Muratova, Olga Song, Guanhong Wu, Yimin Sattabongkot, Jetsumon Takeo, Satoru Otsuki, Hitoshi Torii, Motomi Tsuboi, Takafumi TI IMMUNIZATION WITH RECOMBINANT PROTEINS OF A GAMETOCYTE PROTEIN PFS230 EXPRESSED USING WHEAT GERM CELL-FREE SYSTEM SUCCESSFULLY INDUCE TRANSMISSION-BLOCKING ANTIBODIES AGAINST PLASMODIUM FALCIPARUM SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Tachibana, Mayumi; Otsuki, Hitoshi; Torii, Motomi] Ehime Univ, Grad Sch Med, Dept Mol Parasitol, Toon, Ehime, Japan. [Iriko, Hideyuki] Tottori Univ, Fac Med, Dept Microbiol & Immunol, Tottori 680, Japan. [Muratova, Olga; Song, Guanhong; Wu, Yimin] NIAID, Malaria Vaccine Dev Branch, Rockville, MD USA. [Sattabongkot, Jetsumon] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. [Takeo, Satoru; Tsuboi, Takafumi] Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1043 BP 307 EP 307 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601407 ER PT J AU Zhu, DM Huang, SH Gebregeorgis, E McClellan, H Miller, L Saul, A AF Zhu, Daming Huang, Shuhui Gebregeorgis, Elizabeth McClellan, Holly Miller, Louis Saul, Allan TI DIRECT ALUM FORMULATION IMMUNOASSAY (DAFIA): AN IMMUNOFLUORESCENT ASSAY THAT DIRECTLY DETERMINES THE CONTENT, IDENTITY AND INTEGRITY OF ANTIGENS FORMULATED ON ALHYDROGEL SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Zhu, Daming; Huang, Shuhui; Gebregeorgis, Elizabeth; McClellan, Holly; Miller, Louis; Saul, Allan] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1047 BP 308 EP 308 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601411 ER PT J AU Dixit, R Kumar, S Gupta, L Molina-Cruz, A Rodrigues, J Valenzuela, J Ribeiro, JM Barillas-Mury, C AF Dixit, Rajnikant Kumar, Sanjeev Gupta, Lalita Molina-Cruz, Alvaro Rodrigues, Janneth Valenzuela, Jesus Ribeiro, Jose M. Barillas-Mury, Carolina TI IDENTIFICATION AND MOLECULAR CATALOGING OF HEMOCYTE SPECIFIC IMMUNE GENES FROM MALARIA VECTOR ANOPHELES GAMBIAE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Dixit, Rajnikant; Kumar, Sanjeev; Gupta, Lalita; Molina-Cruz, Alvaro; Rodrigues, Janneth; Valenzuela, Jesus; Ribeiro, Jose M.; Barillas-Mury, Carolina] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1070 BP 314 EP 314 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601434 ER PT J AU Ramanathan, R Abraham, D Myers, TG Nutman, TB AF Ramanathan, Roshan Abraham, David Myers, Timothy G. Nutman, Thomas B. TI DIFFERENTIAL GENE EXPRESSION BETWEEN INFECTIVE AND NON-INFECTIVE STAGE STRONGYLOIDES STERCORALIS LARVAE REVEALED BY MICROARRAY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Ramanathan, Roshan; Myers, Timothy G.; Nutman, Thomas B.] NIH, Bethesda, MD 20892 USA. [Abraham, David] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1153 BP 338 EP 338 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601516 ER PT J AU Molina-Cruz, A Ortega, C DeJong, R Rodrigues, J Jaramillo-Gutierrez, G Abban, E Barillas-Mury, C AF Molina-Cruz, Alvaro Ortega, Corrie DeJong, Randall Rodrigues, Janneth Jaramillo-Gutierrez, Giovanna Abban, Ekua Barillas-Mury, Carolina TI A TEP1 MEDIATED RESPONSE IS REQUIRED BUT NOT SUFFICIENT FOR MELANIZATION OF PLASMODIUM FALCIPARUM IN THE ANOPHELES GAMBIAE MIDGUT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Molina-Cruz, Alvaro] NIH, Bethesda, MD 20892 USA. [Ortega, Corrie; DeJong, Randall; Rodrigues, Janneth; Jaramillo-Gutierrez, Giovanna; Abban, Ekua; Barillas-Mury, Carolina] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 1170 BP 344 EP 344 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601533 ER PT J AU Thangamani, S Boppana, VD Alarcon-Chaidez, F Sun, JX Ribeiro, JC Wikel, SK AF Thangamani, Saravanan Boppana, Venkata D. Alarcon-Chaidez, Francisco Sun, Jianxin Ribeiro, Jose M. C. Wikel, Stephen K. TI FUNCTIONAL CHARACTERIZATION OF A PLATELET AGGREGATION INHIBITOR FROM THE SALIVARY GLANDS OF AEDES AEGYPTI SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Thangamani, Saravanan; Boppana, Venkata D.; Alarcon-Chaidez, Francisco; Sun, Jianxin; Wikel, Stephen K.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RI Thangamani, Saravanan/E-7371-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1172 BP 344 EP 344 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601535 ER PT J AU Janka, J Koita, OA Josepha, M Traore, B Mzayek, F Sangare, L Cisse, O Mendelsohn, L Wang, XD Masur, H Gladwin, M Krogstad, DJ AF Janka, Jacqueline Koita, Ousmane A. Josepha, Maya Traore, Broulaye Mzayek, Fawaz Sangare, Lansana Cisse, Ousmane Mendelsohn, Laurel Wang, Xunde Masur, Henry Gladwin, Mark Krogstad, Donald J. TI NITRIC OXIDE DEPLETION AND ENDOTHELIAL DYSFUNCTION IN CHILDREN WITH MALARIA AND MARKED ANEMIA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Janka, Jacqueline; Mendelsohn, Laurel; Wang, Xunde; Masur, Henry; Gladwin, Mark] NIH, Bethesda, MD 20892 USA. [Koita, Ousmane A.; Josepha, Maya; Sangare, Lansana; Cisse, Ousmane] Univ Bamako, Bamako, Mali. [Traore, Broulaye] Hop Gabriel Toure, Bamako, Mali. [Krogstad, Donald J.] Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 SU S MA 1182 BP 347 EP 347 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601545 ER PT J AU Metenou, S Dembele, B Konate, S Dolo, H Soumaoro, L Diallo, AA Coulibaly, ME Coulibaly, SY Sanogo, D Coulibaly, YI Traore, SF Klion, A Nutman, TB Mahanty, S AF Metenou, Simon Dembele, Benoit Konate, Siaka Dolo, Housseini Soumaoro, Lamine Diallo, Abdallah A. Coulibaly, Michel E. Coulibaly, Siaka Y. Sanogo, Dramane Coulibaly, Yaya I. Traore, Sekou F. Klion, Amy Nutman, Thomas B. Mahanty, Siddhartha TI PATENT FILARIAL INFECTION MODULATES MALARIA-SPECIFIC TYPE 1 CYTOKINE RESPONSES IN AN IL-10 DEPENDENT MANNER IN A FILARIA/MALARIA CO-INFECTED POPULATION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Metenou, Simon; Klion, Amy; Nutman, Thomas B.; Mahanty, Siddhartha] NIH, Bethesda, MD 20892 USA. [Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Soumaoro, Lamine; Diallo, Abdallah A.; Coulibaly, Michel E.; Coulibaly, Siaka Y.; Sanogo, Dramane; Coulibaly, Yaya I.; Traore, Sekou F.] Univ Bamako, Filaria Unit, FMPOS, Bamako, Mali. RI Metenou, Simon/C-1101-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1232 BP 362 EP 362 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601595 ER PT J AU Peters, NC Egen, JG Secundino, N Debrabant, A Kimblin, N Kamhawi, S Lawyer, P Germain, RN Sacks, D AF Peters, Nathan C. Egen, Jackson G. Secundino, Naglia Debrabant, Alain Kimblin, Nicola Kamhawi, Shaden Lawyer, Phillip Germain, Ronald N. Sacks, David TI NEUTROPHILS ARE THE PREDOMINANT INITIAL HOST CELL FOR LEISHMANIA MAJOR AND ARE ESSENTIAL FOR THE ESTABLISHMENT OF SAND FLY TRANSMITTED INFECTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Peters, Nathan C.; Secundino, Naglia; Kimblin, Nicola; Kamhawi, Shaden; Lawyer, Phillip; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Egen, Jackson G.; Germain, Ronald N.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 MA 1241 BP 365 EP 365 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601604 ER PT J AU Ellis, RD Dicko, A Sagara, I Kamate, B Guindo, O Niambele, MB Sogoba, M Doumbo, O AF Ellis, Ruth D. Dicko, Alassane Sagara, Issaka Kamate, Beh Guindo, Ousmane Niambele, Mohamed Balla Sogoba, Moussa Doumbo, Ogobara TI Elevated Levels of Alanine Aminotransferase and Hepatitis A in the Context of a Pediatric Malaria Vaccine Trial in a Village in Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHILDREN AB A Phase 1 study of the apical membrane antigen malaria vaccine AMA1-C1/Alhydrogel was conducted in 2-3-year-old children in a village in Mali. A high frequency of elevated levels of alanine aminotransferase (ALT) caused by hepatitis A was seen, with 8 of 36 children diagnosed by specific IgM antibody over the course of the study. Hepatitis A is a common cause of asymptomatic elevations of ALT levels in children, particularly in less-developed settings. Investigators should be aware of the frequency of hepatitis A in this age group to guard against inadvertently facilitating transmission at study facilities and to properly evaluate symptomatic or asymptomatic elevations of ALT levels. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. Univ Bamako, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Bamako, Mali. Univ Bamako, Dept Publ Hlth, Fac Med Pharm & Dent, Bamako, Mali. RP Ellis, RD (reprint author), 5640 Fishers Lane,TB1,Room 1119, Rockville, MD 20852 USA. EM ellisru@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 7 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2008 VL 79 IS 6 BP 980 EP 982 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZR UT WOS:000261644400032 PM 19052315 ER PT J AU Adler, V Bowne, W Michl, J Sookraj, KA Ikram, K Pestka, S Izotova, L Zenilman, M Friedman, FK Qu, YX Pincus, MR AF Adler, Victor Bowne, Wilbur Michl, Josef Sookraj, Kelley A. Ikram, Kamran Pestka, Sidney Izotova, Lara Zenilman, Michael Friedman, Fred K. Qu, Yongxia Pincus, Matthew R. TI Site-specific phosphorylation of raf in cells containing oncogenic ras-p21 is likely mediated by jun-N-terminal kinase SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE oncogenic ras-p21; raf; phosphorylation; raf-Ser259; raf-Ser338; JNK ID OOCYTE MATURATION; XENOPUS-OOCYTES; PROTEIN; ACTIVATION; INDUCTION; COMPLEXES; PEPTIDES; P21(RAS); PATHWAY; INSULIN AB In a study of interactions between the raf-MEK-MAPK (ERK) and JNK-jun pathways, we found previously that JNK can induce phosphorylation of raf but not vice versa. In this study, we investigate the nature of the JNK-induced phosphorylation of raf. In in vitro experiments in which immuno-bead-bound raf is phosphorylated by activated JNK, we find strong phosphorylation signals at raf-Ser259 and Ser338. The Ser259 phosphorylation is surprising since it is associated with inhibition of migration of raf to the cell membrane where it can interact with ras-p21. We also find that in oocytes induced to mature with oncogenic ras-p21, which induces high levels of phosphorylated JNK and MAPK, the same pattern of phosphorylation of raf occurs. In contrast, in oocytes induced to mature with insulin, which requires activation of wild-type ras-p21, phosphorylation of raf-Ser338 but not raf-Ser259 occurs. In oncogenic ras-transformed human pancreatic cancer MIA-PaCa-2 cells, phosphorylation of both raf serines occurs. Treatment of these cells with the ras peptide, PNC-2 attached to a penetratin sequence that blocks JNK and MAPK phosphorylation and induces tumor cell necrosis, results in a marked decrease in phosphorylation of raf-Ser259, but not that of raf-Ser338. These results suggest that oncogenic ras-p21 induces phosphorylation of both raf-Ser259 and Ser338 and that raf-Ser 259 phosphorylation may be effected by activated JNK. C1 [Adler, Victor; Qu, Yongxia; Pincus, Matthew R.] New York Harbor VA Med Ctr, Dept Pathol, Brooklyn, NY 11209 USA. [Adler, Victor; Qu, Yongxia; Pincus, Matthew R.] New York Harbor VA Med Ctr, Lab Med, Brooklyn, NY 11209 USA. [Adler, Victor; Michl, Josef; Qu, Yongxia; Pincus, Matthew R.] Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. [Bowne, Wilbur; Sookraj, Kelley A.; Ikram, Kamran; Zenilman, Michael] Suny Downstate Med Ctr, Dept Surg, Brooklyn, NY 11203 USA. [Bowne, Wilbur; Sookraj, Kelley A.; Ikram, Kamran] New York Harbor VA Med Ctr, Dept Surg, Brooklyn, NY 11209 USA. [Michl, Josef] Suny Downstate Med Ctr, Dept Microbiol Anat, Brooklyn, NY 11203 USA. [Michl, Josef] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA. [Pestka, Sidney; Izotova, Lara] Robert Wood Johnson Med Sch, Dept Mol Genet Microbiol & Immunol, Piscataway, NJ USA. [Friedman, Fred K.] NIH, Bethesda, MD 20892 USA. RP Pincus, MR (reprint author), New York Harbor VA Med Ctr, Dept Pathol, 800 Poly Pl, Brooklyn, NY 11209 USA. EM matthew.pincus2@med.va.gov RI Friedman, Fred/D-4208-2016 NR 24 TC 4 Z9 4 U1 0 U2 1 PU ASSOC CLINICAL SCIENTISTS PI MIDDLEBURY PA PO BOX 1287, MIDDLEBURY, VT 05753 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD WIN PY 2008 VL 38 IS 1 BP 47 EP 56 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 267ER UT WOS:000253492800009 PM 18316782 ER PT J AU Catov, JM Newman, AB Sutton-Tyrrell, K Harris, TB Tylavsky, F Visser, M Ayonayon, HN Ness, RB AF Catov, Janet M. Newman, Anne B. Sutton-Tyrrell, Kim Harris, Tamara B. Tylavsky, Francis Visser, Marjolein Ayonayon, Hilsa N. Ness, Roberta B. CA Hlth Abc Study TI Parity and Cardiovascular Disease Risk among Older Women: How Do Pregnancy Complications Mediate the Association? SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Parity; Cardiovascular Disease; Pregnancy Complications ID CORONARY-HEART-DISEASE; NATIONAL BIRTH COHORT; BODY-COMPOSITION; RETROSPECTIVE COHORT; PRETERM DELIVERY; REMOTE PROGNOSIS; MATERNAL RECALL; HEALTH; WEIGHT; PREECLAMPSIA AB PURPOSE: To determine whether parity is associated with increased risk of cardiovascular disease (CVD) after accounting for perinatal complications. METHODS: CVD prevalence, number of births, and a history of preeclampsia, term low birth weight, pre-term or stillbirth were evaluated among 540 women (mean age, 80 years; 47% black) enrolled in the Pittsburgh, PA site of the Health, Aging and Body Composition Study. Biomarkers were measured and CVD status was determined by self-report and hospital records. RESULTS: Nulliparous women (n = 89) had lower CVD prevalence compared with parous women (18.0% vs. 30.2%). Parous women without perinatal complications of interest (n = 321) had higher statin use compared with nulliparas, a trend accompanied by lower high,density lipoprotein (HDL) and higher triglycerides among women with perinatal complications (n = 130). After adjustment, parous women with no complicated births had a 1.95-fold (95% confidence interval [CI], 1.03-3.7) higher CVD prevalence compared to nulliparas. Among women with one or more pregnancy complications, CVD prevalence was 2.67 times (Cl, 1.34-5.33) higher. Women with five or more births had the highest CVD prevalence (odds ratio [OR], 2.60; Cl, 1.17-5.76) that was attenuated to 2.27 (1.00-5.15) after adjustment for complications of interest. CONCLUSIONS: History of pregnancy complications and higher statin use accounted for some but not all of the excess CVD prevalence among older parous women. C1 [Catov, Janet M.; Ness, Roberta B.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Catov, Janet M.; Newman, Anne B.; Sutton-Tyrrell, Kim; Ness, Roberta B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD USA. [Tylavsky, Francis] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Dept Nutr & Hlth, Amsterdam, Netherlands. [Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Catov, JM (reprint author), Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, 300 Halket St, Pittsburgh, PA 15213 USA. EM catovjm@upmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIH [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Building Interdisciplinary Research Careers in Womens Health award [BIRCWH-K12HD043441-06] FX This study was supported by NIH contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and was also supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Aging. Dr. Catov is supported by the BIRCWH-K12HD043441-06 (Building Interdisciplinary Research Careers in Womens Health award). NR 35 TC 24 Z9 25 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD DEC PY 2008 VL 18 IS 12 BP 873 EP 879 DI 10.1016/j.annepidem.2008.09.009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 387GI UT WOS:000261939300001 PM 19041585 ER PT J AU Mai, PL Lagos, VI Palomares, MR Weitzel, JN AF Mai, Phuong L. Lagos, Veronica I. Palomares, Melanie R. Weitzel, Jeffrey N. TI Contralateral Risk-Reducing Mastectomy in Young Breast Cancer Patients with and without Genetic Cancer Risk Assessment SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID BILATERAL PROPHYLACTIC MASTECTOMY; BRCA2 MUTATION CARRIERS; FAMILY-HISTORY; WOMEN; EFFICACY; AGE; SUSCEPTIBILITY; STATEMENT; ONCOLOGY; OUTCOMES AB Background: Decisions regarding contralateral risk-reducing mastectomy (CRRM) among women diagnosed with unilateral breast cancer can potentially be influenced by age at diagnosis and other factors. In this study, we examined the use of CRRM before versus after genetic cancer risk assessment (GCRA) in women diagnosed with breast cancer before age 50. Methods: We conducted a retrospective analysis of women with invasive breast cancer diagnosed before age 50 who were seen for GCRA between October 1996 and March 2005. Associations between the presence of generally accepted indications for risk-reducing surgery among women who had CRRM and the timing of GCRA were examined. Results: The cohort included 378 women, of whom 57 had CRRM pre-GCRA and 45 had CRRM post-GCRA after a median follow-up of 26 months. Women who had CRRM pre-GCRA were more likely to not have a generally accepted indication for the procedure than those who did after GCRA (odds ratio [OR] 5.3, 95% confidence interval [95% CI] 1.6-17.8, P = .007). Women diagnosed with breast cancer before BRCA genetic testing became clinically available (1997) were more likely to have had CRRM pre-GCRA than those who were diagnosed more recently (OR 2.9, 95% CI 1.6-5.2, P = .0003). Conclusion: When personal and family history was carefully examined, a substantial proportion of women seen in our clinic did not have a clear indication for CRRM. Decreased use of empiric CRRM among women diagnosed after 1997 may indicate increased awareness and use of GCRA. Thus, judicious application of GCRA may help focus use of surgical risk reduction measures to the most risk-appropriate patients. C1 [Mai, Phuong L.; Lagos, Veronica I.; Palomares, Melanie R.; Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Dept Clin Canc Genet, Duarte, CA 91010 USA. [Mai, Phuong L.] Natl Canc Inst, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Mai, PL (reprint author), City Hope Natl Med Ctr, Dept Clin Canc Genet, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM maip@mail.nih.gov FU NIH [R25 CA85771]; General Clinical Research Center [M01 RR00043] FX This study was supported in part by NIH grant No. R25 CA85771 and by a General Clinical Research Center grant from NIH (M01 RR00043) awarded to the City of Hope National Medical Center, Duarte, CA. The authors would like to express their deepest appreciation to all of the participants in our hereditary cancer registry, without whom this study could not have been accomplished. We are also indebted to Bersabell Asaye and Sharon Sand for their research support. NR 43 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2008 VL 15 IS 12 BP 3415 EP 3421 DI 10.1245/s10434-008-0160-3 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 382PH UT WOS:000261617400014 PM 18836779 ER PT J AU Ettinger, R Kuchen, S Lipsky, PE AF Ettinger, R. Kuchen, S. Lipsky, P. E. TI Interleukin 21 as a target of intervention in autoimmune disease SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B-CELL DIFFERENTIATION; FOLLICULAR-HELPER-CELLS; SECRETING PLASMA-CELLS; T-CELLS; RHEUMATOID-ARTHRITIS; IL-21; CYTOKINE; ACTIVATION; RESPONSES AB Interleukin 21 (IL21) belongs to a family of cytokines that bind to a composite receptor consisting of a private receptor (IL21R) and the common cytokine receptor gamma chain (gamma(C)). The IL21R is widely distributed on lympho-haematopoietic cells and IL21 impacts a number of cell types, including CD8+ memory T cells, NK cells and subsets of CD4 memory T cells. One essential role of IL21 is the promotion of B-cell activation and differentiation or death during humoral immune responses. Increased IL21 production is characteristic of certain autoimmune diseases and is likely to contribute to autoantibody production as well as pathological features of autoimmune disease. The critical role of IL21 in promoting humoral immune responses makes it an important focus of potential therapeutic interventions in conditions characterised by overproduction of pathogenic autoantibodies. C1 [Ettinger, R.; Kuchen, S.; Lipsky, P. E.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD USA. RP Ettinger, R (reprint author), 1 Medimmune Way, Gaithersburg, MD 20878 USA. EM ettingerc@medimmune.com OI Kuchen, Stefan/0000-0003-4899-8132 NR 52 TC 47 Z9 51 U1 0 U2 1 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 DEC PY 2008 VL 67 SU 3 BP 83 EP 86 DI 10.1136/ard.2008.098400 PG 4 WC Rheumatology SC Rheumatology GA 375YH UT WOS:000261149200015 ER PT J AU Greene, WC Debyser, Z Ikeda, Y Freed, EO Stephens, E Yonemoto, W Buckheit, RW Este, JA Cihlar, T AF Greene, Warner C. Debyser, Zeger Ikeda, Yasuhiro Freed, Eric O. Stephens, Edward Yonemoto, Wes Buckheit, Robert W. Este, Jose A. Cihlar, Tomas TI Novel targets for HIV therapy SO ANTIVIRAL RESEARCH LA English DT Review DE Human immunodeficiency virus; APOBEC3G; LEDGF/p75; Vpu; Vif; TRIM 5 alpha; Virus assembly; Maturation ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VPU PROTEIN; PIG-TAILED MACAQUES; TREATMENT-EXPERIENCED PATIENTS; TRANSCRIPTIONAL COACTIVATOR P75; AMINO-ACID SUBSTITUTION; TRANS-MEMBRANE DOMAIN; E3 UBIQUITIN LIGASE; TRANSMEMBRANE DOMAIN; VIF PROTEIN AB There are currently 25 drugs belonging to 6 different inhibitor classes approved for the treatment of human immunodeficiency virus (HIV) infection. However, new anti-HIV agents are still needed to confront the emergence of drug resistance and various adverse effects associated with long-term use of antiretroviral therapy. The 21st International Conference on Antiviral Research, held in April 2008 in Montreal, Canada, therefore featured a special session focused on novel targets for HIV therapy. The session included presentations by world-renowned experts in HIV virology and covered a diverse array of potential targets for the development of new classes of HIV therapies. This review contains concise summaries of discussed topics that included Vif-APOBEC3G, LEDGF/p75, TRIM 5 alpha, virus assembly and maturation, and Vpu. The described viral and host factors represent some of the most noted examples of recent scientific breakthroughs that are opening unexplored avenues to novel anti-HIV target discovery and validation, and should feed the antiretroviral drug development pipeline in the near future. (C) 2008 Elsevier B.V. All rights reserved. C1 [Este, Jose A.] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IrsiCaixa, Badalona 08916, Spain. [Greene, Warner C.; Yonemoto, Wes] Gladstone Inst Virol & Immunol, San Francisco, CA USA. [Debyser, Zeger] KULAK, IRC, Louvain, Flanders, Belgium. [Debyser, Zeger] KULeuven, Louvain, Flanders, Belgium. [Ikeda, Yasuhiro] Mayo Coll Med, Rochester, MN USA. [Freed, Eric O.] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Stephens, Edward] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Buckheit, Robert W.] ImQuest BioSci Inc, Frederick, MD USA. [Cihlar, Tomas] Gilead Sci Inc, Foster City, CA 94404 USA. RP Este, JA (reprint author), Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, IrsiCaixa, Canyet S-N, Badalona 08916, Spain. EM jaeste@irsicaixa.es; tomas.cihlar@gilead.com RI Este, Jose/B-5509-2008 OI Este, Jose/0000-0002-1436-5823 FU Gilead Sciences, Inc. FX The authors wish to thank Mike Bray for useful suggestions and comments and Gilead Sciences, Inc. for providing financial support to organize the ICAR 2008 Mini-Symposium on Novel HIV Targets. NR 159 TC 83 Z9 87 U1 3 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 2008 VL 80 IS 3 BP 251 EP 265 DI 10.1016/j.antiviral.2008.08.003 PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 386AM UT WOS:000261854700003 PM 18789977 ER PT J AU Smee, DF Bailey, KW Wong, MH O'Keefe, BR Gustafson, KR Mishin, VP Gubareva, LV AF Smee, Donald F. Bailey, Kevin W. Wong, Min-Hui O'Keefe, Barry R. Gustafson, Kirk R. Mishin, Vasiliy P. Gubareva, Larisa V. TI Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N SO ANTIVIRAL RESEARCH LA English DT Article DE Influenza; Antiviral; Cyanovirin-N; Mice; Ferrets; Hemagglutinin ID INACTIVATING PROTEIN; NEURAMINIDASE INHIBITORS; IN-VITRO; HEMAGGLUTININ; TRANSMISSION; GLYCOPROTEIN; GP120; BINDS; MODEL AB Cyanovirin-N (CV-N), a protein derived from Nostocellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin HA1 subunit. Mouse-adapted viruses lose sensitivity to CV-N due to HA1 mutations that eliminate these glycosylation sites. Recently we created a hybrid (reassortant) influenza A/WSN/33 (H1N1) virus containing the HA gene of A/New Caledonia/20/99 (H] NI) with an Asp225Gly mutation in the HA1, that was lethal to mice yet retained sensitivity to CV-N. We then utilized this model system to test the efficacy of CV-N against influenza. CV-N efficacy was dose-responsive from 0.0625 to 1 mg/kg/day when administered intranasally (i.n.) twice daily for 4 days starting 4 h prior to virus exposure. In a second study. survival benefit was seen with CV-N treatments (0.5 mg/kg/day for 4 days) beginning at -4 or +6 h, but was significantly reduced at +12 h. The early treatment resulted in up to 100% survival and 1000-fold reduction in lung virus titer on day 3 of the infection. In contrast, ribavirin (a positive control-75 mg/kg/day) treatment resulted in 30% survival and 30-fold decrease in lung virus titers. Lung consolidation scores and lung weights were significantly reduced by CV-N and ribavirin treatment on day 6 of the infection. Ferrets infected with a non-animal adapted influenza A/Charlottesville/31/95 (H1N1) virus were treated intranasally with CV-N (50 mu g twice daily for 5 days starting 24 h before virus challenge). They exhibited 100-fold lower viral titers in nasal washes than placebos 1 day after treatment, but virus titers were equivalent on days 2-7. CV-N has the potential for prophylaxis and early initiation of treatment of influenza virus infections. (C) 2008 Elsevier B.V. All rights reserved. C1 [Smee, Donald F.; Bailey, Kevin W.; Wong, Min-Hui] Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. [O'Keefe, Barry R.; Gustafson, Kirk R.] NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21701 USA. [Mishin, Vasiliy P.; Gubareva, Larisa V.] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. RP Smee, DF (reprint author), Utah State Univ, Inst Antiviral Res, Logan, UT 84322 USA. EM dsmee@cc.usu.edu FU Virology Branch [NO1-AI-15435]; NIAID; NIH; National Cancer Institute; Japanese Society for the Promotion of Science FX This work was supported in part by contract NO1-AI-15435 from the Virology Branch, NIAID, NIH, by the intramural Research Program of the National Cancer Institute, NIH, and by the Japanese Society for the Promotion of Science. The contents of this article do not necessarily reflect the position or policy of the government and no official endorsement should be inferred. The animal experiments were conducted in animal care facilities accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care, International. NR 24 TC 39 Z9 47 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 2008 VL 80 IS 3 BP 266 EP 271 DI 10.1016/j.antiviral.2008.06.003 PG 6 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 386AM UT WOS:000261854700004 PM 18601954 ER PT J AU Yaziji, H Taylor, CR Goldstein, NS Dabbs, DJ Hammond, EH Hewlett, B Floyd, AD Barry, TS Martin, AW Badve, S Baehner, F Cartun, RW Eisen, RN Swanson, PE Hewitt, SM Vyberg, M Hicks, DG AF Yaziji, Hadi Taylor, Clive R. Goldstein, Neal S. Dabbs, David J. Hammond, Elizabeth H. Hewlett, Bryan Floyd, Alton D. Barry, Todd S. Martin, Alvn W. Badve, Sunil Baehner, Frederick Cartun, Richard W. Eisen, Richard N. Swanson, Paul E. Hewitt, Stephen M. Vyberg, Mogen Hicks, David G. CA Stand Ad-Hoc Consensus Comm TI Consensus Recommendations on Estrogen Receptor Testing in Breast Cancer By Immunohistochemistry SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Review DE immunohistochemistry; standardization; estrogen receptor; ER; IHC; breast cancer ID FORMALDEHYDE BINDING; EXPRESSION; FIXATION; SUPERIOR; THERAPY; ASSAYS; TIME AB Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed Lis the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of "False-negative" results worldwide. Standardized testing is only possible after all aspects of ER testing-preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the "ad-hoc committee" of expert pathologists., technologists, and scientists. representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing. C1 [Yaziji, Hadi; Floyd, Alton D.] Vitro Mol Labs, Miami, FL 33143 USA. [Taylor, Clive R.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Barry, Todd S.] Clarient, Aliso Viejo, CA USA. [Goldstein, Neal S.] Adv Diag Lab, Redford, MI USA. [Dabbs, David J.] Magee Womens Hosp, Pittsburgh, PA USA. [Hammond, Elizabeth H.] LDS Hosp, Salt Lake City, UT USA. [Martin, Alvn W.] Univ Louisville, Sch Med, Louisville, KY 40292 USA. [Badve, Sunil; Baehner, Frederick] Indiana Univ, Sch Med, Indianapolis, IN USA. [Cartun, Richard W.] Hartford Hosp, Hartford, CT 06115 USA. [Cartun, Richard W.] Greenwich Hosp, Greenwich, CT USA. [Swanson, Paul E.] Univ Washington, Sch Med, Seattle, WA USA. [Hewitt, Stephen M.] NIH, Bethesda, MD 20892 USA. [Hicks, David G.] Univ Rochester, Sch Med, Rochester, NY USA. [Vyberg, Mogen] NordiQC, Aalborg, Denmark. [Hewlett, Bryan] Lab Serv, Qual Management Program, Toronto, ON, Canada. RP Yaziji, H (reprint author), Vitro Mol Labs, 7000 SW 62nd Ave,Suite PHC, Miami, FL 33143 USA. EM vitromolecular@mac.com RI Vyberg, Mogens/E-7576-2016; OI Vyberg, Mogens/0000-0002-6392-9517; Hewitt, Stephen/0000-0001-8283-1788 NR 28 TC 72 Z9 76 U1 0 U2 10 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 DEC PY 2008 VL 16 IS 6 BP 513 EP 520 DI 10.1097/PAI.0b013e31818a9d3a PG 8 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 380CH UT WOS:000261442800001 PM 18931614 ER PT J AU Stewart, L Glenn, GM Stratton, P Goldstein, AM Merino, MJ Tucker, MA Linehan, WM Toro, JR AF Stewart, Laveta Glenn, Gladys M. Stratton, Pamela Goldstein, Alisa M. Merino, Maria J. Tucker, Margaret A. Linehan, W. Marston Toro, Jorge R. TI Association of Germline Mutations in the Fumarate Hydratase Gene and Uterine Fibroids in Women With Hereditary Leiomyomatosis and Renal Cell Cancer SO ARCHIVES OF DERMATOLOGY LA English DT Article ID RISK-FACTORS; CLINICAL-FEATURES; FAMILIES; FH; ETIOLOGY; HEALTH; RATES; SKIN; AGE AB Objective: To investigate the risk of uterine fibroids and other reproductive risk factors in women with hereditary leiomyomatosis and renal cell cancer (HLRCC). Design: Case-control study. Setting: National Institutes of Health, Rockville, Maryland. Patients: A family-based case-control study was conducted between July 1, 2004, and June 30, 2006, including 105 women from families with HLRCC ascertained throughout North America. A telephone interview was conducted with all participants using a standardized questionnaire that elicited information about their menstrual, pregnancy, uterine fibroid, and hormonal contraceptive use history. Diagnosis of uterine fibroids was confirmed by pathologic diagnosis and by medical record review. DNA was extracted from blood samples and was screened for germline mutations in the fumarate hydratase (FH) gene. Main Outcome Measures: FH germline mutation status, presence of uterine fibroids, age at diagnosis, and symptoms and treatment of uterine fibroids. Results: Of 105 women, 77 reported a history of uterine fibroids. Regardless of uterine fibroid status, 75 of 105 women had a germline mutation in FH (FH(mut) positive). The risk of uterine fibroids in FH(mut)-positive women was statistically significantly increased compared with that in FH(mut)-negative women ( odds ratio [ OR], 7.6; 95% confidence interval [CI], 2.9-20.0), as it was among women clinically affected with HLRCC compared with those clinically unaffected with HLRCC (8.6; 3.1-24.0). The median age at uterine fibroid diagnosis for FH(mut)-positive women ( 28 years) was significantly younger than that for FH(mut)-negative women ( 38 years) (P=. 03). Women with a germline mutation in FH or clinically affected with HLRCC reported younger age at menarche ( P <. 004) compared with FH(mut)-negative women ( P =. 02) or women who were clinically unaffected with HLRCC. Women with HLRCC were more likely to have had treatment for uterine fibroids ( OR, 4.6; 95% CI, 1.4-15.8), including hysterectomy ( P=. 02) at an earlier age compared with women who were clinically unaffected with HLRCC. Conclusions: This study provides the first evidence ( to our knowledge) that women with germline mutations in FH and with clinical HLRCC have an increased risk of developing uterine fibroids. These women also have a younger age at uterine fibroid diagnosis and are more likely to have treatment for uterine fibroids at a younger age than women without HLRCC in their families. C1 [Stewart, Laveta; Glenn, Gladys M.; Goldstein, Alisa M.; Tucker, Margaret A.; Toro, Jorge R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Merino, Maria J.] NCI, Pathol Lab, NIH, Rockville, MD 20892 USA. [Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20892 USA. [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Rockville, MD USA. RP Toro, JR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Execut Plaza S,Room 7012, Rockville, MD 20892 USA. EM toroj@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Division of Cancer Epidemiology and Genetics and Center for Cancer Research; National Cancer Institute; National Institutes of Health FX This study was supported by intramural programs ( Division of Cancer Epidemiology and Genetics and Center for Cancer Research) of the National Cancer Institute, National Institutes of Health. Disclaimer: All authors work for the US government and do not have conflicts of interest with the content or results in this publication. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NR 42 TC 32 Z9 32 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2008 VL 144 IS 12 BP 1584 EP 1592 PG 9 WC Dermatology SC Dermatology GA 384JJ UT WOS:000261740800006 PM 19075141 ER PT J AU Vogelzangs, N Kritchevsky, SB Beekman, ATF Newman, AB Satterfield, S Simonsick, EM Yaffe, K Harris, TB Penninx, BWJH AF Vogelzangs, Nicole Kritchevsky, Stephen B. Beekman, Aartjan T. F. Newman, Anne B. Satterfield, Suzanne Simonsick, Eleanor M. Yaffe, Kristine Harris, Tamara B. Penninx, Brenda W. J. H. TI Depressive Symptoms and Change in Abdominal Obesity in Older Persons SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID INCREASED INTRAABDOMINAL FAT; BODY-COMPOSITION; WAIST CIRCUMFERENCE; VISCERAL FAT; FOLLOW-UP; HYPERCORTISOLEMIC DEPRESSION; PREMENOPAUSAL WOMEN; DIABETES-MELLITUS; ADIPOSE-TISSUE; STRESS SYSTEM AB Context: Depression has been hypothesized to result in abdominal obesity through the accumulation of visceral fat. No large study has tested this hypothesis longitudinally. Objective: To examine whether depressive symptoms predict an increase in abdominal obesity in a large population-based sample of well-functioning older persons. Design: The Health, Aging, and Body Composition Study, an ongoing prospective cohort study with 5 years of follow-up. Setting: Community-dwelling older persons residing in the areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. Participants: A total of 2088 well-functioning white and black persons aged 70 to 79 years. Main Outcome Measures: Baseline depression was defined as a Center for Epidemiological Studies Depression score of 16 or higher. At baseline and after 5 years, overall obesity measures included body mass index ( calculated as weight in kilograms divided by height in meters squared) and percentage of body fat ( measured by dual-energy x-ray absorptiometry). Abdominal obesity measures included waist circumference, sagittal diameter, and visceral fat ( measured by computed tomography). Results: After adjustment for sociodemographics, lifestyle, diseases, and overall obesity, baseline depression was associated with a 5-year increase in sagittal diameter (beta=.054; P=.01) and visceral fat (beta=.080; P=.001). Conclusions: This study shows that depressive symptoms result in an increase in abdominal obesity independent of overall obesity, suggesting that there may be specific pathophysiological mechanisms that link depression with visceral fat accumulation. These results might also help explain why depression increases the risk of diabetes and cardiovascular disease. C1 [Vogelzangs, Nicole; Beekman, Aartjan T. F.; Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, NL-1081 HL Amsterdam, Netherlands. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA 94143 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Vogelzangs, N (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Psychiat, AJ Ernststr 887, NL-1081 HL Amsterdam, Netherlands. EM nicolev@ggzba.nl RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Young Academy of the Royal Netherlands; National Institutes of Health; National Heart, Lung, and Blood Institute [R01-HL72972-01] FX This study was supported by contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 from the National Institute on Aging (NIA); a travel grant from the Young Academy of the Royal Netherlands (Ms Vogelzangs); and in part by the Intramural Research Program of the National Institutes of Health, NIA. Data analyses were supported by grant R01-HL72972-01 from the National Heart, Lung, and Blood Institute. NR 43 TC 93 Z9 95 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2008 VL 65 IS 12 BP 1386 EP 1393 DI 10.1001/archpsyc.65.12.1386 PG 8 WC Psychiatry SC Psychiatry GA 377XT UT WOS:000261286400005 PM 19047525 ER PT J AU Blanco, C Okuda, M Wright, C Hasin, DS Grant, BF Liu, SM Olfson, M AF Blanco, Carlos Okuda, Mayumi Wright, Crystal Hasin, Deborah S. Grant, Bridget F. Liu, Shang-Min Olfson, Mark TI Mental Health of College Students and Their Non-College-Attending Peers Results From the National Epidemiologic Study on Alcohol and Related Conditions SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENERAL-POPULATION SAMPLE; DSM-IV ALCOHOL; PSYCHIATRIC DIAGNOSTIC MODULES; USE DISORDER CRITERIA; UNITED-STATES; SUBSTANCE USE; DRUG-USE; EDUCATIONAL-ATTAINMENT; TREATMENT SERVICES; SEEKING TREATMENT AB Context: Although young adulthood is often characterized by rapid intellectual and social development, college-aged individuals are also commonly exposed to circumstances that place them at risk for psychiatric disorders. Objectives: To assess the 12-month prevalence of psychiatric disorders, sociodemographic correlates, and rates of treatment among individuals attending college and their non-college-attending peers in the United States. Design, Setting, and Participants: Face-to-face interviews were conducted in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions ( N=43 093). Analyses were done for the subsample of college-aged individuals, defined as those aged 19 to 25 years who were both attending ( n=2188) and not attending ( n=2904) college in the previous year. Main Outcome Measures: Sociodemographic correlates and prevalence of 12-month DSM-IV psychiatric disorders, substance use, and treatment seeking among college-attending individuals and their non-college-attending peers. Results: Almost half of college-aged individuals had a psychiatric disorder in the past year. The overall rate of psychiatric disorders was not different between college-attending individuals and their non-college-attending peers. The unadjusted risk of alcohol use disorders was significantly greater for college students than for their non-college-attending peers ( odds ratio=1.25; 95% confidence interval, 1.04-1.50), although not after adjusting for background sociodemographic characteristics ( adjusted odds ratio=1.19; 95% confidence interval, 0.98-1.44). College students were significantly less likely ( unadjusted and adjusted) to have a diagnosis of drug use disorder or nicotine dependence or to have used tobacco than their non-college-attending peers. Bipolar disorder was less common in individuals attending college. College students were significantly less likely to receive past-year treatment for alcohol or drug use disorders than their non-college-attending peers. Conclusions: Psychiatric disorders, particularly alcohol use disorders, are common in the college-aged population. Although treatment rates varied across disorders, overall fewer than 25% of individuals with a mental disorder sought treatment in the year prior to the survey. These findings underscore the importance of treatment and prevention interventions among college-aged individuals. C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Blanco, Carlos; Okuda, Mayumi; Wright, Crystal; Hasin, Deborah S.; Grant, Bridget F.; Liu, Shang-Min; Olfson, Mark] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. [Hasin, Deborah S.; Grant, Bridget F.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013 OI Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599 FU National Institute on Alcohol Abuse and Alcoholism; Intermural Program; National Institutes of Health; National Institutes of Health [DA019606, DA020783, DA023200, MH076051, R01AA08159, K05AA00161, P60 MD000206]; American Foundation for Suicide Prevention; New York State Psychiatric Institute FX The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism and funded in part by the Intermural Program, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. This study is supported by grants DA019606 ( Dr Blanco), DA020783 ( Dr Blanco), DA023200 ( Dr Blanco), MH076051 ( Dr Blanco), R01AA08159 ( Dr Hasin), K05AA00161 ( Dr Hasin), and P60 MD000206 ( Dr Olfson) from the National Institutes of Health, by the American Foundation for Suicide Prevention ( Dr Blanco), and by the New York State Psychiatric Institute ( Drs Blanco, Hasin, and Olfson). NR 73 TC 276 Z9 277 U1 8 U2 36 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2008 VL 65 IS 12 BP 1429 EP 1437 DI 10.1001/archpsyc.65.12.1429 PG 9 WC Psychiatry SC Psychiatry GA 377XT UT WOS:000261286400010 PM 19047530 ER PT J AU Gorin, AA Niemeier, HM Hogan, P Coday, M Davis, C DiLillo, VG Gluck, ME Wadden, TA West, DS Williamson, D Yanovski, SZ AF Gorin, Amy A. Niemeier, Heather M. Hogan, Patricia Coday, Mace Davis, Cralen DiLillo, Vicki G. Gluck, Marci E. Wadden, Thomas A. West, Delia S. Williamson, Donald Yanovski, Susan Z. CA Look AHEAD Research Grp TI Binge Eating and Weight Loss Outcomes in Overweight and Obese Individuals With Type 2 Diabetes Results From the Look AHEAD Trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SELF-REPORT QUESTIONNAIRE; PRETREATMENT PREDICTORS; SOCIOECONOMIC-STATUS; CLINICAL-TRIAL; NATURAL COURSE; DISORDER; WOMEN; POPULATION; BEHAVIOR; INTERVIEW AB Context: Binge eating ( BE) is common in overweight and obese individuals with type 2 diabetes mellitus, but little is known about how BE affects weight loss in this population. Objective: To determine whether BE was related to 1-year weight losses in overweight and obese individuals with type 2 diabetes participating in an ongoing clinical trial. Design, Setting, and Participants: The Look AHEAD ( Action for Health in Diabetes) trial is a randomized controlled trial examining the long-term effect of intentional weight loss on cardiovascular disease in overweight and obese adults with type 2 diabetes. A total of 5145 overweight and obese individuals aged 45 to 76 years with type 2 diabetes participated in this study. Interventions: Participants were randomly assigned to an intensive lifestyle intervention or to enhanced usual care ( a diabetes support and education control condition). Main Outcome Measures: At baseline and 1 year, participants had their weight measured and completed a fitness test and self-report measures of BE and dietary intake. Four groups were created based on BE status at baseline and 1 year ( yes/yes, no/no, yes/no, and no/yes). Analyses controlled for baseline differences between binge eaters and non-binge eaters. Results: Most individuals ( 85.4%) did not report BE at baseline or 1 year (no/no), 7.5% reported BE only at baseline ( yes/no), 3.7% reported BE at both times ( yes/yes), and 3.4% reported BE only at 1 year ( no/ yes), with no differences between intensive lifestyle intervention and diabetes support and education conditions ( P=.14). Across intensive lifestyle intervention and diabetes support and education, greater weight losses were observed in participants who stopped BE at 1 year ( mean [ SE] weight loss, 5.3 [ 0.4] kg) and those who reported no BE at either time ( mean [ SE] weight loss, 4.8 [ 0.1] kg) than in those who continued BE ( mean [ SE] weight loss, 3.1 [ 0.6] kg) and those who began BE at 1 year ( mean [ SE] weight loss, 3.0 [ 0.6] kg) ( P <. 001). Post hoc analyses suggested that these differences were due to changes in caloric intake. Conclusion: Overweight and obese individuals with type 2 diabetes who stop BE appear to be just as successful at weight loss as non-binge eaters after 1 year of treatment. C1 [Gorin, Amy A.] Univ Connecticut, Dept Psychol, Ctr Hlth Intervent & Prevent, Storrs, CT 06269 USA. [Niemeier, Heather M.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. [Hogan, Patricia; Davis, Cralen] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Coday, Mace] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. [DiLillo, Vicki G.] Ohio Wesleyan Univ, Dept Psychol, Delaware, OH 43015 USA. [Gluck, Marci E.] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA. [Wadden, Thomas A.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [West, Delia S.] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Little Rock, AR 72205 USA. [Williamson, Donald] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Gorin, AA (reprint author), Univ Connecticut, Dept Psychol, Ctr Hlth Intervent & Prevent, 2006 Hillside Rd,Unit 1248, Storrs, CT 06269 USA. EM amy.gorin@uconn.edu FU National Institutes of Health [DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, DK046204]; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; Centers for Disease Control and Prevention; Johns Hopkins Medical Institutions Bayview General Clinical Research Center [M01RR02719]; Massachusetts General Hospital Mallinckrodt General Clinical Research Center [M01RR01066]; University of Colorado Health Sciences Center General Clinical Research Center [M01RR00051]; Clinical Nutrition Research Unit [P30 DK48520]; University of Tennessee at Memphis General Clinical Research Center [M01RR0021140]; University of Pittsburgh General Clinical Research Center [M01RR000056 44]; University of Washington/Veterans Affairs Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; Frederic C. Bartter General Clinical Research Center [M01RR01346] FX This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women's Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the Johns Hopkins Medical Institutions Bayview General Clinical Research Center (grant M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center ( grant M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center ( grant M01RR00051) and Clinical Nutrition Research Unit ( grant P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center ( grant M01RR0021140); the University of Pittsburgh General Clinical Research Center ( grant M01RR000056 44); the National Institutes of Health ( grant DK046204); the University of Washington/Veterans Affairs Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter General Clinical Research Center ( grant M01RR01346). The following organizations have committed to making major contributions to the Look AHEAD trial: FedEx Corp; Health Management Resources Corp; LifeScan, Inc, Johnson & Johnson; Optifast, Nestle HealthCare Nutrition, Inc; Roche Pharmaceuticals; Ross Product Division, Abbott Laboratories; and Slim-Fast Foods Co. Previous Presentation: This paper was presented at the 29th Annual Meeting and Scientific Sessions of the Society of Behavioral Medicine; March 27, 2008; San Diego, California. NR 39 TC 32 Z9 33 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2008 VL 65 IS 12 BP 1447 EP 1455 DI 10.1001/archpsyc.65.12.1447 PG 9 WC Psychiatry SC Psychiatry GA 377XT UT WOS:000261286400012 PM 19047532 ER PT J AU Datiles, MB Ansari, RR Suh, KI Vitale, S Reed, GF Zigler, JS Ferris, FL AF Datiles, Manuel B., III Ansari, Rafat R. Suh, Kwang I. Vitale, Susan Reed, George F. Zigler, J. Samuel, Jr. Ferris, Frederick L., III TI Clinical Detection of Precataractous Lens Protein Changes Using Dynamic Light Scattering SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 06-10, 2007 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID BOVINE ALPHA-CRYSTALLIN; AGE-RELATED-CHANGES; LIVING HUMAN LENS; MOLECULAR CHAPERONE; CATARACT FORMATION; GLUTATHIONE-REDUCTASE; NUCLEAR CATARACT; FUNCTIONAL-ROLE; OPACIFICATION; EYE AB Objective: To use dynamic light scattering to clinically assess early precataractous lens protein changes. Methods: We performed a cross-sectional study in 380 eyes of 235 patients aged 7 to 86 years with Age-Related Eye Disease Study clinical nuclear lens opacity grades 0 to 3.8. A dynamic light-scattering device was used to assess alpha-crystallin, a molecular chaperone protein shown to bind other damaged lens proteins, preventing their aggregation. The outcome measure was the alpha-crystallin index, a measure of unbound alpha-crystallin in each lens. The association of the alpha-crystallin index with increasing nuclear opacity and aging was determined. Results: There was a significant decrease in the alpha-crystallin index associated with increasing nuclear lens opacity grades (P<.001). There were significant losses of alpha-crystallin even in clinically clear lenses associated with aging (P<.001). The standard error of measurement was 3%. Conclusions: Dynamic light scattering clinically detects alpha-crystallin protein loss even in clinically clear lenses. alpha-Crystallin index measurements may be useful in identifying patients at high risk for cataracts and as an outcome variable in clinical lens studies. C1 [Datiles, Manuel B., III; Vitale, Susan; Reed, George F.; Zigler, J. Samuel, Jr.; Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Ansari, Rafat R.] NASA, John H Glenn Res Ctr Lewis Field, Cleveland, OH USA. [Suh, Kwang I.] Ohio Aerosp Inst, Cleveland, OH USA. RP Datiles, MB (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N226, Bethesda, MD 20892 USA. EM DatilesM@NEI.NIH.GOV OI Datiles, Manuel III B./0000-0003-4660-1664 FU Intramural NIH HHS [Z99 EY999999] NR 52 TC 36 Z9 37 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2008 VL 126 IS 12 BP 1687 EP 1693 DI 10.1001/archophthalmol.2008.507 PG 7 WC Ophthalmology SC Ophthalmology GA 380RA UT WOS:000261481700011 PM 19064850 ER PT J AU Hewitt, SM Lewis, FA Cao, Y Conrad, RC Cronin, M Danenberg, KD Goralski, TJ Langmore, JP Raja, RG Williams, PM Palma, JF Warrington, JA AF Hewitt, Stephen M. Lewis, Fraser A. Cao, Yanxiang Conrad, Richard C. Cronin, Maureen Danenberg, Kathleen D. Goralski, Thomas J. Langmore, John P. Raja, Rajiv G. Williams, P. Mickey Palma, John F. Warrington, Janet A. TI Tissue Handling and Specimen Preparation in Surgical Pathology Issues Concerning the Recovery of Nucleic Acids From Formalin-Fixed, Paraffin-Embedded Tissue SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION; BREAST-CANCER; MESSENGER-RNA; FIXATION; PRESERVATION; MICROARRAYS; IMMUNOHISTOCHEMISTRY; MICRODISSECTION; ANTIGENICITY AB Context.-Expression profiling by microarrays and real-time polymerase chain reaction-based assays is a powerful tool for classification and prognostication of disease; however, it remains a research tool, largely reliant on frozen tissue. Limiting the utility of expression profiling is the isolation of quality nucleic acids from formalin-fixed, paraffin-embedded tissue. The collection, handling, and processing of tissue directly impacts the biomolecules that can be recovered from it. High-quality nucleic acids can be obtained from formalin-fixed, paraffin-embedded tissue, but greater attention to all steps in the process of tissue handling and preparation is required. Objective.-To summarize the current state-of-the-art of preanalytic factors in tissue handling and processing as they impact the quality of RNA obtainable from formalin-fixed, paraffin-embedded tissue. The goals are to provide recommendations that will improve RNA quality for expression profiling from formalin-fixed, paraffin-embedded tissue and highlight areas for additional research. Tissue is an analyte and it must be handled in a standardized fashion to provide consistent results. Data Sources.-The literature was reviewed. Consultation with industry and academic leaders in the use of RNA for expression profiling was obtained to identify areas for additional research. Conclusions.-Development of RNA-based assays from formalin-fixed, paraffin-embedded tissue is feasible. Greater attention to tissue handing and processing is essential to improve the quality of biospecimens for the development of robust RNA-based assays. Standardization of procedures and vigorous testing of alternative protocols are required to ensure that these assays function as designed. C1 [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. [Lewis, Fraser A.] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Lewis, Fraser A.] Univ Leeds, Leeds, W Yorkshire, England. [Cao, Yanxiang; Conrad, Richard C.] Appl Biosyst Inc, Foster City, CA 94404 USA. [Cronin, Maureen] Genom Hlth Inc, Redwood City, CA USA. [Danenberg, Kathleen D.] Response Genet Inc, Los Angeles, CA USA. [Goralski, Thomas J.] Express Anal Inc, Durham, NC USA. [Langmore, John P.] Rubicon Genom Inc, Ann Arbor, MI USA. [Raja, Rajiv G.] Mol Devices Corp, Sunnyvale, CA USA. [Williams, P. Mickey] Roche Mol Syst, Pleasanton, CA USA. [Palma, John F.] Johnson & Johnson Co, Veridex LLC, San Diego, CA USA. [Warrington, Janet A.] Affymetrix Inc, Santa Clara, CA USA. RP Hewitt, SM (reprint author), NCI, Adv Technol Ctr, MSC 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 NR 37 TC 124 Z9 126 U1 1 U2 3 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 DEC PY 2008 VL 132 IS 12 BP 1929 EP 1935 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 380UN UT WOS:000261491000017 PM 19061293 ER PT J AU Mohan, K Muller, J Atreya, C AF Mohan, Ketha V. Muller, Jacqueline Atreya, Chintamani D. TI Defective rotavirus particle assembly in lovastatin-treated MA104 cells SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN VACCINE; VIRUS; CHOLESTEROL; PROTEIN; INFECTION; PATHWAY; STRAIN; IDENTIFICATION; REPLICATION; MUTATIONS AB Rotavirus is a non-enveloped virus that depends on cellular lipids for cell entry and associates with lipid rafts during assembly. However, the effects of cellular lipids on rotavirus assembly are still not fully understood. The present study analyzes the effects of lovastatin, an inhibitor of cholesterol biosynthesis, during rotavirus infection in MA104 cells with regard to viral growth and particle assembly. Following viral infection, a 2-log relative reduction of viral titers was observed in drug-treated cells, while viral mRNA levels in infected cells remained unaltered in both groups. Furthermore, the levels of some viral proteins in drug-treated cells were elevated. The observed discordance between the viral RNA and protein levels and the decrease in infectivity titers of viral progeny in the drug-treated cells suggested that the drug affects viral assembly, the viral proteins not being properly incorporated into virions. Transmission electron microscopic (TEM) analysis revealed that in drug-treated cells there was an increase in "empty-looking" rotavirus particles devoid of an electron-dense core as compared to the normal, electron-dense particles seen in untreated infected cells. The present study thus provides visual evidence of defective rotavirus particle assembly as a result of cholesterol depletion. C1 [Muller, Jacqueline] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. [Mohan, Ketha V.; Atreya, Chintamani D.] US FDA, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Mohan, K (reprint author), US FDA, CBER, Bldg 29A,Room 2C-15,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov NR 36 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD DEC PY 2008 VL 153 IS 12 BP 2283 EP 2290 DI 10.1007/s00705-008-0261-0 PG 8 WC Virology SC Virology GA 391KJ UT WOS:000262231900012 PM 19030953 ER PT J AU Wittkowski, H Frosch, M Wulffraat, N Goldbach-Mansky, R Kallinich, T Kuemmerle-Deschner, J Fruhwald, MC Dassmann, S Pham, TH Roth, J Foell, D AF Wittkowski, Helmut Frosch, Michael Wulffraat, Nico Goldbach-Mansky, Raphaela Kallinich, Tilmann Kuemmerle-Deschner, Jasmin Fruehwald, Michael C. Dassmann, Sandra Pham, Tuyet-Hang Roth, Johannes Foell, Dirk TI S100A12 Is a Novel Molecular Marker Differentiating Systemic-Onset Juvenile Idiopathic Arthritis From Other Causes of Fever of Unknown Origin SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; EN-RAGE; PRELIMINARY DEFINITION; NEUTROPHIL ACTIVATION; PROTEIN S100A12; STILLS-DISEASE; IL-1 BLOCKADE; RECEPTOR; IMPROVEMENT AB Objective. Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents. Methods. Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leuke-mia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay. Results. The mean +/- 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 +/- 2,690 ng/ml; in patients with FMF, 6,720 +/- 4,960 ng/ml; in patients with NOMID, 720 +/- 450 ng/ml; in patients with MWS, 150 +/- 60 ng/ml; in patients with infections, 470 +/- 160 ng/ml; in patients with ALL, 130 80 ng/ml; in patients with AML, 45 +/- 60 ng/ml; in healthy control subjects, 50 +/- 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively. Conclusion. S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO. C1 [Roth, Johannes] Univ Munster, Dept Pediat, D-48149 Munster, Germany. [Wittkowski, Helmut; Frosch, Michael; Fruehwald, Michael C.; Dassmann, Sandra; Roth, Johannes; Foell, Dirk] Univ Hosp Muenster, Munster, Germany. [Wulffraat, Nico] Wilhelmina Childrens Hosp, Utrecht, Netherlands. [Wulffraat, Nico] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Goldbach-Mansky, Raphaela; Pham, Tuyet-Hang] NIAMSD, NIH, Bethesda, MD 20892 USA. [Kallinich, Tilmann] Charite Childrens Hosp, Berlin, Germany. [Kuemmerle-Deschner, Jasmin] Univ Childrens Hosp, Tubingen, Germany. [Kuemmerle-Deschner, Jasmin] Univ Tubingen, Tubingen, Germany. RP Roth, J (reprint author), Univ Munster, Dept Pediat, Albert Schweitzer Str 33, D-48149 Munster, Germany. EM rothj@uni-muenster.de FU Interdisciplinary Centre for Clinical Research at the University of Muenster [Foe2/005/06]; Deutsche Forschungsgerneinschaft [FO 354/2-2] FX Supported by grants from the Interdisciplinary Centre for Clinical Research at the University of Muenster (project Foe2/005/06) and the Deutsche Forschungsgerneinschaft (DFG project FO 354/2-2). NR 39 TC 56 Z9 59 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2008 VL 58 IS 12 BP 3924 EP 3931 DI 10.1002/art.24137 PG 8 WC Rheumatology SC Rheumatology GA 382EI UT WOS:000261587500031 PM 19035478 ER PT J AU Mamyrova, G O'Hanlon, TP Sillers, L Malley, K James-Newton, L Parks, CG Cooper, GS Pandey, JP Miller, FW Rider, LG AF Mamyrova, Gulnara O'Hanlon, Terrance P. Sillers, Laura Malley, Karen James-Newton, Laura Parks, Christina G. Cooper, Glinda S. Pandey, Janardan P. Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity C TI Cytokine Gene Polymorphisms as Risk and Severity Factors for Juvenile Dermatomyositis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; IDIOPATHIC INFLAMMATORY MYOPATHIES; CUTANEOUS LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; PROMOTER POLYMORPHISM; TNF-ALPHA-308A ALLELE; IMMUNOGENETIC RISK; PROTECTIVE FACTORS; PLASMA-LEVELS; ASSOCIATION AB Objective. To study tumor necrosis factor a (TNF alpha) and interleukin-1 (IL-1) cytokine polymorphisms as possible risk and protective factors, define their relative importance, and examine these as severity factors in patients with juvenile dermatomyositis (DM). Methods. TNFa and IL-1 cytokine polymorphism and HLA typing were performed in 221. Caucasian patients with juvenile DM, and the results were compared with those in 203 ethnically matched healthy volunteers. Results. The genotypes TNF alpha -308AG (odds ratio [OR] 3.6), TNF alpha -238GG (OR 3.5), and IL-1 alpha +4845TT (OR 2.2) were risk factors, and TNF alpha -308GG (OR 0.26) as well as TNF alpha -238AG (OR 0.22) were protective, for the development of juvenile DM. Carriage of a single copy of the TNF alpha -308A (OR 3.8) or IL-1 beta +3953T (OR 1.7) allele was a risk factor, and the TNF alpha -238A (OR 0.29) and IL-1 alpha +4845G (OR 0.46) alleles were protective, for juvenile DM. Random Forests classification analysis showed HLA-DRB1*03 and TNF alpha -308A to have the highest relative importance as risk factors for juvenile DM compared with the other alleles (Gini scores 100% and 90.7%, respectively). TNF alpha -308AA (OR 7.3) was a risk factor, and carriage of the TNF alpha -308G (OR 0.14) and IL-1 alpha -889T (OR 0.41) alleles was protective, for the development of calcinosis. TNF alpha -308AA (OR 7.0) was a possible risk factor, and carriage of the TNFa -308G allele (OR 0.14) was protective, for the development of ulcerations. None of the studied TNF alpha, IL-1 alpha, and IL-1 beta polymorphisms were associated with the disease course, disease severity at the time of diagnosis, or the patient's sex. Conclusion. TNFa and IL-1 genetic polymorphisms contribute to the development of juvenile DM and may also be indicators of disease severity. C1 [Rider, Lisa G.] Natl Inst Environm Sci, Environm Autoimmun Grp, NIH, DHHS,Clin Res Ctr, Bethesda, MD 20892 USA. [Malley, Karen] Malley Res Programming, Rockville, MD USA. [Parks, Christina G.] Natl Inst Environm Hlth Sci, NIH, Durham, NC USA. [Cooper, Glinda S.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Pandey, Janardan P.] Med Univ S Carolina, Charleston, SC USA. RP Rider, LG (reprint author), Natl Inst Environm Sci, Environm Autoimmun Grp, NIH, DHHS,Clin Res Ctr, Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov OI Ilowite, Norman/0000-0002-8298-8563; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593; Parks, Christine/0000-0002-5734-3456 FU National Institute of Environmental Health Sciences; Center for Biologics Evaluation and Research; Environmental Biosciences Program [DE-FC09-02CH11109]; Cure JM Foundation FX Supported in part by the Intramural Research programs of the National Institute of Environmental Health Sciences and the Center for Biologics Evaluation and Research, and by a US Department of Energy cooperative agreement with the Medical University of South Carolina in support of the Environmental Biosciences Program (DE-FC09-02CH11109). Dr. Mamyrova is a Research Fellow of the Cure JM Foundation. NR 33 TC 38 Z9 44 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2008 VL 58 IS 12 BP 3941 EP 3950 DI 10.1002/art.24039 PG 10 WC Rheumatology SC Rheumatology GA 382EI UT WOS:000261587500033 PM 19035492 ER PT J AU Rajan, RM Reynolds, JC Plass, N Chappelle, D Stone, D Snyder, C Goldbach-Mansky, R AF Rajan, Rallis M. Reynolds, James C. Plass, Nicole Chappelle, Dawn Stone, Deborah Snyder, Christopher Goldbach-Mansky, Raphaela TI Improvement of Bone Mineral Density (BMD) in Neonatal-Onset Multisystem Inflammatory Disease (NOMID) after Treatment with the Interleukin 1 (IL-1) Receptor Antagonist Anakinra, Kineret (R) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Rajan, Rallis M.; Reynolds, James C.; Plass, Nicole; Chappelle, Dawn; Stone, Deborah; Snyder, Christopher; Goldbach-Mansky, Raphaela] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2008 VL 58 IS 12 BP 3978 EP 3979 PG 2 WC Rheumatology SC Rheumatology GA 382EI UT WOS:000261587500056 ER PT J AU Brionez, TF Assassi, S Reveille, D Learch, T Diekman, L Ward, MM Weisman, MH Nicassio, P AF Brionez, T. F. Assassi, S. Reveille, D. Learch, T. Diekman, L. Ward, M. M. Weisman, M. H. Nicassio, P. TI Psychological Status and Functional Limitation in Patients with Ankylosing Spondylitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Brionez, T. F.; Assassi, S.; Reveille, D.; Diekman, L.] Univ Texas Houston, Houston, TX USA. [Learch, T.; Weisman, M. H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ward, M. M.] NIAMS, NIH, Bethesda, MD USA. [Nicassio, P.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2008 VL 58 IS 12 BP 4004 EP 4004 PG 1 WC Rheumatology SC Rheumatology GA 382EI UT WOS:000261587500122 ER PT J AU Brionez, TF Assassi, S Reveille, JD Learch, T Diekman, L Ward, MM Weisman, MH Nicassio, P AF Brionez, T. F. Assassi, S. Reveille, J. D. Learch, T. Diekman, L. Ward, M. M. Weisman, M. H. Nicassio, P. TI Pain in Ankylosing Spondylitis (AS): Association with Demographic, Medical, and Psychological Factors. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 72nd Annual Scientific Meeting of the American-College-of-Rheumatology/43rd Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2008 CL San Francisco, CA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 [Brionez, T. F.; Assassi, S.; Reveille, J. D.; Diekman, L.] Univ Texas Houston, Houston, TX USA. [Learch, T.; Weisman, M. H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ward, M. M.] NIAMS, NIH, Bethesda, MD USA. [Nicassio, P.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2008 VL 58 IS 12 BP 4019 EP 4020 PG 2 WC Rheumatology SC Rheumatology GA 382EI UT WOS:000261587500164 ER PT J AU Cohen, TV Hernandez, L Stewart, CL AF Cohen, Tatiana V. Hernandez, Lidia Stewart, Colin L. TI Functions of the nuclear envelope and lamina in development and disease SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE Emery-Dreifuss muscular dystrophy (EDMD); Hutchinson-Gilford progeria syndrome (HGPS); lamina; nuclear envelope ID HUTCHINSON-GILFORD-PROGERIA; DREIFUSS MUSCULAR-DYSTROPHY; A-TYPE LAMINS; CONDUCTION-SYSTEM DISEASE; DILATED CARDIOMYOPATHY; MUSCLE REGENERATION; SYNDROME MUTATION; PROTEIN EMERIN; DEFICIENT MICE; MYOD PATHWAYS AB Recent findings that some 24 inherited diseases and anomalies are caused by defects in proteins of the NE (nuclear envelope) and lamina have resulted in a fundamental reassessment of the functions of the NE and underlying lamina. instead of just regarding the NE and lamina as a molecular filtering device, regulating the transfer of macromolecules between the cytoplasm and nucleus, we now envisage the NE/lamina functioning as a key cellular 'hub' in integrating critical functions that include chromatin organization, transcriptional regulation, mechanical integrity of the cell and signalling pathways, as well as acting as a key component in the organization and function of the cytoskeleton. C1 [Stewart, Colin L.] Inst Med Biol, Singapore 138668, Singapore. [Cohen, Tatiana V.] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. [Hernandez, Lidia] NCI, Med Oncol Branch CCR, Bethesda, MD 20892 USA. RP Stewart, CL (reprint author), Inst Med Biol, 8A Biomed Grove, Singapore 138668, Singapore. EM colin.stewart@imb.a-star.edu.sg FU Biochemical Society FX C.L.S. was sponsored by the Biochemical Society to present this lecture. NR 54 TC 23 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 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2008 VL 36 BP 1329 EP 1334 DI 10.1042/BST0361329 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384MP UT WOS:000261749200046 PM 19021550 ER PT J AU Gursoy, A Keskin, O Nussinov, R AF Gursoy, Attila Keskin, Ozlem Nussinov, Ruth TI Topological properties of protein interaction networks from a structural perspective SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE hub protein; interface; protein interaction network; structural proteomics; topology ID SCALE-FREE NETWORKS; COMPLEX NETWORKS; SYSTEMS BIOLOGY; HUB PROTEINS; EVOLUTIONARY; ESSENTIALITY; PREDICTION; MODULARITY; INTERFACES; CENTRALITY AB Protein-protein interactions are usually shown as interaction networks (graphs), where the proteins are represented as nodes and the connections between the interacting proteins are shown as edges. The graph abstraction of protein interactions is crucial for understanding the global behaviour of the network. In this mini review, we summarize basic graph topological properties, such as node degree and betweenness, and their relation to essentiality and modularity of protein interactions. The classification of hub proteins into date and party hubs with distinct properties has significant implications for relating topological properties to the behaviour of the network. We emphasize that the integration of protein interface structure into interaction graph models provides a better explanation of hub proteins, and strengthens the relationship between the role of the hubs in the cell and their topological properties. C1 [Nussinov, Ruth] SAIC Frederick Inc, Basic Res Program, Ctr Canc Res, Nanobiol Program,NCI Frederick, Frederick, MD 21702 USA. [Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Sariyer, Turkey. [Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Sariyer, 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), SAIC Frederick Inc, Basic Res Program, Ctr Canc Res, Nanobiol Program,NCI Frederick, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU National Cancer Institute; National institutes of Health [N01-C0-12400]; NIH; Center for Cancer Research FX we thank members of the group for discussions and suggestions. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National institutes of Health, under contract number N01-C0-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, neither does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 64 Z9 66 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0300-5127 EI 1470-8752 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD DEC PY 2008 VL 36 BP 1398 EP 1403 DI 10.1042/BST0361398 PN 6 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384MP UT WOS:000261749200059 PM 19021563 ER PT J AU Watanabe, K Nagaoka, T Strizzi, L Mancino, M Gonzales, M Bianco, C Salomon, DS AF Watanabe, Kazuhide Nagaoka, Tadahiro Strizzi, Luigi Mancino, Mario Gonzales, Monica Bianco, Caterina Salomon, David S. TI Characterization of the glycosylphosphatidylinositol-anchor signal sequence of human Cryptic with a hydrophilic extension SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Cripto-1; Cryptic; EGF-CFC family protein; GPI-anchored protein; Nodal ID LEFT-RIGHT AXIS; PROTEINS; CRIPTO; ATTACHMENT; GENE; BIOSYNTHESIS; REQUIREMENT; CORECEPTOR; PREDICTION; PATHWAY AB Epidermal Growth Factor-Cripto-1/FRL-1/Cryptic (EGF-CFC) proteins, including human Cripto-1 (hCFC2/hCR-1) and human Cryptic (hCFC1), are membrane-associated Nodal co-receptors, which have critical roles in vertebrate development. Most of the EGF-CFC proteins have been experimentally proven or predicted to be glycosylphosphatidylinositol (GPI)-anchored proteins. However, unlike other EGF-CFC proteins, hCFC1 does not exhibit a typical GPI-signal sequence, containing a 32-amino acid hydrophilic extension in its COOH-terminal end. Here we experimentally demonstrate that the CCCH-terminal sequence of hCFC1 functions as a GPI-anchoring signal. Moreover, addition of a hydrophilic epitope tag of 55-amino acids (V5-His) after the GPI signal of hCR-1 interfered with generation of a GPI-anchored form of hCR-1. In contrast, addition of the same epitope tag to the end of GPI signal of hCFC1 did not affect the GPI-attachment of hCFC1. The COOH-terminal signal of hCFC1 could produce two different forms of the protein; a GPI-anchored form and an unprocessed form which was more prone to be secreted into the conditioned medium. The hydrophilic extension of hCFC1 negatively regulates the activity of hCFC1 as a Nodal co-receptor, These results demonstrate the presence of endogenous GPI-signal sequence with a hydrophilic extension, which can generate both GPI-anchored and soluble forms of the protein. Published by Elsevier B.V. C1 [Watanabe, Kazuhide; Nagaoka, Tadahiro; Strizzi, Luigi; Mancino, Mario; Gonzales, Monica; Bianco, Caterina; Salomon, David S.] NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Strizzi, Luigi] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Canc Ctr, Childrens Mem Res Ctr, Chicago, IL 60611 USA. RP Salomon, DS (reprint author), Bldg37 Rm1118B 37 Convent Dr, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov OI Nagaoka, Tadahiro/0000-0002-9391-0243 FU NIH FX We dedicate this manuscript to the memory of Ms. Brenda W.Jones who assisted during the inception of this research. We thank Ms. Susan Garfield and Mr. Stephen Wincovitch (Confocal Core facility, National Cancer Institute) for their help in confocal imaging. This work was supported by the NIH Intramural Funding. NR 24 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD DEC PY 2008 VL 1778 IS 12 BP 2671 EP 2681 DI 10.1016/j.bbamem.2008.09.011 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 384CB UT WOS:000261720300002 PM 18930707 ER PT J AU Briddon, SJ Gandia, J Amaral, OB Ferre, S Lluis, C Franco, R Hill, SJ Ciruela, F AF Briddon, Stephen J. Gandia, Jorge Amaral, Olavo B. Ferre, Sergi Lluis, Carme Franco, Rafael Hill, Stephen J. Ciruela, Francisco TI Plasma membrane diffusion of g protein-coupled receptor oligomers SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE G protein-coupled receptor; Receptor oligomerization; Adenosine receptor; Membrane diffusion ID FLUORESCENCE CORRELATION SPECTROSCOPY; RESONANCE ENERGY-TRANSFER; CENTRAL-NERVOUS-SYSTEM; ADENOSINE RECEPTORS; LIVING CELLS; A(2A)-ADENOSINE RECEPTOR; COMPLEXES; HETEROMERS; COMPLEMENTATION; VISUALIZATION AB G protein-coupled receptors are known to form homo-and heteromers at the plasma membrane, but the molecular properties of these oligomers are relatively unknown. Here, we show a method that allows the diffusion of G protein-coupled receptors oligomers in the plasma membrane to be monitored in single cells by combining Bimolecular Fluorescence Complementation and Fluorescence Correlation Spectroscopy. With this approach we have measured, for the first time, the membrane diffusional characteristics of adenosine A, and A(2A) receptor homo-and heterodimers in Chinese Hamster Ovary cells. Interestingly, both homodimers display similar diffusion co-efficients (D) when expressed in living cells (D=5.0 and 4.8x10(-9) cm(2)/s, respectively) but the heterodimer formed by these receptors exhibit a significantly faster plasma membrane diffusion co-efficent (D=5.6x 10(-9) cm(2)/s) when compared to the adenosine A, receptor tagged with the full-length yellow fluorescent protein (D=4.0x10(-9) cm(2)/s). Overall, these results demonstrate differences in plasma membrane diffusion between adenosine receptor homo-and heterodimers, providing new insights into the molecular plasticity of G protein-coupled receptor oligomerization. (C) 2008 Elsevier B.V. All rights reserved. C1 [Gandia, Jorge; Amaral, Olavo B.; Ciruela, Francisco] Univ Barcelona, Fac Med, Dept Patol & Terapeut Expt, IDIBELL,Unitat Farmacol, Barcelona 08907, Spain. [Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain. [Lluis, Carme; Franco, Rafael] Univ Barcelona, CIBERNED, IDIBAPS, E-08028 Barcelona, Spain. [Briddon, Stephen J.; Hill, Stephen J.] Univ Nottingham, Inst Cell Signalling, Nottingham NG7 2UH, England. [Ferre, Sergi] NIDA, Behav Neurosci Branch, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Ciruela, F (reprint author), Univ Barcelona, Fac Med, Dept Patol & Terapeut Expt, IDIBELL,Unitat Farmacol, Barcelona 08907, Spain. EM fciruela@ub.edu RI Amaral, Olavo/B-2874-2009; hill, Stephen/N-6753-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Gandia, Jorge/P-3373-2016; OI Amaral, Olavo/0000-0002-4299-8978; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Gandia, Jorge/0000-0003-1711-8075; Briddon, Stephen/0000-0001-8514-0827; Hill, Stephen/0000-0002-4424-239X FU Ministerio de Educacion y Ciencia [SAF2005-00903]; BBSRC [BB/D521581]; NIH; National Institute on Drug Abuse; Department of Health and Human Services FX This work was supported by grants SAF2005-00903 to F.C. from Ministerio de Educacion y Ciencia and BBSRC BB/D521581 to SJB and SJH and in part by the Intramural Research Program of the NIH, National Institute on Drug Abuse, Department of Health and Human Services. We thank Drjuli Blanco (Fundacio irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Spain) for the cDNAs encoding the human CD4. NR 31 TC 24 Z9 25 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC PY 2008 VL 1783 IS 12 BP 2262 EP 2268 DI 10.1016/j.bbamcr.2008.07.006 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 378TF UT WOS:000261346100005 PM 18691614 ER PT J AU Grigorenko, BL Shadrina, MS Topol, IA Collins, JR Nemukhin, AV AF Grigorenko, B. L. Shadrina, M. S. Topol, I. A. Collins, J. R. Nemukhin, A. V. TI Mechanism of the chemical step for the guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor Tu SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE EF-Tu protein; GTP hydrolysis; Molecular modeling; Enzymatic mechanism ID CRYSTAL-STRUCTURE; PHOSPHORYL TRANSFER; MOLECULAR-DYNAMICS; QM/MM SIMULATIONS; AQUEOUS-SOLUTION; RAS P21; EF-TU; PROTEINS; COMPLEX; HISTIDINE-84 AB Elongation factor Tu (EF-Tu), the protein responsible for delivering aminoacyl-tRNAs (aa-tRNAs) to ribosomal A site during translation, belongs to the group of guanosine-nucleotide (GTP/GDP) binding proteins. Its active 'on'-state corresponds to the GTP-bound form, while the inactive 'off-state corresponds to the GDP-bound form. In this work we focus on the chemical step, GTP+H(2)O -> GDP+Pi, of the hydrolysis mechanism. We apply molecular modeling tools including molecular dynamics simulations and the combined quantum mechanical-molecular mechanical calculations for estimates of reaction energy profiles for two possible arrangements of switch II regions of EF-Tu. In the first case we presumably mimic binding of the ternary complex EF-Tu.GTP.aa-tRNA to the ribosome and allow the histidine (His85) side chain of the protein to approach the reaction active site. In the second case, corresponding to the GTP hydrolysis by EF-Tu alone, the side chain of His85 stays away from the active site, and the chemical reaction GTP+H(2)O-GDP+Pi proceeds without participation of the histidine but through water molecules. In agreement with the experimental observations which distinguish rate constants for the fast chemical reaction in EF-Tu.GTP.aa-tRNA-ribosome and the slow spontaneous GTP hydrolysis in EF-Tu, we show that the activation energy barrier for the first scenario is considerably lower compared to that of the second case. (c) 2008 Elsevier B.V. All rights reserved. C1 [Grigorenko, B. L.; Shadrina, M. S.; Nemukhin, A. V.] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia. [Topol, I. A.; Collins, J. R.] SAIC Frederick Inc, NCI Frederick, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Nemukhin, A. V.] Russian Acad Sci, NM Emanuel Inst Biochem Phys, Moscow 119334, Russia. RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Leninskie Gory 1-3, Moscow 119991, Russia. EM anem@lcc.chem.msu.ru RI Nemukhin, Alexander/P-9662-2015 FU Russian Foundation for Basic Research [07-03-00060]; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This work was partly supported by the grant from the Russian Foundation for Basic Research (project #07-03-00060). We thank the staff and administration of the Advanced Biomedical Computing Center for their support for this project. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health NR 49 TC 22 Z9 23 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD DEC PY 2008 VL 1784 IS 12 BP 1908 EP 1917 DI 10.1016/j.bbapap.2008.08.003 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 383KU UT WOS:000261673300003 PM 18773979 ER PT J AU Navath, RS Kurtoglu, YE Wang, B Kannan, S Romero, R Kannan, RM AF Navath, Raghavendra S. Kurtoglu, Yunus E. Wang, Bing Kannan, Sujatha Romero, Robert Kannan, Rangaramanujam M. TI Dendrimer-Drug Conjugates for Tailored Intracellular Drug Release Based on Glutathione Levels SO BIOCONJUGATE CHEMISTRY LA English DT Article ID INFLAMMATORY CYTOKINE RESPONSES; N-ACETYLCYSTEINE; IN-VITRO; DNA DELIVERY; ANTITUMOR-ACTIVITY; FETAL-DEATH; LIPOPOLYSACCHARIDE; CYSTEINE; NANOPARTICLES; CYTOTOXICITY AB N-Acetyl-L-Cysteine (NAC) is an antioxidant and anti-inflammatory agent with significant potential in clinical applications including stroke and neuroinflammation. The drug shows high plasma binding upon IV administration, requiring high doses and associated side effects. Through the use of an appropriate delivery vehicle, the stability and efficacy of NAC can be significantly improved. Dendrimers are an emerging class of nanoscale drug delivery vehicles, which enable high drug payloads and intracellular delivery. Poly(amidoamine) (PAMAM) dendrimer-NAC conjugates having cleavable disulfide linkages are designed for intracellular delivery based on glutathione levels. We have successfully synthesized two conjugates with a cationic G4-NH(2) and an anionic G3.5-COOH PAMAM dendrimer with NAC payloads of 16 and 18 per dendrimer, respectively, as confirmed by (1)H NMR and MALDI-TOF analysis. NAC release from the conjugates at intracellular and extracellular glutathione (GSH) concentrations were evaluated by reverse phase HPLC (RP-HPLC) analysis, and similar to 70% of NAC payload was released within one hour at intracellular GSH concentrations (similar to 10 mM), whereas negligible NAC release was observed at extracellular GSH levels (2 mu M). FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells (the target cells in vivo). The significantly improved efficacies of dendrimer-NAC conjugates in activated microglial cells was confirmed by measuring the nitrite inhibition in the cell culture medium, which is an indication of the antioxidative property of the drug. Both G4-NH(2) and G3.5-COOH conjugates showed significantly better nitrite inhibition both at 24 and 72 h compared to free NAC, by as much as a factor of 16. The results indicate that PAMAM dendrimer conjugates produce higher local NAC concentration inside the cells, with GSH-sensitive disulfide linker enabling efficient and rapid cellular release of the drug. C1 [Navath, Raghavendra S.; Kurtoglu, Yunus E.; Kannan, Rangaramanujam M.] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. [Navath, Raghavendra S.; Wang, Bing; Romero, Robert; Kannan, Rangaramanujam M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. [Wang, Bing; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Crit Care Med, Detroit, MI 48201 USA. RP Kannan, RM (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA. EM rkannan@eng.wayne.edu FU National Institute of Child Health and Human Development; NIH; DHHS FX This study was supported by the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, DHHS. NR 45 TC 95 Z9 97 U1 2 U2 37 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 DEC PY 2008 VL 19 IS 12 BP 2446 EP 2455 DI 10.1021/bc800342d PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 384TT UT WOS:000261767800021 PM 19053299 ER PT J AU Lahiri, DK Zawia, N Greig, N Sambamurti, K Maloney, B AF Lahiri, Debomoy K. Zawia, Nasser H. Greig, Nigel H. Sambamurti, Kumar Maloney, Bryan TI Early-life events may trigger biochemical pathways for Alzheimer's disease: the "LEARn" model SO BIOGERONTOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Advances in Neurosciences held at the Silver Jubilee Conference of the Indian-Academy-of-Neurosciences CY NOV 22-25, 2007 CL Banaras Hindu Univ, Varanasi, INDIA SP Indian Acad Neurosci HO Banaras Hindu Univ DE Latency; Gene regulation; Methylation; Epigenetic; Amyloid; Lead; Pb ID OXIDATIVE STRESS; DNA METHYLATION; DEVELOPMENTAL ORIGIN; PRECURSOR PROTEIN; AGING BRAIN; GENE; EXPOSURE; DIETARY; DAMAGE; SUPPLEMENTATION AB Alzheimer's disease (AD), the most common form of dementia among the elderly, manifests mostly late in adult life. However, it is presently unclear when the disease process starts and how long the pathobiochemical processes take to develop. Our goal is to address the timing and nature of triggers that lead to AD. To explain the etiology of AD, we have recently proposed a "Latent Early-life Associated Regulation" (LEARn) model, which postulates a latent expression of specific genes triggered at the developmental stage. This model integrates both the neuropathological features (e.g., amyloid-loaded plaques and tau-laden tangles) and environmental factors (e.g., diet, metal exposure, and hormones) associated with the disease. Environmental agents perturb gene regulation in a long-term fashion, beginning at early developmental stages, but these perturbations do not have pathological results until significantly later in life. The LEARn model operates through the regulatory region (promoter) of the gene and by affecting the methylation status within the promoter of specific genes. C1 [Lahiri, Debomoy K.; Maloney, Bryan] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. [Zawia, Nasser H.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA. [Greig, Nigel H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Sambamurti, Kumar] Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. RP Lahiri, DK (reprint author), Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, 791 Union Dr, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu RI Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU Intramural NIH HHS [Z01 AG000311-07]; NIA NIH HHS [R01 AG018379-03, AG18379, AG18884, R01 AG018379, R01 AG018379-01, R01 AG018379-02, R01 AG018379-04, R01 AG018379-05, R01 AG018379-06, R01 AG018379-07, R01 AG018379-08, R01 AG018379-09, R01 AG018884, R01 AG018884-01A2, R01 AG018884-02, R01 AG018884-03, R01 AG018884-04, R01 AG018884-05, R01 AG018884-06A1, R01 AG018884-07] NR 23 TC 36 Z9 37 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1389-5729 J9 BIOGERONTOLOGY JI Biogerontology PD DEC PY 2008 VL 9 IS 6 BP 375 EP 379 DI 10.1007/s10522-008-9162-6 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 368IH UT WOS:000260614300003 PM 18668339 ER PT J AU Zhu, YL Davis, S Stephens, R Meltzer, PS Chen, YD AF Zhu, Yuelin Davis, Sean Stephens, Robert Meltzer, Paul S. Chen, Yidong TI GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus SO BIOINFORMATICS LA English DT Article AB The NCBI Gene Expression Omnibus (GEO) represents the largest public repository of microarray data. However, finding data in GEO can be challenging. We have developed GEOmetadb in an attempt to make querying the GEO metadata both easier and more powerful. All GEO metadata records as well as the relationships between them are parsed and stored in a local MySQL database. A powerful, flexible web search interface with several convenient utilities provides query capabilities not available via NCBI tools. In addition, a Bioconductor package, GEOmetadb that utilizes a SQLite export of the entire GEOmetadb database is also available, rendering the entire GEO database accessible with full power of SQL-based queries from within R. Availability: The web interface and SQLite databases available at http://gbnci.abcc.ncifcrf.gov/geo/. The Bioconductor package is available via the Bioconductor project. The corresponding MATLAB implementation is also available at the same website. Contact: yidong@mail.nih.gov C1 [Zhu, Yuelin; Davis, Sean; Meltzer, Paul S.; Chen, Yidong] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Zhu, Yuelin; Stephens, Robert] NCI Frederick, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Chen, YD (reprint author), NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. OI Davis, Sean/0000-0002-8991-6458 FU NIH, National Cancer Institute, Bethesda, USA FX Funding: Intramural Research Program of the NIH, National Cancer Institute, Bethesda, USA. NR 7 TC 40 Z9 40 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 DEC 1 PY 2008 VL 24 IS 23 BP 2798 EP 2800 DI 10.1093/bioinformatics/btn520 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 376FD UT WOS:000261168600029 PM 18842599 ER PT J AU Justinova, Z Mangieri, RA Bortolato, M Chefer, SI Mukhin, AG Clapper, JR King, AR Redhi, GH Yasar, S Piomelli, D Goldberg, SR AF Justinova, Zuzana Mangieri, Regina A. Bortolato, Marco Chefer, Svetlana I. Mukhin, Alexey G. Clapper, Jason R. King, Alvin R. Redhi, Godfrey H. Yasar, Sevil Piomelli, Daniele Goldberg, Steven R. TI Fatty Acid Amide Hydrolase Inhibition Heightens Anandamide Signaling Without Producing Reinforcing Effects in Primates SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anandamide; FAAH; reinstatement; self-administration; URB597; 2-arachidonoylglycerol ID ENDOGENOUS CANNABINOID ANANDAMIDE; ANTIDEPRESSANT-LIKE ACTIVITY; SQUIRREL-MONKEYS; CONTROLLED-TRIAL; DELTA(9)-TETRAHYDROCANNABINOL THC; ENDOCANNABINOID INACTIVATION; MULTIPLE-SCLEROSIS; NEUROPATHIC PAIN; RAT-BRAIN; COCAINE AB Background: CB(1) cannabinoid receptors in the brain are known to participate in the regulation of reward-based behaviors. However, the contribution of each of the endocannabinoid transmitters, anandamide and 2-arachidonoylglycerol (2-AG), to these behaviors remains undefined. To address this question, we assessed the effects of URB597, a selective anandamide deactivation inhibitor, as a reinforcer of drug-seeking and drug-taking behavior in squirrel monkeys. Methods: We investigated the reinforcing effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 in monkeys trained to intravenously self-administer Delta(9)-tetrahydrocannabinol (THC), anandamide, or cocaine and quantified brain endocannabinoid levels using liquid chromatography/mass spectrometry. We measured brain FAAH activity using an ex vivo enzyme assay. Results: URB597 (.3 mg/kg, intravenous) blocked FAAH activity and increased anandamide levels throughout the monkey brain. This effect was accompanied by a marked compensatory decrease in 2-AG levels. Monkeys did not self-administer URB597, and the drug did not promote reinstatement of extinguished drug-seeking behavior previously maintained by THC, anandamide, or cocaine. Pretreatment with URB597 did not modify self-administration of THC or cocaine, even though, as expected, it significantly potentiated anandamide self-administration. Conclusions: In the monkey brain, the FAAH inhibitor URB597 increases anandamide levels while causing a compensatory down-regulation in 2-AG levels. These effects are accompanied by a striking lack of reinforcing properties, which distinguishes URB597 from direct-acting cannabinoid agonists such as THC. Our results reveal an unexpected functional heterogeneity within the endocannabinoid signaling system and suggest that FAAH inhibitors might be used therapeutically without risk of abuse or triggering of relapse to drug abuse. C1 [Mangieri, Regina A.; Bortolato, Marco; Clapper, Jason R.; King, Alvin R.; Piomelli, Daniele] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. [Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. [Chefer, Svetlana I.; Mukhin, Alexey G.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA. [Piomelli, Daniele] Italian Inst Technol, Genoa, Italy. RP Piomelli, D (reprint author), Univ Calif Irvine, Dept Pharmacol, 3101 Gillespie NRF, Irvine, CA 92697 USA. EM piomelli@uci.edu RI Justinova, Zuzana/A-9109-2011; OI Justinova, Zuzana/0000-0001-5793-7484; Bortolato, Marco/0000-0002-4498-9637 FU National Institute on Drug Abuse; National Institutes of Health; Department of Health and Human Services, Baltimore, Maryland; National Institute on Drug Abuse [072447, 077535]; Department of Psychiatry FX This study was supported in part by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland; by National Institute on Drug Abuse Grants Nos. 072447, and 077535 (to DP); and by the Department of Psychiatry. University of Maryland School of Medicine, Baltimore, Maryland. We thank Kathleen Stilwell, Dr. Ira Baum, Phil White, and Dean Shumway for assistance during the brain removal procedure, and Nataliya Gross and Saurabh Sharma for assistance with biochemical experiments. We also thank Dr. Leigh Panlilio for his comments ore the manuscript. DP is an inventor in a patent disclosing fatty acid amide hydrolase inhibitor, owned by the University of California,;vine, and licensed to Organon Biosciences, a unit of Schering-Plough. All other author report no biomedical financial interests or potential conflicts of interest. NR 42 TC 87 Z9 87 U1 1 U2 5 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 DEC 1 PY 2008 VL 64 IS 11 BP 930 EP 937 DI 10.1016/j.biopsych.2008.08.008 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 375PU UT WOS:000261126600003 PM 18814866 ER PT J AU Soldin, OP O'Mara, DM Aschner, M AF Soldin, Offie P. O'Mara, Daniel M. Aschner, Michael TI Thyroid Hormones and Methylmercury Toxicity SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Review DE Selenium; Selenoenzymes; Deiodinase; Pathophysiology; Thyroxine; Triiodothyronine; Mercury; Neurodevelopment ID MESSENGER-RIBONUCLEIC-ACID; RAT CEREBRAL-CORTEX; NEURONAL MIGRATION; MERCURIC-CHLORIDE; SELENOPROTEIN-P; IODOTHYRONINE DEIODINASE; GLUTATHIONE-PEROXIDASE; ANTERIOR-PITUITARY; II 5'-DEIODINASE; DIETARY SELENIUM AB Thyroid hormones are essential for cellular metabolism, growth, and development. In particular, an adequate supply of thyroid hormones is critical for fetal neurodevelopment. Thyroid hormone tissue activation and inactivation in brain, liver, and other tissues is controlled by the deiodinases through the removal of iodine atoms. Selenium, an essential element critical for deiodinase activity, is sensitive to mercury and, therefore, when its availability is reduced, brain development might be altered. This review addresses the possibility that high exposures to the organometal, methylmercury (MeHg), may perturb neurodevelopmental processes by selectively affecting thyroid hormone homeostasis and function. C1 [Soldin, Offie P.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Ctr Sex Differences,Dept Med,LL, Washington, DC 20057 USA. [Soldin, Offie P.] NICHD, Obstet Pharmacol Res Unit, NIH, Bethesda, MD USA. [Aschner, Michael] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Aschner, Michael] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Aschner, Michael] Vanderbilt Univ, Med Ctr, Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Ctr Sex Differences,Dept Oncol,LL, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Ctr Sex Differences,Dept Physiol,LL, Washington, DC 20057 USA. RP Soldin, OP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Ctr Sex Differences,Dept Med,LL, S-166,3800 Reservoir Rd NW, Washington, DC 20057 USA. EM os35@georgetown.edu FU NIH/NICHD Obstetrics Pharmacology Research Unit (OPRU) [5U10HD047890-S]; Office of Research on Women's Health; Public Health Service [ES07331] FX Dr. Soldin was partially supported by 5U10HD047890-S NIH/NICHD Obstetrics Pharmacology Research Unit (OPRU) and by the Office of Research on Women's Health. Michael Aschner was supported in part by Public Health Service Grant ES07331. NR 77 TC 22 Z9 22 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 EI 1559-0720 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD DEC PY 2008 VL 126 IS 1-3 BP 1 EP 12 DI 10.1007/s12011-008-8199-3 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 378NT UT WOS:000261329300001 PM 18716716 ER PT J AU Pavletic, S Vogelsand, GB AF Pavletic, Steven Vogelsand, Georgia B. TI Treatment of High-Risk Chronic GVHD SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID VERSUS-HOST-DISEASE; CRITERIA C1 [Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Vogelsand, Georgia B.] Johns Hopkins Univ, Baltimore, MD USA. RP Pavletic, S (reprint author), NCI, Bethesda, MD 20892 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2008 VL 14 IS 12 BP 1436 EP 1437 DI 10.1016/j.bbmt.2008.05.016 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 384OR UT WOS:000261754600017 PM 19041069 ER PT J AU Mayrand-Chung, S AF Mayrand-Chung, Shawnmarie TI The Biomarkers Consortium: a novel public-private partnership leading the cutting-edge of biomarker research SO BIOMARKERS IN MEDICINE LA English DT Article DE biomarkers; personalized medicine; research collaboration AB Biomarkers are molecular, biological or physical characteristics that indicate a specific, underlying physiologic state and are used to to identify risk for disease, make diagnoses and guide treatment, thus having the potential to revolutionize biomedical research, drug development and clinical practice. The Biomarkers Consortium has taken the first step towards implementing a cross-sector and cross-disciplinary approach to biomarker development. C1 NIH, OSPA Off Director, Biomarkers Consortium Publ Private Partnership Pr, Bethesda, MD 20892 USA. RP Mayrand-Chung, S (reprint author), NIH, OSPA Off Director, Biomarkers Consortium Publ Private Partnership Pr, Bldg 1,Room213,MSC 0166,9000 Rockville Pike, Bethesda, MD 20892 USA. EM mayrands@od.nih.gov NR 1 TC 0 Z9 0 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD DEC PY 2008 VL 2 IS 6 BP 617 EP 621 DI 10.2217/17520363.2.6.617 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 388LL UT WOS:000262021200019 ER PT J AU Berger, VW AF Berger, Vance W. TI Untitled SO BIOMETRICAL JOURNAL LA English DT Letter DE Fisher's exact test; Randomized test ID STOCHASTIC ORDER; TESTS C1 Univ Maryland Baltimore Cty, Biometry Res Grp, NCI, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), Univ Maryland Baltimore Cty, Biometry Res Grp, NCI, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 5 TC 1 Z9 1 U1 1 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2008 VL 50 IS 6 BP 1093 EP 1095 DI 10.1002/bimj.200810479 PG 3 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 386ES UT WOS:000261865700016 PM 19035556 ER PT J AU Zheng, G AF Zheng, Gang TI Analysis of Ordered Categorical Data: Two Score-Independent Approaches SO BIOMETRICS LA English DT Article DE BASE; MAX; Ordered categorical data; Parametric bootstrap; Robust test; Scores ID EFFICIENCY ROBUST-TESTS; NUISANCE PARAMETER; CONTINGENCY-TABLES; TREND TESTS; STATISTICS; DRAWBACKS; SURVIVAL; MIN; MAX AB A trend test is often employed to analyze ordered categorical data, in which a set of increasing scores is assigned a priori. There is a drawback in this approach, because how to choose a set of scores is not clear. There have been debates on which scores should be used (e. g., Graubard and Korn, 1987, Biometrics 43, 471-476; Ivanova and Berger, 2001, Biometrics 57, 567-570; Senn, 2007, Biometrics 63, 296-298). Conflicting conclusions are often obtained with different sets of scores. Two approaches, which have been applied to genetic case-control studies, are appealing for ordered categorical data, because they take into account the natural order in the data, are score independent, and not contingent on asymptotic theory. These two approaches are applied to a prospective study for detecting association between maternal drinking and congenital malformations. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 15 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2008 VL 64 IS 4 BP 1276 EP 1279 DI 10.1111/j.1541-0420.2008.00992.x PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 374OV UT WOS:000261054500032 PM 18266890 ER PT J AU Li, Y Tiwari, RC AF Li, Yi Tiwari, Ram C. TI Comparing Trends in Cancer Rates Across Overlapping Regions SO BIOMETRICS LA English DT Article DE Age-adjusted cancer rates; Annual percent change (APC); Hypothesis testing; Pitman asymptotic relative efficiency (ARE); Surveillance; Trends ID REGRESSION AB Monitoring and comparing trends in cancer rates across geographic regions or over different time periods have been major tasks of the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) Program as it profiles healthcare quality as well as decides healthcare resource allocations within a spatial-temporal framework. A fundamental difficulty, however, arises when such comparisons have to be made for regions or time intervals that overlap, for example, comparing the change in trends of mortality rates in a local area (e. g., the mortality rate of breast cancer in California) with a more global level (i.e., the national mortality rate of breast cancer). In view of sparsity of available methodologies, this article develops a simple corrected Z-test that accounts for such overlapping. The performance of the proposed test over the two-sample "pooled" t-test that assumes independence across comparison groups is assessed via the Pitman asymptotic relative efficiency as well as Monte Carlo simulations and applications to the SEER cancer data. The proposed test will be important for the SEER*STAT software, maintained by the NCI, for the analysis of the SEER data. C1 [Li, Yi] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Li, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tiwari, Ram C.] NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. EM yili@jimmy.harvard.edu; tiwarir@mail.nih.gov FU NCI FX The authors would like to thank the editor, the associate editor, and an anonymous referee for insightful suggestions that improved the original manuscript. The authors thank Steve Scoppa and Joe Zou of Information Management Services (IMS), Inc., the company that provides biomedical computing support to the NCI, for their valuable contributions. The authors also thank Dr Rocky Feuer for carefully reading an early draft of this work and for many insightful suggestions. NR 8 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2008 VL 64 IS 4 BP 1280 EP 1286 DI 10.1111/j.1541-0420.2008.01002.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 374OV UT WOS:000261054500033 PM 18371122 ER PT J AU Chen, BE Kramer, JL Greene, MH Rosenberg, PS AF Chen, Bingshu E. Kramer, Joan L. Greene, Mark H. Rosenberg, Philip S. TI Untitled SO BIOMETRICS LA English DT Letter C1 [Chen, Bingshu E.] Queens Univ, Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. [Kramer, Joan L.] Natl Home Off, Amer Canc Soc, Atlanta, GA USA. [Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Chen, BE (reprint author), Queens Univ, Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. EM bechen@ctg.queensu.ca OI Chen, Bingshu/0000-0001-6139-0696 NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2008 VL 64 IS 4 BP 1297 EP 1298 DI 10.1111/j.1541-0420.2008.01136_1.x PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 374OV UT WOS:000261054500037 ER PT J AU Dunson, DB Peddada, SD AF Dunson, David B. Peddada, Shyamal D. TI Bayesian nonparametric inference on stochastic ordering SO BIOMETRIKA LA English DT Article ID DENSITY-ESTIMATION; MODELS; DISTRIBUTIONS; CONSISTENCY; MIXTURES; ALTERNATIVES; PRIORS AB We consider Bayesian inference about collections of unknown distributions subject to a partial stochastic ordering. To address problems in testing of equalities between groups and estimation of group-specific distributions, we propose classes of restricted dependent Dirichlet process priors. These priors have full support in the space of stochastically ordered distributions, and can be used for collections of unknown mixture distributions to obtain a flexible class of mixture models. Theoretical properties are discussed, efficient methods are developed for posterior computation using Markov chain Monte Carlo simulation and the methods are illustrated using data from a study of DNA damage and repair. C1 [Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. [Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), Duke Univ, Dept Stat Sci, Box 90251, Durham, NC 27708 USA. EM dunson@stat.duke.edu; peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU U.S. Intramural Research Program; National Institutes of Health; National Institute of Environmental Health Sciences FX This research was supported by the U.S. Intramural Research Program, National Institutes of Health and National Institute of Environmental Health Sciences. The authors thank an anonymous referee for important comments. NR 29 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2008 VL 95 IS 4 BP 859 EP 874 DI 10.1093/biomet/asn043 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 377VN UT WOS:000261279900006 ER PT J AU Clement, JA Kitagaki, J Yang, Y Saucedo, CJ O'Keefe, BR Weissman, AM Mckee, TC McMahon, JB AF Clement, Jason A. Kitagaki, Jirouta Yang, Yili Saucedo, Carrie J. O'Keefe, Barry R. Weissman, Allan M. Mckee, Tawnya C. McMahon, James B. TI Discovery of new pyridoacridine alkaloids from Lissoclinum cf. badium that inhibit the ubiquitin ligase activity of Hdm2 and stabilize p53 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Hdm2; Mdm2; Pyridoacridine; Lissoclinum; Marine natural product; Ascidian ID SMALL-MOLECULE INHIBITORS; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; ONCOPROTEIN MDM2; TUMOR-SUPPRESSOR; MARINE TUNICATE; IDENTIFICATION; BISTRATUM; VARACIN; PROTEIN AB Compounds that stabilize p53 could suppress tumors providing a additional tool to fight cancer. Mdm2, and the human ortholog, Hdm2 serve as ubiquitin E3 ligases and target p53 for ubiquitylation and degradation. Inhibition of Hdm2 stabilizes p53, inhibits cell proliferation and induces apoptosis. Using HTS to discover inhibitors, we identified three new alkaloids, isolissoclinotoxin B, diplamine B, and lissoclinidine B from Lissoclinum cf. badium. Lissoclinidine B inhibited ubiquitylation and degradation of p53, and selectively killed transformed cells harboring wild-type p53, suggesting this compound could be used to develop new treatments. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Kitagaki, Jirouta; Yang, Yili; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Clement, Jason A.; O'Keefe, Barry R.; Mckee, Tawnya C.; McMahon, James B.] NCI, Mol Targets Dev Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Saucedo, Carrie J.] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM amw@nih.gov; mckee@ncifcrf.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX We thank Cheryl Thomas, and Tanya Johnson (MTDP) for performing the Hdm2 assay, John Lloyd (NIDDK, NIH) for collecting MS data, Dave Newman (Natural Products Branch, NCI) and Pat Colin (Coral Reef Research Foundation) for collections, Tom McCloud (SAIC-Frederick) for extraction of the animal material, and Kentaro Takada (MTDP) for helpful discussions. We are also grateful to the NIH Fellows Editorial Board for editorial assistance. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. J.K. is a fellow of Japanese Society for the Promotion of Science. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 48 TC 23 Z9 23 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 1 PY 2008 VL 16 IS 23 BP 10022 EP 10028 DI 10.1016/j.bmc.2008.10.024 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 372UH UT WOS:000260927000014 PM 18977148 ER PT J AU Lam, SN Acharya, P Wyatt, R Kwong, PD Bewley, CA AF Lam, Son N. Acharya, Priyamvada Wyatt, Richard Kwong, Peter D. Bewley, Carole A. TI Tyrosine-sulfate isosteres of CCR5 N-terminus as tools for studying HIV-1 entry SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV-1 gp120; Phenylmethanesulfonic acid; Tyrosine sulfonate; Saturation transfer difference NMR; Surface plasmon resonance; Enzyme-linked immunosorbent assay; Small molecule inhibitor ID ENVELOPE GLYCOPROTEINS; STAUDINGER LIGATION; GP120; RECEPTORS; PEPTIDES; BINDING AB The HIV-1 co-receptor CCR5 possesses sulfo-tyrosine (TYS) residues at its N-terminus (Nt) that are required for binding HIV-1 gp120 and mediating viral entry. By using a 14-residue fragment of CCR5 Nt containing two TYS residues, we recently showed that CCR5 Nt binds gp120 through a conserved region specific for TYS moieties and suggested that this site may represent a target for inhibitors and probes of HIV-1 entry. As peptides containing sulfo-tyrosines are difficult to synthesize and handle due to limited stability of the sulfo-ester moiety, we have now incorporated TYS isosteres into CCR5 Nt analogs and assessed their binding to a complex of gp120-CD4 using saturation transfer difference (STD) NMR and surface plasmon resonance (SPR). STD enhancements for CCR5 Nt peptides containing tyrosine sulfonate (TYSN) in complex with gp120-CD4 were very similar to those observed for sulfated CCR5 Nt peptides indicating comparable modes of binding. STD enhancements for phosphotyrosine-containing CCR5 Nt analogs were greatly diminished consistent with earlier findings showing sulfo-tyrosine to be essential for CCR5 Nt binding to gp120. Tyrosine sulfonate-containing CCR5 peptides exhibited reduced water solubility, limiting their use in assay and probe development. To improve solubility, we designed, synthesized, and incorporated in CCR5 Nt peptide analogs an orthogonally functionalized azido tris(ethylenoxy) L-alanine (L-ate-Ala) residue. Through NMR and SPR experiments, we show a 19-residue TYSN-containing peptide to be a functional, hydrolytically stable CCR5 Nt isostere that was in turn used to develop both SPR-based and ELISA assays to screen for inhibitors of CCR5 binding to gp120-CD4. Published by Elsevier Ltd. C1 [Lam, Son N.; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Acharya, Priyamvada; Wyatt, Richard; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, DHHS, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU NIDDK; NIAID; Intramural Research Programs; Bill and Melinda Gates Foundation Grand Challenges in Global Health Initiative; Intramural AIDS Targeted Antiviral Program FX We thank J. Lloyd for HRMS data, J. Robinson for 412d and 2.2c antibodies, C.- C. Huang for assistance with expression and purification of gp120 and antibodies, and the NIH AIDS Research and Reference Regent Program for soluble CD4. This work was supported by the NIDDK ( C. A. B.) and NIAID ( P. D. K. and R. W.) Intramural Research Programs, a grant from the Bill and Melinda Gates Foundation Grand Challenges in Global Health Initiative ( P. D. K. and R. W.), and the Intramural AIDS Targeted Antiviral Program (IATAP) of the Office of the Director, NIH ( C. A. B.). NR 25 TC 24 Z9 24 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD DEC 1 PY 2008 VL 16 IS 23 BP 10113 EP 10120 DI 10.1016/j.bmc.2008.10.005 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 372UH UT WOS:000260927000025 PM 18952441 ER PT J AU Takeuchi, Y Fujiwara, T Shimone, Y Miyataka, H Satoh, T Kirk, KL Hori, H AF Takeuchi, Yoshio Fujiwara, Tomoya Shimone, Yoshihito Miyataka, Hideki Satoh, Toshio Kirk, Kenneth L. Hori, Hitoshi TI Possible involvement of radical intermediates in the inhibition of cysteine proteases by allenyl esters and amides SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Allene; Cysteine protease; Cysteine protease inhibitor; Oxygen; Radical ID ACTIVE-SITE; THIOL-SUBTILISIN; SERINE RESIDUE; CASPASES; ENZYME; PROTEINASES; TRYPSIN AB In order to investigate crystallographically the mechanism of inhibition of cysteine protease by alpha-methyl-gamma, gamma-diphenylallenecarboxylic acid ethyl ester 3, a cysteine protease inhibitor having in vivo stability, we synthesized N-(alpha-methyl-gamma, gamma-diphenylallenecarbonyl)-L-phenylalanine ethyl ester 4. Reaction of 4 with thiophenol, the SH group of which has similar pK(a) value to that of cysteine protease, produced oxygen-mediated radical adducts 6 and 7 in ambient air but did not proceed under oxygen-free conditions. Catalytic activities of two thiol enzymes including cathepsin B were also lowered in the absence of oxygen. These results suggest that cysteine protease can act through an oxygen-dependent radical mechanism. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Takeuchi, Yoshio; Fujiwara, Tomoya] Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan. [Shimone, Yoshihito; Miyataka, Hideki; Satoh, Toshio] Tokushima Bunri Univ, Fac Pharmaceut Sci, Yamashiro, Tokushima 7708514, Japan. [Kirk, Kenneth L.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. [Hori, Hitoshi] Univ Tokushima, Inst Sci & Technol, Grad Sch, Dept Life Syst, Tokushima 7708506, Japan. RP Takeuchi, Y (reprint author), Toyama Univ, Grad Sch Med & Pharmaceut Sci Res, Sugitani 2630, Toyama 9300194, Japan. EM takeuchi@pha.u-toyama.ac.jp FU NIDDK FX We thank T. Kimoto and C. Nakamura for experimental assistance. K. L. K. acknowledges support from the intramural research funds of NIDDK. NR 27 TC 4 Z9 4 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 1 PY 2008 VL 18 IS 23 BP 6202 EP 6205 DI 10.1016/j.bmcl.2008.10.007 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 370UW UT WOS:000260789600040 PM 18951789 ER PT J AU Hale, CM Shrestha, AL Khatau, SB Stewart-Hutchinson, PJ Hernandez, L Stewart, CL Hodzic, D Wirtz, D AF Hale, Christopher M. Shrestha, Arun L. Khatau, Shyam B. Stewart-Hutchinson, P. J. Hernandez, Lidia Stewart, Colin L. Hodzic, Didier Wirtz, Denis TI Dysfunctional Connections Between the Nucleus and the Actin and Microtubule Networks in Laminopathic Models SO BIOPHYSICAL JOURNAL LA English DT Article ID DREIFUSS MUSCULAR-DYSTROPHY; MEMBRANE PROTEIN; MECHANICAL STIFFNESS; ENVELOPE INTEGRITY; MTOC POLARIZATION; MIGRATING CELLS; SHEAR-STRESS; LAMIN-A; EMERIN; MUTATIONS AB Laminopathies encompass a wide array of human diseases associated to scattered mutations along LMNA, a single gene encoding A-type lamins. How such genetic alterations translate to cellular defects and generate such diverse disease phenotypes remains enigmatic. Recent work has identified nuclear envelope proteins-emerin and the linker of the nucleoskeleton and cytoskeleton (LINC) complex-which connect the nuclear lamina to the cytoskeleton. Here we quantitatively examine the composition of the nuclear envelope, as well as the architecture and functions of the cytoskeleton in cells derived from two laminopathic mouse models, including Hutchinson-Gilford progeria syndrome (Lmna(L530P/L530P)) and Emery-Dreifuss muscular dystrophy (Lmna(-/-)). Cells derived from the overtly aphenotypical model of X-linked Emery-Dreifuss muscular dystrophy (Emd(-/y)) were also included. We find that the centrosome is detached from the nucleus, preventing centrosome polarization in cells under flow-defects that are mediated by the loss of emerin from the nuclear envelope. Moreover, while basal actin and focal adhesion structure are mildly affected, RhoA activation, cell-substratum adhesion, and cytoplasmic elasticity are greatly lowered, exclusively in laminopathic models in which the LINC complex is disrupted. These results indicate a new function for emerin in cell polarization and suggest that laminopathies are not directly associated with cells' inability to polarize, but rather with cytoplasmic softening and weakened adhesion mediated by the disruption of the LINC complex across the nuclear envelope. C1 [Hale, Christopher M.; Shrestha, Arun L.; Khatau, Shyam B.; Wirtz, Denis] Washington Univ, Sch Med, Dept Chem & Biomol Engn, St Louis, MO 63130 USA. [Stewart-Hutchinson, P. J.; Hodzic, Didier] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO USA. [Hernandez, Lidia] Natl Canc Inst, Frederick, MD USA. [Stewart, Colin L.] Inst Med Biol, Singapore, Singapore. [Wirtz, Denis] Johns Hopkins Univ, Howard Hughes Med Inst, Grad Training Program NBMed, Baltimore, MD USA. [Wirtz, Denis] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD USA. RP Wirtz, D (reprint author), Washington Univ, Sch Med, Dept Chem & Biomol Engn, St Louis, MO 63130 USA. EM dhodzic@wustl.edu; wirtz@jhu.edu RI Wirtz, Denis/A-3257-2010; Khatau, Shyam/D-6985-2011; Hale, Christopher/A-6633-2009 OI Hale, Christopher/0000-0002-2360-7759 FU National Institutes of Health [GM084204]; Muscular Dystrophy Association FX This work was partly supported by National Institutes of Health No. grant GM084204 (to D.W. and D.H.) and a Muscular Dystrophy Association grant (to D.H.). NR 60 TC 95 Z9 96 U1 1 U2 11 PU BIOPHYSICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC 1 PY 2008 VL 95 IS 11 BP 5462 EP 5475 DI 10.1529/biophysj.108.139428 PG 14 WC Biophysics SC Biophysics GA 373UR UT WOS:000260999500044 PM 18790843 ER PT J AU Sapsford, KE Sun, S Francis, J Sharma, S Kostov, Y Rasooly, A AF Sapsford, Kim E. Sun, Steven Francis, Jesse Sharma, Shashi Kostov, Yordan Rasooly, Avraham TI A fluorescence detection platform using spatial electroluminescent excitation for measuring botulinum neurotoxin A activity SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Electroluminescent excitation; CCD; Fluorescence; Forster resonance energy transfer (FRET); Botulinum neurotoxin A; Biodetection; Point of care ID LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; ARRAY BIOSENSOR; NEUROTRANSMITTER RELEASE; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MASS-SPECTROMETRY; RAPID DETECTION; B NEUROTOXIN; SENSOR ARRAY AB Current biodetection illumination technologies (laser. LED, tungsten lamp, etc.) are based on spot illumination with additional optics required when spatial excitation is required. Herein we describe a new approach of spatial illumination based on electroluminescence (EL) semiconductor strips available in several wavelengths, greatly simplifying the biosensor design by eliminating the need for additional optics. This work combines EL excitation with charge-coupled device (CCD) based detection (EL-CCD detector) of fluorescence for developing a simple portable detector for botulinum neurotoxin A (BoTN-A) activity analysis. A Forster Resonance Energy Transfer (FRET) activity assay for BoTN-A was used to both characterize and optimize the EL-CCD detector. The system consists of two modules: (1) the detection module which houses the CCD camera and emission filters, and (2) the excitation and sample module, containing the EL strip, the excitation filter and the 9-well sample chip. The FRET activity assay used in this study utilized a FITC/DABCYL-SNAP-25 peptide substrate in which cleavage of the substrate by BoTN-A, or its light chain derivative (LcA), produced an increase in fluorescence emission. EL-CCD detector measured limits of detection (LODs) were similar to those measured using a standard fluorescent plate reader with valves between 0.625 and 1.25 nM (31-62 ng/ml) for LcA and 0.313 nM (45 ng/ml) for the full toxin, BoTN-A. As far as the authors are aware this is the first demonstration of phosphor-based EL strips being used for the spatial illumination/excitation of a surface, coupled with CCD for point of care detection. Published by Elsevier B.V. C1 [Sapsford, Kim E.; Sun, Steven; Francis, Jesse; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Sun, Steven; Francis, Jesse; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Sharma, Shashi] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Rasooly, Avraham] NCI, Rockville, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd,EPN Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Office of Public Health emergency Preparedness (OPHEP) [IAG 224-05-655]; FDA [HHSF223200610765P] FX We would like to thank Dr. Nikolay Sergeev and Mr. Sean Wilson for their technical assistance. This work was supported in part by the Office of Public Health emergency Preparedness (OPHEP) IAG 224-05-655 (to A. Rasooly) and by FDA contract HHSF223200610765P (to Dr. Yordan Kostov). NR 52 TC 31 Z9 31 U1 1 U2 20 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD DEC 1 PY 2008 VL 24 IS 4 BP 618 EP 625 DI 10.1016/j.bios.2008.06.018 PG 8 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 377PB UT WOS:000261262000018 PM 18644709 ER PT J AU Mallinger, AG Thase, ME Haskett, R Buttenfield, J Luckenbaugh, DA Frank, E Kupfer, DJ Manji, HK AF Mallinger, Alan G. Thase, Michael E. Haskett, Roger Buttenfield, Joan Luckenbaugh, David A. Frank, Ellen Kupfer, David J. Manji, Husseini K. TI Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms SO BIPOLAR DISORDERS LA English DT Article DE antimanic; bipolar disorder; lithium; mania; protein kinase C; verapamil ID PROTEIN-KINASE-C; BIPOLAR AFFECTIVE-DISORDER; INTRACELLULAR CALCIUM MOBILIZATION; CELLULAR PLASTICITY CASCADES; STRIATAL SYNAPTOSOMES; I DISORDER; DOPAMINE TRANSPORT; PHOSPHORYLATION; AMPHETAMINE; BRAIN AB Attenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n = 10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3. Response in Phase 2 did not differ significantly between verapamil and continued-lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2. In this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general. C1 [Mallinger, Alan G.] NIMH, Mood & Anxiety Disorders Program, DIRP, NIH,Intramural Res Program, Bethesda, MD 20892 USA. [Mallinger, Alan G.; Thase, Michael E.; Haskett, Roger; Buttenfield, Joan; Frank, Ellen; Kupfer, David J.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Mallinger, AG (reprint author), NIMH, Mood & Anxiety Disorders Program, DIRP, NIH,Intramural Res Program, Bldg 10,Room 3N210,MSC 1290, Bethesda, MD 20892 USA. EM mallingera@mail.nih.gov FU National Institute of Mental Health [MH50634, MH29618]; NIH, National Institute of Mental Health FX This work was supported in part by grants MH50634 (AGM) and MH29618 (EF) from the National Institute of Mental Health, and in part by the Intramural Program of the NIH, National Institute of Mental Health. This work was initially performed at the University of Pittsburgh, prior to AGM official duties as a government employee. The views expressed in this paper do not necessarily represent the views of the NIMH, NIH, or the United States Government. This study is registered with ClinicalTrials. gov (identifier: NCT00518947). NR 68 TC 16 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2008 VL 10 IS 8 BP 856 EP 866 DI 10.1111/j.1399-5618.2008.00636.x PG 11 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 374OU UT WOS:000261054400002 PM 19594501 ER PT J AU Grubb, RL Pinsky, PF Greenlee, RT Izmirlian, G Miller, AB Hickey, TP Riley, TL Mabie, JE Levin, DL Chia, D Kramer, BS Reding, DJ Church, TR Yokochi, LA Kvale, PA Weissfeld, JL Urban, DA Buys, SS Gelmann, EP Ragard, LR Crawford, ED Prorok, PC Gohagan, JK Berg, CD Andriole, GL AF Grubb, Robert L., III Pinsky, Paul F. Greenlee, Robert T. Izmirlian, Grant Miller, Anthony B. Hickey, Thomas P. Riley, Thomas L. Mabie, Jerome E. Levin, David L. Chia, David Kramer, Barnett S. Reding, Douglas J. Church, Timothy R. Yokochi, Lance A. Kvale, Paul A. Weissfeld, Joel L. Urban, Donald A. Buys, Saundra S. Gelmann, Edward P. Ragard, Lawrence R. Crawford, E. David Prorok, Philip C. Gohagan, John K. Berg, Christine D. Andriole, Gerald L. CA PLCO Project Team TI Prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: update on findings from the initial four rounds of screening in a randomized trial SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; screening; PSA; DRE ID ANTIGEN; MORTALITY AB To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality. In all, 38 349 men aged 55-74 years were randomized to undergo annual screening with PSA (abnormal > 4.0 ng/mL) and a DRE. The follow-up of abnormal screening results was at the discretion of subjects' physicians. PLCO staff obtained records related to diagnostic follow-up of positive screen results. Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7-8.8% at T0-T3) and DRE positivity rates (range 6.8-7.6% at T0-T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of > 4.0 ng/mL decreased from 17.9% at T0 to 10.4-12.3% at T1-T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9-3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen-detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7-10 (34%) than screen-detected cancers at T1-T3 (1.5-4.2% stage III/IV and 24-27% Gleason score 7-10 among 1054 cases). The present findings on serial prostate screening are similar to those reported from other multi-round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow-up. C1 [Grubb, Robert L., III; Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Izmirlian, Grant; Levin, David L.; Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Pinsky, Paul F.; Gohagan, John K.; Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Crawford, E. David] Univ Colorado, Anschutz Canc Pavil, Denver, CO 80202 USA. [Gelmann, Edward P.] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. [Chia, David] Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. [Kramer, Barnett S.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA. [Greenlee, Robert T.; Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. [Church, Timothy R.] Univ Minnesota, Minneapolis, MN USA. [Yokochi, Lance A.] Pacific Hlth Res Inst, Honolulu, HI USA. [Kvale, Paul A.] Henry Ford Hlth Syst, Detroit, MI USA. [Weissfeld, Joel L.] Univ Pittsburgh, Med Ctr Canc Pavil, Pittsburgh, PA USA. [Buys, Saundra S.] Huntsman Canc Inst, Salt Lake City, UT USA. [Urban, Donald A.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Ragard, Lawrence R.] Westat Corp, Rockville, MD USA. [Hickey, Thomas P.; Riley, Thomas L.; Mabie, Jerome E.] Informat Management Serv Inc, Rockville, MD USA. RP Andriole, GL (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl,Campus Box 8242, St Louis, MO 63110 USA. EM andrioleg@wudosis.wustl.edu OI Church, Timothy R./0000-0003-3292-5035 FU National Cancer Institute; UCLA FX This work was supported by individual contracts from the National Cancer Institute to each of the 10 screening centres, the coordinating centre, and the clinical laboratory at UCLA. NR 19 TC 73 Z9 73 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 EI 1464-410X J9 BJU INT JI BJU Int. PD DEC PY 2008 VL 102 IS 11 BP 1524 EP 1530 DI 10.1111/j.1464-410X.2008.08214.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 375TD UT WOS:000261135300009 PM 19035857 ER PT J AU Gardner, ER Ahlers, CM Shukla, S Sissung, TM Ockers, SB Price, DK Hamada, A Robey, RW Steinberg, SM Ambudkar, SV Dahut, WL Figg, WD AF Gardner, Erin R. Ahlers, Christoph M. Shukla, Suneet Sissung, Tristan M. Ockers, Sandra B. Price, Douglas K. Hamada, Akinobu Robey, Robert W. Steinberg, Seth M. Ambudkar, Suresh V. Dahut, William L. Figg, William D. TI Association of the ABCG2 C421A polymorphism with prostate cancer risk and survival SO BJU INTERNATIONAL LA English DT Article DE transport; prostate cancer; mutations; diet; survival; risk ID 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; MULTIDRUG TRANSPORTER; HETEROCYCLIC AMINES; DRUG-RESISTANCE; PROTEIN; PHARMACOKINETICS; DISPOSITION; MEAT; PHARMACOGENETICS; LOCALIZATION AB To determine if the C421A single nucleotide polymorphism (SNP) in the ATP-binding cassette transporter ABCG2 increases prostate cancer risk or affects survival. Numerous studies have suggested that dietary, hormonal and environmental factors all play a role in the initiation in prostate cancer; among these, the carcinogenic heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a known substrate of the ABCG2. A SNP of ABCG2, C421A, resulting in a glutamine to lysine change at amino acid 141, has been shown to result in decreased function of the protein. Due to the expression of ABCG2 in the prostate, together with the purported role of dietary carcinogens and steroids in the development and progression of prostate cancer, 311 individuals were genotyped for the ABCG2 C421A SNP, 170 patients with androgen-independent prostate cancer (AIPC) and 141 'healthy' controls. We also evaluated the effect of this SNP on the intracellular accumulation of PhIP and testosterone in vitro. There were no significant differences in the prevalence of prostate cancer based on ABCG2 genetic variation in this population. However, survival was significantly longer for individuals with wild-type ABCG2, as compared with those hetero- or homozygous for the C421A SNP (7.4 years vs 5.3 years, P = 0.044). Intracellular accumulation of PhIP was 80% higher in HEK293 cells transfected with Q141K ABCG2 than in wild-type cells, confirming that this SNP decreases transport of PhIP. In contrast, testosterone was not transported by either wild-type or variant transfected cells, nor did it act as in inhibitor of ABCG2 in subsequent transport assays. Increased exposure to PhIP may decrease survival, but the ABCG2 C421A polymorphism does not appear to increase the risk of prostate cancer. C1 [Ahlers, Christoph M.; Sissung, Tristan M.; Ockers, Sandra B.; Price, Douglas K.; Hamada, Akinobu; Robey, Robert W.; Dahut, William L.; Figg, William D.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick, Frederick, MD 21701 USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI shukla, suneet/B-4626-2012; Figg Sr, William/M-2411-2016 FU NCI; NIH [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the NCI, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 33 TC 12 Z9 13 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD DEC PY 2008 VL 102 IS 11 BP 1694 EP 1699 DI 10.1111/j.1464-410X.2008.07913.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 375TD UT WOS:000261135300039 PM 18710444 ER PT J AU Jaffe, ES Harris, NL Stein, H Isaacson, PG AF Jaffe, Elaine S. Harris, Nancy Lee Stein, Harald Isaacson, Peter G. TI Classification of lymphoid neoplasms: the microscope as a tool for disease discovery SO BLOOD LA English DT Review ID B-CELL LYMPHOMA; REED-STERNBERG CELLS; NON-HODGKINS-LYMPHOMAS; IMMUNOGLOBULIN-GENE REARRANGEMENTS; HEALTH-ORGANIZATION CLASSIFICATION; PRIMARY FOLLICULAR LYMPHOMA; POLYMERASE CHAIN-REACTION; MALIGNANT-LYMPHOMA; HELICOBACTER-PYLORI; BURKITTS-LYMPHOMA AB In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)-cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory. (Blood. 2008;112:4384-4399) C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Harris, Nancy Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stein, Harald] Charite Univ Med Berlin, Inst Pathol, D-13353 Berlin, Germany. [Isaacson, Peter G.] UCL, Sch Med, Dept Histopathol, London W1N 8AA, England. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bldg 10,Room 2B 42,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov NR 175 TC 167 Z9 182 U1 1 U2 12 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 DEC 1 PY 2008 VL 112 IS 12 BP 4384 EP 4399 DI 10.1182/blood-2008-07-077982 PG 16 WC Hematology SC Hematology GA 376XT UT WOS:000261217000010 PM 19029456 ER PT J AU Wu, Z Xue, HH Bernard, J Zeng, R Issakov, D Bollenbacher-Reilley, J Belyakov, IM Oh, S Berzofsky, JA Leonard, WJ AF Wu, Zheng Xue, Hai-Hui Bernard, Jerome Zeng, Rong Issakov, Dmitry Bollenbacher-Reilley, Julie Belyakov, Igor M. Oh, SangKon Berzofsky, Jay A. Leonard, Warren J. TI The IL-15 receptor alpha chain cytoplasmic domain is critical for normal IL-15R alpha function but is not required for trans-presentation SO BLOOD LA English DT Article ID CD8(+) T-CELLS; HUMAN INTERLEUKIN-2 RECEPTOR; NATURAL-KILLER-CELLS; BETA-CHAIN; IMMUNODEFICIENCY DISEASES; LYMPHOID HOMEOSTASIS; SIGNALING PATHWAYS; GAMMA-CHAIN; IN-VIVO; MEMORY AB IL-15 is critical for natural killer (NK)-cell development and function and for memory CD8(+) T-cell homeostasis. The IL-15 receptor consists of IL-15R alpha, IL-2R beta, and the common cytokine receptor gamma chain (gamma(c)). IL-15R alpha is known to "trans-present" IL-15 to an IL-2R beta/gamma(c) heterodimeric receptor on responding cells to initiate signaling. To investigate the importance of the IL-15R alpha cytoplasmic domain, we generated a chimeric receptor consisting of the extracellular domain of IL-15R alpha and intracellular domain of IL-2R alpha (IL-15R alpha(ext)/IL-2R alpha(int)) and examined its function in 32D cells, in knock-in (KI) mice, and in adoptive-transfer experiments. The chimeric protein exhibited decreased cell-surface expression, and KI mice exhibited diminished NK, NKT, and CD8(+) T-cell development and defects in T-cell functional responses. However, 32D cells expressing the chimeric receptor had less IL-15-induced proliferation than wild-type (WT) transfectants with similar levels of IL-15R alpha expression, indicating a signaling role for the IL-15R alpha cytoplasmic domain beyond its effect on expression, and demonstrating that the IL-2R alpha and IL-15R alpha cytoplasmic domains are functionally distinct. Interestingly, adoptive-transfer experiments indicated that the chimeric IL-15R alpha(ext)/ IL-2R alpha(int) receptor still supports trans-presentation. These experiments collectively indicate that IL-15R alpha can act in cis in addition to acting in trans to present IL-15 to responding cells. (Blood. 2008;112:4411-4419) C1 [Wu, Zheng; Xue, Hai-Hui; Bernard, Jerome; Zeng, Rong; Bollenbacher-Reilley, Julie; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Issakov, Dmitry; Belyakov, Igor M.; Oh, SangKon; Berzofsky, Jay A.] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Oh, SangKon] Baylor Univ, Med Ctr, Baylor Inst Immunol Res, Dallas, TX USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7B05, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Intramural Research Programs of NHLBI and NCI, NIH FX We thank Dr Cheng-Yu Liu for generating the IL-15R alphaext/IL-2R alphaint KI mice; Constance Robinson for maintaining the mice strains; and Drs. Yutaka Tagaya, Christian Hinrichs (both from the National Cancer Institute [NCI]), Keji Zhao, Rosanne Spolski, and Jian-Xin Lin (all from NHLBI) for valuable discussions.; This work was supported by the Intramural Research Programs of NHLBI and NCI, NIH. NR 54 TC 15 Z9 15 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 DEC 1 PY 2008 VL 112 IS 12 BP 4411 EP 4419 DI 10.1182/blood-2007-03-080697 PG 9 WC Hematology SC Hematology GA 376XT UT WOS:000261217000013 PM 18796634 ER PT J AU Boni, A Muranski, P Cassard, L Wrzesinski, C Paulos, CM Palmer, DC Gattinoni, L Hinrichs, CS Chan, CC Rosenberg, SA Restifo, NP AF Boni, Andrea Muranski, Pawel Cassard, Lydie Wrzesinski, Claudia Paulos, Chrystal M. Palmer, Douglas C. Gattinoni, Luca Hinrichs, Christian S. Chan, Chi-Chao Rosenberg, Steven A. Restifo, Nicholas P. TI Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriers SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISEASE; METASTATIC BREAST-CANCER; HEMATOPOIETIC STEM-CELLS; TRANSFER THERAPY; GENE-THERAPY; SOLID TUMORS; IMMUNE RECONSTITUTION; ANTITUMOR-ACTIVITY; MELANOMA PATIENTS AB Graft-versus-tumor effects can be achieved after allogeneic bone marrow transplantation in patients with malignancies of the kidney or hematopoietic system but are often accompanied by severe graft-versus-host-disease (GVHD). We sought to maximize graft-versus-tumor while minimizing GVHD using tumor-specific allogeneic effector T cells rather than open-repertoire T cells. We transferred allogeneic CD8(+) pmel-1 or CD4(+) TRP-1 T cells specific for the melanoma-associated antigens, glycoprotein 100 (gp100) and tyrosinase-related protein-1 (TRP-1), respectively, into B16-melanoma bearing mice. Mice receiving a preparative regimen of nonmyeloablating (5 Gy) total body irradiation experienced the rapid rejection of tumor-specific allogeneic lymphocytes with no impact on tumor growth. However, when mice were given more intense total body irradiation conditioning regimens combined with autologous bone marrow transplantation, adoptively transferred allogeneic tumor-specific T lymphocytes persisted at detectable levels for several weeks and mediated significant regression of large, vascularized tumors. We found that the risk of GVHD was low when tumor-specific T cells were transferred and significant toxicity was observed only when substantial numbers of open repertoire allogeneic naive T cells were mixed with the tumor-specific lymphocytes. Taken together, these data indicate that the use of tumor-specific allogeneic CD8(+) T cells or CD4(+) can result in significant antitumor effects in the absence of measurable GVHD. (Blood. 2008; 112: 4746-4754) C1 [Boni, Andrea; Muranski, Pawel; Cassard, Lydie; Wrzesinski, Claudia; Paulos, Chrystal M.; Palmer, Douglas C.; Gattinoni, Luca; Hinrichs, Christian S.; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, NIH, Clin Res Ctr, 10 Ctr Dr,Bldg CRC,Room 3-5762, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU National Cancer Institute, National Institutes of Health FX This study was supported by the intramural program of the National Cancer Institute, National Institutes of Health (Bethesda, MD). NR 74 TC 25 Z9 25 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2008 VL 112 IS 12 BP 4746 EP 4754 DI 10.1182/blood-2008-07-169797 PG 9 WC Hematology SC Hematology GA 376XT UT WOS:000261217000054 PM 18799724 ER PT J AU Mariotti, J Foley, J Ryan, K Buxhoeveden, N Kapoor, V Amarnath, S Fowler, DH AF Mariotti, Jacopo Foley, Jason Ryan, Kaitlyn Buxhoeveden, Nicole Kapoor, Veena Amarnath, Shoba Fowler, Daniel H. TI Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; 2C MOUSE MODEL; CD8(+) T-CELLS; VETO CELLS; IN-VIVO; TOLERANCE INDUCTION; TH2 CELLS; MARROW TRANSPLANTATION; ALLOGRAFT SURVIVAL; CLONAL DELETION AB Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells. (Blood. 2008; 112: 4765-4775) C1 [Mariotti, Jacopo] NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr 3, Bethesda, MD 20892 USA. RP Mariotti, J (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Clin Res Ctr 3, East Labs 3-3330, Bethesda, MD 20892 USA. EM mariottj@mail.nih.gov FU Center for Cancer Research, NCI, Intramural Research Program FX This work was supported by the Center for Cancer Research, NCI, Intramural Research Program. NR 45 TC 17 Z9 18 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2008 VL 112 IS 12 BP 4765 EP 4775 DI 10.1182/blood-2008-05-154278 PG 11 WC Hematology SC Hematology GA 376XT UT WOS:000261217000056 PM 18625883 ER PT J AU Verdelis, K Ling, Y Sreenath, T Haruyama, N MacDougall, M van der Meulen, MCH Lukashova, L Spevak, L Kulkarni, AB Boskey, AL AF Verdelis, Kostas Ling, Yunfeng Sreenath, Taduru Haruyama, Naoto MacDougall, Mary van der Meulen, Marjolein C. H. Lukashova, Lyudmila Spevak, Lyudmila Kulkarni, Ashok B. Boskey, Adele L. TI DSPP effects on in vivo bone mineralization SO BONE LA English DT Article DE Dentin sialophosphoprotein; FTIR spectroscopic imaging; Bone; Micro-computed tomography; FTIRI ID DENTIN MATRIX PROTEIN-1; HYDROXYAPATITE FORMATION; SIBLING PROTEINS; GENE; SIALOPHOSPHOPROTEIN; SIALOPROTEIN; EXPRESSION; BIOMINERALIZATION; VITRO; PHOSPHOPROTEIN AB Dentin sialophosphoprotein has been implicated in the mineralization process based on the defective dentin formation in Dspp null mice (Dspp(-/-)). Dspp is expressed at low levels in bone and Dspp(-/-) femurs assessed by quantitative micro-computed tomography (micro-CT) and Fourier transform infrared spectroscopic imaging (FTIRI) exhibit some mineral and matrix property differences from wildtype femurs in both developing and mature mice. Compared to wildtype, Dspp(-/-) mice initially (5 weeks) and at 7 months had significantly higher trabecular bone volume fractions and lower trabecular separation, while at 9 months, bone volume fraction and trabecular number were lower. Cortical bone mineral density, area, and moments of inertia in Dspp(-/-) were reduced at 9 months. By FTIRI, Dspp(-/-) animals initially (5 months) contained more stoichiometric bone apatite with higher crystallinity (crystal size/perfection) and lower carbonate substitution. This difference progressively reversed with age (significantly decreased crystallinity and increased acid phosphate content in Dspp(-/-) cortical bone by 9 months of age). Mineral density as determined in 3D micro-CT and mineral-to-matrix ratios as determined by 2D FTIRI in individual cortical and trabecular bones were correlated (r(2) = 0.6, p<0.04). From the matrix analysis, the collagen maturity of both cortical and trabecular bones was greater in Dspp(-/-) than controls at 5 weeks: by 9 months this difference in cross-linking pattern did not exist. Variations in mineral and matrix properties observed at different ages are attributable, in part, to the ability of the Dspp gene products to regulate both initial mineralization and remodeling, implying an effect of Dspp on bone turnover. (C) 2008 Elsevier Inc. All rights reserved. C1 [Verdelis, Kostas; Ling, Yunfeng; Lukashova, Lyudmila; Spevak, Lyudmila; Boskey, Adele L.] Hosp Special Surg, Musculoskeletal Integr Program, Mineralized Tissue Lab, New York, NY 10021 USA. [Sreenath, Taduru; Haruyama, Naoto; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [MacDougall, Mary] Univ Alabama, Sch Dent, Inst Oral Hlth Res, Birmingham, AL 35294 USA. [van der Meulen, Marjolein C. H.] Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. [Boskey, Adele L.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Boskey, Adele L.] Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA. RP Boskey, AL (reprint author), Hosp Special Surg, Musculoskeletal Integr Program, Mineralized Tissue Lab, 535 E 70th St, New York, NY 10021 USA. EM boskeya@hss.edu RI van der Meulen, Marjolein/D-1549-2010; Haruyama, Naoto/D-1993-2011; OI van der Meulen, Marjolein/0000-0001-6637-9808; Haruyama, Naoto/0000-0001-6225-5816; Boskey, Adele/0000-0002-6181-2219 FU NIH [DE04141, AR046121]; NIDCR Division of Intramural funds; National Center for Research Resources, National Institutes of Health [C06-RR12538-01] FX Supported by NIH grants DE04141 and AR046121 (AB) and NIDCR Division of Intramural funds (ABK). The investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for Research Resources, National Institutes of Health. NR 43 TC 42 Z9 43 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD DEC PY 2008 VL 43 IS 6 BP 983 EP 990 DI 10.1016/j.bone.2008.08.110 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 385PK UT WOS:000261825900002 PM 18789408 ER PT J AU Van Horn, JD Bandettini, PA Cheng, K Egan, GF Stenger, VA Strother, S Toga, AW AF Van Horn, John Darrell Bandettini, Peter A. Cheng, Kang Egan, Gary F. Stenger, V. Andrew Strother, Stephen Toga, Arthur W. TI New Horizons for the Next Era of Human Brain Imaging, Cognitive, and Behavioral Research: Pacific Rim Interactivity SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Neuroscience; Neuroimaging; Computational biology; Cognition; Behavior; International collaboration; Grid; Pacific rim ID INCIDENT DEMENTIA; FUNCTIONAL MRI; FMRI; MODELS; MEG AB Beginning in the 1990's, substantial advances have been made in the ability to image the living human brain. Functional MRI, PET, and other modalities have been developed to provide a rich means for assessing brain function and structure across spatial and temporal dimensions. Such methods are now the preferred means to examine the brain in vivo, with several thousand articles now appearing in the literature each year. The next era of human brain imaging is upon us now as technological developments reach a level where data can be processed quickly and combined with other biological information to provide fundamentally new applications and insights. This new era will involve and require the collaborative participation of leading research groups from around the world to share information and expertise for understanding observed effects and synthesizing these into new knowledge. One particular community that is gaining in its prominence in the field is that of the Pacific Rim, whose collective research efforts present an important corpus of research effort into brain structure and function. The Pacific Rim represents an important community of researchers interested in the greater sharing of ideas. In this special issue of Brain Imaging and Behavior, we focus on emerging areas of research that utilize brain imaging methodology, and discuss how current developments are driving the expansion of functional imaging research. Moreover, we focus on the robust interaction of researchers from around the Pacific Rim whose collaborations are significantly shaping the future of brain imaging. C1 [Van Horn, John Darrell; Toga, Arthur W.] Univ Calif Los Angeles, Lab Neuro Imaging, Los Angeles, CA 90095 USA. [Bandettini, Peter A.] NIMH, Funct Imaging Methods Unit, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Cheng, Kang] RIKEN, Lab Cognit Brain Mapping, Brain Sci Inst, Wako, Saitama 3510198, Japan. [Egan, Gary F.] Univ Melbourne, Howard Florey Inst, Ctr Neurosci, Melbourne, Vic 3010, Australia. [Stenger, V. Andrew] Dept Med, Honolulu, HI 96813 USA. [Strother, Stephen] Rotman Res Inst, Toronto, ON M6A 2E1, Canada. RP Van Horn, JD (reprint author), Univ Calif Los Angeles, Lab Neuro Imaging, 635 Charles E Young Dr SW,Suite 225, Los Angeles, CA 90095 USA. EM jack.vanhorn@loni.ucla.edu RI Egan, Gary/A-1381-2013; Strother, Stephen/D-6752-2011; Cheng, Kang/A-6448-2016 OI Strother, Stephen/0000-0002-3198-217X; FU International Brain Research Organization (IBRO); University of California Pacific Rim Institute; National Center for Research Resources (NCRR); International Society for Magnetic Resonance in Medicine (ISMRM); Institute for Collaborative Biotechnology (ICB) at UC Santa Barbara; International Neuroinformatics Coordinating Facility (INCF); Sun Microsystems FX The special issue editors wish to recognize the support of the International Brain Research Organization (IBRO), University of California Pacific Rim Institute, the National Center for Research Resources (NCRR), and the International Society for Magnetic Resonance in Medicine (ISMRM), The Institute for Collaborative Biotechnology (ICB) at UC Santa Barbara, The International Neuroinformatics Coordinating Facility (INCF), and Sun Microsystems. We also would like to thanks Ms. Amanda Hammond and Mr. Vaughan Greer of the Laboratory of Neuroimaging (LONI) for their efforts with preparing cover artwork. Finally, we extend our thanks to the Editor-in-Chief of Brain Imaging and Behavior, Professor Andrew Saykin, for his encouragement and enthusiasm for this special issue. NR 36 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD DEC PY 2008 VL 2 IS 4 BP 227 EP 231 DI 10.1007/s11682-008-9045-0 PG 5 WC Neuroimaging SC Neurosciences & Neurology GA 510LQ UT WOS:000271090400001 PM 20169011 ER PT J AU LaKind, JS Berlin, CM Mattison, DR AF LaKind, Judy S. Berlin, Cheston M. Mattison, Donald R. TI The Heart of the Matter on Breastmilk and Environmental Chemicals: Essential Points for Healthcare Providers and New Parents SO BREASTFEEDING MEDICINE LA English DT Review AB The increasing number of environmental chemicals measured in breastmilk is a consequence of improved analytical capabilities and the increased interest in biomonitoring. It has been generally concluded that the benefits to the infant from breastfeeding outweigh potential risks associated with environmental chemical exposures associated with breastfeeding. However, there have been reports of subtle effects on infants associated with chemicals in breastmilk. Associations between concentrations of chemicals in breastmilk and a biochemical or other change in infants may signal the need for further study or regulatory action, whereas on an individual level, these changes may not be considered adverse. For healthcare providers, this distinction is critical, as many in the field are being asked for nuanced information on risks and benefits associated with breastfeeding, and this information is not readily available. Recognizing the challenge faced by healthcare providers, we have explored and developed a case study on dioxins in breastmilk. The essential conclusion for healthcare providers and new parents is that in studies of breastfed versus formula-fed infants across time, including times when levels of environmental chemicals such as dioxins were higher, beneficial effects associated with breastfeeding have been found. The current evidence does not support altering the World Health Organization recommendations promoting and supporting breastfeeding. C1 [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [LaKind, Judy S.] LaKind Associates LLC, Catonsville, MD USA. [LaKind, Judy S.; Berlin, Cheston M.] Penn State Coll Med, Dept Pediat, Milton S Hershey Med Ctr, Hershey, PA USA. [LaKind, Judy S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Mattison, DR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, NIH, US Dept HHS, 6100 Execut Blvd,Room 4A01,MSC 7510, Bethesda, MD 20892 USA. EM Donald.Mattison@nih.hhs.gov RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU National Institute of Child Health and Human Development; National Institutes of Health; American Chemistry Council FX The views expressed in this paper represent those of the authors and do not necessarily represent the views of the National Institute of Child Health and Human Development, National Institutes of Health, or American Chemistry Council. Daniel Q. Naiman, Ph.D., Department of Applied Mathematics and Statistics, The Johns Hopkins University, Baltimore, MD, provided statistical analysis of lung function data. NR 51 TC 11 Z9 11 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD DEC PY 2008 VL 3 IS 4 BP 251 EP U56 DI 10.1089/bfm.2008.0121 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA V11MC UT WOS:000207534700007 PM 19086828 ER PT J AU Fontelo, P Liu, F Zhang, K Ackerman, M AF Fontelo, Paul Liu, Fang Zhang, Kai Ackerman, Michael TI Extending the benefits of One Laptop per Child to health SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 [Fontelo, Paul; Liu, Fang; Zhang, Kai; Ackerman, Michael] Natl Lib Med, Bethesda, MD 20894 USA. RP Fontelo, P (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM fontelo@nlm.nih.gov FU Intramural NIH HHS NR 5 TC 2 Z9 2 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD DEC 1 PY 2008 VL 337 AR a2459 DI 10.1136/bmj.a2459 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 386NU UT WOS:000261890700012 PM 19047193 ER PT J AU Nussenblatt, RB AF Nussenblatt, Robert B. TI Investigation of anterior uveitis SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Editorial Material ID ANGIOTENSIN-CONVERTING ENZYME; SECTORAL IRIS ATROPHY; TUBULOINTERSTITIAL NEPHRITIS; IMMUNOCOMPETENT PATIENTS; CLINICAL-FEATURES; CARD15 MUTATIONS; BLAU-SYNDROME; SARCOIDOSIS; CYTOMEGALOVIRUS; ARTHRITIS C1 NEI, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov NR 28 TC 1 Z9 1 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2008 VL 43 IS 6 BP 630 EP 632 DI 10.3129/i08-156 PG 3 WC Ophthalmology SC Ophthalmology GA 389BC UT WOS:000262063900003 PM 19020626 ER PT J AU Nussenblatt, RB AF Nussenblatt, Robert B. TI Research into anterior uveitis SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA French DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM nussenblattr@nei.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2008 VL 43 IS 6 BP 632 EP 633 PG 2 WC Ophthalmology SC Ophthalmology GA 389BC UT WOS:000262063900004 ER PT J AU Noble, J Hollands, H Forooghian, F Yazdani, A Sharma, S Wong, DT Derzko-Dzulynsky, L AF Noble, Jason Hollands, Hussein Forooghian, Farzin Yazdani, Arash Sharma, Sanjay Wong, David T. Derzko-Dzulynsky, Larissa TI Evaluating the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE LA English DT Article DE anterior uveitis; iritis; investigation; testing; cost-effectiveness ID EPIDEMIOLOGY; PREVALENCE; POPULATION AB Background: To evaluate the cost-effectiveness of anterior uveitis investigation by Canadian ophthalmologists and to assess the role of implementing national clinical guidelines for such investigation. Methods: Based on data extracted from the Canadian National Uveitis Survey (CNUS, 2007 version), the cost of investigating a patient with anterior uveitis, according to current practice patterns of Canadian ophthalmologists, was determined and grouped across 4 clinical scenarios: (i) nongranulomatous anterior uveitis in an adult, (ii) granulomatous anterior uveitis in an adult, (iii) granulomatous anterior uveitis with suspected sarcoidosis in an adult or a child, and (iv) nongranulomatous anterior uveitis in a child. Similarly, the cost of investigating a patient with anterior uveitis as per published evidence-based guidelines was determined and compared with the current practice pattern using a cost-minimization model, sensitivity analyses, and Monte Carlo simulations. Results: Ophthalmologists were found to consistently order more tests than recommended by evidence-based guidelines, across each of the scenarios studied (p < 0.05). Overall, complete blood count, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibody, and rheumatoid factor were the most commonly ordered extraneous tests that were not included in the evidence-based guidelines for the routine investigation of anterior uveitis. Also, there were significant differences in the cost of investigating a patient with anterior uveitis when compared with those predicted by adhering to evidence-based clinical practice guidelines. Cost minimization and sensitivity analyses revealed that published guidelines imparted cost savings when compared with current practice patterns across the 4 clinical scenarios studied (p < 0.01). The maximum additional cost was associated with investigating nongranulomatous anterior uveitis in an adult, where a minimal additional cost of $75 per patient was spent. For granulomatous anterior uveitis in an adult, the additional cost was approximately $40, whereas the additional cost for investigating an adult or a child with suspected sarcoidosis was $36. Only $11 of additional cost was spent in the workup of a child with nongranulomatous anterior uveitis. When applied to the Canadian population, adherence to the Clinical Practice Guidelines recommended by the CNUS may result in cost savings of $600 000 per year to the Canadian health care system. Interpretation: Adherence to the evidence-based Clinical Practice Guidelines recommended by the CNUS may result in significant cost savings, with virtually no loss of sensitivity in the routine investigation of anterior uveitis in Canada. C1 [Noble, Jason; Wong, David T.; Derzko-Dzulynsky, Larissa] Univ Toronto, Dept Ophthalmol & Vis Sci, Toronto, ON, Canada. [Hollands, Hussein; Yazdani, Arash; Sharma, Sanjay] Queens Univ, Dept Ophthalmol, Kingston, ON, Canada. [Hollands, Hussein; Yazdani, Arash; Sharma, Sanjay] Queens Univ, Dept Epidemiol, Kingston, ON, Canada. [Forooghian, Farzin] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Derzko-Dzulynsky, L (reprint author), St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada. EM derzkodzulynskyf@smh.toronto.on.ca NR 21 TC 5 Z9 5 U1 0 U2 1 PU CANADIAN OPHTHAL SOC PI OTTAWA PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA SN 0008-4182 J9 CAN J OPHTHALMOL JI Can. J. Opthalmol.-J. Can. Opthalmol. PD DEC PY 2008 VL 43 IS 6 BP 652 EP 657 DI 10.3129/i08-147 PG 6 WC Ophthalmology SC Ophthalmology GA 389BC UT WOS:000262063900008 PM 19020630 ER PT J AU Boukheris, H Ron, E Dores, GM Stovall, M Smith, SA Curtis, RE AF Boukheris, Houda Ron, Elaine Dores, Graca M. Stovall, Marilyn Smith, Susan A. Curtis, Rochelle E. TI Risk of Radiation-related Salivary Gland Carcinomas Among Survivors of Hodgkin Lymphoma A Population-based Analysis SO CANCER LA English DT Article DE Hodgkin lymphoma; subsequent salivary gland carcinoma; mucoepidermoid carcinoma; radiotherapy; risk ID ATOMIC-BOMB SURVIVORS; LONG-TERM SURVIVORS; 2ND CANCERS; DISEASE; TUMORS; HEAD; NECK; IRRADIATION; CHILDHOOD; RADIOTHERAPY AB BACKGROUND. Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the risk has not been assessed to date. METHODS. The risks of SGC among 20,928 1-year survivors of HL. who were diagnosed between 1973 and 2003 were evaluated in 11 population-based cancer registry areas of the Surveillance, Epidemiology, and End Results (SEER) program. Observed-to-expected ratios (O/E) were assessed by radiation treatment, sex, age at the time of HL diagnosis, calendar year of diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and site of occurrence in the major salivary glands. RESULTS. Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3-78.2]) noted. CONCLUSIONS. HL patients treated with radiotherapy experienced a significantly increased risk of SGC, particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current Study reflect the late effects of former HL treatment approaches, they point to the importance of long-term follow-up and a heightened awareness of SGC risk in this population. Cancer 2008; 113:3153-9. Published 2008 by the American Cancer Society.* C1 [Boukheris, Houda; Ron, Elaine; Dores, Graca M.; Curtis, Rochelle E.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Dores, Graca M.] Dept Vet Affairs Med Ctr, Med Serv, Oklahoma City, OK USA. [Stovall, Marilyn; Smith, Susan A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. RP Boukheris, H (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM boukherh@mail.nih.gov FU National Institutes of Health (NIH); National Cancer Institute FX Supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. NR 30 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2008 VL 113 IS 11 BP 3153 EP 3159 DI 10.1002/cncr.23918 PG 7 WC Oncology SC Oncology GA 373MS UT WOS:000260976600015 PM 18823043 ER PT J AU Paskett, ED Alfano, CM Davidson, MA Andersen, BL Naughton, MJ Sherman, A McDonald, PG Hays, J AF Paskett, Electra D. Alfano, Catherine M. Davidson, Mario A. Andersen, Barbara L. Naughton, Michelle J. Sherman, Aurora McDonald, Paige Green Hays, Jennifer TI Breast Cancer Survivors' Health-related Quality of Life Racial Differences and Comparisons With Noncancer Controls SO CANCER LA English DT Article DE breast cancer; quality of life; health status; race ID INSOMNIA RATING-SCALE; MULTIETHNIC SAMPLE; AFRICAN-AMERICAN; WOMEN; RELIABILITY; CARCINOMA; MORTALITY; ISSUES AB BACKGROUND. Small samples with few minority women and/or the absence of comparisons to peers without cancer histories have limited previous research suggesting racial differences in breast cancer survivors' health-related quality of life (HRQoL). This study not only compared HRQoL of African American and white breast cancer survivors, but also compared the HRQoL of these women to that of same-race women with no cancer history METHODS. Data from the Womens Health Initiative-Observational Study were used, including 5021 cancer survivors and 88,532 women without a history of cancer. Multivariate regression analyses estimated differences in breast cancer survivors' baseline HRQoL (RAND36), depressive symptoms (CES-D short-form), and sleep quality (WHIMS). RESULTS. African American breast cancer survivors reported worse physical functioning and general health compared with white survivors. Among African Americans, survivors reported worse role limitations due to physical health, pain, general health, and vitality than women without a history of cancer. This was most evident in those with more recent diagnoses. Most significant differences between groups were small in magnitude (Cohen d = .21-.36). CONCLUSIONS. These results add to the increasing knowledge of cancer disparities by showing that African American women have small, but clinically meaningful, decrements in physical HRQoL compared with white Survivors and with African American women without cancer. Because African American women also face diagnosis with higher grade tumors and higher breast cancer mortality, more research is needed to examine the physical and psychosocial experiences of African American breast cancer survivors to elucidate the mechanisms leading to poorer outcomes. Cancer 2008; 113:3222-30. (C) 2008 American Cancer Society. C1 [Paskett, Electra D.; Alfano, Catherine M.; Davidson, Mario A.; Andersen, Barbara L.] Ohio State Univ, Ctr Comprehens Canc, Div Populat Sci, Columbus, OH 43210 USA. [Paskett, Electra D.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Alfano, Catherine M.] Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43210 USA. [Andersen, Barbara L.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Naughton, Michelle J.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Sherman, Aurora] Oregon State Univ, Dept Psychol, Corvallis, OR 97331 USA. [McDonald, Paige Green] NCI, Div Canc Control & Populat Sci, Basic & Biobehav Res Branch, Bethesda, MD 20892 USA. [Hays, Jennifer] Texas A&M Univ, Texas A&M Hlth Sci Ctr, Temple, TX USA. RP Paskett, ED (reprint author), 320 W 10th Ave,A356 Starling Loving Hall, Columbus, OH 43210 USA. EM electra.paskett@osumc.edu FU National Heart, Lung and Blood Institute; US Department of Health and Human Services; National Cancer Institute [CA131029] FX Supported by funds from the National Heart, Lung and Blood Institute, US Department of Health and Human Services. Portions of this work were funded by a grant from the National Cancer Institute CA131029. NR 31 TC 43 Z9 44 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2008 VL 113 IS 11 BP 3222 EP 3230 DI 10.1002/cncr.23891 PG 9 WC Oncology SC Oncology GA 373MS UT WOS:000260976600024 PM 18973178 ER PT J AU Kilfoy, B Zhang, YW Shu, XO Gao, YT Ji, BT Yang, G Li, H Rothman, N Chow, WH Zheng, W AF Kilfoy, Briseis A. Zhang, Yawei Shu, Xiao-Ou Gao, Yu-Tang Ji, Bu-Tian Yang, Gong Li, Hong Lan Rothman, Nathaniel Chow, Wong-Ho Zheng, Wei TI Family history of malignancies and risk of breast cancer: prospective data from the Shanghai women's health study SO CANCER CAUSES & CONTROL LA English DT Article DE Family history; Breast cancer ID UTAH POPULATION DATABASE; UNITED-STATES; OVARIAN-CANCER; ORAL-CONTRACEPTIVES; ATTRIBUTABLE RISKS; BRCA2 MUTATIONS; LUNG-CANCER; RELATIVES; PREVALENCE; CARCINOMA AB A population-based cohort study was conducted in Shanghai, China, to investigate the relationship between family cancer history in first-degree relatives and risk of breast cancer. A total of 570 newly diagnosed breast cancer patients were identified from the cohort of 73,222 women during the follow-up period. Breast cancer risk was elevated (RR = 1.74, 95% CI: 1.10-2.73) for those with a family history of breast cancer and the risk was stronger for women who were younger than 55 years (RR = 2.07, 95% CI: 1.17-3.64). In addition, a significantly increased risk was observed for women with a family history of leukemia (RR = 2.06; 95% CI: 1.02-4.15) and among younger women, those who reported having a family history of any cancer (RR = 1.41, 95% CI: 1.10-1.82), lung cancer (RR = 1.72, 95% CI: 1.12-2.65), and esophageal cancer (RR = 2.99, 95% CI: 1.62-5.51). This cohort study suggests that, as previously observed in high risk populations, family history plays an important role in breast cancer also in a low risk population. The link between breast cancer risk and family history of cancers of the lung and esophagus, as well as leukemia, warrants further investigation. C1 [Kilfoy, Briseis A.; Zhang, Yawei] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Kilfoy, Briseis A.; Zhang, Yawei; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Dept Med, Ctr Hlth Serv Res, Nashville, TN USA. [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Med, Nashville, TN USA. [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Gao, Yu-Tang; Li, Hong Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. RP Zhang, YW (reprint author), Yale Univ, Sch Epidemiol & Publ Hlth, 60 Coll St,LEPH 440,POB 208034, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012 FU National Institutes of Health [R01 CA70867]; Intramural Research Program [N02 CP1101066] FX This research was supported by National Institutes of Health research grant R01 CA70867 and by Intramural Research Program contract N02 CP1101066. The authors express their appreciation to Shanghai residents who participated in the study and thank the research staff of the Shanghai Women's Health Study for their dedication and hard work. NR 41 TC 6 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 DEC PY 2008 VL 19 IS 10 BP 1139 EP 1145 DI 10.1007/s10552-008-9181-2 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 370MM UT WOS:000260766300014 PM 18575953 ER PT J AU Daniel Carreon, J Morton, L Devesa, S Clarke, C Gomez, S Glaser, S Sakoda, L Linet, M Wang, S AF Daniel Carreon, J. Morton, Lindsay M. Devesa, Susan S. Clarke, Christina A. Gomez, Scarlett L. Glaser, Sally L. Sakoda, Lori C. Linet, Martha S. Wang, Sophia S. TI Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004 SO CANCER CAUSES & CONTROL LA English DT Article DE Lymphoid neoplasms; Asians ID HEALTH MAINTENANCE ORGANIZATION; BREAST-CANCER INCIDENCE; INCIDENCE PATTERNS; RISK-FACTORS; RACE/ETHNICITY; EPIDEMIOLOGY; CALIFORNIA; TRENDS; RATES; US AB To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups. Incident rates were estimated by age and sex for six Asian ethnic groups-Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese-in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated. During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype. The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors. C1 [Daniel Carreon, J.; Morton, Lindsay M.; Devesa, Susan S.; Sakoda, Lori C.; Linet, Martha S.; Wang, Sophia S.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Clarke, Christina A.; Gomez, Scarlett L.; Glaser, Sally L.] No Calif Canc Ctr, Fremont, CA USA. [Clarke, Christina A.; Gomez, Scarlett L.; Glaser, Sally L.] Stanford Univ, Stanford, CA 94305 USA. RP Daniel Carreon, J (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 5011, Rockville, MD 20852 USA. EM carreonj@mail.nih.gov FU NIH; National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. We would like to thank Marc Goodman and Lynne Wilkens at the Hawaii Tumor Registry for providing population estimates for Hawaii. We would like to thank Steve Scoppa of Information Management Services, Silver Spring, MD, for excellent technical assistance with SEER* Stat and SEER* Prep software programs. NR 27 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2008 VL 19 IS 10 BP 1171 EP 1181 DI 10.1007/s10552-008-9184-z PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 370MM UT WOS:000260766300017 ER PT J AU Leitzmann, MF Ahn, JY Albanes, D Hsing, AW Schatzkin, A Chang, SC Huang, WY Weiss, JM Danforth, KN Grubb, RL Andriole, GL AF Leitzmann, Michael F. Ahn, Jiyoung Albanes, Demetrius Hsing, Ann W. Schatzkin, Arthur Chang, Shih-Chen Huang, Wen-Yi Weiss, Jocelyn M. Danforth, Kim N. Grubb, Robert L., III Andriole, Gerald L. CA PLCO Trial Project Team TI Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO CANCER CAUSES & CONTROL LA English DT Article DE Diabetes; Prostate cancer; Screening; Prostate specific antigen; Prostate volume ID PLASMA-GLUCOSE CONCENTRATION; UNITED-STATES; INSULIN-RESISTANCE; NATIONAL-HEALTH; SERUM LEVELS; BODY-SIZE; US ADULTS; MEN; ANTIGEN; POPULATION AB A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. We prospectively examined the diabetes-prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68-0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum < 8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62-0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum >= 8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74-1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87-3.07; BMI < 25 kg/m(2)) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07-2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI. C1 [Leitzmann, Michael F.; Ahn, Jiyoung; Albanes, Demetrius; Hsing, Ann W.; Schatzkin, Arthur; Chang, Shih-Chen; Huang, Wen-Yi; Weiss, Jocelyn M.; Danforth, Kim N.] NCI, NIH, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. [Grubb, Robert L., III; Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. RP Leitzmann, MF (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, DHHS, 6120 Executive Blvd, Bethesda, MD 20892 USA. EM leitzmann@nih.gov RI Albanes, Demetrius/B-9749-2015 FU Division of Cancer Prevention; National Cancer Institute; NIH; DHHS FX This research was supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Mr. Tom Riley and staff, Information Management Services, Inc., Ms. Barbara O'Brien and staff, Westat, Inc. Most importantly, we acknowledge the study participants for their contributions to making this study possible. NR 74 TC 54 Z9 56 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2008 VL 19 IS 10 BP 1267 EP 1276 DI 10.1007/s10552-008-9198-6 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 370MM UT WOS:000260766300028 PM 18618278 ER PT J AU Leitzmann, MF Koebnick, C Freedman, ND Park, Y Ballard-Barbash, R Hollenbeck, AR Schatzkin, A Abnet, CC AF Leitzmann, Michael F. Koebnick, Corinna Freedman, Neal D. Park, Yikyung Ballard-Barbash, Rachel Hollenbeck, Albert R. Schatzkin, Arthur Abnet, Christian C. TI Physical activity and head and neck cancer risk SO CANCER CAUSES & CONTROL LA English DT Article DE Head and neck cancer; Oral cavity cancer; Pharynx cancer; Larynx cancer; Physical activity ID SALIVARY SECRETORY IGA; HUMAN-PAPILLOMAVIRUS; EPIDEMIOLOGY; DISTRIBUTIONS; INFECTION; EXERCISE AB To investigate the relation of physical activity to head and neck cancer. We prospectively examined the association between physical activity and head and neck cancer in 487,732 men and women, who, at baseline in 1995-1996, were 50-71 years old and free of cancer and emphysema. Follow-up occurred through 31 December 2003. During follow-up, 1,249 participants developed head and neck cancer, of which 42.0%, 18.9%, and 32.5% were located in the oral cavity, pharynx, and larynx, respectively. In analyses adjusted for age and gender, the relative risks (RR) of head and neck cancer for increasing frequency of physical activity (0, < 1, 1-2, 3-4, and >= 5 times per week) were 1.0 (reference), 0.76, 0.66, 0.57, and 0.62 (95% CI = 0.52-0.74), respectively (p for trend < 0.001). After multivariate adjustment including smoking, the relation was attenuated and became statistically non-significant (RR comparing extreme physical activity categories = 0.89, 95% CI = 0.74-1.06; p for trend = 0.272). In analyses of head and neck cancer subtypes, the corresponding RRs for cancers of the oral cavity, pharynx, and larynx were 0.98 (95% CI = 0.75-1.29), 0.70 (95% CI = 0.45-1.08), and 0.82 (95% CI = 0.59-1.13), respectively. Our findings suggest that physical activity is unlikely to play an important role in the prevention of head and neck cancer. C1 [Leitzmann, Michael F.; Freedman, Neal D.; Park, Yikyung; Schatzkin, Arthur; Abnet, Christian C.] NCI, NIH, Dept Hlth & Human Serv, Nutr Epidemiol Branch,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Koebnick, Corinna] Kaiser Permanente So Calif, Pasadena, CA USA. [Freedman, Neal D.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Leitzmann, MF (reprint author), NCI, NIH, Dept Hlth & Human Serv, Nutr Epidemiol Branch,Div Canc Epidemiol & Genet, 6120 Executive Blvd, Bethesda, MD 20892 USA. EM leitzmann@mail.nih.gov; corinna.koebnick@kp.org RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Koebnick, Corinna/P-4767-2016; OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Koebnick, Corinna/0000-0001-8274-0309; Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the NIH; National Cancer Institute FX We are grateful to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We thank Leslie Carroll at Information Management Services and Sigurd Hermansen and Kerry Grace Morrissey from Westat for data support, and Tawanda Roy at the Nutritional Epidemiology Branch for research assistance. Financial Support: This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 29 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2008 VL 19 IS 10 BP 1391 EP 1399 DI 10.1007/s10552-008-9211-0 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 370MM UT WOS:000260766300041 PM 18704714 ER PT J AU Greenburg, DL Rusiecki, J Koutros, S Dosemeci, M Patel, R Hines, CJ Hoppin, JA Alavanja, MCR AF Greenburg, David L. Rusiecki, Jennifer Koutros, Stella Dosemeci, Mustafa Patel, Rahulkumar Hines, Cynthia J. Hoppin, Jane A. Alavanja, Michael C. R. TI Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study SO CANCER CAUSES & CONTROL LA English DT Article DE Captan; Cancer; Agricultural Health Study; Cohort; Prospective; Pesticide; Fungicide; CAS number 133-06-2 ID FUNGICIDES CAPTAN; DNA-DAMAGE; MUTAGENICITY; URINE; ASSAY; RAT AB Objective Captan is a widely used antifungal pesticide whose potential to cause cancer in humans is uncertain. Methods We evaluated the incidence of cancer among pesticide applicators exposed to captan in the Agricultural Health Study. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997. Results Of the 48,986 applicators enrolled 4,383 (9%) had applied captan. Median follow-up time was 9.14 years. Poisson regression analysis was used to estimate relative risks (RR) for cancer subtypes by tertiles of captan exposure. We investigated risk for all cancers combined and sites of cancer for which at least 15 cases occurred among captan-exposed applicators. These sites included cancers of the prostate, lung, and colon, blood-related cancers, and colorectal cancers. During follow-up 2,912 incident primary cases of cancer were identified. No association between the highest tertile of captan exposure (>67.375 intensity-weighted days) and development of all cancers (RR = 0.89; 95% CI, 0.71-1.13) or cancer of any specific site was observed. Conclusion Although our study is limited by low numbers of observed cancer cases and follow-up time of 9.14 years, it does not provide evidence of an increased risk for the development of cancer at the investigated sites. C1 [Greenburg, David L.; Rusiecki, Jennifer; Patel, Rahulkumar] Uniformed Serv Univ Hlth Sci, Dept Med, EDP, Bethesda, MD 20814 USA. [Rusiecki, Jennifer; Koutros, Stella; Dosemeci, Mustafa; Alavanja, Michael C. R.] NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. [Hines, Cynthia J.] NIOSH, Cincinnati, OH 45226 USA. [Hoppin, Jane A.] NIEHS, NIH, Epidemiol Branch, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Rusiecki, J (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, EDP, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM jrusiecki@usuhs.mil FU National Institutes of Health; National Institute of Environmental Health Sciences; National Cancer Institute FX This work was supported by the intramural research program of the National Institutes of Health, the National Institute of Environmental Health Sciences, and National Cancer Institute. NR 32 TC 13 Z9 16 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2008 VL 19 IS 10 BP 1401 EP 1407 DI 10.1007/s10552-008-9187-9 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 370MM UT WOS:000260766300042 PM 18587656 ER PT J AU Hertsgaard, LA Hanson, K Hecht, SS Lindgren, BR Luo, XH Carmella, SG Riley, WT Zylla, EB Murphy, SE Hatsukami, DK AF Hertsgaard, Louise A. Hanson, Karen Hecht, Stephen S. Lindgren, Bruce R. Luo, Xianghua Carmella, Steven G. Riley, William T. Zylla, Emily B. Murphy, Sharon E. Hatsukami, Dorothy K. TI Exposure to a Tobacco-Specific Lung Carcinogen in Adolescent versus Adult Smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; COTININE LEVELS; METABOLITES; BIOMARKERS; CANCER AB Background: Previous studies with adult smokers have shown an association between number of cigarettes smoked per day (CPD) and levels of biomarkers of exposure to the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). This study compared carcinogen and nicotine exposure in adolescent and adult smokers across categories of CPD. Method: Baseline smoking history and biomarker data were merged from six studies to make two samples: one of adolescent smokers and one of adult smokers. Metabolites of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and its glucuronides (NNAL-Gluc) and total cotinine were quantified in urine. Results: CPD was stratified into categories of 5 to 10, 11 to 15, and 1.6 to 20 CPD. Adolescents tended to have lower mean levels of NNAL plus NNAL-Glucs (total NNAL) compared with adults, although differences were not significant overall. Adolescent mean levels of NNAL/CPD were significantly lower than adult levels only in the 11 to 15 CPD category (P = 0.045). However, a significant positive relationship was observed for total NNAL/CPD by age. No significant differences between adolescents and adults were found in mean levels of total cotinine or cotinine/CPD. A subsample of urines from adolescents and adults were analyzed for NNAL-Glucs and NNAL. Adolescents and adults did not significantly differ in the ratio of NNAL-Glucs to NNAL. Conclusions: Adolescent uptake of NNK and nicotine tends to be lower although not statistically different from adults. The lack of significant differences may be due to the wide variation in exposure in adolescents. Some adolescent smokers are exposed to lung carcinogens at levels similar to those of adults. (Cancer Epidemiol Biomarkers Prev 2008;1.7(12):3337-43) C1 [Hertsgaard, Louise A.; Hanson, Karen; Hecht, Stephen S.; Lindgren, Bruce R.; Luo, Xianghua; Carmella, Steven G.; Zylla, Emily B.; Murphy, Sharon E.; Hatsukami, Dorothy K.] Univ Minnesota, Transdisciplinary Tobacco Use Res Ctr, Minneapolis, MN 55414 USA. [Hecht, Stephen S.; Lindgren, Bruce R.; Luo, Xianghua; Carmella, Steven G.; Murphy, Sharon E.; Hatsukami, Dorothy K.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Riley, William T.] NIMH, Rockville, MD 20857 USA. RP Hatsukami, DK (reprint author), Univ Minnesota, Transdisciplinary Tobacco Use Res Ctr, 2701 Univ Ave SE,201, Minneapolis, MN 55414 USA. EM hatsu001@umn.edu RI Luo, Xianghua/D-6934-2011; OI Hecht, Stephen/0000-0001-7228-1356 FU NIH [P50-DA013333, R01-DA014538]; National Cancer Institute [CA083451] FX NIH grants P50-DA013333 and R01-DA014538 and National Cancer Institute grant CA083451. NR 26 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3337 EP 3343 DI 10.1158/1055-9965.EPI-08-0307 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000009 PM 19064548 ER PT J AU Falk, RT Xu, X Keefer, L Veenstra, TD Ziegler, RG AF Falk, Roni T. Xu, Xia Keefer, Larry Veenstra, Timothy D. Ziegler, Regina G. TI A Liquid Chromatography-Mass Spectrometry Method for the Simultaneous Measurement of 15 Urinary Estrogens and Estrogen Metabolites: Assay Reproducibility and Interindividual Variability SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NADPH-DEPENDENT METABOLISM; 16 ALPHA-HYDROXYESTRONE; HUMAN LIVER-MICROSOMES; BREAST-CANCER RISK; POSTMENOPAUSAL WOMEN; HORMONE-LEVELS; CARCINOGENESIS; ESTRADIOL; 2-METHOXYESTRADIOL; VALIDITY AB Background: Accurate, reproducible, and sensitive measurements of endogenous estrogen exposure and individual patterns of estrogen metabolism are needed for etiologic studies of breast cancer. We have developed a high-performance liquid chromatography-tandem mass spectrometry method to quantitate simultaneously 15 urinary estrogens and estrogen metabolites (EM): estrone; estradiol; 3 catechol estrogens; 5 estrogens in the 16 alpha pathway, including estriol; and 5 methoxy estrogens. Methods: Overnight urines were obtained from 45 participants. For the reproducibility study, two blinded, randomized aliquots from 5 follicular and 5 luteal premenopausal women, 5 naturally postmenopausal women, and 5 men were assayed in each of four batches. Assay coefficients of variation and intraclass correlation coefficients were calculated with ANOVA models. Data from the additional 25 participants were added to compare EM levels by menstrual/sex group and assess interindividual variability. Results: For each EM, overall coefficients of variation were <= 10%. Intraclass correlation coefficients for each menstrual/sex group were generally >= 98%. Although geometric mean EM concentrations differed among the four groups, rankings were similar, with estriol, 2-hydroxyestrone, estrone, estradiol, and 16-ketoestradiol accounting for 60% to 75% of total urinary EM. Within each group, interindividual differences in absolute concentrations were consistently high; the range was 10- to 100-fold for nearly all EM. Conclusion: Our high-performance liquid chromatography-tandem mass spectrometry method for measuring 15 urinary EM is highly reproducible, and the range of EM concentrations in each menstrual/sex group is quite large relative to assay variability. Whether these patterns persist in blood and target tissues awaits further development and application of this method. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3411-8) C1 [Falk, Roni T.; Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Xu, Xia; Veenstra, Timothy D.] SAIC Frederick Inc, Adv Technol Program, Lab Proteom & Analyt Technol, Frederick, MD USA. [Keefer, Larry] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Falk, RT (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-5137, Rockville, MD 20892 USA. EM falkr@mail.nih.gov FU National Cancer Institute; NIH [NO1-CO-12400] FX Federal funds from the National Cancer Institute, NIH, under contract NO1-CO-12400, and intramural research funds from National Cancer Institute, NIH. NR 35 TC 41 Z9 42 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3411 EP 3418 DI 10.1158/1055-9965.EPI-08-0355 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000019 PM 19064556 ER PT J AU Anderson, LA Lauria, C Romano, N Brown, EE Whitby, D Graubard, BI Li, Y Messina, A Gafa, L Vitale, F Goedert, JJ AF Anderson, Lesley A. Lauria, Carmela Romano, Nino Brown, Elizabeth E. Whitby, Denise Graubard, Barry I. Li, Yan Messina, Angelo Gafa, Lorenzo Vitale, Francesco Goedert, James J. TI Risk Factors for Classical Kaposi Sarcoma on a Population-based Case-control Study in Sicily SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; HOMOSEXUAL-MEN; HERPES-VIRUS; HUMAN-HERPESVIRUS-8; NICOTINE; INDIVIDUALS; REPLICATION; ASSOCIATION; ANTIBODIES; INFECTION AB Background: Classical Kaposi sarcoma is a rare complication of Kaposi sarcoma-associated herpes virus (KSHV) infection. We conducted a population-based, frequency-matched case-control study in Sicily to further investigate the reported inverse relationship between smoking and classical Kaposi sarcoma and to identify other factors associated with altered risk. Methods: All incident, histologically confirmed classical Kaposi sarcoma cases in Sicily were eligible. A two-stage cluster sample design was applied to select population controls. KSHV seropositivity was determined using four antibody assays (K8.1. and orf73 enzyme immunoassays and two immunofluorenscence assays). Using SAS-callable SUDAAN, we compared the characteristics of classical Kaposi sarcoma cases and KSHV-seropositive controls. Odds ratios (OR) and 95% confidence intervals (CI) are presented. Results: In total, 1.42 classical Kaposi sarcoma cases and 1.23 KSHV-seropositive controls were recruited. Current cigarette smoking was associated with reduced risk of classical Kaposi sarcoma amongst males (OR, 0.20; 95% CI, 0.06-0.67). Edema was associated with classical Kaposi sarcoma, but only when it presented on the lower extremities (OR, 3.65; 95% CI, 1.62-8.23). Irrespective of presentation site, diabetes and oral corticosteroid medications were associated with increased risk (OR, 4.73; 95% CI, 2.02-11.1 and OR, 2.34; 95% CI, 1.23-4.45, respectively). Never smoking, diabetes, and oral corticosteroid medication use were all independently associated with classical Kaposi sarcoma risk. Discussion: We confirmed previous reports that cigarette smoking was associated with a reduced risk of classical Kaposi sarcoma, and we found that risk was lowest among current smokers. We also found that classical Kaposi sarcoma risk was strongly and independently associated with oral corticosteroid use and diabetes. Corroboration of these observations and investigation of possible underlying mechanisms are warranted. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3435-43) C1 [Anderson, Lesley A.] NCI, Infect Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Anderson, Lesley A.] Queens Univ Belfast, Ctr Pub Hlth, Belfast BT7 1NN, Antrim, North Ireland. [Lauria, Carmela; Gafa, Lorenzo] Lega Italiana Lotta Contro & Tumori Sez Ragusa, Ragusa, Italy. [Romano, Nino; Vitale, Francesco] Univ Palermo, Dipartimento Sci Promoz Salute GD Alessandro, Sez Igiene, Palermo, Italy. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Brown, Elizabeth E.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Brown, Elizabeth E.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. [Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. [Messina, Angelo; Goedert, James J.] Univ Catania, Dipartimento Sci Biomed, Catania, Italy. RP Goedert, JJ (reprint author), NCI, Infect Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7068, Rockville, MD USA. EM goedertj@mail.nih.gov FU National Cancer Institute [N02-CP-9102, N01-CO-12400]; The Research and Development Office, Northern Ireland FX Intramural Research Program of the National Cancer Institute, in part under a contract with RTI International (N02-CP-91027) and in part under contract N01-CO-12400. The Research and Development Office, Northern Ireland, funded Dr. Lesley Anderson to participate in the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute. NR 40 TC 27 Z9 27 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3435 EP 3443 DI 10.1158/1055-9965.EPI-08-0671 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000022 PM 19064559 ER PT J AU Wong, HL Pfeiffer, RM Fears, TR Vermeulen, R Ji, SQ Rabkin, CS AF Wong, Hui-Lee Pfeiffer, Ruth M. Fears, Thomas R. Vermeulen, Roel Ji, Shaoquan Rabkin, Charles S. TI Reproducibility end Correlations of Multiplex Cytokine Levels in Asymptomatic Persons SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BEAD ARRAY ASSAYS; T-CELL SUBSETS; SOLUBLE CYTOKINES; INNATE IMMUNITY; HUMAN PLASMA; VALIDATION; SERUM; IMMUNOASSAY; SENSITIVITY; ACTIVATION AB Rationale: Cytokines are humoral regulatory molecules that act together in immunologic pathways underlying pathogenesis. Grossly elevated blood levels characterize certain diseases; variations within physiologic ranges could also have significance. We therefore evaluated the performance characteristics of a multiplex cytokine immunoassay. Methods: We used a fluorescent bead-based (Luminex) immunoassay kit to simultaneously measure interleukin (IL) 1 beta, IL2, IL4, IL5, IL6, IL7, IL8, IL10, IL12p70, IL13, IFN gamma, granulocyte colony-stimulating factor, and tumor necrosis factor-alpha. We tested identical aliquots of serum from 38 asymptomatic individuals on three different days and matched sets of serum, heparinized plasma, and acid citrate dextrose plasma from an additional 38 healthy donors expected to have low cytokine concentrations. We applied multiple imputation to calculate unbiased reproducibility estimates for measurements below the limits of detection. Correlations among the cytokines were assessed by Spearman rank order coefficients and principal components analyses. Results: Of the 13 cytokines, 3 were undetectable (IL1 beta, IL2, IL5) in more than half of the serum samples. Coefficients of variation for replicate serum measurements ranged from 18% to 44%, with intraclass correlation coefficients ranging from 55% to 98%. Only IL4, IL6, and ILS had statistically significant correlations (Spearman rho, 0.42-0.94) between serum and acid citrate dextrose or heparin plasma levels. Conclusions: Interindividual differences outweigh substantial laboratory variation for these assays, yielding high intraclass correlation coefficients despite unimpressive coefficients of variation. Plasma measurements generally are not reflective of serum levels and hence are not interchangeable. With their small volume, low cost per test, and multiplex capacity, Luminex-based cytokine assays have potential utility for epidemiologic studies. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3450-6) C1 [Wong, Hui-Lee] NCI, Infect Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Pfeiffer, Ruth M.; Fears, Thomas R.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Ji, Shaoquan] Millipore Corp, Biosci Div, St Charles, MO USA. RP Wong, HL (reprint author), NCI, Infect Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7073, Rockville, MD 20852 USA. EM wongh@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIH; NIH-Oak Ridge Institute for Science and Education FX NIH intramural research funds and the NIH-Oak Ridge Institute for Science and Education fellowship (H-L. Wong). NR 31 TC 93 Z9 93 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3450 EP 3456 DI 10.1158/1055-9965.EPI-08-0311 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000024 PM 19064561 ER PT J AU Pooley, KA Baynes, C Driver, KE Tyrer, J Azzato, EM Pharoah, PDP Easton, DF Ponder, BAJ Dunning, AM AF Pooley, Karen A. Baynes, Caroline Driver, Kristy E. Tyrer, Jonathan Azzato, Elizabeth M. Pharoah, Paul D. P. Easton, Douglas F. Ponder, Bruce A. J. Dunning, Alison M. TI Common Single-Nucleotide Polymorphisms in DNA Double-Strand Break Repair Genes and Breast Cancer Risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SUSCEPTIBILITY GENES; PROSTATE-CANCER; DAMAGE RESPONSE; RECEPTOR STATUS; NO ASSOCIATION; FANCONI-ANEMIA; SKIN-CANCER; XRCC3; POPULATION; BRCA1 AB The proteins involved in homologous recombination are instrumental in the error-free repair of dsDNA breakages, and common germ-line variations in these genes are, therefore, potential candidates for involvement in breast cancer development and progression. We carried out a search for common, low-penetrance susceptibility alleles by tagging the common variation in 13 genes in this pathway in a two-stage case-control study. We genotyped 100 single-nucleotide polymorphism. (SNP), tagging the 655 common SNPs in these genes, in up to 4,470 cases and 4,560 controls from the SEARCH study. None of these tagging SNP. was associated with breast cancer risk, with the exception of XRCC2 rs3218536, R188H, which showed some evidence of a protective association for the rare allele [per allele odds ratio, 0.89; 959% confidence intervals (959% CI), 0.80-0.99; P trend = 0.03]. Further analyses showed that this effect was confined to a risk of progesterone receptor positive tumors (per rare allele odds ratio, 0.78; 95%, CI, 0.66-0.91; P trend = 0.002). Several other SNPs also showed receptor status-specific susceptibility and evidence of roles in long-term survival, with the rare allele of BRIP1 rs2191249 showing evidence of association with a poorer prognosis (hazard ratio per minor allele, 1.20; 959% CI, 1.07-1.36; P trend = 0.002). In summary, there was little evidence of breast cancer susceptibility with any of the SNP. studied, but larger studies would be needed to confirm subgroup effects. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3482-9) C1 [Pooley, Karen A.; Easton, Douglas F.] Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. [Baynes, Caroline; Driver, Kristy E.; Tyrer, Jonathan; Azzato, Elizabeth M.; Pharoah, Paul D. P.; Dunning, Alison M.] Strangeways Res Lab, Canc Res UK Dept Oncol, Cambridge CB1 8RN, England. [Ponder, Bruce A. J.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England. [Azzato, Elizabeth M.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Pooley, KA (reprint author), Strangeways Res Lab, Canc Res UK Genet Epidemiol Unit, Worts Causeway, Cambridge CB1 8RN, England. EM karenp@srl.cam.ac.uk RI Azzato, Elizabeth/A-1902-2009; OI Dunning, Alison Margaret/0000-0001-6651-7166 FU Cancer Research UK; NIH-University of Cambridge Graduate Partnership Program; National Cancer Institute FX Cancer Research UK. B.A.J. Ponder is a Cancer Research UK Gibb Fellow, P.D.P. Pharoah is a Cancer Research UK Senior Clinical Research Fellow, and D.F. Easton is a Cancer Research UK Principal Research Fellow. EMA is funded by the NIH-University of Cambridge Graduate Partnership Program and the National Cancer Institute. NR 54 TC 21 Z9 21 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3482 EP 3489 DI 10.1158/1055-9965.EPI-08-0594 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000028 PM 19064565 ER PT J AU Flores, R Lu, BB Nielson, C Abrahamsen, M Wolf, K Lee, JH Harris, RB Giuliano, AR AF Flores, Roberto Lu Beibei Nielson, Carrie Abrahamsen, Martha Wolf, Kyle Lee, Ji-Hyun Harris, Robin B. Giuliano, Anna R. TI Correlates of Human Papillomavirus Viral Load with Infection Site in Asymptomatic Men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOMA IN-SITU; CERVICAL INTRAEPITHELIAL NEOPLASIA; HPV; RISK; PARTNERS; LESIONS; CANCER; VIRUS; UTERI; WOMEN AB Numerous studies have evaluated human papillomavirus (HPV) DNA load in women, especially HPV-16 viral load, and its role in cervical carcinogenicity. Few studies have examined HPV viral load in men, none among asymptomatic men. The aim of the current study is to quantify HPV-16 viral load in male anogenital specimens and to explore its correlates with anatomic sites. Two-hundred and ninety-four specimens from 42 men who tested positive for HPV-16 at one or more anatomic sites were evaluated. HPV DNA was detected with PGMY 09/11 primer and genotyped with reverse line blot assay followed by HPV-16 viral quantification using type-specific real-time PCR assay (TaqMan). The quantitative PCR assay showed a higher sensitivity in HPV-16 viral DNA detection compared with the reverse line blot assay. Viral load varied significantly by anatomic site (P = 0.019). Penile shaft specimens had significantly higher viral load than any other anatomic site evaluated except for the anal canal. HPV-16 viral load was positively correlated between proximal anatomic sites: perianal and anal canal (P = 0.003), perianal and scrotum (P = 0.011), scrotum and glans/corona (P = 0.045), and scrotum and penile shaft (P = 0.037). In conclusion, the penile shaft seemed to be the preferred site for HPV-16 viral replication. Viral load correlation between proximal sites suggested a possible autoinoculation in male HPV transmission. (Cancer Epidemiol Biomarkers Prev 2008;1.7(12):3573-6) C1 [Flores, Roberto] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Lu Beibei; Abrahamsen, Martha; Wolf, Kyle; Lee, Ji-Hyun; Giuliano, Anna R.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Nielson, Carrie] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Harris, Robin B.] Mel & Enid Zuckerman Coll Publ Hlth, Arizona Canc Ctr, Tucson, AZ USA. RP Flores, R (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6120 Execut Blvd,EPS Suite T-41, Bethesda, MD 20892 USA. EM rflores@jhsph.edu FU Centers for Disease Control and Prevention, through the Association of American Medical Colleges [U36/CCU319276]; AAMC [MM-0579-03/03] FX Centers for Disease Control and Prevention, through the Association of American Medical Colleges (cooperative agreement; grant U36/CCU319276; AAMC identification no, MM-0579-03/03), NR 24 TC 19 Z9 21 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2008 VL 17 IS 12 BP 3573 EP 3576 DI 10.1158/1055-9965.EPI-08-0467 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000039 PM 19064573 ER PT J AU Demark-Wahnefried, W Polascik, TJ George, SL Switzer, BR Madden, JF Ruffin, MT Snyder, DC Owzar, K Hars, V Albala, DM Walther, PJ Robertson, CN Moul, JW Dunn, BK Brenner, D Minasian, L Stella, P Vollmer, RT AF Demark-Wahnefried, Wendy Polascik, Thomas J. George, Stephen L. Switzer, Boyd R. Madden, John F. Ruffin, Mack T. Snyder, Denise C. Owzar, Kouros Hars, Vera Albala, David M. Walther, Philip J. Robertson, Cary N. Moul, Judd W. Dunn, Barbara K. Brenner, Dean Minasian, Lori Stella, Philip Vollmer, Robin T. TI Flaxseed Supplementation (Not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates on Men Presurgery SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALPHA-LINOLENIC ACID; HIGH-FIBER DIET; MAMMALIAN LIGNANS; CLINICAL-PRACTICE; BREAST-CANCER; DISEASE; RISK; ANTIGEN; CARCINOMA; PLASMA AB Background: Prostate cancer affects one of six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods: We undertook a multisite, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n = 161) scheduled at least 21. days before prostatectomy were randomly assigned to one of the following arms: (a) control (usual diet), (b) flaxseed-supplemented diet (30 g/d), (c) low-fat diet (< 20% total energy), or (d) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and before surgery and analyzed for prostate-specific antigen, sex hormone-binding globulin, testosterone, insulin-like growth factor-I and binding protein-3, C-reactive protein, and total and low-density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results: Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67-positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) versus 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serologic endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P = 0.048). Conclusions: Findings suggest that flaxseed is safe and associated with biological alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3577-87) C1 [Demark-Wahnefried, Wendy] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX 77230 USA. [Polascik, Thomas J.; Albala, David M.; Walther, Philip J.; Robertson, Cary N.; Moul, Judd W.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC 27706 USA. [Polascik, Thomas J.; Albala, David M.; Walther, Philip J.; Robertson, Cary N.; Moul, Judd W.] Duke Univ, Med Ctr, Duke Prostate Ctr, Durham, NC 27706 USA. [George, Stephen L.; Owzar, Kouros] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27706 USA. [George, Stephen L.; Owzar, Kouros; Hars, Vera] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr Biostat, Durham, NC 27706 USA. [Madden, John F.; Vollmer, Robin T.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27706 USA. [Snyder, Denise C.] Duke Univ, Sch Nursing, Durham, NC 27706 USA. [Vollmer, Robin T.] Durham VA Med Ctr, Dept Surg Pathol & Cytopathol, Durham, NC USA. [Switzer, Boyd R.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Ruffin, Mack T.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA. [Brenner, Dean] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Stella, Philip] Michigan Canc Res Consortium CCOP, Ann Arbor, MI USA. [Dunn, Barbara K.; Minasian, Lori] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Demark-Wahnefried, W (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, POB 301439,Unit 1330, Houston, TX 77230 USA. EM wdemarkw@mdanderson.org OI Ruffin, Mack/0000-0001-8336-478X FU NIH [CA85740, CA07464830, M01-RR-30]; ENRECO FX NIH grants CA85740, CA07464830, anti M01-RR-30. Flaxseed was donated by ENRECO. NR 53 TC 68 Z9 72 U1 6 U2 12 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 DEC PY 2008 VL 17 IS 12 BP 3577 EP 3587 DI 10.1158/1055-9965.EPI-08-00118 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 384DH UT WOS:000261724000040 PM 19064574 ER PT J AU Olivo-Marston, SE Zhu, YL Lee, RY Cabanes, A Khan, G Zwart, A Wang, Y Clarke, R Hilakivi-Clarke, L AF Olivo-Marston, Susan E. Zhu, Yuelin Lee, Richard Y. Cabanes, Anna Khan, Galam Zwart, Alan Wang, Yue Clarke, Robert Hilakivi-Clarke, Leena TI Gene Signaling Pathways Mediating the Opposite Effects of Prepubertal Low-Fat and High-Fat n-3 Polyunsaturated Fatty Acid Diets on Mammary Cancer Risk SO CANCER PREVENTION RESEARCH LA English DT Article ID NADP(+)-DEPENDENT ISOCITRATE DEHYDROGENASE; BREAST-CANCER; DNA-DAMAGE; NUDE-MICE; LIPID-PEROXIDATION; OXIDATIVE DAMAGE; EICOSAPENTAENOIC ACID; METALLOTHIONEIN-III; LINOLENIC ACID; CELL-SURVIVAL AB In rats, prepubertal exposure to low-fat diet containing n-3 polyunsaturated fatty acids (PUFA) reduces mammary cell proliferation, increases apoptosis, and lowers risk of mammary tumors in adulthood, whereas prepubertal high-fat n-3 PUFA exposure has opposite effects. To identify signaling pathways mediating these effects, we performed gene microarray analyses and determined protein levels of genes related to mammary epithelial cell proliferation. Nursing female rats and rat pups were fed low-fat (16% energy from fat) or high-fat (39% energy from fat) n-3 or n-6 PUFA diets between postnatal days 5 and 24. cDNA gene expression microarrays were used to identify global changes in the mammary glands of 50-day-old rats. Differences in gene expression were confirmed by real-time quantitative PCR, and immunohistochemistry was used to assess changes in the peroxisome proliferator-activated receptor. and cyclin D1 levels. DNA damage was determined by 8-hydroxy-2'-deoxyguanosine assay. Expressions of the antioxidant genes thioredoxin, heme oxygenase, NADP-dependent isocitrate dehydrogenase, and metallothionein III, as well as peroxisome proliferator-activated receptor. protein, were increased in the mammary glands of 50-day-old rats prepubertally fed the low-fat n-3 PUFA diet. Prepubertal exposure to the high-fat n-3 PUFA diet increased DNA damage and cyclin D1 protein and reduced expression of BRCA1 and cardiotrophin-1. Reduction in mammary tumorigenesis among rats prepubertally fed a low-fat n-3 PUFA diet was associated with an up-regulation of antioxidant genes, whereas the increase in mammary tumorigenesis in the high-fat n-3 PUFA fed rats was linked to up-regulation of genes that induce cell proliferation and down-regulation of genes that repair DNA damage and induce apoptosis. C1 [Olivo-Marston, Susan E.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div,NIH, Bethesda, MD 20892 USA. [Olivo-Marston, Susan E.; Zhu, Yuelin] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Richard Y.; Cabanes, Anna; Khan, Galam; Zwart, Alan; Clarke, Robert; Hilakivi-Clarke, Leena] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Wang, Yue] Virginia Polytech Inst & State Univ, Arlington, VA USA. RP Hilakivi-Clarke, L (reprint author), 3970 Reservoir Rd NW,Res Bldg,Room W405, Washington, DC 20057 USA. EM clarkel@georgetown.edu RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU Department of Defense; National Cancer Institute [5 RO1 CA89950, 1 U54 CA100970]; Susan G. Komen Breast Cancer Research Foundation; American Institute for Cancer Research; National Cancer Institute Cancer Prevention Fellowship FX Predoctoral fellowship grant from Department of Defense (S. E. Olivo-Marston) and National Cancer Institute grants 5 RO1 CA89950 and 1 U54 CA100970, the Susan G. Komen Breast Cancer Research Foundation, and the American Institute for Cancer Research (L. Hilakivi-Clarke). S. E. Olivo-Marston is currently a recipient of a National Cancer Institute Cancer Prevention Fellowship. NR 48 TC 15 Z9 15 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD DEC PY 2008 VL 1 IS 7 BP 532 EP 545 DI 10.1158/1940-6207.CAPR-08-0030 PG 14 WC Oncology SC Oncology GA 420MO UT WOS:000264294100007 PM 19139003 ER PT J AU Huang, FJ Steeg, PS Price, JE Chiu, WT Chou, PC Me, KP Sawaya, R Huang, SY AF Huang, Feng-Ju Steeg, Patricia S. Price, Janet E. Chiu, Wen-Tai Chou, Ping-Chieh Me, Keping Sawaya, Raymond Huang, Suyun TI Molecular Basis for the Critical Role of Suppressor of Cytokine Signaling-1 in Melanoma Brain Metastasis SO CANCER RESEARCH LA English DT Article ID SOCS-BOX MOTIF; MALIGNANT-MELANOMA; GROWTH-FACTOR; ABERRANT METHYLATION; NEGATIVE REGULATOR; STAT3 ACTIVATION; KINASE-ACTIVITY; TUMOR-CELLS; EXPRESSION; ANGIOGENESIS AB Our recent study found that activation of signal transducer and activator of transcription 3 (Stat3) is up-regulated in human brain metastatic cells and contributes to brain metastasis of melanoma. However, the molecular mechanisms underlying this increased Stat3 activation and effect on brain metastasis are unknown. In this report, we showed that the expression of Janus-activated kinase 2 (JAK2), a Stat3 activator, was increased, whereas the expression of a negative regulator of Stat3, suppressor of cytokine signaling-1 (SOCS-1), was reduced in the brain metastatic melanoma cell line A375Br, relative to that in the parental A375P cell line. Consistently, SOCS-1 expression was also lower in the human brain metastatic tissues than in the primary melanoma tissues. Mechanistically, increased JAK2 expression in the A375Br cells was due to, at least in part, its decreased degradation, which was directly correlated with low expression of SOCS-1. Moreover, restoration of SOCS-1 expression resulted in the inhibition of Stat3 activation, whereas depletion of SOCS-1 up-regulated Stat3 activation. These clinical, experimental, and mechanistic findings strongly suggest that increased activation of Stat3 in brain metastatic melanoma cells might be due to decreased SOCS-1 expression. Furthermore, restoration of SOCS-1 expression in brain metastatic A375Br cells significantly inhibited brain metastasis in animal models (P < 0.001). Additionally, alterations of SOCS-1 expression profoundly affected the expression of matrix metalloproteinase-2 (MMP-2), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) and the melanoma cell invasion and angiogenesis. Collectively, these data suggest that the loss of SOCS-1 expression is a critical event, leading to elevated Stat3 signaling and overexpression of MMP-2, bFGF, and VEGF, as well as enhanced invasion and angiogenesis of melanoma cells, consequently promoting brain metastasis. [Cancer Res 2008:68(23):9634-42] C1 [Huang, Suyun] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Unit 64, Houston, TX 77030 USA. [Price, Janet E.; Me, Keping; Huang, Suyun] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Huang, Feng-Ju; Price, Janet E.; Chou, Ping-Chieh; Me, Keping; Huang, Suyun] Univ Texas Houston, Grad Sch Biomed Sci, Program Canc Biol, Houston, TX USA. [Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Huang, SY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Unit 64, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM suhuang@mdanderson.org FU American Cancer Society Research Scholar; National Cancer Institute Cancer Center [CA 16672] FX Grant support: American Cancer Society Research Scholar grant. (S. Huang) and National Cancer Institute Cancer Center Support grant CA 16672.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; We thank Dr. Douglas J. Hilton (The Walter and Eliza Hall Institute for Medical Research) for the SOCS-1 cDNA expression vector and Theresa Willis and Christine F. Wogan for the editorial comments. NR 48 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2008 VL 68 IS 23 BP 9634 EP 9642 DI 10.1158/0008-5472.CAN-08-1429 PG 9 WC Oncology SC Oncology GA 380TU UT WOS:000261488900012 PM 19047140 ER PT J AU Jeon, HS Dracheva, T Yang, SH Meerzaman, D Fukuoka, J Shakoori, A Shilo, K Travis, WD Jen, J AF Jeon, Hyo-Sung Dracheva, Tatiana Yang, Sei-Hoon Meerzaman, Daoud Fukuoka, Junya Shakoori, Abbas Shilo, Konstantin Travis, William D. Jen, Jin TI SMAD6 Contributes to Patient Survival in Non-Small Cell Lung Cancer and Its Knockdown Reestablishes TGF-beta Homeostasis in Lung Cancer Cells SO CANCER RESEARCH LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; EPITHELIAL-CELLS; SIGNAL-TRANSDUCTION; RECEPTOR GENE; EXPRESSION; INHIBITOR; METASTASIS; CARCINOMA; SUPERFAMILY; ANTAGONIST AB The malignant transformation in several types of cancer, including lung cancer, results in a loss of growth inhibition by transforming growth factor-beta (TGF-beta). Here, we show that SMAD6 expression is associated with a reduced survival in lung cancer patients. Short hairpin RNA (shRNA)-mediated knockdown of SMAD6 in lung cancer cell lines resulted in reduced cell viability and increased apoptosis as well as inhibition of cell cycle progression. However, these results were not seen in Beas2B, a normal bronchial epithelial cell line. To better understand the mechanism underlying the association of SMAD6 with poor patient survival, we used a lentivirus construct carrying shRNA for SMAD6 to knock down expression of the targeted gene. Through gene expression analysis, we observed that knockdown of SMAD6 led to the activation of TGF-beta signaling through up-regulation of plasminogen activator inhibitor-1 and phosphorylation of SMAD2/3. Furthermore, SMAD6 knockdown activated the c-Jun NH(2)-terminal kinase pathway and reduced phosphorylation of Rb-1, resulting in increased G(0)-G(1) cell arrest and apoptosis in the lung cancer cell line H1299. These results jointly suggest that SMAD6 plays a critical role in supporting lung cancer cell growth and survival. Targeted inactivation of SMAD6 may provide a novel therapeutic strategy for lung cancers expressing this gene. [Cancer Res 2008;68(23):9686-92] C1 [Jeon, Hyo-Sung; Dracheva, Tatiana; Yang, Sei-Hoon; Fukuoka, Junya; Shakoori, Abbas; Jen, Jin] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Meerzaman, Daoud] NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Shilo, Konstantin] Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Jen, J (reprint author), Mayo Clin, Dept Pulm & Crit Care Med, Stabile 13-74,200 1st St SW, Rochester, MN 55905 USA. EM Jen.Jin@mayo.edu RI Shilo, Konstantin/E-4084-2011 FU Center for Cancer Research; National Cancer Institute FX Grant support: Center for Cancer Research, National Cancer Institute.; The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.; We thank Drs. Lucy Anderson, Katy Flander, and members of Laboratory of Human Carcinogenesis for helpful comments; Dr. Hayoung Hwang for technical advice; and the NIH Fellows Editorial Board and Dorothea Dudek-Creaven for editorial assistance. NR 38 TC 24 Z9 25 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2008 VL 68 IS 23 BP 9686 EP 9692 DI 10.1158/0008-5472.CAN-08-1083 PG 7 WC Oncology SC Oncology GA 380TU UT WOS:000261488900018 PM 19047146 ER PT J AU Chung, SH Wiedmeyer, K Shai, A Korach, KS Lambert, PF AF Chung, Sang-Hyuk Wiedmeyer, Kerri Shai, Anny Korach, Kenneth S. Lambert, Paul F. TI Requirement for Estrogen Receptor alpha in a Mouse Model for Human Papillomavirus-Associated Cervical Cancer SO CANCER RESEARCH LA English DT Article ID MULTICENTRIC CASE-CONTROL; SQUAMOUS CARCINOGENESIS; CELL-CARCINOMA; BREAST-CANCER; GROWTH-FACTOR; TYPE-16 E7; IN-VITRO; MICE; WOMEN; GENE AB The majority of human cervical cancers are associated with the high-risk human papillomaviruses (HPV), which encode the potent E6 and E7 oncogenes. On prolonged treatment with physiologic levels of exogenous estrogen, K14E7 transgenic mice expressing HPV-16 E7 oncoprotein in their squamous epithelia succumb to uterine cervical cancer. Furthermore, prolonged withdrawal of exogenous estrogen results in complete or partial regression of tumors in this mouse model. In the current study, we investigated whether estrogen receptor alpha (ER alpha) is required for the development of cervical cancer in K14E7 transgenic mice. We show that exogenous estrogen fails to promote either dysplasia or cervical cancer in K14E7/ER alpha(-/-) mice despite the continued presence of the presumed cervical cancer precursor cell type, reserve cells, and evidence for E7 expression therein. We also observed that cervical cancers in our mouse models are strictly associated with atypical squamous metaplasia (ASM), which is believed to be the precursor for cervical cancer in women. Consistently, E7 and exogenous estrogen failed to promote ASM in the absence of ER alpha. We conclude that ER alpha plays a crucial role at an early stage of cervical carcinogenesis in this mouse model. [Cancer Res 2008;68(23):9928-34] C1 [Chung, Sang-Hyuk; Wiedmeyer, Kerri; Shai, Anny; Lambert, Paul F.] Univ Wisconsin, Sch Med & Publ Hlth, McArdle Lab Canc Res, Madison, WI 53706 USA. [Korach, Kenneth S.] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC USA. RP Lambert, PF (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, McArdle Lab Canc Res, 1400 Univ Ave, Madison, WI 53706 USA. EM lambert@oncology.cwisc.edu OI Korach, Kenneth/0000-0002-7765-418X FU NIH [CA120847, CA098428, CA113297]; Division of Intramural Research of the National Institute of Environmental Health Sciences FX NIH grants CA120847. CA098428, and CA113297 (P.F. Lambert) and Division of Intramural Research of the National Institute of Environmental Health Sciences (K.S. Korach). NR 50 TC 41 Z9 44 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2008 VL 68 IS 23 BP 9928 EP 9934 DI 10.1158/0008-5472.CAN-08-2051 PG 7 WC Oncology SC Oncology GA 380TU UT WOS:000261488900046 PM 19047174 ER PT J AU Philip, S Swaminathan, S Kuznetsov, SG Kanugula, S Biswas, K Chang, S Loktionova, NA Haines, DC Kaldis, P Pegg, AE Sharant, SK AF Philip, Subha Swaminathan, Srividya Kuznetsov, Sergey G. Kanugula, Sreenivas Biswas, Kajal Chang, Suhwan Loktionova, Natalia A. Haines, Diana C. Kaldis, Philipp Pegg, Anthony E. Sharant, Shyam K. TI Degradation of BRCA2 in Alkyltransferase-Mediated DNA Repair and Its Clinical Implications SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER SUSCEPTIBILITY; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; POLY(ADP-RIBOSE) POLYMERASE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; INDUCED CYTOTOXICITY; ALKYLATING-AGENTS; KNOCKOUT MICE; CROSS-LINKS; GENE; CELLS AB Germ-line mutations in BRCA2 have been linked to early-onset familial breast cancer. BRCA2 is known to play a key role in repairing double-strand breaks. Here, we describe the involvement of BRCA2 in O(6)-alkylguanine DNA alkyltransferase (AGT)-mediated repair of O(6)-methylguanine adducts. We show that BRCA2 physically associates and undergoes repair-mediated degradation with AGT. In contrast, BRCA2 with a 29-amino-acid deletion in an evolutionarily conserved domain does not bind to alkylated AGT; the two proteins are not degraded; and mouse embryonic fibroblasts are specifically sensitive to alkylating agents that result in O(6)-methylguanine adducts. We show that O(6)-benzylguanine (O(6)BG), a nontoxic inhibitor of AGT, can also induce BRCA2 degradation. BRCA2 is a viable target for cancer therapy because BRCA2-deficient cells are hypersensitive to chemotherapeutic DNA-damaging agents. We show a marked effect of O(6)BG pretreatment on cell sensitivity to cisplatin. We also show the efficacy of this approach on a wide range of human tumor cell lines, which suggests that chemosensitization of tumors by targeted degradation of BRCA2 may be an important consideration when devising cancer therapeutics. [Cancer Res 2008;68(23):9973-81] C1 [Philip, Subha; Swaminathan, Srividya; Kuznetsov, Sergey G.; Biswas, Kajal; Chang, Suhwan; Kaldis, Philipp; Sharant, Shyam K.] NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Haines, Diana C.] NCI, Sci Applicat Int Corp Frederick Inc, Pathol Histotechnol Lab, Frederick, MD 21702 USA. [Kanugula, Sreenivas; Loktionova, Natalia A.; Pegg, Anthony E.] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. RP Sharant, SK (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Bldg 560,Room 32-31C,1050 Boyles St, Frederick, MD 21702 USA. EM ssharan@mail.ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU NIH [CA018137]; postdoctotral program of Korean Science and Engineering Foundation FX Center for Cancer Research. National Cancer Institute. NIH (S.K. Sharan, P. Kaldis. A.E. Pegg, and S. Kanugula); NIH grant CA018137 (A.E. Pegg and S. Kanugula); and postdoctotral program of Korean Science and Engineering Foundation (KOSEF; S. Chang). NR 46 TC 9 Z9 9 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2008 VL 68 IS 23 BP 9973 EP 9981 DI 10.1158/0008-5472.CAN-08-1179 PG 9 WC Oncology SC Oncology GA 380TU UT WOS:000261488900051 PM 19047179 ER PT J AU Sung, SY Hsieh, CL Law, A Zhau, HE Pathak, S Multani, AS Lim, S Coleman, IM Wu, LC Figg, WD Dahut, WL Nelson, P Lee, JK Amin, MB Lyles, R Johnstone, PAJ Marshall, FF Chung, LWK AF Sung, Shian Ying Hsieh, Chia-Ling Law, Andrew Zhau, Haiyen E. Pathak, Sen Multani, Asha S. Lim, Sharon Coleman, Ilsa M. Wu, Li-Chin Figg, William D. Dahut, William L. Nelson, Peter Lee, Jae K. Amin, Mahul B. Lyles, Robert Johnstone, Peter A. J. Marshall, Fray F. Chung, Leland W. K. TI Coevolution of Prostate Cancer and Bone Stroma in Three-Dimensional Coculture: Implications for Cancer Growth and Metastasis SO CANCER RESEARCH LA English DT Article ID CELLS; TUMOR; EXPRESSION; PROGRESSION; MODEL; GENE; TUMORIGENESIS; ACCELERATION; FIBROBLASTS; MECHANISMS AB Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes with reactive oxygen species serving as mediators. The evolved stromal cells are highly inductive of human PCa growth in mice, and expressed increased levels of extracellular matrix (versican and tenascin) and chemokine (BDFN, CCL5, CXCL5, and CXCL16) genes. These genes were validated in clinical tissue and/or serum specimens and could be the predictors for invasive and bone metastatic PCa. These results, combined with our previous observations, support the concept of permanent genetic and behavioral changes of PCa epithelial cells after being either cocultured with prostate or bone stromal cells as three-dimensional prostate organoids or grown as tumor xenografts in mice. These observations collectively suggest coevolution of cancer and stromal cells occurred under three-dimensional growth condition, which ultimately accelerates cancer growth and metastasis. [Cancer Res 2008;68(23):9996-10003] C1 [Zhau, Haiyen E.; Marshall, Fray F.; Chung, Leland W. K.] Emory Univ, Sch Med, Dept Urol, Mol Urol & Therapeut Program, Atlanta, GA 30322 USA. [Hsieh, Chia-Ling; Johnstone, Peter A. J.] Emory Univ, Sch Med, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Lim, Sharon; Amin, Mahul B.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Lyles, Robert] Emory Univ, Rollin Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Pathak, Sen; Multani, Asha S.] Univ Texas MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. [Law, Andrew] Univ Virginia, Dept Urol, Charlottesville, VA USA. [Lee, Jae K.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Coleman, Ilsa M.; Nelson, Peter] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Figg, William D.; Dahut, William L.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Sung, Shian Ying; Hsieh, Chia-Ling; Wu, Li-Chin] China Med Univ & Hosp, Ctr Mol Med, Taichung, Taiwan. [Sung, Shian Ying; Hsieh, Chia-Ling; Wu, Li-Chin] China Med Univ & Hosp, Grad Inst Canc Biol, Taichung, Taiwan. [Hsieh, Chia-Ling] Asia Univ, Dept Biotechnol, Taichung, Taiwan. RP Chung, LWK (reprint author), Emory Univ, Sch Med, Dept Urol, Mol Urol & Therapeut Program, 1365B Clifton Rd,Room B5101, Atlanta, GA 30322 USA. EM lwchung@emory.edu RI Figg Sr, William/M-2411-2016 FU NCI [CA-098912, CA-766201]; NSC [96-2320-B-093-033-MY3, 96-2628-B-039-029-MY3] FX Grant support: NCI CA-098912 and CA-766201. NSC 96-2320-B-093-033-MY3 and NSC 96-2628-B-039-029-MY3. NR 49 TC 72 Z9 74 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2008 VL 68 IS 23 BP 9996 EP 10003 DI 10.1158/0008-5472.CAN-08-2492 PG 8 WC Oncology SC Oncology GA 380TU UT WOS:000261488900054 PM 19047182 ER PT J AU Dakir, ELH Feigenbaum, L Linnoila, RI AF Dakir, E. L. Habib Feigenbaum, Lionel Linnoila, R. Ilona TI Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation SO CARCINOGENESIS LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CLARA CELL; BRONCHIAL EPITHELIUM; CORNIFIED ENVELOPE; INDUCED APOPTOSIS; TRANSGENIC MICE; PROTEIN GENE; VITAMIN-A; CANCER; CARCINOMA AB Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the impact of K14 in the pulmonary epithelium that normally lacks both squamous differentiation and K14 expression, human keratin 14 gene hK14 was constitutively expressed in mouse airway progenitor cells using a mouse Clara cell specific 10 kDa protein (CC10) promoter. While the lungs of CC10-hK14 transgenic mice developed normally, we detected increased expression of K14 and the molecular markers of squamous differentiation program such as involucrin, loricrin, small proline-rich protein 1A, transglutaminase 1 and cholesterol sulfotransferase 2B1. In contrast, wild-type lungs were negative. Aging CC10-hK14 mice revealed multifocal airway cell hyperplasia, occasional squamous metaplasia and their lung tumors displayed evidence for multidirectional differentiation. We conclude that constitutive expression of hK14 initiates squamous differentiation program in the mouse lung, but fails to promote squamous maturation. Our study provides a novel model for assessing the mechanisms of premalignant lesions in vivo by modifying differentiation and proliferation of airway progenitor cells. C1 [Dakir, E. L. Habib; Linnoila, R. Ilona] NCI, NIH, Expt Pathol Sect, Cell & Canc Biol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] Natl Canc Inst, Lab Anim Sci, Frederick, MD 20702 USA. RP Linnoila, RI (reprint author), NCI, NIH, Expt Pathol Sect, Cell & Canc Biol Branch,Ctr Canc Res, 37 Convent Dr,Room 1056B, Bethesda, MD 20892 USA. EM linnoila@mail.nih.gov RI 2008, Ibsal/A-1268-2012 FU National Cancer Institute of the National Institutes of Health FX This research was funded by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 46 TC 17 Z9 19 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2008 VL 29 IS 12 BP 2377 EP 2384 DI 10.1093/carcin/bgn190 PG 8 WC Oncology SC Oncology GA 380HW UT WOS:000261457800018 ER PT J AU Bility, MT Devlin-Durante, MK Blazanin, N Glick, AB Ward, JM Kang, BH Kennett, MJ Gonzalez, FJ Peters, JM AF Bility, Moses T. Devlin-Durante, Meghann K. Blazanin, Nicholas Glick, Adam B. Ward, Jerrold M. Kang, Boo Hyon Kennett, Mary J. Gonzalez, Frank J. Peters, Jeffrey M. TI Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) inhibits chemically induced skin tumorigenesis SO CARCINOGENESIS LA English DT Article ID FATTY-ACID CATABOLISM; EPIDERMAL-CELL LINES; MOUSE SKIN; TERMINAL DIFFERENTIATION; METABOLIC SYNDROME; SKELETAL-MUSCLE; GLUCOSE-METABOLISM; LIPID-METABOLISM; DELTA AGONIST; TISSUE FACTOR AB Peroxisome proliferator-activated receptor (PPAR)beta/delta-null mice exhibit enhanced tumorigenesis in a two-stage chemical carcinogenesis model as compared with wild-type mice. Previous work showed that ligand activation of PPAR beta/delta induces terminal differentiation and inhibits proliferation of primary keratinocytes, and this effect does not occur in the absence of PPAR beta/delta expression. In the present studies, the effect of ligand activation of PPAR beta/delta on skin tumorigenesis was examined using both in vivo and ex vivo skin carcinogenesis models. Inhibition of chemically induced skin tumorigenesis was observed in wild-type mice administered GW0742, and this effect was likely the result of ligand-induced terminal differentiation and inhibition of replicative DNA synthesis. These effects were not found in similarly treated PPAR beta/delta-null mice. Ligand activation of PPAR beta/delta also inhibited cell proliferation and induced terminal differentiation in initiated/neoplastic keratinocyte cell lines representing different stages of skin carcinogenesis. These studies suggest that topical administration of PPAR beta/delta ligands may be useful as both a chemopreventive and/or a chemotherapeutic approach to inhibit skin cancer. C1 [Bility, Moses T.; Devlin-Durante, Meghann K.; Blazanin, Nicholas; Glick, Adam B.; Kennett, Mary J.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Bility, Moses T.; Devlin-Durante, Meghann K.; Blazanin, Nicholas; Glick, Adam B.; Peters, Jeffrey M.] Penn State Univ, Huck Inst Life Sci, Integrat Biosci Grad Program, University Pk, PA 16802 USA. [Glick, Adam B.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, Bethesda, MD 20892 USA. [Ward, Jerrold M.] NIAID, SoBran Inc, Bethesda, MD 20892 USA. [Kang, Boo Hyon] Non Clin Pathol Res Ctr, Seoul 153801, South Korea. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU National Institutes of Health [CA124533] FX The National Institutes of Health (CA124533 to J. M. P.). NR 54 TC 27 Z9 27 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2008 VL 29 IS 12 BP 2406 EP 2414 DI 10.1093/carcin/bgn219 PG 9 WC Oncology SC Oncology GA 380HW UT WOS:000261457800022 PM 18799709 ER PT J AU Soutoglou, E AF Soutoglou, Evi TI DNA lesions and DNA damage response Even long lasting relationships need a "break" SO CELL CYCLE LA English DT Article DE tethering; DNA damage; DNA repair; chromatin; repair foci ID DOUBLE-STRAND BREAKS; RADIATION-INDUCED FOCI; HISTONE H2AX; REPAIR PROTEINS; IN-VIVO; MRE11-RAD50-NBS1 COMPLEX; CHROMATIN RETENTION; MAMMALIAN RAD51; ATM ACTIVATION; NUCLEAR FOCI AB The elucidation of the spatiotemporal map of the DNA damage response (DDR) has been critical to our understanding of how cells are protected against insults to genomic integrity. Recruitment and transient immobilization at DNA breaks is a typical characteristic of many DDR proteins. Here, I discuss evidence that stable association of DDR proteins with chromatin is sufficient to activate the DDR even in the absence of damage. These observations critically support the notion that nuclear repair compartments play a primary role in triggering and amplifying DDR. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Soutoglou, E (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM soutogle@mail.nih.gov FU HFSPO; NIH; NCI; Center for Cancer Research FX I am grateful to Tom Misteli, Gianluca Pegoraro and Sara Snyder for helpful comments and to Simon Biddie for help with the figure and critical reading of the manuscript. This work was supported by HFSPO and the Intramural Research Program of the NIH, NCI, and Center for Cancer Research. NR 56 TC 8 Z9 8 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2008 VL 7 IS 23 BP 3653 EP 3658 PG 6 WC Cell Biology SC Cell Biology GA 377OI UT WOS:000261260100009 PM 19029795 ER PT J AU Fulco, M Sartorelli, V AF Fulco, Marcella Sartorelli, Vittorio TI Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues SO CELL CYCLE LA English DT Review DE SIRT1; AMPK; nampt; PGC1-alpha; calorie restriction; starvation; gluconeogenesis; insulin ID ACTIVATED PROTEIN-KINASE; CALORIE RESTRICTION EXTENDS; LIFE-SPAN EXTENSION; TRANSCRIPTIONAL COACTIVATOR PGC-1; STIMULATED INSULIN-SECRETION; SMALL-MOLECULE ACTIVATORS; PROMOTES CELL-SURVIVAL; PANCREATIC BETA-CELLS; FATTY-ACID OXIDATION; RAT SKELETAL-MUSCLE AB The ability to adapt and respond to nutrients is an ancient cellular function, conserved from unicellular to the most complex multicellular organisms, including mammals. Mammals adapt to changes in nutritional status through the modulation of tissue-specific metabolic pathways so as to maintain energy homeostasis. At least two proteins are activated in response to reduced nutrient availability: AMP-activated protein kinase (AMPK) and NAD(+)-dependent deacetylase SIRT1. AMPK functions as a sensor of cellular energy status and as a master regulator of metabolism. When ATP levels decrease, AMPK is activated to boost ATP production and to inhibit ATP usage, thus restoring energy balance. Similarly, SIRT1 is activated in response to changes in the energy status to promote transcription of genes that mediate the metabolic response to stress, starvation or calorie restriction. Several observations support a model where, in response to stress and reduced nutrients, a metabolic pathway is activated within which AMPK and SIRT1 concordantly function to ensure an appropriate cellular response and adaptation to environmental modifications. In this perspective, we compare and contrast the roles of SIRT1 and AMPK in several metabolic tissues and propose a working model of how the AMPK-SIRT1 axis may be regulated to control functions relevant to organismal physiology and pathophysiology. C1 [Fulco, Marcella; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA. RP Sartorelli, V (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, 50 S Dr,Room 1351, Bethesda, MD 20892 USA. EM sartorev@mail.nih.gov FU National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health FX We would like to thank James Ryall (NIAMS, NIH) for discussion and critical reading of the manuscript. This work was supported by the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases of the National Institutes of Health. NR 160 TC 74 Z9 82 U1 0 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2008 VL 7 IS 23 BP 3669 EP 3679 PG 11 WC Cell Biology SC Cell Biology GA 377OI UT WOS:000261260100012 PM 19029811 ER PT J AU Lu, SJ Borst, DE Horowits, R AF Lu, Shajia Borst, Diane E. Horowits, Robert TI Expression and Alternative Splicing of N-RAP During Mouse Skeletal Muscle Development SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE myofibrillogenesis; myotube; sarcomere ID CULTURED CHICK CARDIOMYOCYTES; NEBULIN-RELATED PROTEIN; TIME QUANTITATIVE PCR; STRIATED-MUSCLE; LIM PROTEIN; CARDIAC MYOFIBRILLOGENESIS; MYOTONIC-DYSTROPHY; GENE-EXPRESSION; PRECARDIAC MESODERM; INTERCALATED DISKS AB N-RAP alternative splicing and protein localization were studied in developing skeletal Muscle tissue from pre- and postnatal mice and in fusing primary myotubes in Culture. Messages encoding N-RAP-s and N-RAP-c, the predominant isoforms of N-RAP detected in adult skeletal muscle and heart, respectively, were present in a 5:1 ratio in skeletal muscle isolated from E16.5 embryos. N-RAP-s mRNA levels increased three-fold over the first 3 weeks of postnatal development, while N-RAP-c mRNA levels remained low. N-RAP alternative splicing during myotube differentiation in culture was similar to the pattern observed in embryonic and neonatal muscle, with N-RAP-s expression increasing and N-RAP-c mRNA levels remaining low. In both developing skeletal muscle and cultured myotubes, N-RAP protein was primarily associated with developing myofibrillar structures containing alpha-actinin, but was not present in mature myofibrils. The results establish that N-RAP-s is the predominant spliced form of N-RAP present throughout skeletal muscle development. Cell Motil. Cytoskeleton 65: 945-954, 2008. Published 2008 Wiley-Liss, Inc. C1 [Lu, Shajia; Horowits, Robert] NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Borst, Diane E.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1154,MSC 8024, Bethesda, MD 20892 USA. EM horowits@helix.nih.gov FU Uniformed Services University of the Health Sciences [CO70VY] FX Contracct grant sponsor: Uniformed Services University of the Health Sciences; Contract grant number: CO70VY. NR 36 TC 7 Z9 7 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD DEC PY 2008 VL 65 IS 12 BP 945 EP 954 DI 10.1002/cm.20317 PG 10 WC Cell Biology SC Cell Biology GA 381UT UT WOS:000261562100003 PM 18792955 ER PT J AU Hou, L Pavan, WJ AF Hou, Ling Pavan, William J. TI Transcriptional and signaling regulation in neural crest stem cell-derived melanocyte development: do all roads lead to Mitf? SO CELL RESEARCH LA English DT Review DE neurocristopathy; Waardenburg syndrome; white spotting mice; pigment cells; differentiation ID ENDOTHELIN RECEPTOR-B; C-KIT RECEPTOR; WAARDENBURG-HIRSCHSPRUNG-DISEASE; CULTURED MAST-CELLS; TYROSINE KINASE; SACCHAROMYCES-CEREVISIAE; DOPACHROME-TAUTOMERASE; MOUSE MELANOCYTES; HUMAN PIEBALDISM; SYNDROME TYPE-2 AB Human neurocristopathies include a number of syndromes, tumors, and dysmorphologies of neural crest (NC) stem cell derivatives. In recent years, many white spotting genes have been associated with hypopigmentary disorders and deafness in neurocristopathies resulting from NC stem cell-derived melanocyte deficiency during development. These include PAX3, SOX10, MITF, SNAI2, EDNRB, EDN3, KIT, and KITL. Recent studies have revealed surprising new insights into a central role of MITF in the complex network of interacting genes in melanocyte development. In this perspective, we provide an overview of some of the current findings and explore complex functional roles of these genes during NC stem cell-derived melanocyte development. C1 [Hou, Ling] Wenzhou Med Coll, Dev Cell Biol & Dis Program, State Key Lab Cultivat Base, Wenzhou 325003, Zhejiang, Peoples R China. [Hou, Ling] Wenzhou Med Coll, Key Lab Vis Sci, China Minist Hlth, Hosp Eye, Wenzhou 325003, Zhejiang, Peoples R China. [Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Hou, L (reprint author), Wenzhou Med Coll, Dev Cell Biol & Dis Program, State Key Lab Cultivat Base, 270 Xueyuan Rd, Wenzhou 325003, Zhejiang, Peoples R China. EM lhou@mail.eye.ac.cn OI Hou, Ling/0000-0003-0705-8099 FU National Natural Science Foundation of China [30771149]; National Human Genome Research Institute, National Institutes of Health FX We would like to thank Dr Heinz Arnheiter (NIH/NINDS) for generously contributing to the images, and Dr Laura Baxter and Dr Yingzi Yang (NIH/NHGRI) for thoughtful comments on the manuscript. We also acknowledge the support by the National Natural Science Foundation of China (30771149) and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 149 TC 74 Z9 86 U1 0 U2 11 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD DEC PY 2008 VL 18 IS 12 BP 1163 EP 1176 DI 10.1038/cr.2008.303 PG 14 WC Cell Biology SC Cell Biology GA 385MI UT WOS:000261817900003 PM 19002157 ER PT J AU Levin, TC Wickliffe, KE Leppla, SH Moayeri, M AF Levin, Tera C. Wickliffe, Katherine E. Leppla, Stephen H. Moayeri, Mahtab TI Heat shock inhibits caspase-1 activity while also preventing its inflammasome-mediated activation by anthrax lethal toxin SO CELLULAR MICROBIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; BACILLUS-ANTHRACIS; MACROPHAGE SENSITIVITY; PROTEASOME INHIBITION; PROTEIN-DEGRADATION; PROTECTIVE ANTIGEN; NALP3 INFLAMMASOME; INNATE IMMUNITY; STRESS-RESPONSE; KINASE-KINASE AB Anthrax lethal toxin (LT) rapidly kills macrophages from certain mouse strains in a mechanism dependent on the breakdown of unknown protein(s) by the proteasome, formation of the Nalp1b (NLRP1b) inflammasome and subsequent activation of caspase-1. We report that heat-shocking LT-sensitive macrophages rapidly protects them against cytolysis by inhibiting caspase-1 activation without upstream effects on LT endocytosis or cleavage of the toxin's known cytosolic substrates (mitogen-activated protein kinases). Heat shock protection against LT occurred through a mechanism independent of de novo protein synthesis, HSP90 activity, p38 activation or proteasome inhibition and was downstream of mitogen-activated protein kinase cleavage and degradation of an unknown substrate by the proteasome. The heat shock inhibition of LT-mediated caspase-1 activation was not specific to the Nalp1b (NLRP1b) inflammasome, as heat shock also inhibited Nalp3 (NLRP3) inflammasome-mediated caspase-1 activation in macrophages. We found that heat shock induced pro-caspase-1 association with a large cellular complex that could prevent its activation. Additionally, while heat-shocking recombinant caspase-1 did not affect its activity in vitro, lysates from heat-shocked cells completely inhibited recombinant active caspase-1 activity. Our results suggest that heat shock inhibition of active caspase-1 can occur independently of an inflammasome platform, through a titratable factor present within intact, functioning heat-shocked cells. C1 [Levin, Tera C.; Wickliffe, Katherine E.; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Moayeri, M (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov FU NIH; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. We thank Devorah Crown for help with bone marrow isolation and Rasem Fattah for toxin preparation. We also thank a reviewer for insightful suggestions. NR 66 TC 14 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD DEC PY 2008 VL 10 IS 12 BP 2434 EP 2446 DI 10.1111/j.1462-5822.2008.01220.x PG 13 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 369YP UT WOS:000260730100006 PM 18671821 ER PT J AU Lippmann, J Rothenburg, S Deigendesch, N Eitel, J Meixenberger, K van Laak, V Slevogt, H N'Guessan, PD Hippenstiel, S Chakraborty, T Flieger, A Suttorp, N Opitz, B AF Lippmann, Juliane Rothenburg, Stefan Deigendesch, Nikolaus Eitel, Julia Meixenberger, Karolin van Laak, Vincent Slevogt, Hortense N'Guessan, Philippe Dje Hippenstiel, Stefan Chakraborty, Trinad Flieger, Antje Suttorp, Norbert Opitz, Bastian TI IFN beta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI) SO CELLULAR MICROBIOLOGY LA English DT Article ID INNATE IMMUNE-RESPONSES; HANDED Z-DNA; LISTERIA-MONOCYTOGENES; RIG-I; ADENOSINE-DEAMINASE; BINDING DOMAINS; ADAPTER PROTEIN; DAI DLM-1/ZBP1; RNA HELICASE; HUMAN ADAR1 AB Intracellular bacteria and cytosolic stimulation with DNA activate type I IFN responses independently of Toll-like receptors, most Nod-like receptors and RIG-like receptors. A recent study suggested that ZBP1 (DLM-1/DAI) represents the long anticipated pattern recognition receptor which mediates IFN alpha/beta responses to cytosolic DNA in mice. Here we show that Legionella pneumophila infection, and intracellular challenge with poly(dA-dT), but not with poly(dG-dC), induced expression of IFN beta, full-length hZBP1 and a prominent splice variant lacking the first Z alpha domain (hZBP1 Delta Z alpha) in human cells. Overexpression of hZBP1 but not hZBP1 Delta Z alpha slightly amplified poly(dA-dT)-stimulated IFN beta reporter activation in HEK293 cells, but had no effect on IFN beta and IL-8 production induced by bacteria or poly(dA-dT) in A549 cells. We found that mZBP1 siRNA impaired poly(dA-dT)-induced IFN beta responses in mouse L929 fibroblasts at a later time point, while multiple hZBP1 siRNAs did not suppress IFN beta or IL-8 expression induced by poly(dA-dT) or bacterial infection in human cells. In contrast, IRF3 siRNA strongly impaired the IFN beta responses to poly(dA-dT) or bacterial infection. In conclusion, intracellular bacteria and cytosolic poly(dA-dT) activate IFN beta responses in different human cells without requiring human ZBP1. C1 [Lippmann, Juliane; Eitel, Julia; Meixenberger, Karolin; van Laak, Vincent; Slevogt, Hortense; N'Guessan, Philippe Dje; Hippenstiel, Stefan; Suttorp, Norbert; Opitz, Bastian] Charite Univ Med Berlin, Dept Internal Med Infect Dis & Pulm Med, D-13353 Berlin, Germany. [Rothenburg, Stefan] Natl Inst Child & Human Dev, NIH, Bethesda, MD 20892 USA. [Deigendesch, Nikolaus] Univ Hosp Hamburg Eppendorf, Inst Immunol, Hamburg, Germany. [Chakraborty, Trinad] Univ Giessen, Inst Med Microbiol, D-35392 Giessen, Germany. [Flieger, Antje] Res Grp NG5 Pathogenesis Legionella Infect, Robert Koch Inst, D-13353 Berlin, Germany. RP Opitz, B (reprint author), Charite Univ Med Berlin, Dept Internal Med Infect Dis & Pulm Med, Augustenburger Pl 1, D-13353 Berlin, Germany. EM bastian.opitz@charite.de RI Rothenburg, Stefan/A-8340-2008 FU International Max Planck Research School; Deutsche Forschungsgemeinschaft; Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin; Jurgen Manchot Stiftung FX We are grateful to A. Kuhn, F. Schreiber, J. Hellwig and D. Stoll for excellent technical assistance and D. Freyer for generously providing L929 cells. This work was supported in part by the International Max Planck Research School for Infectious Diseases and Immunology to J. L., and by grants given by the Deutsche Forschungsgemeinschaft, the Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin and the Jurgen Manchot Stiftung to B.O. Parts of this work will be included in the PhD thesis of J.L. NR 52 TC 51 Z9 55 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD DEC PY 2008 VL 10 IS 12 BP 2579 EP 2588 DI 10.1111/j.1462-5822.2008.01232.x PG 10 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 369YP UT WOS:000260730100016 PM 18771559 ER PT J AU Jang, YH Ahn, BH Namkoong, S Kim, YM Jin, JK Kim, YS Min, DS AF Jang, Young Hoon Ahn, Bong-Hyun Namkoong, Seung Kim, Young Myeong Jin, Jae-Kwang Kim, Yong-Sun Min, Do Sik TI Differential regulation of apoptosis by caspase-mediated cleavage of phospholipase D isozymes SO CELLULAR SIGNALLING LA English DT Article DE PLD; Caspases; Cleavage; Activity; Apoptosis ID ADP-RIBOSYLATION FACTOR; ALZHEIMERS-DISEASE; CELL-PROLIFERATION; FAMILY; ACTIVATION; EXPRESSION; MECHANISMS AB Phospholipase D (PLD) has been implicated in survival and anti-apoptosis, but the molecular mechanism by which it responds to apoptotic stimuli is poorly unknown. Here, we demonstrate that cleavage of PLD isozymes as specific substrates of caspase differentially regulates apoptosis. PLD1 is cleaved at one internal site (DDVD(545)S) and PLD2 is cleaved at two or three sites (PTGD(13)ELD(16)S and DEVD(28)T) in the front of N-terminus. Cleavage of PLD was endogenously detected in post-mortem Alzheimer brain together with activated caspase-3, suggesting the physiological relevance. The cleavage of PLD1 but not PLD2 might act as an inactivating process since PLD1 but not PLD2 activity is significantly decreased during apoptosis, suggesting that differential cleavage of PLD isozymes could affect its enzymatic activity. Moreover, caspase-resistant mutant of PLD1 showed more potent anti-apoptotic capacity than that of wild type PLD1, whereas PLD2 maintained anti-apoptotic potency in spite of its cleavage during apoptosis. Moreover, PLD2 showed more potent anti-apoptotic effect than that of PLD1 in overexpression and knockdown experiments, suggesting that difference in anti-apoptotic potency between PLD1 and PLD2 might be due to its intrinsic protein property. Taken together, our results demonstrate that differential cleavage pattern of PLD isozymes by caspase might affect its enzymatic activity and anti-apoptotic function. (c) 2008 Elsevier Inc. All rights reserved. C1 [Jang, Young Hoon; Min, Do Sik] Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea. [Ahn, Bong-Hyun] NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. [Namkoong, Seung; Kim, Young Myeong] Kangwon Natl Univ, Sch Med, Vasc Syst Res Ctr, Dept Mol & Cellular Biochem, Chunchon, Kangwon Do, South Korea. [Jin, Jae-Kwang; Kim, Yong-Sun] Hallym Univ, Ilsong Inst Life Sci, Anyang, Kyonggi Do, South Korea. RP Min, DS (reprint author), Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea. EM minds@pusan.ac.kr FU Pusan National University FX This work was supported for 2 years by Pusan National University Research Grant. NR 34 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2008 VL 20 IS 12 BP 2198 EP 2207 DI 10.1016/j.cellsig.2008.07.010 PG 10 WC Cell Biology SC Cell Biology GA 381UG UT WOS:000261560800004 PM 18694819 ER PT J AU Di Martino, A Scheres, A Margulies, DS Kelly, AMC Uddin, LQ Shehzad, Z Biswal, B Walters, JR Castellanos, FX Milham, MP AF Di Martino, A. Scheres, A. Margulies, D. S. Kelly, A. M. C. Uddin, L. Q. Shehzad, Z. Biswal, B. Walters, J. R. Castellanos, F. X. Milham, M. P. TI Functional Connectivity of Human Striatum: A Resting State fMRI Study SO CEREBRAL CORTEX LA English DT Review ID ANTERIOR CINGULATE CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PRIMATE BASAL GANGLIA; EVENT-RELATED FMRI; HUMAN BRAIN; ORBITOFRONTAL CORTEX; RHESUS-MONKEY; CORTICOSTRIATAL PROJECTIONS; EFFERENT CONNECTIONS; MACACA-FASCICULARIS AB Classically regarded as motor structures, the basal ganglia subserve a wide range of functions, including motor, cognitive, motivational, and emotional processes. Consistent with this broad-reaching involvement in brain function, basal ganglia dysfunction has been implicated in numerous neurological and psychiatric disorders. Despite recent advances in human neuroimaging, models of basal ganglia circuitry continue to rely primarily upon inference from animal studies. Here, we provide a comprehensive functional connectivity analysis of basal ganglia circuitry in humans through a functional magnetic resonance imaging examination during rest. Voxelwise regression analyses substantiated the hypothesized motor, cognitive, and affective divisions among striatal subregions, and provided in vivo evidence of a functional organization consistent with parallel and integrative loop models described in animals. Our findings also revealed subtler distinctions within striatal subregions not previously appreciated by task-based imaging approaches. For instance, the inferior ventral striatum is functionally connected with medial portions of orbitofrontal cortex, whereas a more superior ventral striatal seed is associated with medial and lateral portions. The ability to map multiple distinct striatal circuits in a single study in humans, as opposed to relying on meta-analyses of multiple studies, is a principal strength of resting state functional magnetic resonance imaging. This approach holds promise for studying basal ganglia dysfunction in clinical disorders. C1 [Di Martino, A.; Margulies, D. S.; Kelly, A. M. C.; Uddin, L. Q.; Shehzad, Z.; Castellanos, F. X.; Milham, M. P.] NYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY 10016 USA. [Di Martino, A.] Univ Cagliari, Div Child & Adolescent Neuropsychiat, Dept Neurosci, I-09126 Cagliari, Italy. [Scheres, A.] Univ Arizona, Dept Psychol, Tucson, AZ 85701 USA. [Biswal, B.] Univ Med & Dent New Jersey, Dept Radiol, Newark, NJ 07103 USA. [Walters, J. R.] NINDS, Neurophysiol Pharmacol Sect, Bethesda, MD 20892 USA. [Castellanos, F. X.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Milham, MP (reprint author), NYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, 215 Lexington Ave, New York, NY 10016 USA. EM milham01@med.nyu.edu RI Milham, Michael/K-9501-2014; Di Martino, Adriana/L-2497-2014; Kelly, Clare/H-4629-2016; Margulies, Daniel/L-4719-2016; OI Kelly, Clare/0000-0001-8253-357X; Margulies, Daniel/0000-0002-8880-9204; Uddin, Lucina/0000-0003-2278-8962; Di Martino, Adriana/0000-0001-6927-290X; Castellanos, Francisco/0000-0001-9192-9437 FU Stavros S. Niarchos Foundation; National Alliance for Research on Schizophrenia and Depression FX Stavros S. Niarchos Foundation; and the National Alliance for Research on Schizophrenia and Depression. NR 106 TC 391 Z9 393 U1 13 U2 75 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2008 VL 18 IS 12 BP 2735 EP 2747 DI 10.1093/cercor/bhn041 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 373LQ UT WOS:000260973800003 PM 18400794 ER PT J AU Tsujimoto, S Genovesio, A Wise, SP AF Tsujimoto, Satoshi Genovesio, Aldo Wise, Steven P. TI Transient Neuronal Correlations Underlying Goal Selection and Maintenance in Prefrontal Cortex SO CEREBRAL CORTEX LA English DT Article ID SPATIAL WORKING-MEMORY; INFERIOR TEMPORAL CORTEX; MONKEYS MACACA-MULATTA; SPIKE TRAINS; CROSS-CORRELATION; DOUBLE DISSOCIATION; CELL ASSEMBLIES; FRONTAL-CORTEX; BASAL GANGLIA; MOTOR CORTEX AB We reported previously that as monkeys used abstract response strategies to choose spatial goals, 1 population of prefrontal cortex neurons encoded future goals (F cells), whereas a largely separate population encoded previous goals (P cells). Here, to better understand the mechanisms of goal selection and maintenance, we studied correlated activity among pairs of these neurons. Among the 3 possible types of pairs, F-F and F-P pairs often exhibited significant correlations when and after monkeys selected future goals but P-P pairs rarely did. These correlations were stronger when monkeys shifted from a previous goal than when they stayed with that goal. In addition, members of F-F pairs usually preferred the same goal and thus shared both prospective coding and spatial tuning properties. In contrast, cells composing F-P pairs usually had different spatial preferences and thus shared neither coding nor spatial tuning properties. On the assumption that the neurons composing a pair send convergent outputs to target neurons, their correlated activity could enhance their efficacy in context-dependent goal selection, goal maintenance, and the transformation of goal choices into action. C1 [Tsujimoto, Satoshi; Genovesio, Aldo; Wise, Steven P.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Tsujimoto, S (reprint author), NIMH, Lab Syst Neurosci, Bldg 49,Room B1EE17,49 Convent Dr,MSC 4401, Bethesda, MD 20892 USA. EM tsujimotos@mail.nih.gov RI Tsujimoto, Satoshi/B-8223-2011 FU National Institutes of Health; National Institute of Mental Health [Z01MH-01092-29]; Japan Society for the Promotion of Science FX Intramural Research Program of the National Institutes of Health, National Institute of Mental Health (Z01MH-01092-29). Japan Society for the Promotion of Science (research fellowship to S. T.). NR 77 TC 23 Z9 23 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2008 VL 18 IS 12 BP 2748 EP 2761 DI 10.1093/cercor/bhn033 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 373LQ UT WOS:000260973800004 PM 18359779 ER PT J AU Hanakawa, T Dimyan, MA Hallett, M AF Hanakawa, Takashi Dimyan, Michael A. Hallett, Mark TI Motor Planning, Imagery, and Execution in the Distributed Motor Network: A Time-Course Study with Functional MRI SO CEREBRAL CORTEX LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY; PREMOTOR CORTEX; HUMAN BRAIN; PRIMATE PREMOTOR; PARIETAL CORTEX; HAND AREA; MOVEMENT; HUMANS; FMRI AB Activation of motor-related areas has consistently been found during various motor imagery tasks and is regarded as the central mechanism generating motor imagery. However, the extent to which motor execution and imagery share neural substrates remains controversial. We examined brain activity during preparation for and execution of physical or mental finger tapping. During a functional magnetic resonance imaging at 3 T, 13 healthy volunteers performed an instructed delay finger-tapping task either in a physical mode or mental mode. Number stimuli instructed subjects about a finger-tapping sequence. After an instructed delay period, cue stimuli prompted them either to execute the tapping movement or to imagine it. Two types of planning/preparatory activity common for movement and imagery were found: instruction stimulus-related activity represented widely in multiple motor-related areas and delay period activity in the medial frontal areas. Although brain activity during movement execution and imagery was largely shared in the distributed motor network, imagery-related activity was in general more closely related to instruction-related activity than to the motor execution-related activity. Specifically, activity in the medial superior frontal gyrus, anterior cingulate cortex, precentral sulcus, supramarginal gyrus, fusiform gyrus, and posterolateral cerebellum likely reflects willed generation of virtual motor commands and analysis of virtual sensory signals. C1 [Hanakawa, Takashi; Dimyan, Michael A.; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Hanakawa, Takashi] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Cort Funct Disorders, Kodaira, Tokyo 1878502, Japan. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Dimyan, Michael/B-1715-2012; OI Dimyan, Michael/0000-0002-9715-9741 FU National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); Ministry of Education, Culture, Sports, Science, and Technology, Japan [17500210]; Priority Areas [17022023] FX Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH); NINDS, NIH (Intramural Competitive Fellowship to T. H.); Ministry of Education, Culture, Sports, Science, and Technology, Japan (Grant-in-Aid on Fundamental Research (C) (17500210) to T. H.); Priority Areas (Mobiligence Project 17022023); Pfizer grant to the Foundation for the NIH (to M. A. D.). NR 73 TC 152 Z9 160 U1 1 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2008 VL 18 IS 12 BP 2775 EP 2788 DI 10.1093/cercor/bhn036 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 373LQ UT WOS:000260973800006 PM 18359777 ER PT J AU Lee, C Gyorgy, A Maric, D Sadri, N Schneider, RJ Barker, JL Lawson, M Agoston, DV AF Lee, Cheol Gyorgy, Andrea Maric, Dragan Sadri, Navid Schneider, Robert J. Barker, Jeffery L. Lawson, Michael Agoston, Denes V. TI Members of the NuRD Chromatin Remodeling Complex Interact with AUF1 in Developing Cortical Neurons SO CEREBRAL CORTEX LA English DT Article ID DNA-BINDING PROTEIN; BHLH TRANSCRIPTION FACTORS; MESSENGER-RNA DECAY; GENE-EXPRESSION; HISTONE H3; CELL-CYCLE; TISSUE; NEUROGENESIS; REGION; CNS AB Chromatin remodeling plays an important role in coordinating gene expression during cortical development, however the identity of molecular complexes present in differentiating cortical neurons that mediate the process remains poorly understood. The A + U-rich element-binding factor 1 (AUF1) is a known regulator of messenger RNA stability and also acts as a transcription factor upon binding to AT-rich DNA elements. Here we show that AUF1 is specifically expressed in subsets of proliferating neural precursors and differentiating postmitotic neurons of the developing cerebral cortex. Moreover, AUF1 is coexpressed with histone deacetylase 1 (HDAC1) and metastasis-associated protein 2 (MTA2), members of the nucleosome remodeling and histone deacetylase complex. AUF1 specifically and simultaneously binds to HDAC1, MTA2, and AT-rich DNA element, its gene regulatory function is modulated by the extent of histone acetylation and in animals lacking AUF1, the composition of the complex is modified. These results suggest that AUF1 is involved in integrating genetic and epigenetic signals during cortical development through recruiting HDAC1 and MTA2 to AT-rich DNA elements. C1 [Lee, Cheol; Agoston, Denes V.] USUHS, Sch Med, Neurosci Program, Bethesda, MD 20814 USA. [Lee, Cheol; Gyorgy, Andrea; Lawson, Michael; Agoston, Denes V.] USUHS, Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Maric, Dragan; Barker, Jeffery L.] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. [Sadri, Navid; Schneider, Robert J.] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. RP Agoston, DV (reprint author), USUHS, Sch Med, Neurosci Program, 4301 Jones Br Rd, Bethesda, MD 20814 USA. EM vagoston@usuhs.edu OI sadri, navid/0000-0001-5051-717X; Schneider, Robert/0000-0001-5807-5564 FU USUHS Intramural grant; National Institute of Child Health and Human Development grant FX USUHS Intramural grant; and National Institute of Child Health and Human Development grant NR 51 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2008 VL 18 IS 12 BP 2909 EP 2919 DI 10.1093/cercor/bhn051 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 373LQ UT WOS:000260973800018 PM 18413351 ER PT J AU Morgan, RE Ahn, S Nzimiro, S Fotie, J Phelps, MA Cotrill, J Yakovich, AJ Sackett, DL Dalton, JT Werbovetz, KA AF Morgan, Rachel E. Ahn, Sunnoo Nzimiro, Sandra Fotie, Jean Phelps, Mitch A. Cotrill, Jeffrey Yakovich, Adam J. Sackett, Dan L. Dalton, James T. Werbovetz, Karl A. TI Inhibitors of Tubulin Assembly Identified through Screening a Compound Library SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE Tubulin; screen; library; Leishmania ID NATIONAL-CANCER-INSTITUTE; CLINICAL-TRIALS GROUP; TRYPANOSOMA-BRUCEI; SOLID TUMORS; IN-VIVO; PEDIATRIC-PATIENTS; COLCHICINE SITE; ANTITUMOR AGENT; PHASE-II; MICROTUBULE AB Tubulin is the proposed target for drugs against cancer and helminths and is also a validated target in kinetoplastid parasites. With the aim of identifying new lead compounds against Leishmania sp., tubulin isolated from L. tarentolae was used to screen a 10 000 compound library. One compound, Chembridge No. 7992831 (5), displayed an IC(50) of 13 mu m against Leishmania tubulin in an in vitro assembly assay and showed a greater than threefold selectivity over mammalian tubulin. Another compound, Chembridge No. 9067250 (8), exhibited good activity against mammalian tubulin (IC(50) = 5.0 mu m). This compound was also toxic to several cancer cell lines with IC(50) values in the region of 1 mu m. Subsequent testing of analogues of 8 contained within the library identified two compounds with greater potency against mammalian tubulin (IC(50) values of 1.1 and 2.8 mu m). The more potent antitubulin agent also showed promising activity against cancer cell lines in vitro, with IC(50) values ranging from 0.18 to 0.73 mu m. C1 [Ahn, Sunnoo; Phelps, Mitch A.; Cotrill, Jeffrey; Dalton, James T.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Sackett, Dan L.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. [Morgan, Rachel E.; Nzimiro, Sandra; Fotie, Jean; Yakovich, Adam J.; Werbovetz, Karl A.] Ohio State Univ, Div Med Chem & Pharmacognosy, Coll Pharm, Columbus, OH 43210 USA. RP Morgan, RE (reprint author), Univ Dundee, Div Biol Chem & Drug Discovery, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland. EM R.E.Morgan@dundee.ac.uk RI Werbovetz, Karl/E-4290-2011; Phelps, Mitch/H-3941-2013; OI Phelps, Mitch/0000-0002-1615-5280; dalton, James T/0000-0002-3915-7326 FU NIH [R01 AI 061021] FX This work was funded by NIH Grant R01 AI 061021 (to K.A.W.). The contribution of D.L.S. was supported by the intramural research program of the National Institute of Child Health and Human Development, NIH. We also thank Dr Chenglong Li for helpful discussions. NR 45 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD DEC PY 2008 VL 72 IS 6 BP 513 EP 524 DI 10.1111/j.1747-0285.2008.00729.x PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 375MH UT WOS:000261117500006 PM 19090918 ER PT J AU Yagi, H Frank, H Seidel, A Jerina, DM AF Yagi, Haruhiko Frank, Heinrich Seidel, Albrecht Jerina, Donald M. TI Revised Assignment of Absolute Configuration of the cis- and trans-N(6)-Deoxyadenosine Adducts at C(14) of (+/-)-11 beta,12 alpha-Dihydroxy-13 alpha,14 alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene by Stereoselective Synthesis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 7,8-DIOL 9,10-EPOXIDE ADDUCTS; TUMOR-INITIATING ACTIVITY; RAT MAMMARY-GLAND; REGION 11,12-DIOL 13,14-EPOXIDES; LINE-NARROWING SPECTROSCOPY; FJORD-REGION; MOUSE SKIN; AROMATIC-HYDROCARBON; 11,12-DIHYDRODIOL 13,14-EPOXIDES; DEOXYADENOSINE ADDUCTS AB We have reassigned relative and absolute configurations by unambiguous stereoselective syntheses of the cis- (13(S) and 13(R)) and trans-N(6)-deoxyadenosine (dAdo) adduct diastereomers (14(S) and 14(R)) derived from (+/-)-11 beta,12 alpha-dihydroxy-13 alpha,14 alpha-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]P DE-2), previously reported by Li et al. [(1999) Chem. Res. Toxicol. 12, 758-767]. Two stereoselective methods, asymmetric aminohydroxylation of the (+/-)-trans-11,12-dihydrodiol (3) with 3',5'-di-O-(tert -butyldimethylsilyl)-2'-deoxyadenosine (4) and the highly stereoselective cis addition of 4 to (+/-)-DB[a,l]P DE-2 in hexafluoropropan-2-ol (HFP), were employed. Both afforded a 1: 1 mixture of the cis-N(6)-dAdo adduct diastereomers, which were separated as triacetates (5(S) and 5(R)) in comparable yields (similar to 80%). The corresponding trans adduct diastereomers (10(S) and 10(R)) were obtained by coupling the aminotriol derived from trans opening of (+/-)-DB[a,l]P DE-2 with 6-fluoro-(2'-deoxy-3,5-di-tert-butyldimethylsilyloxy-beta-D-erythro-pentafuranosyl)purine (9) and subsequent acetylation in similar to 70% yield. The cis-5(S) and -5(R) and trans-10(S) and -10(R) were separately treated with 7% HF-pyridine followed by ammonolysis in NH(3)- saturated MeOH to give the dAdo adducts with all hydroxyl groups free (13(S), 13(R), 14(S), and 14(R)). Comparison of the (1)H NMR and CD spectra of these presently synthesized dAdo adducts with spectra of the previously reported compounds revealed that the interpretation of the 'H NMR and CD spectra and assignment of the relative stereochemistry (cis/trans) and absolute configuration made by Li et al. were at variance with our results. The above highly stereoselective syntheses of (+/-)-DB[a,l]P DE-2 adducted dAdo derivatives enabled efficient preparation of each of the four possible stereoisomeric 5'-dimethoxytrityl-3'-phosphoramidites for use in oligonucleotide synthesis. C1 [Yagi, Haruhiko; Jerina, Donald M.] NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. [Frank, Heinrich; Seidel, Albrecht] Prof Dr Gernot Grimmer Fdn, Biochem Inst Environm Carcinogens, D-22927 Grosshansdorf, Germany. RP Jerina, DM (reprint author), NIDDK, Bioorgan Chem Lab, Natl Inst Hlth, DHHS, Bethesda, MD 20892 USA. EM dmjerina@nih.gov FU Intramural Program of the NIH (National Institute of Diabetes and Digestive and Kidney Diseases); European Union [513943] FX We are greatly indebted to Dr. Jane M. Sayer at NIDDK for helpful discussions and suggestions. This research was supported by the Intramural Program of the NIH (National Institute of Diabetes and Digestive and Kidney Diseases). H.F. and A.S. are partners of ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No. 513943). NR 34 TC 5 Z9 5 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2008 VL 21 IS 12 BP 2379 EP 2392 DI 10.1021/tx800268f PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 384HU UT WOS:000261736700018 PM 19053320 ER PT J AU Gonzalez, FJ Ma, X Yang, Q Idle, JR AF Gonzalez, Frank J. Ma, Xiaochao Yang, Qian Idle, Jeffrey R. TI Humanized Mouse Models to Predict Chemical Safety and Metabolism SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 236th National Meeting of the Division of Chemical Toxicology of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc, Div Chem Toxicol C1 [Gonzalez, Frank J.; Ma, Xiaochao; Yang, Qian] NCI, Lab Metab, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Fac Med, Inst Pharmacol, Prague, Czech Republic. EM fjgonz@helix.nih.gov; jeff@cyp2d6.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2008 VL 21 IS 12 MA 32 BP 2439 EP 2439 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 384HU UT WOS:000261736700054 ER PT J AU Alexis, F Basto, P Levy-Nissenbaum, E Radovic-Moreno, AF Zhang, L Pridgen, E Wang, AZ Marein, SL Westerhof, K Molnar, LK Farokhzad, OC AF Alexis, Frank Basto, Pamela Levy-Nissenbaum, Etgar Radovic-Moreno, Aleksandar F. Zhang, Liangfang Pridgen, Eric Wang, Andrew Z. Marein, Shawn L. Westerhof, Katrina Molnar, Linda K. Farokhzad, Omid C. TI HER-2-Targeted Nanoparticle-Affibody Bioconjugates for Cancer Therapy SO CHEMMEDCHEM LA English DT Article DE targeted therapy; antitumor agents; affibodies; nanoparticles; PLA-PEG copolymers ID METASTATIC BREAST-CANCER; IN-VIVO; DRUG-DELIVERY; MOLECULES; FORMULATION; PACLITAXEL; RECEPTOR; BINDING C1 [Alexis, Frank; Levy-Nissenbaum, Etgar; Marein, Shawn L.; Westerhof, Katrina; Farokhzad, Omid C.] Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. [Alexis, Frank; Basto, Pamela; Levy-Nissenbaum, Etgar; Wang, Andrew Z.; Marein, Shawn L.; Westerhof, Katrina; Farokhzad, Omid C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Alexis, Frank; Basto, Pamela; Levy-Nissenbaum, Etgar; Radovic-Moreno, Aleksandar F.; Zhang, Liangfang; Wang, Andrew Z.; Westerhof, Katrina; Farokhzad, Omid C.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Pridgen, Eric] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Wang, Andrew Z.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Molnar, Linda K.] NCI, NIH, Bethesda, MD 20892 USA. RP Alexis, F (reprint author), Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA. EM ofarokhzad@partners.org RI Wang, Andrew /F-9719-2011; OI Wang, Andrew/0000-0002-9781-4494 FU US National Institutes of Health [EB003647] FX This work was supported by the US National Institutes of Health grant EB003647 and by a generous gift from Ms. Anne C. Gallo to Brigham and Women's Hospital toward this research. NR 28 TC 77 Z9 79 U1 1 U2 24 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD DEC PY 2008 VL 3 IS 12 BP 1839 EP 1843 DI 10.1002/cmdc.200800122 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386IO UT WOS:000261877100002 PM 19012296 ER PT J AU Hermone, AR Burnett, JC Nuss, JE Tressler, LE Nguyen, TL Solaja, BA Vennerstrom, JL Schmidt, JJ Wipf, P Bavari, S Gussio, R AF Hermone, Ann R. Burnett, James C. Nuss, Jonathan E. Tressler, Lyal E. Nguyen, Tam L. Solaja, Bogdan A. Vennerstrom, Jonathan L. Schmidt, James J. Wipf, Peter Bavari, Sina Gussio, Rick TI Three-Dimensional Database Mining Identifies a Unique Chemotype that Unites Structurally Diverse Botulinum Neurotoxin Serotype A Inhibitors in a Three-Zone Pharmacophore SO CHEMMEDCHEM LA English DT Article DE molecular modeling; screening; drug discovery; biologically active compounds; botulinum neurotoxin ID TOXIN TYPE-A; ZINC ENDOPEPTIDASE; NEUROTRANSMITTER RELEASE; CLOSTRIDIUM-BOTULINUM; PROTEOLYTIC ACTIVITY; PROTEASE INHIBITORS; UNLABELED USES; VAMP/SYNAPTOBREVIN; CHEMISTRY; THERAPY AB A search query consisting of two aromatic centers and two cationic centers was defined based on previously identified small molecule inhibitors of the botulinum neurotoxin serotype A light chain (BoNT/A LC) and used to mine the National Cancer Institute Open Repository. Ten small molecule hits were identified, and upon testing, three demonstrated inhibitory activity. Of these, one was structurally unique, possessing a rigid diazochrysene scaffold. The steric limitations of the diazachrysene imposed a separation between the overlaps of previously identified inhibitors, revealing an extended binding mode. As a result, the pharmacophore for BoNT/A LC inhibition has been modified to encompass three zones. To demonstrate the utility of this model, a novel three-zone inhibitor was mined and its activity was confirmed. C1 [Hermone, Ann R.; Burnett, James C.; Nguyen, Tam L.] NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. [Nuss, Jonathan E.; Tressler, Lyal E.; Schmidt, James J.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Solaja, Bogdan A.] Univ Belgrade, Fac Chem, Belgrade 11001, Serbia. [Vennerstrom, Jonathan L.] Univ Nebraska Med Ctr, Coll Pharm, Omaha, NE 68198 USA. [Wipf, Peter] Univ Pittsburgh, Combinatorial Chem Ctr, Pittsburgh, PA 15260 USA. [Gussio, Rick] NCI, Informat Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Hermone, AR (reprint author), NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, POB 8, Frederick, MD 21702 USA. EM sina.bavari@us.army.mil; gussio@ncifcrf.gov OI Solaja, Bogdan/0000-0002-9975-2725 FU Defense Threat Reduction Agency [3.10024 06]; MRMC; NCI; National Institutes of Health; National Cancer Institute [N01-CO-12400] FX This research was funded by Defense Threat Reduction Agency project 3.10024 06 RD B and Interagency Agreement Y3 CM 100505 (MRMC and NCI, National Institutes of Health). Additionally, this project has been funded in whole or in port with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. NR 46 TC 28 Z9 28 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD DEC PY 2008 VL 3 IS 12 BP 1905 EP 1912 DI 10.1002/cmdc.200800241 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 386IO UT WOS:000261877100011 PM 19006141 ER PT J AU DelCarmen-Wiggins, R AF DelCarmen-Wiggins, Rebecca TI Introduction to the Special Section: Transformative Research on Emotion Regulation and Dysregulation SO CHILD DEVELOPMENT PERSPECTIVES LA English DT Editorial Material DE emotion regulation; neurodevelopment; translational models; transformational research ID STILL-FACE; PSYCHOPATHOLOGY AB Scholars are giving increased attention to the need to incorporate research on more basic developmental processes into new paradigms for understanding and treating mental illness in children. and adolescents. The study of emotion regulation, rooted in neurodevelopment, has proven a fruitful model for understanding and characterizing problems of behavior and risk in children and adolescents. This article summarizes NIMH initiatives designed to encourage transformational research on the neurodevelopment origins of mental illness. It highlights the NIMH Strategic Plan. and the Report on Transformative Neurodevelopment Research as part of an introduction to a collection of articles that grew out of a previously organized NIMH workshop on developmental and translational models of emotion regulation and dysregulation. C1 NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. RP DelCarmen-Wiggins, R (reprint author), NIMH, Div Dev Translat Res, 6001 Execut Blvd,Room 6-181, Bethesda, MD 20892 USA. EM rdelcarm@nih.gov NR 9 TC 1 Z9 1 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1750-8592 J9 CHILD DEV PERSPECT JI Child Develop. Perspect. PD DEC PY 2008 VL 2 IS 3 BP 121 EP 123 DI 10.1111/j.1750-8606.2008.00053.x PG 3 WC Psychology, Developmental SC Psychology GA 499YK UT WOS:000270262600001 ER PT J AU Perelman, PL Graphodatsky, AS Dragoo, JW Serdyukova, NA Stone, G Cavagna, P Menotti, A Nie, W O'Brien, PCM Wang, J Burkett, S Yuki, K Roelke, ME O'Brien, SJ Yang, F Stanyon, R AF Perelman, P. L. Graphodatsky, A. S. Dragoo, J. W. Serdyukova, N. A. Stone, G. Cavagna, P. Menotti, A. Nie, W. O'Brien, P. C. M. Wang, J. Burkett, S. Yuki, K. Roelke, M. E. O'Brien, S. J. Yang, F. Stanyon, R. TI Chromosome painting shows that skunks (Mephitidae, Carnivora) have highly rearranged karyotypes SO CHROMOSOME RESEARCH LA English DT Article DE evolution; karyotype; Procyonidae; raccoon; skunk; stone marten ID PHYLOGENETIC-RELATIONSHIPS; ORDER CARNIVORA; MUSTELIDAE CARNIVORA; MOLECULAR PHYLOGENY; CONSTITUTIVE HETEROCHROMATIN; GENOME ORGANIZATION; PINNIPED KARYOTYPES; AMERICAN MINK; RIBOSOMAL-RNA; DOMESTIC CAT AB The karyotypic relationships of skunks (Mephitidae) with other major clades of carnivores are not yet established. Here, multi-directional chromosome painting was used to reveal the karyological relationships among skunks and between Mephitidae (skunks) and Procyonidae (raccoons). Representative species from three genera of Mephitidae (Mephitis mephitis, 2n = 50; Mephitis macroura, 2n = 50; Conepatus leuconotus, 2n = 46; Spilogale gracilis, 2n = 60) and one species of Procyonidae (Procyon lotor, 2n = 38) were studied. Chromosomal homology was mapped by hybridization of five sets of whole-chromosome paints derived from stone marten (Martes foina, 2n = 38), cat, skunks (M. mephitis; M. macroura) and human. The karyotype of the raccoon is highly conserved and identical to the hypothetical ancestral musteloid karyotype, suggesting that procyonids have a particular importance for establishing the karyological evolution within the caniforms. Ten fission events and five fusion events are necessary to generate the ancestral skunk karyotype from the ancestral carnivore karyotype. Our results show that Mephitidae joins Canidae and Ursidae as the third family of carnivores that are characterized by a high rate of karyotype evolution. Shared derived chromosomal fusion of stone marten chromosomes 6 and 14 phylogenetically links the American hog-nosed skunk and eastern spotted skunk. C1 [Perelman, P. L.; Graphodatsky, A. S.; Serdyukova, N. A.] SB RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia. [Perelman, P. L.; Roelke, M. E.; O'Brien, S. J.] NCI, Lab Genom Div, Frederick, MD 21702 USA. [O'Brien, P. C. M.] Univ Cambridge, Dept Vet Med, Ctr Vet Sci, Cambridge CB3 0ES, England. [Dragoo, J. W.] Univ New Mexico, Dept Biol, Museum SW Biol, Albuquerque, NM 87131 USA. [Nie, W.; Wang, J.] Chinese Acad Sci, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China. [Yang, F.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [Stanyon, R.] Univ Florence, Dept Evolutionary Biol, I-50122 Florence, Italy. [Yuki, K.] McGill Univ, Dept Human Genet, Montreal, PQ H3G 1A4, Canada. [Cavagna, P.] Univ Genoa, Dept Anthropol Sci, I-16128 Genoa, GE, Italy. RP Perelman, PL (reprint author), SB RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia. EM pol@bionet.nsc.ru RI Graphodatsky, Alexander/B-4922-2010; Dragoo, Jerry/B-5486-2011; Serdyukova, Natalia/N-6476-2015; Perelman, Polina/N-8088-2015; OI Graphodatsky, Alexander/0000-0002-8282-1085; Perelman, Polina/0000-0002-0982-5100; Stanyon, Roscoe/0000-0002-7229-1092 FU Russian Academy of Science; Siberian Branch of the Russian Academy of Science; MIUR; NIH; NCI; CCR; NCI-Frederick FX Gwen Dragoo provided valuable assistance in obtaining skin biopsies for several of the skunk samples. This study was funded in part by research grants of the Russian Fund for Basic Research, programmes of the Russian Academy of Science: Molecular and Cell Biology, Biosphere Origin and Evolution, Dynamics of Genofunds of Plants, Animals and Human and Integration programme of the Siberian Branch of the Russian Academy of Science (A.S.G.). R.S. was partially supported by a grant 'Mobility' of Italian and foreign researchers residing abroad' from MIUR. The research of G. S. and MER were supported by the Intramural Research Program of the NIH, NCI, CCR, NCI-Frederick. NR 82 TC 7 Z9 8 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD DEC PY 2008 VL 16 IS 8 BP 1215 EP 1231 DI 10.1007/s10577-008-1270-2 PG 17 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 387QN UT WOS:000261966800012 PM 19051045 ER PT J AU Stone, KD Prussin, C AF Stone, K. D. Prussin, C. TI Immunomodulatory therapy of eosinophil-associated gastrointestinal diseases SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Review ID ANTI-IL-5 MEPOLIZUMAB THERAPY; HUMANIZED MONOCLONAL-ANTIBODY; HYPEREOSINOPHILIC SYNDROME; GASTROESOPHAGEAL-REFLUX; FLUTICASONE PROPIONATE; ASTHMATIC RESPONSE; ELIMINATION DIET; CYCLOSPORINE-A; DOUBLE-BLIND; MAST-CELLS AB Eosinophil-associated gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EE) and eosinophilic gastroenteritis (EG), are a spectrum of increasingly recognized inflammatory diseases characterized by gastrointestinal symptoms and eosinophilic infiltration of the gastrointestinal tract. Significant morbidity is associated with the development of esophageal strictures in some patients. Immune-mediated reactions to food allergens appear to drive the inflammation in a subset of patients, especially those with solitary EE, but dietary interventions remain difficult in EE and are less effective in EG. Despite the increasing incidence of these disorders and their increased recognition by physicians, there are currently no medications that either United States or European Union regulatory agencies have specifically approved for use in EGIDs. This lack of safe and effective therapies for EGIDs is a major obstacle in the care of these patients and underscores the need for new therapeutic approaches. This review briefly discusses the currently available 'off label' drug treatments for EGIDs, most notably topical and systemic corticosteroids. Pathogenesis studies of EGIDs suggest possible therapeutic targets, and conversely, clinical trials of mechanistically-targeted therapeutics give insight into disease pathogenesis. Thus, EGID pathogenesis is discussed as an introduction to mechanistically-targeted immunotherapeutics. The two biologic categories that have been used in EGIDs, anti-IgE (omalizumab) and anti-IL-5 (SCH55700/reslizumab and mepolizumab), are discussed. Because there are similarities in the pathogenesis of EGIDs with asthma and atopic dermatitis, biologic therapeutics currently in early trials for asthma management are also briefly discussed as potential therapeutic agents for EGIDs. Given the deficiencies of current therapeutics and the rapidly advancing knowledge of the pathogenesis of these disorders, EGIDs are an ideal model for translating recent advances in understanding immunopathogenesis into mechanistically-based therapeutics. Further understanding of the early events in pathogenesis is also needed to develop preventive and disease-modifying treatments. Cite this as: K. D. Stone and C. Prussin, Clinical and Experimental Allergy, 2008 (38) 1858-1865. C1 [Stone, K. D.; Prussin, C.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C207, Bethesda, MD 20892 USA. EM calman@nih.gov OI Prussin, Calman/0000-0002-3917-3326 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 53 TC 28 Z9 30 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD DEC PY 2008 VL 38 IS 12 BP 1858 EP 1865 DI 10.1111/j.1365-2222.2008.03122.x PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 375TI UT WOS:000261135800005 PM 19037962 ER PT J AU Beare, PA Chen, C Bouman, T Pablo, J Unal, B Cockrell, DC Brown, WC Barbian, KD Porcella, SF Samuel, JE Felgner, PL Heinzen, RA AF Beare, Paul A. Chen, Chen Bouman, Timo Pablo, Jozelyn Unal, Berkay Cockrell, Diane C. Brown, Wendy C. Barbian, Kent D. Porcella, Stephen F. Samuel, James E. Felgner, Philip L. Heinzen, Robert A. TI Candidate Antigens for Q Fever Serodiagnosis Revealed by Immunoscreening of a Coxiella burnetii Protein Microarray SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; VACCINIA VIRUS; IDENTIFICATION; CLONING; MICE; HUMANS; ANTIBODIES; INFECTION; RESPONSES AB Q fever is a widespread zoonosis caused by Coxiella burnetii. Diagnosis of Q fever is usually based on serological testing of patient serum. The diagnostic antigen of test kits is formalin-fixed phase I and phase II organisms of the Nine Mile reference strain. Deficiencies of this antigen include (i) potential for cross-reactivity with other pathogens; (ii) an inability to distinguish between C. burnetii strains; and (iii) a need to propagate and purify C. burnetii, a difficult and potentially hazardous process. Consequently, there is a need for sensitive and specific serodiagnostic tests utilizing defined antigens, such as recombinant C. burnetii protein(s). Here we describe the use of a C. burnetii protein microarray to comprehensively identify immunodominant antigens recognized by antibody in the context of human C. burnetii infection or vaccination. Transcriptionally active PCR products corresponding to 1,988 C. burnetii open reading frames (ORFs) were generated. Full-length proteins were successfully synthesized from 75% of the ORFs by using an Escherichia coli-based in vitro transcription and translation system (IVTT). Nitrocellulose microarrays were spotted with crude IVTT lysates and probed with sera from acute Q fever patients and individuals vaccinated with Q-Vax. Immune sera strongly reacted with approximately 50 C. burnetii proteins, including previously identified immunogens, an ankyrin repeat-domain containing protein, and multiple hypothetical proteins. Recombinant protein corresponding to selected array-reactive antigens was generated, and the immunoreactivity was confirmed by enzyme-linked immunosorbent assay. This sensitive and high-throughput method for identifying immunoreactive C. burnetii proteins will aid in the development of Q fever serodiagnostic tests based on recombinant antigen. C1 [Beare, Paul A.; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, Hamilton, MT 59840 USA. [Barbian, Kent D.; Porcella, Stephen F.] NIAID, Rocky Mt Labs, Genom Unit, Res Technol Sect,Res Technol Branch,NIH, Hamilton, MT 59840 USA. [Chen, Chen; Bouman, Timo; Samuel, James E.] Texas A&M Hlth Sci Ctr, Dept Microbiol & Mol Pathogenesis, College Stn, TX 77843 USA. [Pablo, Jozelyn; Unal, Berkay; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. [Brown, Wendy C.] Washington State Univ, Dept Vet Microbiol & Pathol, Pullman, WA 99164 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Coxiella Pathogenesis Sect,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; National Institute of Allergy and Infectious Diseases [U54 AI057156, R01 AI057768, U54 AI065359, U01 AI061363] FX We thank Harlan Caldwell for critical review of the manuscript, Chad Burk, and Siddiqua Hirst for microarray probing and analysis, and Shahed Toosi for assistance in molecular cloning.; This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (R.A.H.) and by the Public Heath Service grants U54 AI057156, R01 AI057768, U54 AI065359, and U01 AI061363 from the National Institute of Allergy and Infectious Diseases (J.E.S. and P. L. F.). NR 34 TC 61 Z9 62 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD DEC PY 2008 VL 15 IS 12 BP 1771 EP 1779 DI 10.1128/CVI.00300-08 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 379GN UT WOS:000261384800005 PM 18845831 ER PT J AU Callahan, MJ Nagymanyoki, Z Bonome, T Johnson, ME Litkouhi, B Sullivan, EH Hirsch, MS Matulonis, UA Liu, J Birrer, MJ Berkowitz, RS Mok, SC AF Callahan, Michael J. Nagymanyoki, Zoltan Bonome, Tomas Johnson, Michael E. Litkouhi, Babak Sullivan, Elizabeth H. Hirsch, Michelle S. Matulonis, Ursula A. Liu, Joyce Birrer, Michael J. Berkowitz, Ross S. Mok, Samuel C. TI Increased HLA-DMB Expression in the Tumor Epithelium Is Associated with Increased CTL Infiltration and Improved Prognosis in Advanced-Stage Serous Ovarian Cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-of-Gynecologic Oncologists CY MAR 03-07, 2007 CL San Diego, CA SP Soc Gynecol Oncologists ID T-CELLS; COLORECTAL-CANCER; DR EXPRESSION; LYMPHOCYTES; SURVIVAL; CARCINOMAS AB Purpose:To evaluate the possible mechanisms influencing the infiltration of CD8 T lymphocytes into the tumor epithelium of advanced-stage serous ovarian cancers. Experimental Design: Immunohistochemical localization of CD8 T lymphocytes was done on a homogeneous population of 184 high-grade, advanced-stage serous ovarian cancer tissue specimens. Microarray analysis was done on microdissected tumor epithelium from 38 specimens to identify genes up-regulated or down-regulated in specimens with differing numbers of tumor-infiltrating CD8 T lymphocytes. Quantitative real-time PCR and immunohistochemistry were used to validate a candidate gene. Univariate and multivariate survival analyses were done combining CD8T lymphocyte number and HLA-DMB expression with standard prognostic factors. Results: Marked CD8 T lymphocyte infiltration of the tumor epithelium is associated with a 20-month improvement in median overall survival. Additionally, when combined with cytoreduction status and age, CD8 T lymphocyte status is an independent prognostic factor for survival. Microarray analysis showed HLA-DMB, a component of the MHC II antigen presentation machinery, to be differentially expressed in specimens with an abundance of tumor-infiltrating CD8 T lymphocytes. This relationship was validated at both mRNA and protein levels. As well, high HLA-DMB expression in the tumor epithelium was associated with a significant improvement in median overall survival in both univariate and multivariate analyses. Conclusions: Tumor cell expression of HLA-DM8 is associated with increased numbers of tumor-infiltrating CD8 T lymphocytes and both are associated with improved survival in advanced-stage serous ovarian cancer. C1 [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Hirsch, Michelle S.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Bonome, Tomas; Birrer, Michael J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Matulonis, Ursula A.; Liu, Joyce] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Callahan, Michael J.; Nagymanyoki, Zoltan; Johnson, Michael E.; Litkouhi, Babak; Sullivan, Elizabeth H.; Berkowitz, Ross S.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Lab Gynecol Oncol, Boston, MA 02115 USA. RP Mok, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, T4-3908,1515 Holcombe Blvd, Houston, TX 77030 USA. EM scmok@mdanderson.org FU Intramural NIH HHS; NCI NIH HHS [P50 CA105009, P50 CA105009-050002, P50CA105009, R01 CA133057, R33 CA103595, R33 CA103595-04, R33CA103595] NR 22 TC 36 Z9 37 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2008 VL 14 IS 23 BP 7667 EP 7673 DI 10.1158/1078-0432.CCR-08-0479 PG 7 WC Oncology SC Oncology GA 379JK UT WOS:000261392300012 PM 19047092 ER PT J AU Burstein, HJ Chen, YH Parker, LM Savoie, J Younger, J Kuter, I Ryan, PD Garber, JE Chen, H Campos, SM Shulman, LN Harris, LN Gelman, R Winer, EP AF Burstein, Harold J. Chen, Yu-Hui Parker, Leroy M. Savoie, Jennifer Younger, Jerry Kuter, Irene Ryan, Paula D. Garber, Judy E. Chen, Helen Campos, Susana M. Shulman, Lawrence N. Harris, Lyndsay N. Gelman, Rebecca Winer, Eric P. TI VEGF as a Marker for Outcome Among Advanced Breast Cancer Patients Receiving anti-VEGF Therapy with Bevacizumab and Vinorelbine Chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; ANGIOGENESIS; GROWTH AB Background: Anti-vascular endothelial growth factor therapy (VEGF) is an important new treatment modality in oncology.We sought to determine the efficacy and safety of the humanized monoclonal anti-VEGF antibody, bevacizumab, and vinorelbine as treatment for refractory breast cancer and to explore the role of plasma VEGF as a predictor of treatment outcome. Experimental Design: Eligible patients had received one or two prior chemotherapy regimens for metastatic breast cancer or recurred within 12 months of adjuvant therapy and had measurable disease and adequate end-organ function. Patients received bevacizumab 10 mg/kg every 2 weeks, and vinorelbine each week, until tumor progression or prohibitive toxicity. Plasma VEGF was measured at baseline. Results: Among 56 women treated on protocol, bevacizumab and vinorelbine yielded a 34% response rate (95% confidence interval, 22-48%) and median time to progression of 5.5 months. Activity was observed regardless of tumor hormone receptor status or type or extent of prior chemotherapy. Side effects included uncomplicated neutropenia, hypertension, nasal congestion/epistaxis, and neuropathy, consistent with well-described side effects of the respective agents. Three patients had impaired wound healing following surgical procedures. There were only rare instances of thrombosis or clinically significant proteinuria. Lower levels of baseline VEGF were associated with longer time to progression. Conclusions: Bevacizumab and vinorelbine are well tolerated and effective as treatment for refractory breast cancer. Plasma VEGF warrants further evaluation as a prognostic marker for treatment outcome in advanced breast cancer patients receiving anti-VEGF therapy. C1 [Burstein, Harold J.; Chen, Yu-Hui; Parker, Leroy M.; Savoie, Jennifer; Garber, Judy E.; Campos, Susana M.; Shulman, Lawrence N.; Gelman, Rebecca; Winer, Eric P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Younger, Jerry; Kuter, Irene; Ryan, Paula D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Harris, Lyndsay N.] Natl Canc Inst, Bethesda, MD USA. [Chen, Helen] Yale Univ, Sch Med, New Haven, CT USA. RP Burstein, HJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org FU Cancer Therapy Evaluation Program/National Cancer Institute and Genentech FX Cancer Therapy Evaluation Program/National Cancer Institute and Genentech. NR 18 TC 83 Z9 86 U1 0 U2 2 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 DEC 1 PY 2008 VL 14 IS 23 BP 7871 EP 7877 DI 10.1158/1078-0432.CCR-08-0593 PG 7 WC Oncology SC Oncology GA 379JK UT WOS:000261392300036 PM 19047116 ER PT J AU Dickler, MN Rugo, HS Eberle, C Brog, E Caravelli, JF Panageas, KS Boyd, J Yeh, B Lake, DE Dang, CT Gilewski, TA Bromberg, JF Seidman, AD D'Andrea, GM Moasser, MM Melisko, M Park, JW Dancey, J Norton, L Hudis, CA AF Dickler, Maura N. Rugo, Hope S. Eberle, CareyA. Brog, Edi Caravelli, James F. Panageas, Katherine S. Boyd, Jeff Yeh, Benjamim Lake, Diana E. Dang, Chau T. Gilewski, Teresa A. Bromberg, Jacqueline F. Seidman, Andrew D. D'Andrea, Gabriella M. Moasser, Mark M. Melisko, Michele Park, John W. Dancey, Janet Norton, Larry Hudis, Clifford A. TI A Phase II Trial of Erlotinib in Combination with Bevacizumab in Patients with Metastatic Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; ADJUVANT CHEMOTHERAPY; ANTIBODY BEVACIZUMAB; MONOCLONAL-ANTIBODY; NUDE-MICE; CARCINOMA; PLUS; GEFITINIB AB Purpose: To evaluate the efficacy and toxicity of eflotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway. Experimental Design: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of >= 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis. Results: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%).The level of EGFR expression was not predictive of response to therapy. Conclusions: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy. C1 [Dickler, Maura N.; Eberle, CareyA.; Lake, Diana E.; Dang, Chau T.; Gilewski, Teresa A.; Bromberg, Jacqueline F.; Seidman, Andrew D.; D'Andrea, Gabriella M.; Norton, Larry; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, New York, NY 10021 USA. [Brog, Edi; Yeh, Benjamim; Moasser, Mark M.; Melisko, Michele; Park, John W.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Caravelli, James F.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Biostat, New York, NY 10021 USA. [Rugo, Hope S.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Boyd, Jeff] Mem Hlth Univ Med Ctr, Savannah, GA 31404 USA. [Dancey, Janet] NCI, Bethesda, MD 20892 USA. RP Dickler, MN (reprint author), Mem Sloan Kettering Canc Ctr, Breast Canc Med Serv, 1275 York Ave, New York, NY 10021 USA. EM dicklerm@mskcc.org OI D'Andrea-Carlino, Gabriella/0000-0002-7357-2160; Norton, Larry/0000-0003-3701-9250 FU Clinical Trials Evaluation Program; National Cancer Institute; Genentech; Jodi Spiegel Fisher Cancer Foundation FX Clinical Trials Evaluation Program, National Cancer Institute, Genentech, Inc. and the Jodi Spiegel Fisher Cancer Foundation. NR 49 TC 63 Z9 64 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 DEC 1 PY 2008 VL 14 IS 23 BP 7878 EP 7883 DI 10.1158/1078-0432.CCR-08-0141 PG 6 WC Oncology SC Oncology GA 379JK UT WOS:000261392300037 PM 19047117 ER PT J AU Moulder, SL Symmans, WF Booser, DJ Madden, TL Lipsanen, C Yuan, L Brewster, AM Cristofanilli, M Hunt, KK Buchholz, TA Zwiebel, J Valero, V Hortobagyi, GN Esteva, FJ AF Moulder, Stacy L. Symmans, W. Fraser Booser, Daniel J. Madden, Timothy L. Lipsanen, Cindy Yuan, Linda Brewster, Abenaa M. Cristofanilli, Massimo Hunt, Kelly K. Buchholz, Thomas A. Zwiebel, James Valero, Vicente Hortobagyi, Gabriel N. Esteva, Francisco J. TI Phase I/II Study of G3139 (Bcl-2 Antisense Oligonucleotide) in Combination with Doxorubicin and Docetaxel in Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-LUNG-CANCER; PROTEIN EXPRESSION; SOLID TUMORS; I TRIAL; THERAPY; CHEMOTHERAPY; RESISTANCE; APOPTOSIS; CYCLOPHOSPHAMIDE; CARBOPLATIN AB Purpose: Preclinical data showed enhancement of breast cancer cell death when G3139 was combined with anthracyclines and taxanes. We evaluated the efficacy and safety of a Bcl-2 antisense oligonucleotide, G3139, in combination with doxorubicin (A) and docetaxel (T) in patients with locally advanced breast cancer (LABC). Experimental Design: Following a brief phase I to determine the phase 11 dose, patients with locally advanced breast cancer received G3139 administered by continuous i.v. infusion for 5 to 7 days with bolus A (50 mg/m(2)) and T (75 mg/m(2)) administered on either day 3 or 6 of therapy with G3139. Cycles were repeated every 21 days x 6 in the neoadjuvant setting. Serial plasma samples were obtained for pharmacokinetic analysis. Tissue samples were obtained before and after therapy for pharmacodynamic analysis of Bcl-2 expression. Results: Thirty patients (median age, 49 years; range, 24-71 years) received 160 cycles. During the phase I portion of the trial, the dose of G3139 was escalated from 3 to 7 mg/kg/d (i.v. for 5 days) in combination with AT. During the phase II portion of the trial, several doses and schedules of G3139 were evaluated. There were no pathologic complete responses. Pharmacodynamic studies showed limited Bcl-2 down-regulation in the primary tumors. Conclusions: G3139 in combination with doxorubicin and docetaxel is well tolerated. No pathologic complete response was seen and pharmacodynamic studies showed very little down-regulation of Bcl-2 in primary tumors, perhaps related to issues with insufficient drug delivery to the intact tumor. C1 [Moulder, Stacy L.; Symmans, W. Fraser; Booser, Daniel J.; Madden, Timothy L.; Lipsanen, Cindy; Yuan, Linda; Brewster, Abenaa M.; Cristofanilli, Massimo; Hunt, Kelly K.; Buchholz, Thomas A.; Valero, Vicente; Hortobagyi, Gabriel N.; Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Moulder, Stacy L.; Symmans, W. Fraser; Booser, Daniel J.; Madden, Timothy L.; Lipsanen, Cindy; Yuan, Linda; Brewster, Abenaa M.; Cristofanilli, Massimo; Hunt, Kelly K.; Buchholz, Thomas A.; Valero, Vicente; Hortobagyi, Gabriel N.; Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Moulder, Stacy L.; Symmans, W. Fraser; Booser, Daniel J.; Madden, Timothy L.; Lipsanen, Cindy; Yuan, Linda; Brewster, Abenaa M.; Cristofanilli, Massimo; Hunt, Kelly K.; Buchholz, Thomas A.; Valero, Vicente; Hortobagyi, Gabriel N.; Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Moulder, Stacy L.; Symmans, W. Fraser; Booser, Daniel J.; Madden, Timothy L.; Lipsanen, Cindy; Yuan, Linda; Brewster, Abenaa M.; Cristofanilli, Massimo; Hunt, Kelly K.; Buchholz, Thomas A.; Valero, Vicente; Hortobagyi, Gabriel N.; Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Moulder, Stacy L.; Symmans, W. Fraser; Booser, Daniel J.; Madden, Timothy L.; Lipsanen, Cindy; Yuan, Linda; Brewster, Abenaa M.; Cristofanilli, Massimo; Hunt, Kelly K.; Buchholz, Thomas A.; Valero, Vicente; Hortobagyi, Gabriel N.; Esteva, Francisco J.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Zwiebel, James] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Esteva, FJ (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Unit 1354,1515 Holcombe Blvd, Houston, TX 77030 USA. EM fjesteva@mdanderson.org OI Esteva, Francisco/0000-0003-2437-3920 FU National Cancer Institute; NIH [U01 CA062461, K23 CA82119, N01 CM17003] FX National Cancer Institute, NIH grants U01 CA062461, K23 CA82119, and N01 CM17003. NR 36 TC 33 Z9 35 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 DEC 1 PY 2008 VL 14 IS 23 BP 7909 EP 7916 DI 10.1158/1078-0432.CCR-08-1104 PG 8 WC Oncology SC Oncology GA 379JK UT WOS:000261392300041 PM 19047121 ER PT J AU Heath, EI Hillman, DW Vaishampayan, U Sheng, SJ Sarkar, F Harper, F Gaskins, M Pitot, HC Tan, W Ivy, SP Pili, R Carducci, MA Erlichman, C Liu, G AF Heath, Elisabeth I. Hillman, David W. Vaishampayan, Ulka Sheng, Shijie Sarkar, Fazlul Harper, Felicity Gaskins, Melvin Pitot, Henry C. Tan, Winston Ivy, S. Percy Pili, Roberto Carducci, Michael A. Erlichman, Charles Liu, Glenn TI A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Hormone-Refractory Metastatic Prostate Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSIVE MASPIN; CLINICAL-TRIALS; INTERLEUKIN-6; EXPRESSION; MITOXANTRONE; PREDNISONE; INHIBITOR; DOCETAXEL; CHAPERONE; RECEPTOR AB Purpose: 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a benzoquinone ansamycin antibiotic with antiproliferative activity in several mouse xenograft models, including prostate cancer models. A two-stage phase 11 study was conducted to assess the activity and toxicity profile of 17-AAG administered to patients with metastatic, hormone-refractory prostate cancer. Experimental Design: Patients with at least one prior systemic therapy and a rising prostate-specific antigen (PSA) were eligible. Patients received 17-AAG at a dose of 300 mg/m(2) i.v weekly for 3 of 4 weeks. The primary objective was to assess the PSA response. Secondary objectives were to determine overall survival, to assess toxicity, and to measure interleukin-6, interleukin-8, and maspin levels and quality of life. Results: Fifteen eligible patients were enrolled.The median age was 68 years and the median PSA was 261 ng/mL. Patients received 17-AAG for a median number of two cycles. Severe adverse events included grade 3 fatigue (four patients), grade 3 lymphopenia (two patients), and grade 3 back pain (two patients). The median PSA progression-free survival was 1.8 months (95% confidence interval, 1.3-3.4 months). The 6-month overall survival was 71% (95% confidence interval, 52-100%). Conclusions: 17-AAG did not show any activity with regard to PSA response. Due to insufficient PSA response, enrollment was stopped at the end of first stage per study design. The most significant severe toxicity was grade 3 fatigue. Further evaluation of 17-AAG at a dose of 300 mg/m(2) i.v. weekly as a single agent in patients with metastatic, hormone-refractory prostate cancer who received at least one prior systemic therapy is not warranted. C1 [Heath, Elisabeth I.; Vaishampayan, Ulka; Sheng, Shijie; Sarkar, Fazlul; Harper, Felicity] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Hillman, David W.; Pitot, Henry C.; Erlichman, Charles] Mayo Clin, Ctr Canc, Rochester, MN USA. [Gaskins, Melvin] Howard Univ, Coll Med, Washington, DC USA. [Tan, Winston] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. [Pili, Roberto; Carducci, Michael A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Liu, Glenn] Univ Wisconsin, Carbone Comprehens Canc Ctr, Madison, WI USA. RP Heath, EI (reprint author), Wayne State Univ, Karmanos Canc Inst, 4100 John R,4 HWCRC, Detroit, MI 48201 USA. EM heathe@karmanos.org FU Cancer Research; [U01-CA062487-12]; [N01-CM-17104]; [R01CA84176] FX U01-CA062487-12, N01-CM-17104, R01CA84176, and Fund for Cancer Research. NR 28 TC 113 Z9 116 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2008 VL 14 IS 23 BP 7940 EP 7946 DI 10.1158/1078-0432.CCR-08-0221 PG 7 WC Oncology SC Oncology GA 379JK UT WOS:000261392300046 PM 19047126 ER PT J AU Gahl, WA AF Gahl, William A. TI Newborn Screening for Wilson Disease: Does Liquid Chromatography-Tandem Mass Spectrometry Provide the Solution? SO CLINICAL CHEMISTRY LA English DT Editorial Material ID DIAGNOSIS C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, NIH, Rm 10C-103,MSC 1851,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov FU Intramural NIH HHS NR 12 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 2008 VL 54 IS 12 BP 1941 EP 1942 DI 10.1373/clinchem.2008.116327 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 377JZ UT WOS:000261248800001 PM 19042985 ER PT J AU Gray, TR Magri, R Shakleya, DM Huestis, MA AF Gray, Teresa R. Magri, Raquel Shakleya, Diaa M. Huestis, Marilyn A. TI Meconium Nicotine and Metabolites by Liquid Chromatography-Tandem Mass Spectrometry: Differentiation of Passive and Nonexposure and Correlation with Neonatal Outcome Measures SO CLINICAL CHEMISTRY LA English DT Article ID HUMAN PLACENTAL COTYLEDON; TOBACCO-SMOKE EXPOSURE; HUMAN LIVER-MICROSOMES; MATERNAL SMOKING; BIRTH-WEIGHT; COTININE DETERMINATION; PREGNANCY OUTCOMES; CIGARETTE-SMOKING; N-GLUCURONIDATION; SERUM COTININE AB BACKGROUND: Meconium analysis is a diagnostically sensitive and objective alternative to maternal self-report for detecting prenatal tobacco exposure. Nicotine and metabolite disposition in meconium is poorly characterized, and correlation of analytes' concentrations with neonatal outcomes is unexplored. Our objectives were to quantify nicotine, cotinine, trans-3'-hydroxycotinine (OH-cotinine), nornicotine, norcotinine, and glucuronide concentrations in meconium, identify the best biomarkers of in utero tobacco exposure, compare meconium concentrations of tobacco-exposed and nonexposed neonates, and investigate concentration-outcome relationships. METHODS: We quantified concentrations of nicotine and 4 metabolites with and without hydrolysis simultaneously in meconium from tobacco-exposed and nonexposed neonates by liquid chromatography-tandem mass spectrometry. We compared meconium concentrations to birth weight, length, head circumference, gestational age, and 1- and 5-min Apgar scores. RESULTS: Nicotine, cotinine, and OH-cotinine were the most prevalent and abundant meconium tobacco biomarkers and were found in higher concentrations in tobacco-exposed neonates. Whereas cotinine and OH-cotinine are glucuronide bound, performing the lengthy and costly enzymatic hydrolysis identified only 1 additional positive specimen. Unconjugated nicotine, cotinine, or OH-cotinine meconium concentration >10 ng/g most accurately discriminated active from passive and nonexposed neonates. There was no significant correlation between quantitative nicotine and metabolite meconium results and neonatal Outcomes, although presence of a nicotine biomarker predicted decreased head circumference. CONCLUSIONS: Unconjugated nicotine, cotinine, and OH-cotinine should be analyzed in meconium to detect in utero tobacco exposure, as approximately 25% of positive specimens did not contain cotinine. Immunoassay testing monitoring cotinine only would underestimate the prevalence of prenatal tobacco exposure. (C) 2008 American Association for Clinical Chemistry C1 [Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA. [Magri, Raquel] Hosp Pereira Rossell, Colegio Iberoamericano Adicc, Montevideo 4707, Uruguay. RP Huestis, MA (reprint author), 251 Bayview Blvd,Suite 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU NIH; National Institute on Drug Abuse; Generalitat Valenciana FX Funding: This research was funded by the intramural Research Program of the NIH, National Institute on Drug Abuse, and by the Generalitat Valenciana. NR 31 TC 17 Z9 18 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 2008 VL 54 IS 12 BP 2018 EP 2027 DI 10.1373/clinchem.2008.109173 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 377JZ UT WOS:000261248800013 PM 18845770 ER PT J AU Haqq, AM Grambow, SC Muehlbauer, M Newgard, CB Svetkey, LP Carrel, AL Yanovski, JA Purnell, JQ Freemark, M AF Haqq, Andrea M. Grambow, Steven C. Muehlbauer, Michael Newgard, Christopher B. Svetkey, Laura P. Carrel, Aaron L. Yanovski, Jack A. Purnell, Jonathan Q. Freemark, Michael TI Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development SO CLINICAL ENDOCRINOLOGY LA English DT Article ID FASTING PLASMA GHRELIN; GROWTH-HORMONE DEFICIENCY; INCREASES FOOD-INTAKE; BODY-MASS INDEX; CIRCULATING GHRELIN; INSULIN-RESISTANCE; ADIPONECTIN RATIO; SYNDROME ADULTS; OBESITY; SECRETION AB Prader-Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of ghrelin excess in the pathogenesis of obesity is unclear. To determine if high ghrelin levels precede the onset of obesity in young PWS children. A cross-sectional study of 33 infants with PWS and 28 healthy control subjects (C). Fasting ghrelin and other satiety hormones were measured. Median total serum ghrelin in young children with PWS trended higher, but did not differ significantly from those in C of similar age, weight-for-age z-score and sex. However, there was more variability in ghrelin concentrations of young PWS. Eleven of 33 PWS subjects had ghrelin levels greater than the 95th percentile for ghrelin values in the C subjects (> 2871 pg/ml). Six of the PWS subjects with high ghrelin levels had weight-for-age z-scores < 0. Ghrelin concentrations in PWS and C infants exceeded those in older children. In youngsters with PWS, leptin was higher, suggesting a relative excess of fat to lean body mass and plasma adiponectin was increased. Young infants with PWS who have not yet developed hyperphagia or obesity have median fasting ghrelin levels similar to controls. However, a subset (33%) of young PWS is hyperghrelinaemic; approximately one-half of those with hyperghrelinaemia have BMI z-score < 0. The age-related decline in ghrelin is blunted in PWS. C1 [Haqq, Andrea M.; Freemark, Michael] Duke Univ, Med Ctr, Dept Pediat, Div Pediat Endocrinol, Durham, NC 27710 USA. [Haqq, Andrea M.; Muehlbauer, Michael; Newgard, Christopher B.; Svetkey, Laura P.] Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27710 USA. [Grambow, Steven C.] Durham Vet Affairs Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27705 USA. [Grambow, Steven C.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Carrel, Aaron L.] Univ Wisconsin, Childrens Hosp, Dept Pediat, Madison, WI USA. [Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MA USA. [Purnell, Jonathan Q.] Oregon Hlth & Sci Univ, Ctr Study Weight Regulat, Portland, OR 97201 USA. [Purnell, Jonathan Q.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Haqq, AM (reprint author), DUMC 3080,Rm 308 Bell Bldg, Durham, NC 27710 USA. EM haqq0001@mc.duke.edu RI Grambow, Steven/E-1422-2015; OI Grambow, Steven/0000-0001-6037-3253; Yanovski, Jack/0000-0001-8542-1637 FU Duke University Medical Center; General Clinical Research Center [MO1-RR-30]; National Center for Research Resources; NIH [1K23-RR-021979]; NIDDK [R01 DK071161, Z01-HD-00641]; NICHD; NIH; Lawson Wilkins Pediatric Endocrine Society; Sarah W. Stedman Nutrition and Metabolism Center FX This study was conducted through the Duke University Medical Center, General Clinical Research Center (MO1-RR-30, National Center for Research Resources, Clinical Research Centers Program, NIH) and was supported by 1K23-RR-021979 (to A. M. H.) and NIDDK R01 DK071161 (to J.Q.P.), Z01-HD-00641 from the Intramural Research Program of the NICHD, NIH (to J. A. Y.) and additional funding from the Lawson Wilkins Pediatric Endocrine Society and the Sarah W. Stedman Nutrition and Metabolism Center. NR 38 TC 31 Z9 32 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2008 VL 69 IS 6 BP 911 EP 920 DI 10.1111/j.1365-2265.2008.03385.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 374PA UT WOS:000261055000012 PM 18710462 ER PT J AU Terrault, NA Im, K Boylan, R Bacchetti, P Kleiner, DE Fontana, RJ Hoofnagle, JH Belle, SH AF Terrault, Norah A. Im, Kelly Boylan, Ross Bacchetti, Peter Kleiner, David E. Fontana, Robert J. Hoofnagle, Jay H. Belle, Steven H. CA Virahep-C Study Grp TI Fibrosis Progression in African Americans and Caucasian Americans With Chronic Hepatitis C SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID INJECTION-DRUG USERS; MULTISTATE MARKOV-MODELS; VIRUS-INFECTION; LIVER FIBROSIS; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; RISK-FACTORS; DISEASE; PREVALENCE; SURVIVAL AB Background & Aims: Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. Methods: With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype I infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. Results: The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% tower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. Conclusions: The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs. C1 [Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Boylan, Ross; Bacchetti, Peter] Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Im, Kelly] Univ Pittsburgh, Pittsburgh, PA USA. [Fontana, Robert J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hoofnagle, Jay H.] NIDDK, NIH, Bethesda, MD USA. RP Terrault, NA (reprint author), Univ Calif San Francisco, Dept Med, S357,513 Parnassus Ave, San Francisco, CA 94143 USA. EM norah.terrault@ucsf.edu OI Kleiner, David/0000-0003-3442-4453 FU NIDDK; National Center on Minority Health and Health Disparities (NCMHD); Cooperative Research and Development Agreement (CRADA); Roche Laboratories, Inc [U01DK60329, U01 DK 60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341]; National Center for Research Resources (NCRR) [M01 RR00645, M02 RR000079, M01 RR000042, M01 RR00046]; National Institutes of Health [R01 A1069952]; National Cancer Institute FX The authors disclose the following: The clinical study was a cooperative agreement funded by the NIDDK and co-funded by the National Center on Minority Health and Health Disparities (NCMHD), with a Cooperative Research and Development Agreement (CRADA) with Roche Laboratories, Inc. Grant numbers: U01DK60329, U01 DK 60340, U01 DK60324, U01 DK60344, U01 DK60327, U01 DK60335, U01 DK60352, U01 DK60342, U01 DK60345, U01 DK60309, U01 DK60346, U01 DK60349, U01 DK60341. Other support provided by National Center for Research Resources (NCRR) General Clinical Research Centers Program grants M01 RR00645 (New York Presbyterian), M02 RR000079 (University of California, San Francisco), M01 RR16500 (University of Maryland), M01 RR000042 (University of Michigan), and M01 RR00046 (University of North Carolina). The study was also funded by R01 A1069952 from the National Institutes of Health and was supported in part by the Intramural Research Program of the National Cancer Institute. NR 33 TC 25 Z9 25 U1 0 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 DEC PY 2008 VL 6 IS 12 BP 1403 EP 1411 DI 10.1016/j.cgh.2008.08.006 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384DK UT WOS:000261724300019 PM 19081528 ER PT J AU Fleming, TR Powers, JH AF Fleming, Thomas R. Powers, John H. TI Issues in Noninferiority Trials: The Evidence in Community-Acquired Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Workshop on Issues in the Design and Conduct of Clinical Trials of Antibacterial Drugs in the Treatment of Community-Acquired Pneumonia CY JAN 17-18, 2008 CL Silver Spring, MD SP FDA, Infect Dis Soc Amer ID RABBIT ANTIPNEUMOCOCCUS SERA; SURROGATE END-POINTS; PNEUMOCOCCIC PNEUMONIA; CLINICAL-TRIALS; EMPIRICAL-EVIDENCE; B. 693; SULFAPYRIDINE; THERAPY; HORSE; INTERVENTIONS AB When investigators hypothesize that experimental interventions provide advantages other than improved effectiveness, they can use noninferiority (NI) trials to determine whether one can rule out the possibility that those interventions have unacceptably worse effectiveness than the standard "active control" regimen. To conduct valid NI trials, there must be evidence from historical studies that provides reliable, reproducible, and precise estimates of the effect of the active control, compared with that of placebo, on the specific outcomes investigators plan to use in the NI trial; this effect should be of substantial magnitude, and the estimates of the active control's effect from historical studies must represent its effect in the planned NI trial had a placebo group been included. These conditions allow formulation of an NI margin such that, if the NI trial establishes that the effectiveness of the experimental intervention is not worse than the effectiveness of the active control by more than the NI margin, then one can conclude that the experimental regimen (1) preserves a substantial fraction of the effect of the active control and (2) will not result in a clinically meaningful loss of effectiveness. After general discussion of NI trial design issues, we consider the design of NI trials to evaluate antimicrobials in the treatment of community-acquired pneumonia. We present an extensive literature review, allowing estimation of the historical effect of active control regimens in community-acquired pneumonia primarily on the basis of evidence related to use of sulfonamides or penicillin. This review allows formulation of NI margins that are specific to age and bacteremia status of patients. C1 [Fleming, Thomas R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Powers, John H.] NIAID, SAIC, Collaborat Clin Res Branch, NIH, Bethesda, MD 20892 USA. [Powers, John H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM tfleming@u.washington.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [R37 AI029168, R01 AI029168, R37 AI 29168, R37 AI029168-19] NR 57 TC 37 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2008 VL 47 SU 3 BP S108 EP S120 DI 10.1086/591390 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 368XI UT WOS:000260655900002 PM 18986275 ER PT J AU Duncko, R Cui, LH Hille, J Grillon, C Merikangas, KR AF Duncko, Roman Cui, Lihong Hille, Jeffrey Grillon, Christian Merikangas, Kathleen R. TI Startle reactivity in children at risk for migraine SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Migraine; Anxiety; Startle; Children; Genetic ID ANXIETY DISORDERS; EVOKED-POTENTIALS; CORTICAL POTENTIALS; PREPULSE INHIBITION; MDMA ECSTASY; HEADACHE; HABITUATION; REFLEX; ELECTROPHYSIOLOGY; EXCITABILITY AB Objective: Numerous studies have shown a higher responsiveness and/or a lack of habituation to sensory Stimuli of various modalities in migraine. This Study investigated psychophysiological responses to aversive acoustic stimuli in children at risk for migraine. Methods: We measured eyeblink responses to acoustic Stimuli (40 ms bursts of white noise at 102 dB) during anticipation Of unpleasant stimuli in 74 adolescents (40 females, age 17.6 +/- 2.9). A mixed effects linear model was applied to test group differences in startle reactivity during baseline, safe and threat conditions among adolescents by maternal and personal history of migraine. Results: The strongest association with migraine Vulnerability emerged for baseline startle reactivity, which was significantly elevated in high risk youth with a history of maternal migraine. This group off-spring also had enhanced startle response during the threat condition and the threat-safe difference. Conclusion: Our findings indicate that migraine is associated with a higher acoustic startle responsiveness that is present already in children at risk for developing the disorder. Significance: The significant effect of both maternal history of anxiety disorder and migraine on baseline startle indicates that these two diagnostic entities might in part share common pathophysiological mechanisms, and that the anxiety-migraine comorbidity should be considered when investigating each of these disorders. Published by Elsevier Ireland Ltd. on behalf of International Federation of Clinical Neurophysiology. C1 [Duncko, Roman; Cui, Lihong; Merikangas, Kathleen R.] NIMH, Dev Genet Epidemiol Branch, Intramural Res Program, Bethesda, MD 20892 USA. [Hille, Jeffrey] Genentech Inc, San Francisco, CA USA. [Grillon, Christian] NIMH, Sect Cognit Psychophysiol, Intramural Res Program, Bethesda, MD 20892 USA. RP Duncko, R (reprint author), NIMH, Dev Genet Epidemiol Branch, Intramural Res Program, NIH Bldg 35,Roorn 1A-110-35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM dunckor@mail.nih.gov FU National Institute of Mental Health; National Institutes of Health FX This research was Supported in part by the Intramural Program of the National Institute of Mental Health, National Institutes of Health. NR 46 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD DEC PY 2008 VL 119 IS 12 BP 2733 EP 2737 DI 10.1016/j.clinph.2008.09.005 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 387WA UT WOS:000261981100013 PM 18951839 ER PT J AU Ravizzini, G Meirelles, GSP Horwitz, SM Grewal, RK AF Ravizzini, Gregory Meirelles, Gustavo S. P. Horwitz, Steven M. Grewal, Ravinder K. TI F-18 FDG Uptake in Subcutaneous Panniculitis-Like T-Cell Lymphoma SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE subcutaneous panniculitis-like T-cell lymphoma; positron emission tomography; F-18-FDG ID GENOMIC ABERRATIONS AB A 41-year-old male presented to an outside institution complaining of a lump under the skin of his right abdomen. CT scan reported ill-defined densities with streaky inflammatory changes in the anterior abdominal wall. Excisional biopsy of the subcutaneous adipose tissues of the right anterior abdominal wall was consistent with subcutaneous panniculitis-like T-cell lymphoma. Flow cytometry demonstrated CD3(+) and CD8(+) population. On immunohistochemistry, most lymphoid cells were positive for CD3, CD45RO, CD5, and CD8 and negative for CD10, CD43, CD4, CD20, and CD56. The MlB-1 proliferative index was 30%. Bone marrow biopsy revealed no evidence of lymphomatous involvement. C1 [Ravizzini, Gregory; Meirelles, Gustavo S. P.; Grewal, Ravinder K.] Mem Sloan Kettering Canc Ctr, Nucl Med Serv, New York, NY 10021 USA. [Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. RP Ravizzini, G (reprint author), NCI, Mol Imaging Program, 9000 Rockville Pike,Bldg 10,Room 1B40, Bethesda, MD 20874 USA. EM ravizzig@mail.nih.gov NR 8 TC 13 Z9 13 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD DEC PY 2008 VL 33 IS 12 BP 903 EP 905 DI 10.1097/RLU.0b013e31818bf2c7 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 376VS UT WOS:000261211700026 PM 19033805 ER PT J AU Evans, WJ Morley, JE Argiles, J Bales, C Baracos, V Guttridge, D Jatoi, A Kalantar-Zadeh, K Lochs, H Mantovani, G Marks, D Mitch, WE Muscaritoli, M Najand, A Ponikowski, P Rossi Fanelli, F Schambelan, M Schols, A Schuster, M Thomas, D Wolfe, R Anker, SD Boyce, A Nuckolls, G AF Evans, William J. Morley, John E. Argiles, Josep Bales, Connie Baracos, Vickie Guttridge, Denis Jatoi, Aminah Kalantar-Zadeh, Kamyar Lochs, Herbert Mantovani, Giovanni Marks, Daniel Mitch, William E. Muscaritoli, Maurizio Najand, Armine Ponikowski, Piotr Rossi Fanelli, Filippo Schambelan, Morrie Schols, Annemie Schuster, Michael Thomas, David Wolfe, Robert Anker, Stefan D. Boyce, Amanda Nuckolls, Glen TI Cachexia: A new definition SO CLINICAL NUTRITION LA English DT Editorial Material DE Anorexia; Muscle wasting; Inflammation; Involuntary weight toss; Wasting disease ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; TERMINAL CANCER-PATIENTS; CHRONIC HEART-FAILURE; WEIGHT-LOSS; BODY-COMPOSITION; PHYSICAL PERFORMANCE; SURVIVAL PREDICTION; EXERCISE CAPACITY; HIV-INFECTION AB On December 13th and 14th a group of scientists and clinicians met in Washington, DC, for the cachexia consensus conference. At the present time, there is no widely agreed upon operational definition of cachexia. The lack of a definition accepted by clinician and researchers has limited identification and treatment of cachectic patient as well as the development and approval of potential therapeutic agents. The definition that emerged is: "cachexia, is a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle with or without toss of fat mass. The prominent clinical feature of cachexia is weight loss in adults (corrected for fluid retention) or growth failure in children (excluding endocrine disorders). Anorexia, inflammation, insulin resistance and increased muscle protein breakdown are frequently associated with cachexia. Cachexia is distinct from starvation, age-related loss of muscle mass, primary depression, malabsorption and hyperthyroidism and is associated with increased morbidity. While this definition has not been tested in epidemiological or intervention studies, a consensus operational definition provides an opportunity for increased research. (C) 2008 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Evans, William J.] Univ Arkansas Med Sci, Donald W Reynolds Inst Aging, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. [Anker, Stefan D.] Charite CVK, Berlin, Germany. [Argiles, Josep] Univ Barcelona, Barcelona, Spain. [Bales, Connie] Duke Univ, Durham, NC USA. [Baracos, Vickie] Univ Alberta, Edmonton, AB, Canada. [Boyce, Amanda] NIH, Bethesda, MD 20892 USA. [Guttridge, Denis] Ohio State Univ, Columbus, OH 43210 USA. [Jatoi, Aminah] Mayo Clin, Rochester, MN USA. [Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Lochs, Herbert] Charite CCM, Berlin, Germany. [Mantovani, Giovanni] Univ Cagliari, Cagliari, Italy. [Marks, Daniel] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Mitch, William E.] Baylor Coll Med, Houston, TX 77030 USA. [Morley, John E.] St Louis Univ, St Louis, MO 63103 USA. [Muscaritoli, Maurizio; Rossi Fanelli, Filippo] Univ Roma La Sapienza, Rome, Italy. [Najand, Armine] MEGS, Alpharetta, GA USA. [Nuckolls, Glen] NIH, Bethesda, MD 20892 USA. [Ponikowski, Piotr] Clin Mil Hosp, Wroclaw, Poland. [Schambelan, Morrie] Univ Calif San Francisco, Gen Hosp, San Francisco, CA 94143 USA. [Schols, Annemie] Univ Hosp, Maastricht, Netherlands. [Schuster, Michael] New York Presbytarian, New York, NY USA. [Thomas, David] St Louis Univ, St Louis, MO 63103 USA. [Wolfe, Robert] Univ Arkansas, Little Rock, AR 72204 USA. RP Evans, WJ (reprint author), Univ Arkansas Med Sci, Donald W Reynolds Inst Aging, Cent Arkansas Vet Healthcare Syst, 4301 W Markham,Slot 806, Little Rock, AR 72205 USA. EM evanswilliam@uams.edu; Mortey@SLU.edu; Argiles@porthos.bio.ub.es; bales001@mc.duke.edu; Vickieb@Cancerboard.ab.ca; guttridge-l@medctr.osu.edu; Jatoi.Aminah@Jatoi.edu; kkatantar@rei.edu; herbert.lochs@charite.de; mantovan@pacs.unca.it; marksd@ohsu.edu; Mitch@bcm.edu; Maurizio.Muscaritoti@uniroma1.it; piotrponikowski@4wsk.pt; fitippo.rossifanetti@uniromal.it; morrie@sfghgcrc.ucsf.edu; a.schots@puL.unimaas.nl; mwschuster@pol.net; Drthomas@SLU.edu; Rwolfe2@uams.edu; s.anker@cachexia.de; BoyceA@NIH.gov; nuckollg@nih.gov RI morley, john/F-9177-2011; Rossi Fanelli, Filippo/E-9587-2011; Ponikowski, Piotr/O-6454-2015; OI morley, john/0000-0001-6444-2965; Rossi Fanelli, Filippo/0000-0002-8674-1672; Ponikowski, Piotr/0000-0002-3391-7064; Baracos, Vickie/0000-0002-9609-1001; Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 NR 43 TC 652 Z9 676 U1 9 U2 71 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 EI 1532-1983 J9 CLIN NUTR JI Clin. Nutr. PD DEC PY 2008 VL 27 IS 6 BP 793 EP 799 DI 10.1016/j.clnu.2008.06.013 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 385JU UT WOS:000261811300001 PM 18718696 ER PT J AU Spong, CY AF Spong, Catherine Y. TI Diagnosis, Prevention, and Treatment of Cerebral Palsy Foreword SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Spong, Catherine Y.] NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03E, Bethesda, MD 20892 USA. EM spongc@dir49.nichd.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2008 VL 51 IS 4 BP 740 EP 741 DI 10.1097/GRF.0b013e31818c0059 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 369ZO UT WOS:000260732600011 PM 18981798 ER PT J AU Nelson, KB AF Nelson, Karin B. TI Causative Factors in Cerebral Palsy SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE cerebral palsy; prematurity; perinatal stroke; maternal fever in labor; placenta ID FETAL THROMBOTIC VASCULOPATHY; PERINATAL ARTERIAL STROKE; NORMAL BIRTH-WEIGHT; RISK-FACTORS; PRETERM BIRTH; PERIVENTRICULAR LEUKOMALACIA; INFANTS; PREGNANCY; TERM; CHORIOAMNIONITIS AB Causative factors in cerebral palsy (CP) vary to some degree according to gestational age group and clinical CP subtype. Such catastrophes of birth as placental abruption, cord prolapse, and uterine rupture sharply heighten risk of CP. These conditions are fortunately uncommon, and are sometimes not survived; individually and collectively they account for only a small proportion of CP. Among other factors associated with increased risk of CP are prematurity, intrauterine exposure to infection or maternal fever in labor, ischemic stroke, congenital malformations, atypical intrauterine growth (restricted or excessive for gestational age), and complications of multiple gestations. Although any 1 factor, if severe, may be sufficient to cause CP, more often it is the presence of multiple risk factors that overwhelms defense mechanisms and leads to CP. The contribution of genetic vulnerabilities that interact with environmental stressors is an emerging aspect of our understanding of causative factors in CP. C1 [Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA. [Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Nelson, KB (reprint author), NIH, Bldg 31,Room 8A03, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov FU Intramural NIH HHS NR 54 TC 59 Z9 60 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 2008 VL 51 IS 4 BP 749 EP 762 DI 10.1097/GRF.0b013e318187087c PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 369ZO UT WOS:000260732600013 PM 18981800 ER PT J AU Kapogiannis, BG Mattison, DR AF Kapogiannis, B. G. Mattison, D. R. TI Adolescents in Clinical Trials SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID MULTIPLE-DOSE PHARMACOKINETICS; CHILDREN; DRUG; PHARMACODYNAMICS; TOLERABILITY; CLEARANCE; CANCER; SAFETY; ADULTS AB Drug development is a lengthy, costly, and complex process, with clinical trials essential for characterizing dosing, safety, and efficacy in treated populations. After regulatory approval, aggressive marketing ensures that most drugs are used by a broad spectrum of ages, genders, races, and ethnic groups. unfortunately, not all groups are adequately represented in clinical trials; adolescents are commonly overlooked. This commentary explores how adolescents are considered during drug development, with a special focus on the influence of inherent psychosocial, biological, ethical, and regulatory issues in their recruitment and participation in clinical studies leading to drug licensing. C1 [Mattison, D. R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. [Kapogiannis, B. G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Adolescent Med Trials Network HIV AIDS Intervent, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. RP Mattison, DR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. EM Donald.Mattison@nih.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 38 TC 7 Z9 7 U1 1 U2 2 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 DEC PY 2008 VL 84 IS 6 BP 655 EP 659 DI 10.1038/clpt.2008.191 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377EX UT WOS:000261235600007 PM 19008903 ER PT J AU Becker, RE Greig, NH AF Becker, Robert E. Greig, Nigel H. TI Alzheimer's Disease Drug Development: Old Problems Require New Priorities SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Clinical trials; drug development; Alzheimer's disease; measurement errors; biomarkers; protocols ID SURROGATE END-POINTS; QUALITY-OF-LIFE; MILD COGNITIVE IMPAIRMENT; CLINICAL-TRIALS; MEASUREMENT ERROR; RATING-SCALE; BIOMARKERS; CRITERIA; STRATEGIES; DIAGNOSIS AB Alzheimer's disease (AD) clinical drug development and patient care depend on rating instruments, research designs and methods, and translations of clinical trial (CT) results into the clinic without support from standardized protocols able to control (i) random measurement error intrusions into observations, (ii) inaccuracy and bias introduced by clinical evaluators, (iii) conformity of research sites to conditions of research protocols, (iv) the ability of the CT to model for practitioners the most effective use of the drug with individual patients, and (v) other factors able to invalidate research and patient care data. This relaxed attitude with regard to AD methods may be changing now with Alzheimer's Disease Neuroimaging Initiative (ADNI) evidence that carefully standardized protocols are needed to validate biomarkers for use in AD diagnosis, drug development, and patient care. In the fields of psychiatry and AD, recent studies have detected serious inaccuracies, imprecision, biases and compromises of study protocols able to invalidate CT outcome data and conclusions drawn from these data. This limited but troubling evidence reinforces ADNI calls for more detailed methodological protocols. Based on the limits to precision and accuracy associated with rated outcomes in CTs and patient care, we call for priority to be given to the qualification and use of biomarkers as outcome variables in AD drug development and patient care and, to insure effective uses of biomarkers, to development of protocol guided practices being modeled in ADNI research. To meet clinical pharmacology's therapeutic aims we conclude that AD CTs need to set for clinicians the conditions of use of drugs shown efficacious, biomarker surrogate endpoints as drug targets, and not to function merely as tests for efficacy conducted under field conditions determined by current clinical practices. C1 [Becker, Robert E.; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Becker, RE (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM rebecker2008@comcast.net FU Intramural NIH HHS [, Z01 AG000311-08] NR 51 TC 12 Z9 12 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 1871-5273 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PD DEC PY 2008 VL 7 IS 6 BP 499 EP 511 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 397HZ UT WOS:000262654800002 PM 19128207 ER PT J AU Rudebeck, PH Bannerman, DM Rushworth, MFS AF Rudebeck, P. H. Bannerman, D. M. Rushworth, M. F. S. TI The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Review ID ORBITAL PREFRONTAL CORTEX; PRIMATE ORBITOFRONTAL CORTEX; TREATMENT-RESISTANT DEPRESSION; HIPPOCAMPAL-FORMATION LESIONS; SUPERIOR TEMPORAL SULCUS; MONKEYS MACACA-MULATTA; DEEP BRAIN-STIMULATION; RHESUS-MONKEYS; MACAQUE MONKEYS; CINGULATE CORTEX AB Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses. C1 [Rudebeck, P. H.; Bannerman, D. M.; Rushworth, M. F. S.] Univ Oxford, Oxford, England. RP Rudebeck, PH (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Suite 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM rudebeckp@mail.nih.gov RI Rudebeck, Peter/G-7931-2012; OI Rudebeck, Peter/0000-0002-1411-7555 FU Medical Research Council [G0600994, ]; Wellcome Trust [, 087736] NR 127 TC 86 Z9 86 U1 6 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD DEC PY 2008 VL 8 IS 4 BP 485 EP 497 DI 10.3758/CABN.8.4.485 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 391DP UT WOS:000262213900012 PM 19033243 ER PT J AU Urban, DJ Zheng, W Goker-Alpan, O Jadhav, A LaMarca, ME Inglese, J Sidransky, E Austin, CP AF Urban, Daniel J. Zheng, Wei Goker-Alpan, Ozlem Jadhav, Ajit LaMarca, Mary E. Inglese, James Sidransky, Ellen Austin, Christopher P. TI Optimization and Validation of Two Miniaturized Glucocerebrosidase Enzyme Assays for High Throughput Screening SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Glucocerebrosidase; beta-glucosidase; Gaucher disease; small molecule; assay optimization; assay miniaturization; HTS; quantitative high throughput screening; qHTS ID LYSOSOMAL STORAGE DISORDERS; ACID-BETA-GLUCOSIDASE; GAUCHER-DISEASE; INHIBITORS; IDENTIFICATION; STRATEGIES; DIAGNOSIS; CHAPERONE; MUTATION; EBSELEN AB Glucocerebrosidase (GC) catalyzes the hydrolysis of glucocerebroside to glucose and ceramide in lysosomes. Mutations in the glucocerebrosidase gene (GBA) result in Gaucher disease, an autosomal recessive lysosomal storage disorder. Many of the mutations encountered in patients with Gaucher disease are missense alterations that may cause misfolding, decreased stability and/or mistrafficking of this lysosomal protein. Some inhibitors of GC have been shown to act as chemical chaperones, stabilizing the conformation of mutant proteins and thus restoring their function. High throughput screening (HTS) of small molecule libraries for such compounds with potential for chaperone therapy requires an accurate, reproducible and sensitive assay method. We have adapted and optimized two fluorogenic GC enzyme assays and miniaturized them into the 1536-well plate format for HTS. The two substrates, 4-methylumbelliferyl beta-D-glucopyranoside and resorufin D-glucopyranoside, have K(m) values of 768 mu M and 33 mu M, respectively, and different emission spectra. Paired screening with the two assays helps to eliminate false inference of activity due to autofluorescence or fluorescence quenching by the screened compounds. Test screens with the LOPAC library indicated that both assays were robust for HTS, and gave comparable results for GC inhibitor activities. These two assays can be used to identify both GC activators and inhibitors with potential therapeutic value. C1 [Zheng, Wei; Jadhav, Ajit; Inglese, James; Austin, Christopher P.] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Urban, Daniel J.; Goker-Alpan, Ozlem; LaMarca, Mary E.; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Zheng, W (reprint author), NHGRI, Chem Genom Ctr, NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov; sidranse@mail.nih.gov RI Zheng, Wei/J-8889-2014 OI Zheng, Wei/0000-0003-1034-0757 FU NIH; National Human Genome Research Institute FX We thank Noel Southall for informatics assistance and discussion, and Paul Shinn and Adam Yasgar for assistance with compound management. This research was supported by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 34 TC 22 Z9 22 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 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD DEC PY 2008 VL 11 IS 10 BP 817 EP 824 DI 10.2174/138620708786734244 PG 8 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 380VW UT WOS:000261495200005 PM 19075603 ER PT J AU Song, JJ Deng, W Lee, HJ Kwon, D AF Song, Joon Jin Deng, Weiguo Lee, Ho-Jin Kwon, Deukwoo TI Optimal classification for time-course gene expression data using functional data analysis SO COMPUTATIONAL BIOLOGY AND CHEMISTRY LA English DT Article DE Time-course gene expression; Functional data analysis; Classification; Functional principal component analysis ID SUPPORT VECTOR MACHINES; DISCRIMINATION; TOOLS AB Classification problems have received considerable attention in biological and medical applications. In particular, classification methods combining to microarray technology play an important role in diagnosing and predicting disease, such as cancer, in medical research. Primary objective in classification is to build an optimal classifier based on the training sample in order to predict unknown class in the test sample. In this paper, we propose a unified approach for optimal gene classification with conjunction with functional principal component analysis (FPCA) in functional data analysis (FNDA) framework to classify time-course gene expression profiles based on information from the patterns. To derive an optimal classifier in FNDA, we also propose to find optimal number of bases in the smoothing step and functional principal components in FPCA using a cross-validation technique, and compare the performance of some popular classification techniques in the proposed setting. We illustrate the propose method with a simulation study and a real world data analysis. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Song, Joon Jin; Deng, Weiguo] Univ Arkansas, Dept Math Sci, Fayetteville, AR 72701 USA. [Lee, Ho-Jin] Schering Plough Res Inst, Kenilworth, NJ 07033 USA. [Kwon, Deukwoo] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Rockville, MD 20852 USA. RP Song, JJ (reprint author), Univ Arkansas, Dept Math Sci, Fayetteville, AR 72701 USA. EM jjsong@uark.edu FU Arkansas Biosciences Institute (ABI) FX This research was partially supported by Arkansas Biosciences Institute (ABI) (J.J. Song). NR 25 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1476-9271 J9 COMPUT BIOL CHEM JI Comput. Biol. Chem. PD DEC PY 2008 VL 32 IS 6 BP 426 EP 432 DI 10.1016/j.compbiolchem.2008.07.007 PG 7 WC Biology; Computer Science, Interdisciplinary Applications SC Life Sciences & Biomedicine - Other Topics; Computer Science GA 377NI UT WOS:000261257500006 PM 18755633 ER PT J AU Sutin, AR Robins, RW AF Sutin, Angelina R. Robins, Richard W. TI When the "I" looks at the "Me": Autobiographical memory, visual perspective, and the self SO CONSCIOUSNESS AND COGNITION LA English DT Review DE Visual perspective; Field perspective; Observer perspective; Self; Autobiographical memory; Phenomenology; Episodic memory; Appraisal; Self-verification; Self-enhancement ID VANTAGE POINT; AUTONOETIC CONSCIOUSNESS; IMAGERY PERSPECTIVE; EXPERIENCE; EMOTIONS; TIME; PHENOMENOLOGY; RECOLLECTION; CONSTRUCTION; ATTRIBUTIONS AB This article presents a theoretical model of the self processes involved in autobiographical memories and proposes competing hypotheses for the role of visual perspective in autobiographical memory retrieval. Autobiographical memories can be retrieved from either the 1st person perspective, in which individuals see the event through their own eyes, or from the 3rd person perspective, in which individuals see themselves and the event from the perspective of an external observer. A growing body of research suggests that the visual perspective from which a memory is retrieved has important implications for a person's thoughts, feelings, and goals, and is integrally related to a host of self-evaluative processes. We review the relevant research literature, present our theoretical model, and outline directions for future research. Published by Elsevier Inc. C1 [Sutin, Angelina R.] NIA, Biomed Res Ctr, NIH, DHHS, Baltimore, MD 21224 USA. [Robins, Richard W.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. RP Sutin, AR (reprint author), NIA, Biomed Res Ctr, NIH, DHHS, 251 Bayview Blvd,Suite 100 Room 4B325, Baltimore, MD 21224 USA. EM sutina@nia.nih.gov FU Intramural NIH HHS [Z99 AG999999] NR 60 TC 39 Z9 39 U1 4 U2 41 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD DEC PY 2008 VL 17 IS 4 BP 1386 EP 1397 DI 10.1016/j.concog.2008.09.001 PG 12 WC Psychology, Experimental SC Psychology GA 381TK UT WOS:000261558600039 PM 18848783 ER PT J AU Meert, K Eggly, S AF Meert, Kathleen Eggly, Susan CA CPCCRN TI PHYSICIANS' PERSPECTIVES ON FOLLOW-UP CONFERENCES WITH PARENTS AFTER A CHILD'S DEATH IN THE PICU SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 38th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 31-FEB 04, 2009 CL Nashville, TN SP Soc Crit Care Med C1 [Meert, Kathleen; Eggly, Susan] Wayne State Univ, Detroit, MI USA. [CPCCRN] NICHD, NIH, Bethesda, MD 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2008 VL 36 IS 12 SU S MA 418 BP A103 EP A103 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 376WM UT WOS:000261213700383 ER PT J AU Rice, TW Wheeler, AP Hite, RD Stapleton, RD AF Rice, Todd W. Wheeler, Arthur P. Hite, Robert D. Stapleton, Renee D. CA ARDs Network TI ENTERAL INTAKE AND PATIENT CHARACTERISTICS IN VENTILATED ACUTE LUNG INJURY (ALI) PATIENTS SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 38th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 31-FEB 04, 2009 CL Nashville, TN SP Soc Crit Care Med C1 [Rice, Todd W.; Wheeler, Arthur P.] Vanderbilt Univ, Nashville, TN USA. [Hite, Robert D.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Stapleton, Renee D.] Univ Vermont, Burlington, VT USA. [ARDs Network] NHLBI, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2008 VL 36 IS 12 SU S MA 435 BP A107 EP A107 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 376WM UT WOS:000261213700400 ER PT J AU Sandiford, P Dai, H Saadani-Makki, F Chugani, D Kannan, S Romero, R AF Sandiford, Penelope Dai, Hui Saadani-Makki, Fadoua Chugani, Diane Kannan, Sujatha Romero, Roberto TI ACTIVATED MICROGLIA INFLUENCE THE NEUROINFLAMMATORY RESPONSE IN A NEONATAL RABBIT MODEL OF CEREBRAL PALSY SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 38th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 31-FEB 04, 2009 CL Nashville, TN SP Soc Crit Care Med C1 [Sandiford, Penelope; Dai, Hui; Saadani-Makki, Fadoua; Chugani, Diane; Kannan, Sujatha] Wayne State Univ, Childrens Hosp Michigan, Detroit, MI USA. [Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2008 VL 36 IS 12 SU S MA 144 BP A31 EP A31 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 376WM UT WOS:000261213700112 ER PT J AU Zimmerman, JJ Jack, R AF Zimmerman, Jerry J. Jack, Rhona CA Collaborative Pediat Critical Care TI COMPARISON OF CENTRIFUGAL ULTRAFILTRATION (CU) TO EQUILIBRIUM DIALYSIS (ED) FOR FREE CORTISOL (FC) FRACTIONATION SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 38th Critical Care Congress of the Society-of-Critical-Care-Medicine CY JAN 31-FEB 04, 2009 CL Nashville, TN SP Soc Crit Care Med C1 [Zimmerman, Jerry J.; Jack, Rhona; Collaborative Pediat Critical Care] Seattle Childrens Hosp, NIH, NICHD, Seattle, WA 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2008 VL 36 IS 12 SU S MA 636 BP A163 EP A163 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 376WM UT WOS:000261213700600 ER PT J AU Simons-Morton, DG AF Simons-Morton, Denise G. TI The Glycemia-Cardiovascular Disease Hypothesis DO RECENT CLINICAL TRIALS RESOLVE THE QUESTION? SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Editorial Material ID BLOOD-GLUCOSE CONTROL; DIABETES-MELLITUS; TYPE-2; COMPLICATIONS; RISK; METAANALYSIS; DESIGN C1 NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Simons-Morton, DG (reprint author), NHLBI, Div Prevent & Populat Sci, Bldg 10, Bethesda, MD 20892 USA. EM simonsd@nhlbi.nih.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD DEC PY 2008 VL 1 IS 3 BP 185 EP 186 DI 10.1111/j.1752-8062.2008.00065.x PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532RU UT WOS:000272768000007 PM 20443845 ER PT J AU Cole, NB AF Cole, N. B. TI Metal Catalyzed Oxidation of Alpha-Synuclein - A Role for Oligomerization in Pathology? SO CURRENT ALZHEIMER RESEARCH LA English DT Review DE Parkinson's disease; alpha-synuclein; metals; oxidation; dopamine; oligomerization; cross-linking; neuromelanin ID SOLUBLE AMYLOID OLIGOMERS; GLYCATION END-PRODUCTS; AMINO-ACID-RESIDUES; LEWY BODY DISEASE; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; IN-VITRO; LIPID-PEROXIDATION; NEURODEGENERATIVE DISEASES; FREE-RADICALS AB A number of studies have demonstrated a role for transition metals and oxidative stress in the etiology of Parkinson's disease (PD). Genetic and biochemical evidence also clearly links the protein alpha-synuclein (alpha Syn) to PD and a number of associated diseases. In these "synucleinopathies", alpha Syn is deposited, often in oligomerized forms, as cytoplasmic inclusions known as Lewy bodies and Lewy neurites. alpha Syn cross-linking/oligomerization can occur via a number of processes, most stimulated by metal catalyzed oxidation (MCO). In PD, the increased sensitivity of midbrain neurons expressing high levels of oxidizable catecholamines may provide one clue to account for degeneration of these neurons. In other regions of the nervous system that develop Lewy body pathology, the mode of alpha Syn oligomerization is less clear. Thus, the relationship between alpha Syn and MCO, either direct or indirect, represents a particular concern for possible treatment of these various diseases. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Cole, NB (reprint author), NHLBI, Biochem Lab, 50 South Dr MSC 8012, Bethesda, MD 20892 USA. EM ncole@mail.nih.gov FU NINDS; National Institutes of Health FX Supported by the Intramural Research Program of the NINDS, National Institutes of Health. NR 121 TC 4 Z9 4 U1 0 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 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD DEC PY 2008 VL 5 IS 6 BP 599 EP 606 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 406HS UT WOS:000263286200013 PM 19075587 ER PT J AU Micale, RT D'Agostini, F Steele, VE La Maestra, S De Flora, S AF Micale, Rosanna T. D'Agostini, Francesco Steele, Vernon E. La Maestra, Sebastiano De Flora, Silvio TI Budesonide and Phenethyl Isothiocyanate Attenuate DNA Damage in Bronchoalveolar Lavage Cells of Mice Exposed to Environmental Cigarette Smoke SO CURRENT CANCER DRUG TARGETS LA English DT Review DE Budesonide; phenethyl isothiocyanate; environmental cigarette smoke; bronchoalveolar lavage cells; alkaline halo test ID PULMONARY ALVEOLAR MACROPHAGES; CANCER CHEMOPREVENTIVE AGENTS; A/J MICE; RESPIRATORY-TRACT; N-ACETYLCYSTEINE; LUNG-CANCER; CYTOGENETIC ALTERATIONS; AEROSOLIZED BUDESONIDE; GENE-EXPRESSION; COMET ASSAY AB Chemoprevention by dietary and pharmacological means provides a strategy for attenuating the health risks resulting from cigarette smoking and in particular from passive exposure to environmental cigarette smoke (ECS). We evaluated the ability of the glucocorticoid budesonide and of the natural agent phenethyl isothiocyanate (PEITC) to affect DNA damage in bronchoalveolar lavage (BAL) cells of CD-1 mice exposed to ECS, starting within 12 h after birth and continuing until the end of the experiment. After weanling, based on a preliminary subchronic toxicity study, groups of mice received daily either budesonide (24 mg/kg diet) or PEITC (1,000 mg/kg diet). After 2 weeks of treatment, all mice were sacrificed and subjected to BAL, mainly recovering pulmonary alveolar macrophages. Evaluation of single-cell DNA strand breaks was made by using the alkaline halo test, a modification of the comet assay. The analysis of 481 BAL cells yielded the following results (expressed as nuclear spread factor): (a) Sham-exposed mice: mean 0.84 (lower-upper 95% confidence intervals 0.74-0.94); (b) ECS-exposed mice: 2.77 (2.46-3.09); (c) ECS-exposed mice treated with PEITC: 1.15 (1.05-1.26); (d) ECS-exposed mice treated with budesonide: 1.37 (1.25-1.49). Thus, exposure to ECS resulted in a significant increase of DNA damage as compared with sham, and both PEITC and budesonide significantly attenuated this damage. In conclusion, the analysis of sentinel cells collected by BAL, a semi-invasive technique that is commonly used in humans for diagnostic purposes, showed that the investigated chemopreventive agents are able to revert the DNA damage produced by passive exposure to cigarette smoke. C1 [Micale, Rosanna T.; D'Agostini, Francesco; La Maestra, Sebastiano; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Steele, Vernon E.] NCI, Rockville, MD 20852 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it FU U.S. National Cancer Institute [NO1-CN-53301] FX This study was supported by U.S. National Cancer Institute contract NO1-CN-53301. We thank Prof. G. Ravera for assistance in statistical analysis. NR 46 TC 6 Z9 6 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 EI 1873-5576 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD DEC PY 2008 VL 8 IS 8 BP 703 EP 708 DI 10.2174/156800908786733423 PG 6 WC Oncology SC Oncology GA 380VY UT WOS:000261495400006 PM 19075593 ER PT J AU Pavkov, ME Knowler, WC Hanson, RL Nelson, RG AF Pavkov, Meda E. Knowler, William C. Hanson, Robert L. Nelson, Robert G. TI Diabetic Nephropathy in American Indians, with a Special Emphasis on the Pima Indians SO CURRENT DIABETES REPORTS LA English DT Article ID STAGE RENAL-DISEASE; URINARY ALBUMIN EXCRETION; BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; KIDNEY-DISEASE; RISK-FACTORS; TYPE-2; MELLITUS; MICROALBUMINURIA; MORTALITY AB Diabetes affects American Indians disproportionately compared with other racial/ethnic groups in the United States and is almost exclusively type 2 diabetes. Much of our knowledge about diabetes in American Indians comes from studies in a few tribes. The most extensively studied American Indians are the Pima Indians from the Gila River Indian Community in Arizona, who participated in a longitudinal study of diabetes and its complications between 1965 and 2007. They have one of the highest reported incidence and prevalence of type 2 diabetes in the world, and kidney disease attributable to diabetes is a major cause of morbidity and mortality. In this article, we examine the course, determinants, and trends of diabetic kidney disease in American Indians, with special emphasis on studies conducted in the Pima Indians. We also review therapeutic strategies for managing diabetic kidney disease. C1 [Nelson, Robert G.] NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIDDK, Diabet Epidemiol & Clin Res Sect, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rgnelson@mail.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. No other potential conflicts of interest relevant to this article were reported. NR 52 TC 9 Z9 9 U1 0 U2 2 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1534-4827 J9 CURR DIABETES REP JI Curr. Diabetes Rep. PD DEC PY 2008 VL 8 IS 6 BP 486 EP 493 DI 10.1007/s11892-008-0083-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375GJ UT WOS:000261101800010 PM 18990306 ER PT J AU Aszalos, A AF Aszalos, Adorjan TI Role of ATP-Binding Cassette (ABC) Transporters in Interactions Between Natural Products and Drugs SO CURRENT DRUG METABOLISM LA English DT Review DE P-glycoprotein; multidrug resistance protein; breast cancer resistance protein; flavonoids; mycotoxins; food-drug interactions ID CANCER RESISTANCE PROTEIN; GLYCOPROTEIN-MEDIATED TRANSPORT; CACO-2 CELL MONOLAYERS; SEVILLE ORANGE JUICE; BLOOD-BRAIN-BARRIER; P-GLYCOPROTEIN; GRAPEFRUIT JUICE; MULTIDRUG-RESISTANCE; IN-VITRO; (ABCG2)-MEDIATED TRANSPORT AB Medicinal use of natural products such as extracts of plants has existed for many years in China and in other countries and they are now available worldwide. Citrus fruit juices are consumed on a daily basis around the world. Modern medicine provides well-tested compounds or drugs for most sicknesses. However, the simultaneous consumption of plant extracts, food supplements, and fruit juices with drugs can create metabolic aberrations in humans. Interactions between drugs used simultaneously are regulated by government agencies. Not regulated, but warned against in drug inserts are potential interactions between drugs and food and food-additives containing certain compounds with potential side effects. Summarized here are the results of investigations that point out possible interactions at the level of transporter molecules by drugs and compounds of natural origin. These transporter molecules play important roles in absorption in the intestines, at the blood brain barrier, in the liver, the kidney and in some other parts of the human body. Drugs and metabolites pass through these pumps and may compete with compounds from food supplements. The most studied natural compounds that are potential modulators of these transport molecules are flavonoids, found in fruit juices, vegetables, flowers and tea. Mycotoxins found in cereal grains are also shown to modulate transporter proteins. We detail here how such constituents of natural origin were shown to modulate three types of the major transporter molecules, P-glycoprotein (ABCB1), multidrug resistance proteins (ABCCs) and breast cancer resistance protein (ABCG2). Interference of these natural compounds with drugs at the transporter level is also discussed. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2112, Bethesda, MD 20892 USA. EM aszalosa@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX The author appreciates the encouragement and hospitality of Dr. Michael Gottesman, chief of the Laboratory of Cell Biology, and the editorial assistance of Mr. George Leiman. This research was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 73 TC 30 Z9 31 U1 1 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD DEC PY 2008 VL 9 IS 10 BP 1010 EP 1018 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 406IZ UT WOS:000263289500003 PM 19075617 ER PT J AU Shukla, V Coumoul, X Vassilopoulos, A Deng, CX AF Shukla, Vivek Coumoul, Xavier Vassilopoulos, Athanassios Deng, Chu-Xia TI IGF Signaling Pathway as a Selective Target of Familial Breast Cancer Therapy SO CURRENT MOLECULAR MEDICINE LA English DT Review DE BRCA1; IGF/IGF-receptor; inhibitor; siRNA; mouse model ID GROWTH-FACTOR-I; ACTIVATED PROTEIN-KINASE; CELL-CYCLE CHECKPOINT; SINGLE-CHAIN ANTIBODY; FACTOR RECEPTOR; MESSENGER-RNA; PHOSPHATIDYLINOSITOL 3-KINASE; TUMOR-GROWTH; TRANSCRIPTIONAL REGULATION; MONOCLONAL-ANTIBODY AB Hereditary breast cancers affect women who have an increased risk of developing tumors because of a familial history. In most cases, they can be attributed to mutations in the breast cancer associated gene 1 and 2 (BRCA1 and BRCA2). Recent studies have demonstrated a link between the insulin-like growth factor (IGF) signaling pathway and familial breast cancer incidence. IGF and IGF receptors represent a family of biological growth factors and transducers, which have been involved in both physiological and pathological processes. It has been shown that BRCA1 regulates expression of several members of the IGF family. Here, we will examine our understanding of the functions of IGF/IGF-receptor signaling, the development of new inhibitors of this pathway and the related mechanisms of familial breast cancer formation. C1 [Shukla, Vivek; Vassilopoulos, Athanassios; Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Coumoul, Xavier] Univ Paris 05, Ctr Univ St Peres, INSERM, UMR S747, F-75006 Paris, France. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, Diabet Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU National Institute of Diabetes; Digestive and Kidney Diseases; National Institutes of Health, USA FX We thank Dr. John T. Lahusen for the critical reading of the manuscript. This research was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, USA. NR 188 TC 3 Z9 3 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 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD DEC PY 2008 VL 8 IS 8 BP 727 EP 740 DI 10.2174/156652408786733694 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 386OO UT WOS:000261892700003 PM 19075671 ER PT J AU Oliveira, JB Notarangelo, LD Fleisher, TA AF Oliveira, Joao B. Notarangelo, Luigi D. Fleisher, Thomas A. TI Applications of flow cytometry for the study of primary immune deficiencies SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE flow cytometry; immunophenotype; intracellular protein; primary immune deficiency; protein phosphorylation ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; X-LINKED AGAMMAGLOBULINEMIA; COMMON VARIABLE IMMUNODEFICIENCY; WISKOTT-ALDRICH-SYNDROME; BRUTONS TYROSINE KINASE; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; CYTOTOXIC LYMPHOCYTES; HYPOMORPHIC MUTATION; FAMILY-MEMBERS; T-CELLS AB Purpose of review This review focuses on the current applications of flow cytometry for the diagnosis and evaluation of primary immune deficiencies (PIDs). Recent findings The immunophenotypic evaluation of selected FIN provides diagnostic clues as well as information useful to classify patients and predict clinical outcome. In addition, the, evaluation of intracellular proteins associated with selected PIN has evolved as a useful diagnostic screening method. Finally, functional flow cytometry can now help to clarify possible sites of genetic defects associated with specific PIDs. Summary The range of PIDs in which flow cytometry has proven to be useful from a clinical and diagnostic purpose has significantly expanded. This now includes not only patients presenting with clinical histories consistent with classical antibody deficiencies and severe combined immune deficiency, but also patients with more limited infectious histories. Included among these are patients with genetic defects associated with Mendelian susceptibility to mycobacterial disease focusing the evaluation on specific surface protein expression and cell function analysis. In addition, flow cytometry appears to provide a useful screening approach to evaluate for possible toll-like receptor-pathway defects. Furthermore, immunophenotyping and intracellular flow cytometry have proven to be valuable discriminators in the evaluation of patients with immune dysregulation syndromes including immune dysregulation, polyendocrinopathy, enteropathy, X-linked, and autoimmune lymphoproliferative syndrome. Finally, flow cytometry has been shown to be useful to screen patients with possible X-linked lymphoproliferative syndrome and familial hemophagocytic lymphohistiocytosis. C1 [Fleisher, Thomas A.] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. RP Fleisher, TA (reprint author), NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bldg 10,Room 2C306,10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM tfleishe@mail.nih.gov RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Oliveira, Joao/0000-0001-9388-8173 FU Intramural NIH HHS NR 41 TC 16 Z9 18 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2008 VL 8 IS 6 BP 499 EP 509 DI 10.1097/ACI.0b013e328312c790 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 375TJ UT WOS:000261135900001 PM 18978463 ER PT J AU Wada, T Candotti, F AF Wada, Taizo Candotti, Fabio TI Somatic mosaicism in primary immune deficiencies SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE mutation rate; reversion; second-site mutation; selective advantage ID WISKOTT-ALDRICH-SYNDROME; IN-VIVO REVERSION; SEVERE COMBINED IMMUNODEFICIENCY; ADENOSINE-DEAMINASE DEFICIENCY; T-CELL; INHERITED MUTATION; 2ND-SITE MUTATION; REVERTANT MOSAICISM; SYNDROME PROTEIN; ADA DEFICIENCY AB Purpose of review Spontaneous genetic reversions and second-site mutations resulting in revertant somatic mosaicism are poorly understood phenomena with a seemingly frequent occurrence in primary immunodeficiency diseases. Here we summarize the several cases that have been reported thus far with particular focus on the most recent observations. Recent findings Revertant cells have been associated with attenuated clinical phenotypes in some, although not all, immunodeficient patients who presented with somatic mosaicism. Interestingly, the latest studies suggest that revertant cells may also be responsible for immune dysregulation. In addition, extensive molecular analysis of revertant cells has revealed that an unexpectedly large variety of genetic changes can be responsible for their emergence. Summary The occurrence of revertant somatic mosaicism in patients affected with primary immunodeficiency diseases is likely much more common than originally anticipated. The study of this fascinating phenomenon continues to provide clues as to the possible underlying mechanisms and to inform, albeit indirectly, the process of development of cell and gene therapy for these diseases. C1 [Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Wada, Taizo] Kanazawa Univ, Grad Sch Med Sci, Dept Pediat, Kanazawa, Ishikawa 9201192, Japan. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Blg 49,Rm 3AO4,MSC 4442, Bethesda, MD 20892 USA. EM fabio@nhgr.nih.gov FU National Institutes of Health FX This work was supported with funds from the NHGRI intramural program of the National Institutes of Health. NR 26 TC 30 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2008 VL 8 IS 6 BP 510 EP 514 DI 10.1097/ACI.0b013e328314b651 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 375TJ UT WOS:000261135900002 PM 18978464 ER PT J AU Paulson, ML Freeman, AF Holland, SM AF Paulson, Michelle L. Freeman, Alexandra F. Holland, Steven M. TI Hyper IgE syndrome: an update on clinical aspects and the role of signal transducer and activator of transcription 3 SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE hyper IgE syndrome; Job's syndrome; recurrent infections; signal transducer and activator of transcription 3; Th17 cells ID HYPERIMMUNOGLOBULINEMIA-E SYNDROME; IMMUNOGLOBULIN-E SYNDROME; INFECTION JOBS SYNDROME; COLD STAPHYLOCOCCAL ABSCESSES; CORONARY-ARTERY ANEURYSMS; T-CELLS; RECURRENT INFECTIONS; ATOPIC-DERMATITIS; STAT3 MUTATIONS; BONE-RESORPTION AB Purpose of review Hyper IgE syndrome (HIES) is a primary immunodeficiency characterized by eczema, recurrent skin and lung infections, elevated serum IgE, and connective tissue and skeletal abnormalities. We present newly recognized aspects of the clinical phenotype and discuss recent genetic and immunologic findings. Recent findings In 2007, mutations in signal transducer and activator of transcription 3 (STAT3) were determined to be the cause of autosomal-dominant HIES. Mutations lead to disruption of STAT3-dependent pathways, which are crucial for signaling of many cytokines, including IL-6 and IL-10. On the one hand, cells from STAT3-defective patients have a proinflammatory profile with elevated TNF alpha and IFN gamma; on the other hand, STAT3 mutations result in the inability to produce IL-17 or form Th17 cells. Summary HIES was previously defined on the basis of clinical manifestations and laboratory markers that were not specific to the disease. With the identification of STAT3 mutations as the cause of HIES, we can definitively characterize the disease at molecular and immunologic levels. Future study of HIES and STAT3 will help us understand eczema, IgE regulation, infection susceptibility, coronary artery disease, scoliosis, and bronchiectasis as well as provide mechanistic insights into treatment. C1 [Paulson, Michelle L.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA. [Freeman, Alexandra F.] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. RP Holland, SM (reprint author), Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU Division of Intramural Research; MAID; NIH [N01-CO-12400]; National Cancer Institute FX The present work is supported by the Division of Intramural Research, MAID, NIH. It has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 62 TC 30 Z9 30 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD DEC PY 2008 VL 8 IS 6 BP 527 EP 533 DI 10.1097/ACI.0b013e3283184210 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 375TJ UT WOS:000261135900005 PM 18978467 ER PT J AU Song, MH Miliaras, NB Peel, N O'Connell, KF AF Song, Mi Hye Miliaras, Nicholas B. Peel, Nina O'Connell, Kevin F. TI Centrioles: some self-assembly required SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID DE-NOVO FORMATION; CENTROSOME DUPLICATION; C-ELEGANS; PERICENTRIOLAR MATERIAL; CELL-CYCLE; CAENORHABDITIS-ELEGANS; DROSOPHILA SPD-2; VERTEBRATE CELLS; 9-FOLD SYMMETRY; PROTEIN SPD-2 AB Centrioles play an important role in organizing microtubules and are precisely duplicated once per cell cycle. New (daughter) centrioles typically arise in association with existing (mother) centrioles (canonical assembly), suggesting that mother centrioles direct the formation of daughter centrioles. However, under certain circumstances, centrioles can also selfassemble free of an existing centriole (de novo assembly). Recent work indicates that the canonical and de novo pathways utilize a common mechanism and that a mother centriole spatially constrains the self-assembly process to occur within its immediate vicinity. Other recently identified mechanisms further regulate canonical assembly so that during each cell cycle, one and only one daughter centriole is assembled per mother centriole. C1 [Song, Mi Hye; Miliaras, Nicholas B.; Peel, Nina; O'Connell, Kevin F.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP O'Connell, KF (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM kevino@intra.niddk.nih.gov OI Peel, Nina/0000-0002-4277-4106; Song, Mi Hye/0000-0001-8326-6602 FU National Institutes Health (NIH); National Institute of Diabetes and Digestive and Kidney Diseases FX The work in the authors' laboratory is supported by the Intramural Research Program of the National Institutes Health (NIH) and by the National Institute of Diabetes and Digestive and Kidney Diseases. NR 40 TC 9 Z9 10 U1 1 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2008 VL 20 IS 6 BP 688 EP 693 DI 10.1016/j.ceb.2008.09.001 PG 6 WC Cell Biology SC Cell Biology GA 389BW UT WOS:000262066100012 PM 18840522 ER PT J AU Busser, BW Bulyk, ML Michelson, AM AF Busser, Brian W. Bulyk, Martha L. Michelson, Alan M. TI Toward a systems-level understanding of developmental regulatory networks SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID EMBRYONIC STEM-CELLS; CORE TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-EMBRYO; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAYS; PROTEIN COMPLEXES; HUMAN FIBROBLASTS; HEART PRECURSORS AB Developmental regulatory networks constitute all the interconnections among molecular components that guide embryonic development. Developmental transcriptional regulatory networks (TRNs) are circuits of transcription factors and cis-acting DNA elements that control expression of downstream regulatory and effector genes. Developmental networks comprise functional subnetworks that are deployed sequentially in requisite spatiotemporal patterns. Here, we discuss integrative genomics approaches for elucidating TRNs, with an emphasis on those involved in Drosophila mesoderm development and mammalian embryonic stem cell maintenance and differentiation. As examples of regulatory subnetworks, we consider the transcriptional and signaling regulation of genes that interact to control cell morphology and migration. Finally, we describe integrative experimental and computational strategies for defining the entirety of molecular interactions underlying developmental regulatory networks. C1 [Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bulyk, Martha L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol HST, Boston, MA 02115 USA. [Busser, Brian W.; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, NIH, Bethesda, MD 20892 USA. RP Bulyk, ML (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM mlbulyk@receptor.med.harvard.edu; michelsonam@nhibi.nih.gov FU Heart Lung and Blood Institute; National Institutes of Health; NIH/NIUMS [U01 GM076603]; NIH/NHLBI [U01 HL081755] FX BWB arid AMM were supported by the Division of Intramural Research of the National. Heart Lung and Blood Institute, National Institutes of Health. MLB was supported in part by grants U01 GM076603 from NIH/NIUMS and U01 HL081755 from NIH/NHLBI NR 78 TC 27 Z9 30 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 2008 VL 18 IS 6 BP 521 EP 529 DI 10.1016/j.gde.2008.09.003 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 407YE UT WOS:000263399400008 PM 18848887 ER PT J AU Mohebtash, M Madan, RA Gulley, JL Arlen, PM AF Mohebtash, Mahsa Madan, Ravi A. Gulley, James L. Arlen, Philip M. TI Therapeutic prostate cancer vaccines: A review of the latest developments SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE Castration-resistant prostate cancer; dendritic cell; GVAX; HER-2; poxviral vector; prostate cancer; prostate-specific antigen; vaccine ID PULSED DENDRITIC CELLS; PHASE-III TRIAL; BREAST-CANCER; CELLULAR IMMUNOTHERAPY; ACTIVE IMMUNIZATION; METASTATIC MELANOMA; CLINICAL-RESPONSES; TUMOR-REGRESSION; E75 VACCINE; IMMUNITY AB Therapeutic cancer vaccines are well-tolerated immunotherapy modalities designed to activate the immune system to kill cancer cells without a significant effect on healthy cells. An improved understanding of tumor immunology has led to improved strategies in vaccine development, which in turn have resulted in improved outcomes. This review discusses different types of cancer vaccines, with a focus on prostate cancer vaccines because of the high prevalence of prostate cancer and the wide variety of approaches used in prostate cancer immunotherapy. C1 [Mohebtash, Mahsa; Madan, Ravi A.; Gulley, James L.; Arlen, Philip M.] NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Arlen, PM (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM pa52s@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z01 BC010666-03] NR 42 TC 2 Z9 3 U1 0 U2 0 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD DEC PY 2008 VL 9 IS 12 BP 1296 EP 1301 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 394RD UT WOS:000262464200005 PM 19037836 ER PT J AU Birbaumer, N Murguialday, AR Cohen, L AF Birbaumer, Niels Murguialday, Ander Ramos Cohen, Leonardo TI Brain-computer interface in paralysis SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE amyotrophic lateral sclerosis; movement restoration; stroke ID NEUROFEEDBACK TREATMENT; SELF-REGULATION; ALS PATIENTS; BCI; MOTOR; COMMUNICATION; EPILEPSY; CORTEX; POTENTIALS; MECHANISMS AB Purpose of review Communication with patients suffering from locked-in syndrome and other forms of paralysis is an unsolved challenge. Movement restoration for patients with chronic stroke or other brain damage also remains a therapeutic problem and available treatments do not offer significant improvements. This review considers recent research in brain-computer interfaces (BCIs) as promising solutions to these challenges. Recent findings Experimentation with nonhuman primates suggests that intentional goal directed movements of the upper limbs can be reconstructed and transmitted to external manipulandurn or robotic devices controlled from a relatively small number of microelectrodes implanted into movement-relevant brain areas after some training, opening the door for the development of BCI or brain-machine interfaces in humans. Although noninvasive BCIs using electroencephalographic recordings or event-related-brain-potentials in healthy individuals and patients with amyotrophic lateral sclerosis or stroke can transmit up to 80 bits/min of information, the use of BCIs - invasive or noninvasive - in severely or totally paralyzed patients has met some unforeseen difficulties. Summary Invasive and noninvasive BCIs using recordings from nerve cells, large neuronal pools such as electrocorticogram and electroencephalography, or blood flow based measures such as functional magnetic resonance imaging and near-infrared spectroscopy show potential for communication in locked-in syndrome and movement restoration in chronic stroke, but controlled phase III clinical trials with larger populations of severely disturbed patients are urgently needed. C1 [Birbaumer, Niels; Murguialday, Ander Ramos] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. [Birbaumer, Niels] Ist Ricovero & Cura Carattere Sci, IRCCS Osped San Camillo, Venezia Lido, Italy. [Murguialday, Ander Ramos] Fatron Fdn, San Sebastian, Spain. [Cohen, Leonardo] NINDS, Human Cort Physiol Sect, Bethesda, MD 20892 USA. [Cohen, Leonardo] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. RP Birbaumer, N (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM niels.birbaumer@uni-tuebingen.de OI Ramos-Murguialday, Ander/0000-0002-1549-4029 FU Deutsche Forschungsgemeinschaft (DFG); NIH; NINDS; Bundesministerium fur Bildung und Forschung (BMBF) FX Supported by the Deutsche Forschungsgemeinschaft (DFG), NIH, NINDS, Bundesministerium fur Bildung und Forschung (BMBF). NR 41 TC 111 Z9 118 U1 5 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2008 VL 21 IS 6 BP 634 EP 638 DI 10.1097/WCO.0b013e328315ee2d PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 379HK UT WOS:000261387100003 PM 18989104 ER PT J AU Rajan, A Giaccone, G AF Rajan, Arun Giaccone, Giuseppe TI Treatment of Advanced Thymoma and Thymic Carcinoma SO CURRENT TREATMENT OPTIONS IN ONCOLOGY LA English DT Article ID WORLD-HEALTH-ORGANIZATION; PHASE-II TRIAL; INVASIVE THYMOMA; EPITHELIAL TUMORS; MALIGNANT THYMOMA; HISTOLOGIC CLASSIFICATION; MULTIMODALITY TREATMENT; METASTATIC THYMOMA; SINGLE-INSTITUTION; MYASTHENIA-GRAVIS AB Although thymic epithelial tumors are rare, they are relatively common among neoplasms of the anterior superior mediastinum. They usually exhibit indolent behavior, but do have the capacity to invade surrounding structures and metastasize to distant sites. Thymic carcinomas are rare, but are highly aggressive tumors that are associated with a poor prognosis. The mainstay of therapy is complete surgical resection. Locally advanced thymoma and thymic carcinoma require a multimodality treatment approach with a combination of surgery, chemotherapy, and radiation therapy to decrease the chances of recurrence and improve survival. The risk of disease recurrence lasts for a number of years after completion of primary therapy. A majority of cases of recurrent disease present as pleural recurrences. Once again, surgical resection of recurrent disease represents the cornerstone of successful therapy and is critical to long-term survival. In recent years, a better understanding of the biologic basis of thymic epithelial tumors has led to the emergence of targeted therapy directed against this malignancy. C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 51 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1527-2729 J9 CURR TREAT OPTION ON JI Curr. Treat. Options Oncol. PD DEC PY 2008 VL 9 IS 4-6 BP 277 EP 287 DI 10.1007/s11864-009-0083-7 PG 11 WC Oncology SC Oncology GA 459XO UT WOS:000267146600005 PM 19381821 ER PT J AU Nikolaeva, LG Maystat, TV Pylypchuk, VS Volyanskii, YL Frolov, VM Kutsyna, GA AF Nikolaeva, Lyudmila G. Maystat, Tatiana V. Pylypchuk, Volodymyr S. Volyanskii, Yuri L. Frolov, Valery M. Kutsyna, Galyna A. TI Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin SO CYTOKINE LA English DT Article DE AIDS; Botanical; Herbal; Immunotherapy; XDR ID CO-INFECTED PATIENTS; RECEIVING ANTITUBERCULOSIS THERAPY; TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-TUBERCULOSIS; INTERFERON-GAMMA; ADJUVANT IMMUNOTHERAPY; LATENT TUBERCULOSIS; IFN-GAMMA; REACTIVATION; RESISTANCE AB Dzherelo (Immunoxel) and Anemin when combined with standard anti-tuberculosis therapy (ATT) were shown to produce better clinical outcome than chemotherapy alone. Sixty HIV-positive patients with active pulmonary TB were equally divided into three matched groups to receive either ATT, ATT + Dzherelo, or ATT + Dzherelo + Anemin. Peripheral blood samples were measured by ELISA for plasma levels of IL-2, IL-6, TNF-alpha, IFN-gamma, and IFN-alpha. After 6 months of follow-up Dzherelo and Dzherelo + Anemin combinations produced 61% (P = 0.005) and 44.4% (P = 0.06) higher levels of 11-2, whereas in ATT group they were reduced by 33.1% (P = 0.002). The levels of IL-6 increased by 17% (P = 0.15) in ATT group, but declined in both immune intervention groups by 26.2% (P = 0.007) and 21.3% (P = 0.22). TNF-alpha was suppressed in two immunotherapy groups by 19.1% (P = 0.06) and 76.3% (P = 0.02), respectively, but had risen by 14% (P = 0.42) in ATT patients. The pattern of production of IFN-gamma was opposite to that of TNF-alpha, but statistical significance was stronger in patients receiving ATT and Dzherelo + Anemin than in Dzherelo group: -34% (P = 0.004), +31.9% (P = 0.008), and +17.3% (P = 0.33), respectively. Moderately decreased levels of IFN-alpha were observed in all treatment arms (range 0.9-16.6%) but differences were not significant. Despite considerable intra-group variation in cytokine production, the baseline intergroup averages were not statistically different indicating that the results were not biased by sample heterogeneity. Immunomodulators used in this study possibly act by enhancing natural immune response against TB. Expanded study of other cytokines and correlates relevant to control and protection from TB and HIV is needed in order to identify biomarkers of favorable treatment outcome, which may aid design of better immune interventions and vaccines. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Nikolaeva, Lyudmila G.; Maystat, Tatiana V.] Kharkov Med Acad Postgrad Educ, Kharkov Reg AIDS Prophylaxis & Prevent Ctr, UA-61044 Kharkov, Ukraine. [Pylypchuk, Volodymyr S.] Ekomed LLC, UA-04208 Kiev, Ukraine. [Volyanskii, Yuri L.] II Mechnikov Inst Microbiol & Immunol, UA-61057 Kharkov, Ukraine. [Frolov, Valery M.; Kutsyna, Galyna A.] Luhansk Reg AIDS Ctr, UA-91045 Lugansk, Ukraine. [Frolov, Valery M.; Kutsyna, Galyna A.] Luhansk State Med Univ, UA-91045 Lugansk, Ukraine. RP Kutsyna, GA (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA. EM kutsyna@list.ru FU Bill and Melinda Gates Foundation's Global Health Travel Award FX We thank all participants who volunteered in this study. The support of clinical staff and technicians who contributed to this study has been of tremendous help to us. We are grateful to other colleagues who shared their insight and provided helpful suggestions based on their own experience with phytoconcentrates used in present study. This work was presented in part at the Keystone Symposia on HIV Pathogenesis and HIV Vaccines, March 27-Apr 1, 2008, Banff, Alberta, Canada, through a grant from Bill and Melinda Gates Foundation's Global Health Travel Award, which is gratefully acknowledged. NR 30 TC 13 Z9 13 U1 0 U2 5 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 DEC PY 2008 VL 44 IS 3 BP 392 EP 396 DI 10.1016/j.cyto.2008.10.009 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 397WG UT WOS:000262692300012 PM 19027322 ER PT J AU Spidlen, J Leif, RC Moore, W Roederer, M Brinkman, RR AF Spidlen, Josef Leif, Robert C. Moore, Wayne Roederer, Mario Brinkman, Ryan R. CA Int Soc Advancement Cytometry Data TI Gating-ML: XML-Based Gating Descriptions in Flow Cytometry SO CYTOMETRY PART A LA English DT Article DE flow cytometry; gating; XML; data standard; compensation; transformation; bioinformatics ID DATA STANDARDS; BIOINFORMATICS AB The lack of software interoperability with respect to gating due to lack of a standardized mechanism for data exchange has traditionally been a bottleneck, preventing reproducibility of flow cytometry (FCM) data analysis and the usage of multiple analytical tools. To facilitate interoperability among FCM data analysis tools, members of the International Society for the Advancement of Cytometry (ISAC) Data Standards Task Force (DSTF) have developed an XML-based mechanism to formally describe gates (Gating-ML). Gating-ML, an open specification for encoding gating, data transformations and compensation, has been adopted by the ISAC DSTF as a Candidate Recommendation. Gating-ML can facilitate exchange of gating descriptions the same way that FCS facilitated for exchange of raw FCM data. Its adoption will open new collaborative opportunities as well as possibilities for advanced analyses and methods development. The ISAC DSTF is satisfied that the standard addresses the requirements for a gating exchange standard.(C) 2008 international Society for Advancement of Cytometry C1 [Spidlen, Josef; Int Soc Advancement Cytometry Data] British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Leif, Robert C.] Newport Instruments, San Diego, CA USA. [Moore, Wayne] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Roederer, Mario] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Brinkman, RR (reprint author), British Columbia Canc Res Ctr, Terry Fox Lab, 675 West 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM rbrinkman@bccrc.ca RI Brinkman, Ryan/B-1108-2008 OI Brinkman, Ryan/0000-0002-9765-2990 FU Michael Smith Foundation for Health; ISAC FX RRB is a Research Scholar of Michael Smith Foundation for Health, and an ISAC Scholar. James Wood is especially thanked for chairing the ISAC DSTF review process. NR 31 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD DEC PY 2008 VL 73A IS 12 BP 1151 EP 1157 DI 10.1002/cyto.a.20637 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 375TF UT WOS:000261135500008 PM 18773465 ER PT J AU Nayar, R Solomon, D AF Nayar, R. Solomon, D. TI Support from authors of the Bethesda system SO CYTOPATHOLOGY LA English DT Letter ID BSCC TERMINOLOGY C1 [Nayar, R.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Solomon, D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Nayar, R (reprint author), Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. EM r-nayar@northwestern.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD DEC PY 2008 VL 19 IS 6 DI 10.1111/j.1365-2303.2008.00631.x PG 2 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 375VD UT WOS:000261140800015 ER PT J AU Zahn-Waxler, C Park, JH Usher, B Belouad, F Cole, P Gruber, R AF Zahn-Waxler, Carolyn Park, Jong-Hyo Usher, Barbara Belouad, Francesca Cole, Pamela Gruber, Reut TI Young children's representations of conflict and distress: A longitudinal study of boys and girls with disruptive behavior problems SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID NARRATIVE REPRESENTATIONS; DEVELOPMENTAL PSYCHOPATHOLOGY; PRESCHOOL-CHILDREN; RATING-SCALE; GENDER; CHILDHOOD; SELF; ASSOCIATIONS; ADOLESCENCE; AGGRESSION AB We investigated narratives, symbolic play, and emotions in children who varied in severity of disruptive behavior problems. Children's representations of hypothetical situations of conflict and distress were assessed at 4-5 and 7 years. Behavior problems also were assessed then and again at 9 years. Children's aggressive and caring themes differentiated nonproblem children, children whose problems remained or worsened with age, and those whose problems improved over time. Differences in boys and girls whose problems continued sometimes reflected exaggerations of prototypic gender differences seen across the groups. Boys with problems showed more hostile themes (physical aggression and anger), whereas girls with problems showed more caring (prosocial) themes relative to the other groups. Modulated (verbal) aggression, more common in girls than boys, showed developmentally appropriate increases with age. However, this was true only for children without problems and those whose problems improved. We consider how these findings contribute to an understanding the inner worlds of boys and girls who differ in their early developmental trajectories for behavior problems. C1 [Zahn-Waxler, Carolyn; Park, Jong-Hyo] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. [Usher, Barbara; Belouad, Francesca] NIMH, Bethesda, MD 20892 USA. [Cole, Pamela] Penn State Univ, University Pk, PA 16802 USA. [Gruber, Reut] McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Zahn-Waxler, C (reprint author), Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA. EM czahnwaxler@wisc.edu FU Intramural NIH HHS NR 47 TC 13 Z9 13 U1 2 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 2008 VL 20 IS 1 BP 99 EP 119 DI 10.1017/S0954579408000059 PG 21 WC Psychology, Developmental SC Psychology GA 255WQ UT WOS:000252689300005 PM 18211730 ER PT J AU Kumar, A Lualdi, M Lewandoski, M Kuehn, MR AF Kumar, Amit Lualdi, Margaret Lewandoski, Mark Kuehn, Michael R. TI Broad Mesodermal and Endodermal Deletion of Nodal at Postgastrulation Stages Results Solely in Left/Right Axial Defects SO DEVELOPMENTAL DYNAMICS LA English DT Article DE left right axis; conditional mutagenesis; Nodal; T-Cre; lateral plate mesoderm ID LEFT-RIGHT ASYMMETRY; EARLY MOUSE EMBRYO; POSTERIOR NOTOCHORD; GENE-EXPRESSION; CRE RECOMBINASE; LATERAL PLATE; MICE; EPIBLAST; RECEPTOR; ROLES AB Nodal signaling is a critical regulator of multiple aspects of early vertebrate development including asymmetry along the left/right (LR) axis. To study Nodal function occurring specifically in the postgastrulation embryo, we have used Cre/loxP based conditional mutagenesis. A floxed allele of Nodal was generated and shown to have wild-type function. This allele was then used in conjunction with the T-Cre line, which expresses Cre recombinase broadly in the mesodermal and definitive endodermal lineages posterior to the cranial region. T-Cre activity leads to complete deletion of Nodal before its normal transient expression in the early somite stage lateral plate mesoderm, thereby causing severe LR developmental defects. No other abnormalities were found, suggesting that Nodal signaling has no additional essential functions in developmental patterning within the extensive mesodermal and endodermal domains marked by T-Cre activity. Developmental Dynamics 237:3591-3601, 2008. Published 2008 Wiley-Liss, Inc. C1 [Kumar, Amit; Lualdi, Margaret; Kuehn, Michael R.] NCI, Lab Prot Dynam & Signaling, NCI Frederick, NIH, Frederick, MD 21702 USA. [Lewandoski, Mark] NCI, Canc & Dev Biol Lab, NCI Frederick, NIH, Frederick, MD 21702 USA. RP Kuehn, MR (reprint author), NCI, Lab Prot Dynam & Signaling, NCI Frederick, NIH, Bldg 560 Rm 12-90, Frederick, MD 21702 USA. EM mkuehn@mail.nih.gov RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU Intramural NIH HHS [Z01 BC010256-12] NR 28 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2008 VL 237 IS 12 BP 3591 EP 3601 DI 10.1002/dvdy.21665 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 383NC UT WOS:000261679300013 PM 18773491 ER PT J AU Krakoff, J Ma, LJ Kobes, S Knowler, WC Hanson, RL Bogardus, C Baier, LJ AF Krakoff, Jonathan Ma, Lijun Kobes, Sayuko Knowler, William C. Hanson, Robert L. Bogardus, Clifton Baier, Leslie J. TI Lower Metabolic Rate in Individuals Heterozygous for Either a Frameshift or a Functional Missense MC4R Variant SO DIABETES LA English DT Article ID MELANOCORTIN-4 RECEPTOR GENE; X-RAY ABSORPTIOMETRY; PIMA-INDIANS; ENERGY-EXPENDITURE; OBESE ADULTS; INSULIN; POPULATION; SYSTEM; BODY; MUTATIONS AB OBJECTIVE-Humans with functional variants in the melanocortin 4 receptor (MC4R) are obese, hyperpliagic, and hyperinsulinemic but have been reported to have no difference in energy expenditure. RESEARCH DESIGN AND METHODS-We investigated the association of two MC4R variants, Arg165Gln (R165Q) and A insertion at nucleotide 100 (NT100), with adiposity in 310741 full-heritage Pima Indians, a subset of whom had metabolic measures including 24-h energy expenditure (n = 252) and resting metabolic rate (RMR) (n = 364). RESULTS-Among the 3,074 subjects, 43 were heterozygous for R165Q and 14 for NT100 (frequency = 0.007 and 0.002). Mean (+/-SD) BMI Was higher among subjects with R165Q (39.3 +/- 8.6 kg/m(2)) or NT100 (41.2 +/- 7.8) than subjects without either variant (37.1 +/- 8.4) (P = 0.04 and 0.02, adjusted for age, sex, and birth year and accounting for family membership). The 24-h energy expenditure (four with NT100; three with R165Q) or RMR (six with NT100; two with R165Q) was lower in heterozygous subjects but only met statistical significance when heterozygous subjects were combined and compared with subjects without either variant: least-squares means, 2,163 kcal/24 h (95% CI 2,035-2,291) vs. 2,307 kcal/24 h (2,285-2,328), P = 0.03 for 24-h energy expenditure, and 1,617 kcal/24 h (1,499-1,734) vs. 1,754 kcal/24 h (1:736-1,772), P = 0.02 for RMR; adjusted for age, sex, fat-free mass, and fat mass). For RMR, this difference persisted, even after accounting for family membership. CONCLUSIONS-Pima Indians heterozygous for R165Q or NT100 in MC4R have higher BMIs and lower energy expenditure (by similar to 140 kcal/day), indicating that, lower energy expenditure was a component of the increased adiposity. Diabetes 57: 3267-3272, 2008 C1 [Krakoff, Jonathan; Ma, Lijun; Kobes, Sayuko; Knowler, William C.; Hanson, Robert L.; Bogardus, Clifton; Baier, Leslie J.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. RP Krakoff, J (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. EM jkrakoff@mail.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; American Diabetes Association FX This Study was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. L.M. was supported by a grant from the American Diabetes Association.; We thank the members of the Gila River Indian Community for their support and the staff of the Phoenix Epidemiology and Clinical Research Branch. NR 37 TC 31 Z9 32 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2008 VL 57 IS 12 BP 3267 EP 3272 DI 10.2337/db08-0577 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 378HW UT WOS:000261312800014 PM 18835933 ER PT J AU Hivert, MF Manning, AK McAteer, JB Florez, JC Dupuis, J Fox, CS O'Donnell, CJ Cupples, LA Meigs, JB AF Hivert, Marie-France Manning, Alisa K. McAteer, Jarred B. Florez, Jose C. Dupuis, Josee Fox, Caroline S. O'Donnell, Christopher J. Cupples, L. Adrienne Meigs, James B. TI Common Variants in the Adiponectin Gene (ADIPOQ) Associated With Plasma Adiponectin Levels, Type 2 Diabetes, and Diabetes-Related Quantitative Traits The Framingham Offspring Study SO DIABETES LA English DT Article ID APM1 GENE; INSULIN-RESISTANCE; SUSCEPTIBILITY GENES; METABOLIC SYNDROME; PROXIMAL PROMOTER; POLYMORPHISMS; CAUCASIANS; OBESITY; RISK; FAMILIES AB OBJECTIVE-Variants in ADIPOQ have been inconsistently associated with adiponectin levels or diabetes. Using comprehensive linkage disequilibrium mapping, we genotyped single nucleotide polymorphisms (SNPs) in ADIPOQ to evaluate the association of common variants with adiponectin levels and risk of diabetes. RESEARCH DESIGN AND METHODS-Participants in the Framingham Offspring Study (n = 2,543, 53% women) were measured for glycemic phenotypes and incident diabetes over 28 years of follow-up; adiponectin levels were quantified at exam 7. We genotyped 22 tag SNPs that captured common (minor allele frequency >0.05) variation at r(2) > 0.8 across ADIPOQ plus 20 kb 5' and 10 kb 3' of the gene. We used linear mixed effects models to test additive associations of each SNP with adiponectin levels and glycemic phenotypes. Hazard ratios (HRs) for incident diabetes were estimated using an adjusted Cox proportional hazards model. RESULTS-Two promoter SNPs in strong linkage disequilibrium with each other (r(2) = 0.80) were associated with adiponectin levels (rs17300539; P(nominal) [P(n)] 2.6 x 10(-8); P(empiric) [P(e)] = 0.0005 and rs822387; P(n) = 3.8 x 10(-5); P(e) = 0.001). A 3'-untranslated region (3'UTR) SNP (rs6773957) was associated with adiponectin levels (P(n) = 4.4 x 10(-4); P(e) = 0.005). A nonsynonymous coding SNP (rs17366743, Y111H) was confirmed to be associated with diabetes incidence (HR 1.94 [95% CI 1.16-3.25] for the minor C allele; P(n) = 0.01) and with higher mean fasting glucose over 28 years of follow-up (P(n) = 0.0004; P(e) = 0.004). No other significant associations were found with other adiposity and metabolic phenotypes. CONCLUSIONS-Adiponectin levels are associated with SNPs in two different regulatory regions (5' promoter and 3'UTR), whereas diabetes incidence and time-averaged fasting glucose are associated with a missense SNP of ADIPOQ. Diabetes 57: 3353-3359, 2008 C1 [Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hivert, Marie-France; Florez, Jose C.; O'Donnell, Christopher J.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Manning, Alisa K.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res & Diabet Unit, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU Centre de Recherche Medicale de l'Universite de Sherbrooke; Canadian Institute of Health Research Fellowships Health Professional Award; National Institutes of Health (NIH) [K23-DK-65978-04, 1S10-RR-163736-01A1]; NIDDK [K24-DK-080140]; Sanofi-Aventis; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Center for Research Resources (NCRR); General Clinical Research Centers Program [M01-RR-01066] FX M.-F.H. has received support, from the Centre de Recherche Medicale de l'Universite de Sherbrooke and a Canadian Institute of Health Research Fellowships Health Professional Award. J.C.F. has received National Institutes of Health (NIH) Research Career Award K23-DK-65978-04. J.B.M. has received NIDDK Grant K24-DK-080140, an American Diabetes Association Career Development Award, and a research grant from Sanofi-Aventis. This work was supported by National Heart, Lung, and Blood Institute's Framingham Heart Study Contract N01-HC-25195; by NIH, National Center for Research Resources (NCRR), General Clinical Research Centers Program Grant M01-RR-01066; and by the Boston University Linux Cluster for Genetic Analysis funded by NIH NCRR Shared Instrumentation Grant 1S10-RR-163736-01A1. NR 24 TC 87 Z9 89 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2008 VL 57 IS 12 BP 3353 EP 3359 DI 10.2337/db08-0700 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 378HW UT WOS:000261312800025 PM 18776141 ER PT J AU Howard, BV Best, L Comuzzie, A Ebbesson, SOE Epstein, SE Fabsitz, RR Howard, WJ Silverman, A Wang, H Zhu, JH Umans, J AF Howard, Barbara V. Best, Lyle Comuzzie, Anthony Ebbesson, Sven O. E. Epstein, Stephen E. Fabsitz, Richard R. Howard, Wm. James Silverman, Angela Wang, Hong Zhu, Jianhui Umans, Jason TI C-Reactive Protein, Insulin Resistance, and Metabolic Syndrome in a Population With a High Burden of Subclinical Infection Insights from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study SO DIABETES CARE LA English DT Article ID SYSTEMIC INFLAMMATION; DIABETES-MELLITUS; RISK; ATHEROSCLEROSIS; GLUCOSE; ADULTS AB OBJECTIVE - To explore relationships between C-reactive protein (CRP), subclinical infection, insulin resistance, and metabolic syndrome. RESEARCH DESIGN AND METHODS - Data from 1,174 Eskimos, aged >= 18 years, from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study were analyzed; 40 participants with diabetes were eliminated. Baseline assessment included interviews, physical exam, and blood and urine sampling. Metabolic syndrome was assessed using Adult Treatment Panel III criteria. CRP and antibodies to common pathogens were measured. RESULTS - Although CRP was related in univariate analyses to insulin resistance and metabolic syndrome, relations were attenuated or eliminated after adjustment for relevant covariates. CRP was not higher among those with impaired fasting glucose (IFG), and pathogen burden was not related to insulin resistance, metabolic syndrome, or IFG. CONCLUSIONS - Pathogen burden and inflammation do not seem to be related to insulin resistance, metabolic syndrome, or IFG in this population. The inflammatory process may reflect insulin resistance or its correlates but most likely is not causative. C1 [Howard, Barbara V.; Epstein, Stephen E.; Silverman, Angela; Wang, Hong; Zhu, Jianhui; Umans, Jason] MedStar Res Inst, Hyattsville, MD USA. [Best, Lyle] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Comuzzie, Anthony] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, Nome, AK USA. [Fabsitz, Richard R.] NHLBI, Bethesda, MD 20892 USA. [Howard, Wm. James] Washington Hosp Ctr, Washington, DC 20010 USA. RP Howard, BV (reprint author), MedStar Res Inst, Hyattsville, MD USA. EM barbara.v.howard@medstar.net FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [RO1-HL64244, U01 HL082458, M10RR0047-34] FX We thank Norton Sound Health Corporation, the village leadership, and Rachel Schaperow for her editorial services. NR 15 TC 13 Z9 13 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2008 VL 31 IS 12 BP 2312 EP 2314 DI 10.2337/dc08-0815 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 381RB UT WOS:000261552500018 PM 18796618 ER PT J AU Friedman, A Marrero, D Ma, Y Ackermann, R Narayan, KMV Barrett-Connor, E Watson, K Knowler, WC Horton, ES AF Friedman, Allon Marrero, David Ma, Yong Ackermann, Ronald Narayan, K. M. Venkat Barrett-Connor, Elizabeth Watson, Karol Knowler, William C. Horton, Edward S. CA Diabet Prevention Program Res Grp TI Value of Urinary Albumin-to-Creatinine Ratio as a Predictor of Type 2 Diabetes in Pre-Diabetic Individuals SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE ATHEROSCLEROSIS; CARDIOVASCULAR EVENTS; PREVENTION PROGRAM; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; LIFE-STYLE; MICROALBUMINURIA; HYPERTENSION; MELLITUS; CLASSIFICATION AB OBJECTIVE - The albumin-to-creatinine ratio (ACR) reflects urinary albumin excretion and is increasingly being accepted as an important clinical outcome predictor. Because of the great public health need for a simple and inexpensive test to identify individuals at high risk for developing type 2 diabetes, it has been suggested that the ACR might serve this purpose. We therefore determined whether the ACR could predict incident diabetes in a well-characterized cohort of pre-diabetic Americans. RESEARCH DESIGN AND METHODS - A total of 3,188 Diabetes Prevention Program (DPP) participants with a mean BMI of 34 kg/m(2) and elevated fasting glucose, impaired glucose tolerance, and baseline urinary albumin excretion measurements were followed for incident diabetes over a mean of 3.2 years. RESULTS - Of the participants, 94% manifested ACR levels below the microalbuminuria range and 21% ultimately developed diabetes during follow-up. Quartiles of ACR (median [range] within quartiles: 1, 3.0 [0.7-3.7]; 2, 4.6 [3.7-5.5]; 3, 7.1 [5.5-9.7]; and 4, 16.5 [9.7-1,578]) were positively associated with age, markers of adiposity and insulin secretion and resistance, blood pressure, and use of antiltypertensive agents with antiproteinuric effects and inversely related to male sex and serum creatinine. An elevated hazard rate for developing diabetes with doubling of ACR disappeared after adjustment for covariates. Within the DPP intervention groups (placebo, lifestyle, and metformin), we found no consistent trend in incident diabetes by quartile or decile of ACR. CONCLUSIONS - An ACR at levels below the microalbuminuria range does not independently predict incident diabetes in adults at high risk of developing type 2 diabetes. C1 [Friedman, Allon; Ma, Yong] George Washington Univ, Coordinating Ctr, Diabet Prevent Program, Rockville, MD USA. [Friedman, Allon; Marrero, David; Ackermann, Ronald] Indiana Univ, Indianapolis, IN 46204 USA. [Narayan, K. M. Venkat] Emory Univ, Atlanta, GA 30322 USA. [Barrett-Connor, Elizabeth] Univ Calif San Diego, San Diego, CA 92103 USA. [Watson, Karol] Univ Calif Los Angeles, Alhambra, CA USA. [Knowler, William C.] NIH, Phoenix, AZ USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Friedman, A (reprint author), George Washington Univ, Coordinating Ctr, Diabet Prevent Program, Rockville, MD USA. EM dppmail@biostat.bsc.gwu.edu RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 FU National Institutes of Health [K23 RR019615] FX A.N.F. is supported by the National Institutes of Health (K23 RR019615). NR 22 TC 16 Z9 18 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2008 VL 31 IS 12 BP 2344 EP 2348 DI 10.2337/dc08-0148 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 381RB UT WOS:000261552500024 PM 18796622 ER PT J AU Le, DSNT Miles, R Savage, PJ Cornell, E Tracy, RP Knowler, WC Krakoff, J AF Le, Duc Son N. T. Miles, Rachelle Savage, Peter J. Cornell, Elaine Tracy, Russell P. Knowler, William C. Krakoff, Jonathan TI The association of plasma fibrinogen concentration with diabetic microvascular complications in young adults with early-onset of type 2 diabetes SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Pima Indians; Young onset type 2 diabetes; Diabetic nephropathy; Diabetic retinopathy; Fibrinogen concentration; inflammatory and hemostatic markers ID PIMA-INDIANS; ENDOTHELIAL DYSFUNCTION; KIDNEY-DISEASE; RENAL-DISEASE; RISK-FACTOR; RETINOPATHY; MELLITUS; NEPHROPATHY; FIBRINOLYSIS; COAGULATION AB Aims: Diabetic nephropathy is an important risk factor for cardiovascular diseases (CVD). The underlying etiology is not fully understood but may be related to changes in inflammatory and hemostatic markers with kidney disease. We investigated the associations of the markers with microvascular complications in Pima Indians (PI) with early-onset type 2 diabetes (T2DM). Methods: C-reactive protein, interleukine-6, fibrinogen, D-dimer, plasmin-antiplasmin complex and plasminogen activator inhibitor-1 were measured in 104 PI (age: 32 +/- 4y) with diabetes and 59 (32 4y) with fasting glucose < 110 mg/dl and 2-h glucose < 140 mg/dl. Urine albumin to creatinine ratio (ACR) was used as marker of nephropathy. Severity of retinopathy was classified in the worse eye by direct ophthalmoscopy as none, background and proliferative. Results: Of these markers, only fibrinogen was associated with ACR (r = 0.25, p < 0.01). After adjustment for age, sex, percentage Pima heritage, smoking status, diabetes duration, blood pressure and use of aspirin, antihypertensive and antihyperglycemic agents, general linear models (with natural log-transformed values of fibrinogen and ACR as dependent and independent variables, respectively) revealed that a one percent increase in ACR would yield a 0.02% increase in the fibrinogen (R = 0.02, p < 0.05). Plasma fibrinogen was also significantly increased with severity of diabetic retinopathy (p < 0.05). Conclusions: Increased plasma fibrinogen concentration was associated with diabetic microvascular disease, in particular with nephropathy. This may help to explain the etiologic link between nephropathy and CVD. Published by Elsevier Ireland Ltd. C1 [Le, Duc Son N. T.; Krakoff, Jonathan] DHHS, Obes & Diabet Clin Res Sect, NIDDK, NIH, Phoenix, AZ USA. [Miles, Rachelle; Knowler, William C.; Krakoff, Jonathan] DHHS, Diabet Epidemiol & Clin Res Sect, NIDDK, NIH, Phoenix, AZ USA. [Savage, Peter J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Cornell, Elaine; Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, Essex, England. RP Le, DSNT (reprint author), DHHS, Obes & Diabet Clin Res Sect, NIDDK, NIH, 4212 N 16th St,Room 5-35, Phoenix, AZ USA. EM ducsonmd@gmail.com FU Intramural NIH HHS NR 34 TC 13 Z9 16 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD DEC PY 2008 VL 82 IS 3 BP 317 EP 323 DI 10.1016/j.diabres.2008.08.019 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 388YW UT WOS:000262057400005 PM 18922595 ER PT J AU Scuteri, A Vuga, M Najjar, SS Mehta, V Everson-Rose, SA Sutton-Tyrrell, K Matthews, K Lakatta, EG AF Scuteri, A. Vuga, M. Najjar, S. S. Mehta, V. Everson-Rose, S. A. Sutton-Tyrrell, K. Matthews, K. Lakatta, E. G. . TI Education eclipses ethnicity in predicting the development of the metabolic syndrome in different ethnic groups in midlife: the Study of Women's Health Across the Nation (SWAN) SO DIABETIC MEDICINE LA English DT Article DE ethnicity; longitudinal studies; metabolic syndrome; socio-economic status; women ID NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; RISK-FACTORS; CAROTID ATHEROSCLEROSIS; PERIMENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; HEART-DISEASE; PREVALENCE; ATTAINMENT AB To determine the respective roles of socio-economic status (SES) and ethnicity in the risk of incident metabolic syndrome in middle-aged women. A total of 3302 pre- and peri-menopausal women, not receiving hormone therapy at baseline, took part in the Study of Women's Health Across the Nation, a multi-site, community-based, longitudinal study of the menopausal transition. The main outcome measures were to ascertain the prevalence of the metabolic syndrome and the incidence of the metabolic syndrome over 5 years of follow-up. At baseline, the prevalence of the metabolic syndrome was 21% (n = 673). Among 2512 women without metabolic syndrome at baseline, 12.8% (n = 321) developed the metabolic syndrome during 5 years of follow-up. Both ethnicity and SES were significant univariate predictors of incident metabolic syndrome. In multivariate logistic regression models that included age at baseline, menopausal status and site, baseline smoking and alcohol consumption at follow-up visit 1, as well as baseline values of each of the components of the metabolic syndrome, only education was an independent predictor of incident metabolic syndrome. Approximately 13% of peri-menopausal women developed the metabolic syndrome during the 5-year follow-up period. Education, but not ethnicity, was an independent predictor of incident metabolic syndrome risk. Diabet. Med. 25, 1390-1399 (2008). C1 [Scuteri, A.] UO Geriatria INRCA, IRCCS, I-00189 Rome, Italy. [Scuteri, A.; Najjar, S. S.; Lakatta, E. G. .] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Vuga, M.; Mehta, V.; Sutton-Tyrrell, K.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Everson-Rose, S. A.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Everson-Rose, S. A.] Univ Minnesota, Program Hlth Dispar Res, Minneapolis, MN USA. [Matthews, K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Scuteri, A (reprint author), UO Geriatria INRCA, IRCCS, Via Cassia 1167, I-00189 Rome, Italy. EM angeloelefante@interfree.it FU National Institutes of Health (NIH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; DHHS, through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR) FX The Study of Women's Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. We thank the study staff at each site and all the women who participated in SWAN. NR 27 TC 7 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD DEC PY 2008 VL 25 IS 12 BP 1390 EP 1399 DI 10.1111/j.1464-5491.2008.02596.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 377KD UT WOS:000261249200003 PM 19046236 ER PT J AU Rafiq, S Melzer, D Weedon, MN Lango, H Saxena, R Scott, LJ Palmer, CNA Morris, AD McCarthy, MI Ferrucci, L Hattersley, AT Zeggini, E Frayling, TM AF Rafiq, S. Melzer, D. Weedon, M. N. Lango, H. Saxena, R. Scott, L. J. Palmer, C. N. A. Morris, A. D. McCarthy, M. I. Ferrucci, L. Hattersley, A. T. Zeggini, E. Frayling, T. M. CA DIAGRAM Consortium TI Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE Autoimmune disease; Genes; Genetic epidemiology; Inflammation; Mendelian randomisation; SNP; Type 2 diabetes ID GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; C-REACTIVE PROTEIN; MIGRATION INHIBITORY FACTOR; RECEPTOR IL-6R GENE; SUSCEPTIBILITY LOCI; INTERLEUKIN-1-RECEPTOR ANTAGONIST; RHEUMATOID-ARTHRITIS; MONICA/KORA AUGSBURG; SERUM CONCENTRATIONS AB There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p<0.01) in a further set of 3,125 cases and 3,596 controls from the UK. We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p <= 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99-1.03]), is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates, based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09-1.21] per 0.28 SD increase in IL-18 levels). Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk, including type 1 diabetes, alter type 2 diabetes risk. C1 [Rafiq, S.; Melzer, D.; Weedon, M. N.; Lango, H.; Hattersley, A. T.; Frayling, T. M.] Univ Exeter, Peninsula Med Sch, Exeter EX1 2LU, Devon, England. [Saxena, R.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Saxena, R.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, R.] Broad Inst Harvard & MIT, Med & Populat Genet Program, Cambridge, MA USA. [Scott, L. J.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Scott, L. J.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Palmer, C. N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Populat Pharmacogenet Grp, Biomed Res Ctr, Dundee DD1 9SY, Scotland. [Morris, A. D.] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Div Med & Therapeut, Dundee DD1 9SY, Scotland. [McCarthy, M. I.; Zeggini, E.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, M. I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Med, Churchill Hosp, Oxford, England. [Ferrucci, L.] Natl Inst Ageing, Gerontol Res Ctr, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MA USA. RP Frayling, TM (reprint author), Univ Exeter, Peninsula Med Sch, Magdalen Rd, Exeter EX1 2LU, Devon, England. EM Tim.Frayling@pms.ac.uk RI Palmer, Colin/C-7053-2008; Morris, Andrew/C-2837-2009; Lango Allen, Hana/G-9026-2012; OI Palmer, Colin/0000-0002-6415-6560; Lango Allen, Hana/0000-0002-7803-8688; Rafiq, Sajjad/0000-0003-4873-4540; Zeggini, Eleftheria/0000-0003-4238-659X; Melzer, David/0000-0002-0170-3838 FU Intramural NIH HHS [Z01 AG000965-02]; NIA NIH HHS [R01 AG024233, R01 AG24233]; NIDDK NIH HHS [R01 DK062370, R56 DK062370, U01 DK062370]; Wellcome Trust [, 079557] NR 51 TC 28 Z9 28 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2008 VL 51 IS 12 BP 2205 EP 2213 DI 10.1007/s00125-008-1160-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 369HT UT WOS:000260686000008 PM 18853133 ER PT J AU Franks, PW Jablonski, KA Delahanty, LM McAteer, JB Kahn, SE Knowler, WC Florez, JC AF Franks, P. W. Jablonski, K. A. Delahanty, L. M. McAteer, J. B. Kahn, S. E. Knowler, W. C. Florez, J. C. CA Diabet Prevention Program Res Grp TI Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Article DE Adiposity; Diabetes Prevention Program; FTO; Gene-environment interaction; Genetic; INSIG2; Lifestyle; Metformin; Obesity; Randomised controlled trial; Troglitazone ID BODY-MASS INDEX; LIFE-STYLE INTERVENTION; PHYSICAL-ACTIVITY; RS9939609 POLYMORPHISM; CHILDHOOD OBESITY; ADULT OBESITY; PIMA-INDIANS; ASSOCIATION; VARIANTS; REPRODUCIBILITY AB The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated gene (FTO) and the rs7566605 SNP located 10 kb upstream of the insulin-induced gene 2 gene (INSIG2) have been proposed as risk factors for common obesity. We tested for genotype-treatment interactions on changes in obesity-related traits in the Diabetes Prevention Program (DPP). The DPP is a randomised controlled trial of 3,548 high-risk individuals from 27 participating centres throughout the USA who were originally randomised to receive metformin, troglitazone, intensive lifestyle modification or placebo to prevent the development of type 2 diabetes. Measures of adiposity from computed tomography were available in a subsample (n=908). This report focuses on the baseline and 1 year results. The minor A allele at FTO rs9939609 was positively associated with baseline BMI (p=0.003), but not with baseline adiposity or the change at 1 year in any anthropometric trait. For the INSIG2 rs7566605 genotype, the minor C allele was associated with more subcutaneous adiposity (second and third lumbar vertebrae [L2/3]) at baseline (p=0.04). During follow-up, CC homozygotes lost more weight than G allele carriers (p=0.009). In an additive model, we observed nominally significant gene-lifestyle interactions on weight change (p=0.02) and subcutaneous (L2/3 [p=0.01] and L4/5 [p=0.03]) and visceral (L2/3 [p=0.02]) adipose areas. No statistical evidence of association with physical activity energy expenditure or energy intake was observed for either genotype. Within the DPP study population, common variants in FTO and INSIG2 are nominally associated with quantitative measures of obesity, directly and possibly by interacting with metformin or lifestyle intervention. Trial registration: ClinicalTrials.gov NCT00004992 Funding: The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), the National Institute of Child Health and Human Development (NICHD), the National Center on Minority Health and Health Disparities (NCMHD) and the Office of Research on Women's Health (ORWH). C1 [Franks, P. W.] George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, Rockville, MD 20852 USA. [Franks, P. W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Med Sect, S-90185 Umea, Sweden. [Delahanty, L. M.; Florez, J. C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [McAteer, J. B.; Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McAteer, J. B.; Florez, J. C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Kahn, S. E.] VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. [Kahn, S. E.] Univ Washington, Seattle, WA 98195 USA. [Knowler, W. C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA. [Florez, J. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Franks, PW (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, Ctr Biostat, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM paul.franks@medicin.umu.se OI Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS [Z01 DK069092-02]; NIDDK NIH HHS [K23 DK065978, K23 DK65978-04, R01 DK072041, R01 DK072041-02] NR 39 TC 71 Z9 72 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2008 VL 51 IS 12 BP 2214 EP 2223 DI 10.1007/s00125-008-1158-x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 369HT UT WOS:000260686000009 PM 18839134 ER PT J AU McLaughlin, T Deng, A Gonzales, O Aillaud, M Yee, G Lamendola, C Abbasi, F Connolly, AJ Sherman, A Cushman, SW Reaven, G Tsao, PS AF McLaughlin, T. Deng, A. Gonzales, O. Aillaud, M. Yee, G. Lamendola, C. Abbasi, F. Connolly, A. J. Sherman, A. Cushman, S. W. Reaven, G. Tsao, P. S. TI Insulin resistance is associated with a modest increase in inflammation in subcutaneous adipose tissue of moderately obese women SO DIABETOLOGIA LA English DT Article DE Adipocyte; Adipose tissue; Inflammation; Insulin resistance; Obesity ID MEDIATED GLUCOSE DISPOSAL; NONOBESE PIMA-INDIANS; INCREASED EXPRESSION; SUPPRESSION TEST; INDIVIDUALS; METABOLISM; GENES; ALPHA; CELLS; MICE AB We have previously described differences in adipose cell size distribution and expression of genes related to adipocyte differentiation in subcutaneous abdominal fat obtained from insulin-sensitive (IS) and -resistant (IR) persons, matched for degree of moderate obesity. To determine whether other biological properties also differ between IR and IS obese individuals, we quantified markers of inflammatory activity in adipose tissue from overweight IR and IS individuals. Subcutaneous abdominal tissue was obtained from moderately obese women, divided into IR (n=14) and IS (n=19) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test. Inflammatory activity was assessed by comparing expression of nine relevant genes and by immunohistochemical quantification of CD45- and CD68-containing cells. SSPG concentrations were approximately threefold higher in IR than in IS individuals. Expression levels of CD68, EMR1, IL8, IL6 and MCP/CCL2 mRNAs were modestly but significantly increased (p<0.05) in IR compared with IS participants. Results of immunohistochemical staining were consistent with gene expression data, demonstrating modest differences between IR and IS individuals. Crown-like structures, in which macrophages surround single adipocytes, were rarely seen in tissue from either subgroup. A modest increase in inflammatory activity was seen in subcutaneous adipose tissue from IR compared with equally obese IS individuals. Together with previous evidence of impaired adipose cell differentiation in IR vs equally obese individuals, it appears that at least two biological processes in subcutaneous adipose tissue characterize the insulin-resistant state independent of obesity per se. Trial registration ClinicalTrials.gov NCT00285844 Funding The study was funded by grants from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the NIDDK Intramural Research Program. C1 [McLaughlin, T.] Stanford Univ, Sch Med, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. [Deng, A.; Gonzales, O.; Aillaud, M.; Yee, G.; Lamendola, C.; Abbasi, F.; Reaven, G.; Tsao, P. S.] Stanford Univ, Sch Med, Dept Cardiovasc Med, Stanford, CA 94305 USA. [Connolly, A. J.] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. [Sherman, A.; Cushman, S. W.] NIDDK, NIH, Bethesda, MD USA. RP McLaughlin, T (reprint author), Stanford Univ, Sch Med, Dept Med, Div Endocrinol, 300 Pasteur Dr,Rm S025, Stanford, CA 94305 USA. EM tmclaugh@stanford.edu FU Intramural NIH HHS [Z01 DK013029-01]; NCRR NIH HHS [K23 RR016071, 5K23 RR16071, M01 RR000070, RR 000070]; NIDDK NIH HHS [1 R01 DK071309-01, 5R01DK071333, R01 DK071309, R01 DK071333] NR 18 TC 30 Z9 30 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 2008 VL 51 IS 12 BP 2303 EP 2308 DI 10.1007/s00125-008-1148-z PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 369HT UT WOS:000260686000019 PM 18825363 ER PT J AU Green, O Murray, P Gea-Banacloche, JC AF Green, O'Neil Murray, Patrick Gea-Banacloche, Juan C. TI Sepsis caused by Elizabethkingia miricola successfully treated with tigecycline and levofloxacin SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Elizabethkingia; Miricola; Human; Disease ID CHRYSEOBACTERIUM-MENINGOSEPTICUM AB Elizabethkingia miricola is a Gram-negative rod that was initially isolated from condensation water of the space station Mir. This is the 1st reported case of human disease caused by this organism. Published by Elsevier Inc. C1 [Murray, Patrick] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Gea-Banacloche, Juan C.] NIH, Dept Infect Dis, Ctr Clin, Bethesda, MD 20892 USA. [Green, O'Neil] New York Hosp Queens Weill Cornell Med Coll, Dept Internal Med, Flushing, NY 11355 USA. RP Murray, P (reprint author), NIH, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM pmurray@cc.nih.gov FU Intramural NIH HHS [NIH0011112313]; PHS HHS [NIH0011112313] NR 3 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD DEC PY 2008 VL 62 IS 4 BP 430 EP 432 DI 10.1016/j.diagmicrobio.2008.07.015 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 381RR UT WOS:000261554100013 PM 18842380 ER PT J AU Nakane, H Hirota, S Brooks, PJ Nakabeppu, Y Nakatsu, Y Nishimune, Y Iino, A Tanaka, K AF Nakane, Hironobu Hirota, Seiichi Brooks, Philip J. Nakabeppu, Yusaku Nakatsu, Yoshimichi Nishimune, Yoshitake Iino, Akihiro Tanaka, Kiyoji TI Impaired spermatogenesis and elevated spontaneous tumorigenesis in xeroderma pigmentosum group A gene (Xpa)-deficient mice SO DNA REPAIR LA English DT Article DE Xeroderma pigmentosum (XP); Nucleotide excision repair (NER); Spermatogenesis; Spontaneous tumorigenesis; Knockout mice ID NUCLEOTIDE EXCISION-REPAIR; XPA-DEFICIENT MICE; HEMATOPOIETIC STEM-CELLS; DNA-REPAIR; KNOCKOUT MICE; ULTRAVIOLET-B; IN-VITRO; MOUSE; MUTATIONS; DAMAGE AB We have reported that xeroderma pigmentosum group A (Xpa) gene-knockout mice [Xpa (-/-) mice] are deficient in nucleotide excision repair (NER) and highly sensitive to UV-induced skin carcinogenesis. Although xeroderma pigmentosum group A patients show growth retardation, immature sexual development, and neurological abnormalities as well as a high incidence of UV-induced skin tumors, Xpa (-/-) mice were physiologically and behaviorally normal. In the present study, we kept Xpa (-/-) mice for 2 years under specific pathogen-free (SPF) conditions and found that the testis diminished in an age-dependent manner, and degenerating seminiferous tubules and no spermatozoa were detected in the 24-month-old Xpa (-/-) mice. In addition, a higher incidence of spontaneous tumorigenesis was observed in the 24-month-old Xpa (-/-) mice compared to Xpa (+/+) controls. Xpa (-/-) mice provide a useful model for investigating the aging and internal tumor formation in XPA patients. (C) 2008 Elsevier B.V. All rights reserved. C1 [Nakane, Hironobu; Iino, Akihiro] Tottori Univ, Fac Med, Div Genome Morphol, Dept Funct Morphol & Regulatory Sci, Tottori 6838503, Japan. [Nakane, Hironobu; Nakatsu, Yoshimichi; Tanaka, Kiyoji] Osaka Univ, Grad Sch Frontier Biosci, Human Cell Biol Grp, Suita, Osaka 5650871, Japan. [Tanaka, Kiyoji] Japan Sci & Technol Agcy, SORST, Suita, Osaka 5650871, Japan. [Hirota, Seiichi] Hyogo Med Univ, Dept Surg Pathol, Nishinomiya, Hyogo 6638501, Japan. [Brooks, Philip J.] NIAAA, Mol Neurobiol Sect, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Nakabeppu, Yusaku] Kyushu Univ, Med Inst Bioregulat, Dept Neurosci & Immunol, Div Neurofunct Genom, Fukuoka 8128582, Japan. [Nishimune, Yoshitake] Osaka Univ, Microbial Dis Res Inst, Dept Sci Lab Anim Expt, Suita, Osaka 5650871, Japan. RP Nakane, H (reprint author), Tottori Univ, Fac Med, Div Genome Morphol, Dept Funct Morphol & Regulatory Sci, Nishi Cho 86, Tottori 6838503, Japan. EM mnakane@med.tottori-u.ac.jp; ktanaka@fbs.osaka-u.acjp RI Nakabeppu, Yusaku/A-8902-2011 FU Ministry of Education, Culture, Sports, Science and Technology of Japan [18591782, 20591898, 17109006]; Solution Oriented Research for Science and Technology (SORST) of Japan Science and Technology Agency (JST) FX This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant numbers: 18591782, 20591898 to H.N. and 17109006 to K.T.), and by a Grant for Solution Oriented Research for Science and Technology (SORST) of Japan Science and Technology Agency (JST) to K.T. We thank Dr. Junji Tsuchida for helpful advice, and Akinori Fukuyama, Kenji Morihara and Toshio Kameie for excellent technical support. NR 52 TC 11 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 1 PY 2008 VL 7 IS 12 BP 1938 EP 1950 DI 10.1016/j.dnarep.2008.08.003 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 380UJ UT WOS:000261490500002 PM 18790090 ER PT J AU Christmann, M Tomicic, MT Gestrich, C Roos, WP Bohr, VA Kaina, B AF Christmann, Markus Tomicic, Maja T. Gestrich, Christopher Roos, Wynand P. Bohr, Vilhelm A. Kaina, Bernd TI WRN protects against topo I but not topo II inhibitors by preventing DNA break formation SO DNA REPAIR LA English DT Article DE Topoisomerase inhibition; Camptothecin; Topotecan; Etoposide; WRN; DNA breaks; Apoptosis ID WERNER-SYNDROME PROTEIN; TOPOISOMERASE-I; PHOSPHODIESTERASE TDP1; COVALENT COMPLEXES; CLEAVAGE COMPLEXES; REPLICATION ARREST; MAMMALIAN-CELLS; POLYMERASE-BETA; S-PHASE; CAMPTOTHECIN AB The Werner syndrome helicase/3'-exonuclease (WRN) is a major component of the DNA repair and replication machinery. To analyze whether WRN is involved in the repair of topoisomerase-induced DNA damage we utilized U2-OS cells, in which WRN is stably down-regulated (wrn-kd), and the corresponding wild-type cells (wrn-wt). We show that cells not expressing WRN are hypersensitive to the toxic effect of the topoisomerase I inhibitor topotecan, but not to the topoisomerase II inhibitor etoposide. This was shown by mass survival assays, colony formation and induction of apoptosis. Upon topotecan treatment WRN deficient cells showed enhanced DNA replication inhibition and S-phase arrest, whereas after treatment with etoposide they showed the same cell cycle response as the wildtype. A considerable difference between WRN and wild-type cells was observed for DNA single- and double-strand break formation in response to topotecan. Topotecan induced DNA single-strand breaks 6 h after treatment. In both wrn-wt and wrn-kd cells these breaks were repaired at similar kinetics. However, in wrn-kd but not wrn-wt cells they were converted into DNA double-strand breaks (DSBs) at high frequency, as shown by neutral comet assay and phosphorylation of H2AX. Our data provide evidence that WRN is involved in the repair of topoisomerase I, but not topoisomerase II-induced DNA damage, most likely via preventing the conversion of DNA single-strand breaks into DSBs during the resolution of stalled replication forks at topo I-DNA complexes. We suggest that the WRN status of tumor cells impacts anticancer therapy with topoisomerase I, but not topoisomerase II inhibitors. (C) 2008 Elsevier B.V. All rights reserved. C1 [Christmann, Markus; Tomicic, Maja T.; Gestrich, Christopher; Roos, Wynand P.; Kaina, Bernd] Johannes Gutenberg Univ Mainz, Dept Toxicol, D-55131 Mainz, Germany. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Kaina, B (reprint author), Johannes Gutenberg Univ Mainz, Dept Toxicol, Obere Zahlbacher Str 67, D-55131 Mainz, Germany. EM kaina@uni-mainz.de RI Roos, Wynand/B-4846-2008 OI Roos, Wynand/0000-0002-0474-7414 FU Deutsche Krebshilfe [106748]; Deutsche Forschungsgemeinschaft [CH 665/2-1]; Maifor [0428000]; National Instutues on Aging, NIH FX The work was supported by Deutsche Krebshilfe 106748, Deutsche Forschungsgemeinschaft CH 665/2-1 and Maifor 0428000. This work was in part supported by the intramural Research Program of the National Instutues on Aging, NIH. NR 53 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD DEC 1 PY 2008 VL 7 IS 12 BP 1999 EP 2009 DI 10.1016/j.dnarep.2008.08.008 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 380UJ UT WOS:000261490500008 PM 18805512 ER PT J AU Ma, X Cheung, C Krausz, KW Shah, YM Wang, T Idle, JR Gonzalez, FJ AF Ma, Xiaochao Cheung, Connie Krausz, Kristopher W. Shah, Yatrik M. Wang, Ting Idle, Jeffrey R. Gonzalez, Frank J. TI A Double Transgenic Mouse Model Expressing Human Pregnane X Receptor and Cytochrome P450 3A4 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN CYP3A4 GENE; HUMAN LIVER; XENOBIOTIC RECEPTOR; PHARMACOKINETIC INTERACTION; TRANSCRIPTIONAL REGULATION; DRUG-INTERACTIONS; MICE; METABOLISM; PXR; IDENTIFICATION AB Cytochrome P450 3A4 (CYP3A4), the most abundant human cytochrome P450 in liver, participates in the metabolism of similar to 50% of clinically used drugs. The pregnane X receptor (PXR), a member of the nuclear receptor superfamily, is the major activator of CYP3A4 transcription. However, because of species differences in response to PXR ligands, it is problematic to use rodents to assess CYP3A4 regulation and function. The generation of double transgenic mice expressing human PXR and CYP3A4 (TgCYP3A4/hPXR) would provide a solution to this problem. In the current study, a TgCYP3A4/hPXR mouse model was generated by bacterial artificial chromosome transgenesis in Pxr-null mice. In TgCYP3A4/hPXR mice, CYP3A4 was strongly induced by rifampicin, a human-specific PXR ligand, but not by pregnenolone 16 alpha-carbonitrile, a rodent-specific PXR ligand. Consistent with CYP3A expression, hepatic CYP3A activity increased similar to 5-fold in TgCYP3A4/hPXR mice pretreated with rifampicin. Most antihuman immunodeficiency virus protease inhibitors are CYP3A substrates and their interactions with rifamycins are a source of major concern in patients coinfected with human immunodeficiency virus and Mycobacterium tuberculosis. By using TgCYP3A4/hPXR mice, human PXR-CYP3A4-mediated rifampicin-protease inhibitor interactions were recapitulated, as the metabolic stability of amprenavir, nelfinavir, and saquinavir decreased 52, 53, and 99%, respectively, in the liver microsomes of TgCYP3A4/hPXR mice pretreated with rifampicin. In vivo, rifampicin pretreatment resulted in an similar to 80% decrease in the area under the serum amprenavir concentration-time curve in TgCYP3A4/hPXR mice. These results suggest that the TgCYP3A4/hPXR mouse model could serve as a useful tool for studies on CYP3A4 transcription and function in vivo. C1 [Ma, Xiaochao; Cheung, Connie; Krausz, Kristopher W.; Shah, Yatrik M.; Wang, Ting; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Natl Inst Hlth, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU National Cancer Institute Intramural Research Program; U.S. Smokeless Tobacco Company FX This study was funded by the National Cancer Institute Intramural Research Program. J.R.I. is grateful to the U.S. Smokeless Tobacco Company for a grant for collaborative research. NR 37 TC 37 Z9 38 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD DEC PY 2008 VL 36 IS 12 BP 2506 EP 2512 DI 10.1124/dmd.108.022723 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 378SU UT WOS:000261345000016 PM 18799805 ER PT J AU Jabbi, M Keysers, C AF Jabbi, Mbemba Keysers, Christian TI Inferior Frontal Gyrus Activity Triggers Anterior Insula Response to Emotional Facial Expressions SO EMOTION LA English DT Article DE emotional contagion; facial mimicry; mirror neuron system; insula; interior frontal gyrus ID COMMON NEURAL BASIS; MIRROR NEURONS; SOCIAL COGNITION; ACTION RECOGNITION; POLITICAL LEADERS; GRANGER CAUSALITY; PREMOTOR CORTEX; EMPATHY; OTHERS; PAIN AB The observation of movies of facial expressions of others has been shown to recruit similar areas involved in experiencing one's own emotions: the inferior frontal gyrus (IFG). the anterior insula and adjacent frontal operculum (IFO). The Causal link bet between activity in these 2 regions, associated with motor and emotional simulation, respectively, has remained unknown. Here using psychophysiological interaction and Granger Causality Modeling, we show that activity in the IFO is causally triggered by activity in the IFG. and that this effective connectivity is specific to the IFG. These findings shed new light oil the intricate relationship between motor and affective components of emotional empathy. C1 [Keysers, Christian] Univ Groningen, BCN Neuroimaging Ctr, Univ Med Ctr Groningen, Dept Neurosci,Social Brain Lab, NL-9713 AW Groningen, Netherlands. [Jabbi, Mbemba] NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch, Genes Cognit & Psychoss Program, Bethesda, MD 20892 USA. RP Keysers, C (reprint author), Univ Groningen, BCN Neuroimaging Ctr, Univ Med Ctr Groningen, Dept Neurosci,Social Brain Lab, Antonius Deusinglaan 2, NL-9713 AW Groningen, Netherlands. EM c.m.keysers@rug.nl RI Keysers, Christian/H-6251-2013 OI Keysers, Christian/0000-0002-2845-5467 NR 59 TC 64 Z9 65 U1 3 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD DEC PY 2008 VL 8 IS 6 BP 775 EP 780 DI 10.1037/a0014194 PG 6 WC Psychology, Experimental SC Psychology GA 383MQ UT WOS:000261678100004 PM 19102588 ER PT J AU Lai, EW Perera, SM Havekes, B Timmers, HJLM Brouwers, FM McElroy, B Adams, KT Ohta, S Wesley, RA Eisenhofer, G Pacak, K AF Lai, Edwin W. Perera, Shiromi M. Havekes, Bas Timmers, Henri J. L. M. Brouwers, Frederieke M. McElroy, Beverly Adams, Karen T. Ohta, Shoichiro Wesley, Robert A. Eisenhofer, Graeme Pacak, Karel TI Gender-related differences in the clinical presentation of malignant and benign pheochromocytoma SO ENDOCRINE LA English DT Article DE Pheochromocytoma; Gender; Symptoms; Catecholamines ID CATECHOLAMINE; RESPONSES; PLASMA; NOREPINEPHRINE; PARAGANGLIOMAS; METANEPHRINES; PHENOTYPES; GENOTYPE; AGONISTS; BRAIN AB Signs and symptoms associated with pheochromocytomas are predominantly caused by catecholamine excess, but tend to be highly variable and non-specific. In this study, we evaluated 23 male and 35 female pheochromocytoma patients for symptoms and signs of pheochromocytoma with special regard to gender-related differences in presentation. Total symptom score comparison between genders showed significant differences (12.0 vs. 7.8, P-value 0.0001). Female patients reported significantly more headache (80% vs. 52%), dizziness (83% vs. 39%), anxiety (85% vs. 50%), tremor (64% vs. 33%), weight change (88% vs. 43%), numbness (57% vs. 24%), and changes in energy level (89% vs. 64%). Females and males displayed comparable biochemical phenotypes (60% and 65% noradrenergic phenotype, respectively). Use of alpha- and/or beta-blockade between males and females did not differ significantly. Subgroup analyses and multiple regression analysis revealed gender differences to be irrespective of benign or malignant disease, use of adrenoceptor-blockade, age and biochemical phenotype. We conclude female patients have significantly more self-reported pheochromocytoma signs and symptoms than male patients irrespective of biochemical phenotype and tumor presentation which may be related to distinct catecholamine receptor sensitivity. Clinicians should be aware of these complaints in female pheochromocytoma patients and offer adequate treatment if indicated. C1 [Lai, Edwin W.; Perera, Shiromi M.; Havekes, Bas; Timmers, Henri J. L. M.; Brouwers, Frederieke M.; McElroy, Beverly; Adams, Karen T.; Ohta, Shoichiro; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Havekes, Bas] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. [Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands. [Wesley, Robert A.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Eisenhofer, Graeme] Univ Dresden, Div Clin Neurochem, Dept Med, Dresden, Germany. [Eisenhofer, Graeme] Univ Dresden, Div Clin Neurochem, Dept Clin Chem, Dresden, Germany. RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bldg 10,CRC,1-Room 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU NIH, NICHD FX This research was supported ( in part) by the Intramural Research Program of the NIH, NICHD. NR 24 TC 7 Z9 8 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 2008 VL 34 IS 1-3 BP 96 EP 100 DI 10.1007/s12020-008-9108-4 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 397GG UT WOS:000262650300014 PM 18982461 ER PT J AU Timmers, HJLM Brouwers, FM Hermus, ARMM Sweep, FCGJ Verhofstad, AAJ Verbeek, ALM Pacak, K Lenders, JWM AF Timmers, H. J. L. M. Brouwers, F. M. Hermus, A. R. M. M. Sweep, F. C. G. J. Verhofstad, A. A. J. Verbeek, A. L. M. Pacak, K. Lenders, J. W. M. TI Metastases but not cardiovascular mortality reduces life expectancy following surgical resection of apparently benign pheochromocytoma SO ENDOCRINE-RELATED CANCER LA English DT Article ID FEATURES; PARAGANGLIOMAS; RECURRENCE; DIAGNOSIS; HPLC AB The treatment of choice for non-metastatic pheochromocytoma is surgical resection. Its goals are to abolish catecholamine hypersecretion, normalize blood pressure, and prevent further tumor growth or progression to metastatic disease. Data on long-term mortality and morbidity after pheochromocytoma surgery are limited. We here report a retrospective study on the long-term outcome after surgery for apparently benign pheochromocytoma at the Radboud University Nijmegen Medical Centre. Data on clinical presentation, treatment, post-surgical blood pressure and recurrence, metastasis and death were collected of 69 consecutive patients (January 1966-December 2000; follow-up: until death or January 2006). Survival was compared with survival of a matched reference population. Two patients died of surgical complications. All ten patients with metastatic disease (including three diagnosed at first surgery) died. At follow-up, 40 patients were alive and recurrence free and three patients were lost to follow up. Two patients experienced a benign recurrence. Mean +/- S.D. follow-up was 10.2 +/- 7.5 (median 9, range 1-38) years. Kaplan-Meier estimates for 5- and 10-year survival since surgery were 85.8% (95% CI: 77.2-94.4%) and 74.2% (95% CI: 62.0-86.4%) for patients versus 95.5 and 89.4% in the reference population (P<0.05). Sixty-four percent of all patients with hypertension prior to surgery showed a significant decrease in blood pressure, but remained hypertensive after surgery. In conclusion, compared with the general population patients have a reduced life expectancy following pheochromocytoma surgery, due to their risk of developing metastatic disease. Only one-third becomes normotensive without antihypertensive medication. Therefore, lifelong follow-up is warranted. C1 [Timmers, H. J. L. M.; Hermus, A. R. M. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol 741, NL-6500 HB Nijmegen, Netherlands. [Brouwers, F. M.; Lenders, J. W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. [Sweep, F. C. G. J.] Radboud Univ Nijmegen, Med Ctr, Dept Chem Endocrinol, NL-6500 HB Nijmegen, Netherlands. [Verhofstad, A. A. J.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol Epidemiol & Biostat, NL-6500 HB Nijmegen, Netherlands. [Pacak, K.] NICHHD, Dept Reprod & Adult Endocrinol Program, NIH, Bethesda, MD USA. RP Timmers, HJLM (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol 741, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM h.timmers@endo.umcn.nl RI Verbeek, A.L.M./H-8103-2014; Hermus, A.R.M.M./H-8043-2014; Sweep, C.G.J./H-8096-2014; Lenders, J.W.M./L-4487-2015 NR 21 TC 21 Z9 22 U1 0 U2 1 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD DEC PY 2008 VL 15 IS 4 BP 1127 EP 1133 DI 10.1677/ERC-08-0049 PG 7 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 396KL UT WOS:000262590500025 PM 18824558 ER PT J AU Tang, WY Newbold, R Mardilovich, K Jefferson, W Cheng, RYS Medvedovic, M Ho, SM AF Tang, Wan-Yee Newbold, Retha Mardilovich, Katerina Jefferson, Wendy Cheng, Robert Y. S. Medvedovic, Mario Ho, Shuk-Mei TI Persistent Hypomethylation in the Promoter of Nucleosomal Binding Protein 1 (Nsbp1) Correlates with Overexpression of Nsbp1 in Mouse Uteri Neonatally Exposed to Diethylstilbestrol or Genistein SO ENDOCRINOLOGY LA English DT Article ID DNA METHYLATION; BREAST-CANCER; DEVELOPMENTAL EXPOSURE; CHROMATIN FUNCTION; BISPHENOL-A; IN-UTERO; EXPRESSION; WOMEN; ADENOCARCINOMA; ABNORMALITIES AB Neonatal exposure of CD-1 mice to diethylstilbestrol (DES) or genistein (GEN) induces uterine adenocarcinoma in aging animals. Uterine carcinogenesis in this model is ovarian dependent because its evolution is blocked by prepubertal ovariectomy. This study seeks to discover novel uterine genes whose expression is altered by such early endocrine disruption via an epigenetic mechanism. Neonatal mice were treated with 1 or 1000 mu g/kg DES, 50 mg/kg GEN, or oil (control) on d 1-5. One group of treated mice was killed before puberty on d 19. Others were ovariectomized or left intact, and killed at 6 and 18 months of age. Methylation-sensitive restriction fingerprinting was performed to identify differentially methylated sequences associated with neonatal exposure to DES/GEN. Among 14 candidates, nucleosomal binding protein 1 (Nsbp1), the gene for a nucleosome-core-particle binding protein, was selected for further study because of its central role in chromatin remodeling. In uteri of immature control mice, Nsbp1 promoter CpG island (CGI) was minimally methylated. Once control mice reached puberty, the Nsbp1 CGI became hypermethylated, and gene expression declined further. In contrast, in neonatal DES/GEN-treated mice, the Nsbp1 CGI stayed anomalously hypomethylated, and the gene exhibited persistent overexpression throughout life. However, if neonatal DES/GEN-treated mice were ovariectomized before puberty, the CGI remained minimally to moderately methylated, and gene expression was subdued except in the group treated with 1000 mu g/kg DES. Thus, the life reprogramming of uterine Nsbp1 expression by neonatal DES/GEN exposure appears to be mediated by an epigenetic mechanism that interacts with ovarian hormones in adulthood. (Endocrinology 149: 5922-5931, 2008) C1 [Ho, Shuk-Mei] Univ Cincinnati, Med Ctr, Dept Environm Hlth, Sch Med, Cincinnati, OH 45267 USA. [Medvedovic, Mario; Ho, Shuk-Mei] Univ Cincinnati, Sch Med, Ctr Environm Genet, Cincinnati, OH 45267 USA. [Ho, Shuk-Mei] Univ Cincinnati, Sch Med, Ctr Canc, Cincinnati, OH 45267 USA. [Tang, Wan-Yee; Mardilovich, Katerina; Cheng, Robert Y. S.; Ho, Shuk-Mei] Univ Massachusetts, Sch Med, Dept Surg, Div Urol, Worcester, MA 01605 USA. [Newbold, Retha; Jefferson, Wendy] NIEHS, Mol Toxicol Lab, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. RP Ho, SM (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, Sch Med, Kettering Complex,Room 128,3223 Eden Ave,POB 6700, Cincinnati, OH 45267 USA. EM shuk-mei.ho@uc.edu OI Cheng, Robert/0000-0003-0287-6439 FU National Institutes of Health (NIH) [ES013071, ES006096, ES015584, ES015905, CA015776, CA112532, HG003749]; National Institute of Environmental Health Sciences; Department of Defense Prostate Cancer [W81XWH-06-1-0373] FX We thank Ping Zhou, Jennifer Barker, Monica Summe, and Carol Szeto for sample preparation.; Received May 9, 2008. Accepted July 24, 2008.; Address all correspondence and requests for reprints to: Shuk-Mei Ho, Department of Environmental Health, Kettering Complex, Room 128, 3223 Eden Avenue, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, Ohio 45267-0056. E-mail: shuk-mei.ho@uc.edu.; This research was supported by the Intramural Research Program of the National Institutes of Health (NIH)-National Institute of Environmental Health Sciences (to R.N. and W.J.), NIH Grants ES013071, ES006096, ES015584, ES015905, CA015776, and CA112532 (to S.-M. H.), and HG003749 (to M. M.), and the Department of Defense Prostate Cancer Program Grant W81XWH-06-1-0373 (to W.-Y.T.).; Present address for K. M.: Department of Cancer Biology, University of Massachusetts Medical School, 364 Plantation Street, LRB Room 426, Worcester, Massachusetts 01605.; Present address for R.Y.S.C.: National Cancer Institute at Frederick, National Institutes of Health, Building 528, Room 141, P.O. Box B, Frederick, Maryland 21702.; Disclosure Statement: The authors have nothing to disclose. NR 57 TC 99 Z9 104 U1 0 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2008 VL 149 IS 12 BP 5922 EP 5931 DI 10.1210/en.2008-0682 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 376AX UT WOS:000261156300004 PM 18669593 ER PT J AU Neumann, S Kleinau, G Costanzi, S Moore, S Jiang, JK Raaka, BM Thomas, CJ Krause, G Gershengorn, MC AF Neumann, Susanne Kleinau, Gunnar Costanzi, Stefano Moore, Susanna Jiang, Jian-kang Raaka, Bruce M. Thomas, Craig J. Krause, Gerd Gershengorn, Marvin C. TI A Low-Molecular-Weight Antagonist for the Human Thyrotropin Receptor with Therapeutic Potential for Hyperthyroidism SO ENDOCRINOLOGY LA English DT Article ID THYROID-STIMULATING HORMONE; PROTEIN-COUPLED RECEPTOR; VIRUS TYPE-1 ENTRY; CRYSTAL-STRUCTURE; DRUG DISCOVERY; LIGAND DOCKING; BINDING; RHODOPSIN; LIMITATIONS; AGONISTS AB Low-molecular-weight (LMW) antagonists for TSH receptor (TSHR) may have therapeutic potential as orally active drugs to block stimulating antibodies (TsAbs) in Graves' hyperthyroidism. We describe an approach to identify LMW ligands for TSHR based on Org41841, a LMW partial agonist for the LH/choriogonadotropin receptor and TSHR. We used molecular modeling and functional experiments to guide the chemical modification of Org41841. We identified an antagonist (NIDDK/CEB-52) that selectively inhibits activation of TSHR by both TSH and TsAbs. Whereas initially characterized in cultured cells overexpressing TSHRs, the antagonist was also active under more physiologically relevant conditions in primary cultures of human thyrocytes expressing endogenous TSHRs in which it inhibited TSH- and TsAb-induced up-regulation of mRNA transcripts for thyroperoxidase. Our results establish this LMW compound as a lead for the development of higher potency antagonists and serve as proof of principle that LMW ligands that target TSHR could serve as drugs in patients with Graves' disease. (Endocrinology 149: 5945-5950, 2008) C1 [Neumann, Susanne; Moore, Susanna; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Jiang, Jian-kang; Thomas, Craig J.] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] NIDDKD, Lab Biol Modeling, Bethesda, MD 20892 USA. [Kleinau, Gunnar; Krause, Gerd] Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany. RP Neumann, S (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Human Genome Research Institute; National Institutes of Health FX We thank Francesco Celi and Valentina Congedo for providing human thyroid tissue and Elizabeth Geras-Raaka for advice and assistance in preparing thyrocytes. We also thank John C. Morris for providing sera samples from patients with Graves' disease and Marguerite Lichay and Mudit Kaushal for technical assistance.; Received June 4, 2008. Accepted July 22, 2008.; Address all correspondence and requests for reprints to: Marvin C. Gershengorn, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892-8029. E-mail: marving@intra.niddk.nih.gov.; This work was supported by the intramural research programs of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Human Genome Research Institute, National Institutes of Health.; Disclosure Statement: The authors have nothing to disclose. NR 29 TC 42 Z9 47 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2008 VL 149 IS 12 BP 5945 EP 5950 DI 10.1210/en.2008-0836 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 376AX UT WOS:000261156300008 PM 18669595 ER PT J AU Weiss, J Bernhardt, ML Laronda, MM Hurley, LA Glidewell-Kenney, C Pillai, S Tong, M Korach, KS Jameson, JL AF Weiss, Jeffrey Bernhardt, Miranda L. Laronda, Monica M. Hurley, Lisa A. Glidewell-Kenney, Christine Pillai, Suresh Tong, Minghan Korach, Kenneth S. Jameson, J. Larry TI Estrogen Actions in the Male Reproductive System Involve Estrogen Response Element-Independent Pathways SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR-ALPHA-BINDING; BETA ER-BETA; MALE-MICE; ENDOGENOUS ESTROGENS; EFFERENT DUCTULES; LEYDIG-CELL; GENE; RAT; EXPRESSION; CLONING AB The estrogen receptor-alpha (ER alpha) acts through multiple pathways, including estrogen response element (ERE)-dependent (classical) and ERE-independent (nonclassical) mechanisms. We previously created a mouse model harboring a two-amino-acid mutation of the DNA-binding domain (E207A, G208A) that precludes direct binding of ER alpha to an ERE. After crossing heterozygous mutant mice with an ER alpha knockout (ERKO) line, it was possible to assess the degree of physiological rescue by the isolated ER alpha nonclassical allele (-/AA; AA) when compared with ERKO mice (-/-) and to wild type (+/+; WT). In male ERKO mice up to 8 months of age, testosterone levels were high, although LH levels were similar to WT. Testosterone was normal in the AA mice, indicating that the AA allele rescues the enhanced testosterone biosynthesis in ERKO mice. Male ERKO mice exhibited distention of the seminiferous tubules as early as 2-3 months of age as a consequence of decreased water resorption in the efferent ducts. By 3-4 months of age, ERKO mice had impaired spermatogenesis in approximately 40% of their tubules, and sperm counts and motility declined in association with the histological changes. In the AA mice, histological defects were greatly reduced or absent, and sperm counts and motility were rescued. Levels of aquaporins 1 and 9, which contribute to water uptake in the efferent ducts, were reduced in ERKO mice and partially or fully rescued in AA mice, whereas another water transporter, sodium-hydrogen exchanger-3, was decreased in both ERKO and AA mice. We conclude that non-ERE-dependent estrogen pathways are sufficient to rescue the defective spermatogenesis observed in ERKO mice and play a prominent role in ER alpha action in the testis, including pathways that regulate water resorption and androgen biosynthesis. ( Endocrinology 149: 6198-6206, 2008) C1 [Weiss, Jeffrey; Bernhardt, Miranda L.; Hurley, Lisa A.; Glidewell-Kenney, Christine; Pillai, Suresh; Tong, Minghan; Jameson, J. Larry] Northwestern Univ, Feinberg Sch Med, Med Deans Adm, Dept Med, Chicago, IL 60611 USA. [Korach, Kenneth S.] Natl Inst Environm Hlth Sci, Receptor Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Jameson, JL (reprint author), Northwestern Univ, Feinberg Sch Med, Med Deans Adm, Dept Med, Morton 40-656,303 E Chicago Ave, Chicago, IL 60611 USA. EM ljameson@northwestern.edu RI Laronda, Monica/F-9136-2014; OI Bernhardt, Miranda/0000-0001-5424-5685; Jameson, James/0000-0001-9538-4059; Korach, Kenneth/0000-0002-7765-418X FU National Institutes of Health/National Institute of Child Health and Human Development (NICHD) [PO1 HD21921, T32 GM008061, U54-HD28934]; University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core; Division of Intramural Research of the National Institute of Environmental Health Sciences FX This work was supported by National Institutes of Health/National Institute of Child Health and Human Development (NICHD) Grant PO1 HD21921, Training Grant T32 GM008061, NICHD (SCCPRR) Grant U54-HD28934 ( University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core), and the Division of Intramural Research of the National Institute of Environmental Health Sciences. NR 38 TC 22 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 2008 VL 149 IS 12 BP 6198 EP 6206 DI 10.1210/en.2008-0122 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 376AX UT WOS:000261156300035 PM 18719025 ER PT J AU Koujitani, T Ton, TVT Lahousse, SA Hong, HHL Wakamatsu, N Sills, RC AF Koujitani, Takatoshi Ton, Tai-Vut T. Lahousse, Stephanie A. Hong, Hue-Hua L. Wakamatsu, Nobuko Sills, Robert C. TI K-ras Cancer Gene Mutations in Lung Tumors From Female Swiss (CD-1) Mice Exposed Transplacentally to 3 '-Azido-3 '-Deoxythymidine SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE zidovudine; transplacental carcinogenesis; mouse gestation; K-ras oncogene; nucleoside reverse transcriptase inhibitor (NRTI) ID OXIDATIVE DNA-DAMAGE; TO-CHILD TRANSMISSION; ESCHERICHIA-COLI; LESIONS SPIROIMINODIHYDANTOIN; B6C3F1 MICE; CORD BLOOD; IN-UTERO; AZT; ZIDOVUDINE; NUCLEOSIDE AB A transplacental carcinogenicity study was conducted by exposing pregnant Swiss (CD-1 I mice to 0, 50, 100, 200, or 300 mg 3'-azido-3'-deoxythymidine (AZT)/kg body weight (BW) daily for the duration of gestation (18-19 days) [National Toxicology Program, 2006]. The incidence of alveolar/bronchiolar adenomas and carcinomas in the 200 and 300 mg/kg groups was significantly higher (P = 0.027 and 0.007, respectively) in male offspring, but not in females (P = 0.338 and 0.315, respectively). The purpose of the present study was to evaluate K-ras mutation status in lung tumors from the female offspring in AZT exposed groups and to determine whether at the molecular level there were signature K-ras mutations in lung tumors that were different from spontaneous tumors. K-ras mutation was detected by cycle sequencing of polymerase chain reaction (PCR)-amplified DNA, isolated from formalin-fixed, paroffin-embedded lung tumors. K-ras mutations were detected in 17 of 28 (61 %) lung tumors from the female offspring in AZT exposed groups. No K-ras mutations were detected in the 8 tumors examined from the female control group. The predominant mutations were Codon 12 G -> T transversions in the 50, 100, and 300 mg/kg groups, and Codon 12 G -> C transversions in the 200 and 300 mg/kg groups. K-ras Codon 12 G -> T transversions (TGT mutations) may be induced by oxidative DNA damage and 8-oxoguanine (8-oxoG), while K-ras Codon 12 G -> C transversions (CGT mutations) may be due to further oxidative lesions of guanine and 8-oxoG. Environ. Mol. Mutagen. 49:720726, 2008. Published 2008 Wiley-Liss, Inc. C1 [Sills, Robert C.] NIEHS, Mol Pathol Grp, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Wakamatsu, Nobuko] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. RP Sills, RC (reprint author), NIEHS, Mol Pathol Grp, Cellular & Mol Pathol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sills@nichs.nih.gov FU Intramural Research Program of the National Institute of Health; National Institute of Environmental Health Science FX Grant sponsor: Intramural Research Program of the National Institute of Health, National Institute of Environmental Health Science. NR 48 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD DEC PY 2008 VL 49 IS 9 BP 720 EP 726 DI 10.1002/em.20420 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 384EA UT WOS:000261725900006 PM 18800350 ER PT J AU Lubin, JH Moore, LE Fraumeni, JF Cantor, KA AF Lubin, Jay H. Moore, Lee E. Fraumeni, Joseph F., Jr. Cantor, Kenneth A. TI Respiratory Cancer and Inhaled Inorganic Arsenic in Copper Smelters Workers: A Linear Relationship with Cumulative Exposure that Increases with Concentration SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE arsenic; dose-response relationship; lung neoplasms; occupational diseases ID PREMALIGNANT SKIN-LESIONS; MONOMETHYLARSONOUS ACID; DRINKING-WATER; THIOREDOXIN REDUCTASE; INTERNAL CANCERS; LUNG-CANCER; HUMAN URINE; FOLLOW-UP; METHYLATION; RISK AB BACKCROUND: Inhalation of high levels of airborne inorganic arsenic is a recognized cause of respiratory cancer. Although multiple epidemiologic studies have demonstrated this association, there have been few analyses of the mathematical relationship between cumulative arsenic exposure and risk of respiratory cancer, and no assessment as to whether and how arsenic concentration may modify this association. OBJECTIVES: The objective is an evaluation of the shape of the relationship between respiratory cancer mortality and cumulative inhaled arsenic exposure among copper smelter workers, and the modification of that relationship by arsenic concentration. METHODS: We used Poisson regression methods to analyze data from a cohort of arsenic-exposed copper smelter workers under a linear-exponential model for the excess relative risk. RESULTS: Within categories of arsenic concentration, the association between respiratory cancer and cumulative arsenic exposure was consistent with linearity. The slope of the linear relationship with cumulative exposure increased with increasing arsenic concentration category. CONCLUSIONS: Our results suggested a direct concentration effect from inhaled inorganic arsenic, whereby the excess relative risk for a fixed cumulative exposure was greater when delivered at a higher concentration and shorter duration than when delivered at a lower concentration and longer duration. C1 [Lubin, Jay H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Moore, Lee E.; Cantor, Kenneth A.] Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Fraumeni, Joseph F., Jr.] NCI, Off Director, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8042, Rockville, MD 20852 USA. EM lubinj@mail.nih.gov FU National Cancer institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer institute, National Institutes of Health. NR 46 TC 41 Z9 41 U1 0 U2 14 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 DEC PY 2008 VL 116 IS 12 BP 1661 EP 1665 DI 10.1289/ehp.11515 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 377ZG UT WOS:000261290300028 PM 19079717 ER PT J AU Beseler, CL Stallones, L Hoppin, JA Alavanja, MCR Blair, A Keefe, T Kamel, F AF Beseler, Cheryl L. Stallones, Lorann Hoppin, Jane A. Alavanja, Michael C. R. Blair, Aaron Keefe, Thomas Kamel, Freya TI Depression and Pesticide Exposures among Private Pesticide Applicators Enrolled in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cumulative exposure; depression; farm applicators; pesticides; pesticide poisoning ID CHRONIC NEUROLOGICAL SEQUELAE; ORGANOPHOSPHATE PESTICIDES; PON1 POLYMORPHISMS; GENDER DIFFERENCES; MAJOR DEPRESSION; FARM RESIDENTS; SHEEP DIP; SYMPTOMS; COHORT; NEUROTOXICITY AB BACKGROUND: We evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina. METHODS: There were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226-752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression. RESULTS: After adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74-3.79] than intermediate (OR = 1.07; 95% CI, 0.87-1.31) or high (OR = 1.11; 95% CI, 0.87-1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33-2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16-2.04). CONCLUSION: These findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute,to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning. C1 [Beseler, Cheryl L.] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Epidemiol, Omaha, NE 68198 USA. [Beseler, Cheryl L.; Stallones, Lorann] Colorado State Univ, Dept Psychol, Colorado Injury Control Res Ctr, Ft Collins, CO 80523 USA. [Beseler, Cheryl L.] Univ Nebraska Med Ctr, Dept Environm Agr & Occupat Hlth, Omaha, NE 68198 USA. [Hoppin, Jane A.; Kamel, Freya] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Alavanja, Michael C. R.; Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Keefe, Thomas] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. RP Beseler, CL (reprint author), Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Epidemiol, 984395 UNMC, Omaha, NE 68198 USA. EM cbeseler@unmc.edu OI Kamel, Freya/0000-0001-5052-6615 FU National Institutes of Health (NIH) Intramural Research Program FX This research was supported in part by the National Institutes of Health (NIH) Intramural Research Program (Division of Cancer Epidemiology and Genetics, National Cancer Institute, and the National Institute of Environmental Health Sciences). NR 40 TC 52 Z9 54 U1 5 U2 22 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 DEC PY 2008 VL 116 IS 12 BP 1713 EP 1719 DI 10.1289/ehp.11091 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 377ZG UT WOS:000261290300036 PM 19079725 ER PT J AU Huff, J Jacobson, MF Davis, DL AF Huff, James Jacobson, Michael F. Davis, Devra Lee TI Longer Rodent Bioassay: Huff et al. Respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID EXPOSURE C1 [Huff, James] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Jacobson, Michael F.] Ctr Sci Publ Interest, Washington, DC USA. [Davis, Devra Lee] Univ Pittsburgh, Inst Canc, Dept Epidemiol, Ctr Environm Oncol,Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM huff1@niehs.nih.gov NR 7 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 116 IS 12 BP A517 EP A518 DI 10.1289/ehp.11964R PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 377ZG UT WOS:000261290300004 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Sorting out the mix in microbial genomics SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID CELL-LINE K562; SP-NOV; GEN. NOV.; THERMOBACTEROIDES-PROTEOLYTICUS; ACIDITHIOBACILLUS-FERROOXIDANS; LEPTOSPIRILLUM-FERROOXIDANS; PHENYLOBACTERIUM-ZUCINEUM; DICTYOGLOMUS-THERMOPHILUM; BACTERIAL PHYLUM; SEQUENCE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU NIH; National Library of Medicine FX M.Y.G. is supported by the Intramural Research Program of the NIH, National Library of Medicine. The author's opinions do not reflect the views of NCBI, NLM or the National Institutes of Health. NR 40 TC 4 Z9 4 U1 0 U2 4 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 DEC PY 2008 VL 10 IS 12 BP 3187 EP 3192 DI 10.1111/j.1462-2920.2008.01811.x PG 6 WC Microbiology SC Microbiology GA 370EF UT WOS:000260744800001 PM 19025554 ER PT J AU Lim, YM Cho, YW Shamim, S Solomon, J Birn, R Luh, WM Gaillard, WD Ritzl, EK Theodore, WH AF Lim, Young-Min Cho, Yong-Won Shamim, Sadat Solomon, Jeffrey Birn, Rasmus Luh, Wen Ming Gaillard, William D. Ritzl, Eva K. Theodore, William H. TI Usefulness of pulsed arterial spin labeling MR imaging in mesial temporal lobe epilepsy SO EPILEPSY RESEARCH LA English DT Article DE Arterial spin labeling; Magnetic resonance imaging; Cerebral blood flow; Temporal lobe epilepsy; H(2) (15)O PET ID CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE; RELATIVE CONTRIBUTIONS; QUANTIFYING CBF; QUIPSS II; ICTAL EEG; PERFUSION; BRAIN; PET AB Purpose: Arterial spin labeling (ASL) is a developing magnetic resonance imaging (MRI) method for noninvasive measurement of cerebral blood flow (CBF). The purpose of this study was to evaluate the usefulness of ASL for detecting interictal temporal hypoperfusion in temporal lobe epilepsy (TLE). ASL-derived CBF measurements were compared with those derived from H(2) (15)O positron emission tomography (PET). Methods: 11 normal controls and 10 patients with medically intractable TLE were studied. Pulsed ASIL (PASL) with quantitative imaging of perfusion using a single subtraction, second version (QUIPSS II) was performed in all subjects and H(2) (15)O PET was performed in patients. Regional CBF values in the mesial and lateral temporal lobes were measured utilizing quantitative analysis of perfusion images. A perfusion asymmetry index (AI) was calculated for each region. Results: In patients, mean CBF in the mesial temporal lobe was not significantly different between PASL and H(2) (15)O PET, and ipsilateral mesial temporal CBF was tower than contralateral. CBF with both techniques. PASL detected significant mesial temporal perfusion asymmetry agreeing with EEG laterality in four patients. H(2) (15)O PET found ipsitateral interictal hypoperfusion in three. Both scans found unilateral hypoperfusion in one patient with bilateral EEG discharges. Conclusions: Pulsed ASIL may be a promising approach to detecting interictal hypoperfusion in TLE. This method has potential as a clinical alternative to H(2) (15)O PET due to noninvasiveness and easy accessibility. (C) 2008 Published by Elsevier B.V. C1 [Lim, Young-Min; Cho, Yong-Won; Shamim, Sadat; Gaillard, William D.; Ritzl, Eva K.; Theodore, William H.] NINDS, Clin Epidemiol Sect, NIH, Bethesda, MD 20892 USA. [Solomon, Jeffrey] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Birn, Rasmus] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Luh, Wen Ming] NIMH, OFC DIR, NIH, Bethesda, MD 20892 USA. RP Lim, YM (reprint author), NINDS, Clin Epidemiol Sect, NIH, Bldg 10,Room 5N-258, Bethesda, MD 20892 USA. EM timy@ninds.nih.gov FU Intramural NIH HHS [Z01 NS002236-32] NR 45 TC 34 Z9 47 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD DEC PY 2008 VL 82 IS 2-3 BP 183 EP 189 DI 10.1016/j.eplepsyres.2008.08.001 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 387HF UT WOS:000261941600010 PM 19041041 ER PT J AU Covey, LS Botello-Harbaum, M Glassman, AH Masmela, J LoDuca, C Salzman, V Fried, J AF Covey, Lirio S. Botello-Harbaum, Maria Glassman, Alexander H. Masmela, Jenny LoDuca, Catherine Salzman, Victoria Fried, Jane TI SMOKERS' RESPONSE TO COMBINATION BUPROPION, NICOTINE PATCH, AND COUNSELING TREATMENT BY RACE/ETHNICITY SO ETHNICITY & DISEASE LA English DT Article DE Tobacco Dependence; Smoking Cessation; Race/Ethnicity; Bupropion; Nicotine Patch; Nicotine Replacement Therapy ID FAGERSTROM TOLERANCE QUESTIONNAIRE; SMOKING-CESSATION; CLINICAL-TRIALS; DETERMINANTS; PREDICTORS; DEPENDENCE; EFFICACY; BEHAVIOR; HISTORY; GENDER AB Background: Evidence on how to tailor nicotine dependence treatment to specific race/ethnic groups is limited. The present study investigated responses to established smoking cessation treatments among African American, Hispanic, and White adults. Methods: Participants were 559 smokers (1126 African American, 73 Hispanic, and 360 White). All received treatment for eight weeks with open-label bupropion, the nicotine patch, and individual counseling. The dependent variable was tobacco abstinence during the last four weeks of treatment. The independent variables were race/ethnicity and other known predictors of abstinence, including sex, age, smoking history (nicotine dependence level, number of cigarettes smoked daily, serum cotinine level and expired carbon monoxide, number of past quit attempts, and age when daily smoking began), confidence in ability to stop smoking, body mass index, psychological status, and psychiatric history (past major depression and alcohol dependence). Results: The total proportion of abstainers in the sample was 53%, with proportional differences by race/ethnicity (Whites 60%, African Americans 38%, Hispanics 41%). Compared to Whites, the odds ratios (OR) for quitting, adjusted for moderators of race/ethnicity and other predictors of abstinence, were significantly lower among African Americans (OR .44, 95% confidence interval [95% Cl] .27-.72) and Hispanics (OR .46, 95% Cl .26-.81). Conclusion: Disparity in smoking cessation treatment outcome among African American and Hispanic smokers compared to Whites implies that the burden of tobacco-related illness will continue to fall disproportionately among minority racial/ethnic groups. Gaining knowledge on the effectiveness of nicotine dependence treatments and on the factors that facilitate or impede a successful response by minority smokers is a public health priority. (Ethn Dis. 2008;18:59-64) C1 [Covey, Lirio S.; Glassman, Alexander H.; Masmela, Jenny; LoDuca, Catherine; Salzman, Victoria; Fried, Jane] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Covey, Lirio S.; Glassman, Alexander H.; Fried, Jane] Columbia Univ, Med Ctr, New York, NY USA. [Botello-Harbaum, Maria] NICHHD, Washington, DC USA. RP Covey, LS (reprint author), 1051 Riverside Dr, New York, NY 10032 USA. EM lsc3@columbia.edu FU National Institute on Drug Abuse (NIDA) [R01 13490] FX Supported by the National Institute on Drug Abuse (NIDA), R01 #13490 (Covey). Medications provided by GlaxoSmithKline, Inc. A NIDA Minority Researcher Supplement and the Intramural Research Program of the National Institute of Child Health and Human Development supported Dr. Botello-Harbaum's participation in this research. NR 35 TC 29 Z9 29 U1 9 U2 17 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2008 VL 18 IS 1 BP 59 EP 64 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 489MA UT WOS:000269423000011 PM 18447101 ER PT J AU Simon, R AF Simon, Richard TI Lost in translation: Problems and pitfalls in translating laboratory observations to clinical utility SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Breast ID NEGATIVE BREAST-CANCER; DNA MICROARRAY DATA; ERROR ESTIMATION; TRIAL DESIGN; GENE; VALIDATION; PREDICTION; SELECTION; CLASSIFICATION; RECURRENCE AB Developments in whole genome biotechnology have dramatically increased the opportunities for developing more effective therapeutics and for targeting them to patients who require them and who can benefit from them. This can have profound benefits for patients and for the economics of health care. There are, however, many obstacles to overcome in achieving this revolution. The effectiveness of translational research in oncology is seriously limited by many factors, both structural and scientific. Some of the obstacles involve the failure of biomedical organisations to develop and fund new models of inter-disciplinary collaboration needed to attract and support the best and brightest quantitative scientists to predictive medicine. Many of the challenges are scientific, requiring paradigm changes in the way drugs are developed and in the way clinical trials are designed and analysed. Some of these issues are addressed here, specifically in the context of developing molecular diagnostics in a manner that moves retrospective correlative science to prospective predictive medicine. Published by Elsevier Ltd. C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Div Canc Treatment & Diag, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 39 TC 33 Z9 36 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 2008 VL 44 IS 18 BP 2707 EP 2713 DI 10.1016/j.ejca.2008.09.009 PG 7 WC Oncology SC Oncology GA 387HC UT WOS:000261941300002 PM 18977655 ER PT J AU Kushnir-Sukhov, NM Brittain, E Scott, L Metcalfe, DD AF Kushnir-Sukhov, N. M. Brittain, E. Scott, L. Metcalfe, D. D. TI Clinical correlates of blood serotonin levels in patients with mastocytosis SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE 5HT; mast cells; mastocytosis; platelets; serotonin; tryptase ID IRRITABLE-BOWEL-SYNDROME; SYSTEMIC MASTOCYTOSIS; CARCINOID DISEASE; DOUBLE-BLIND; WHOLE-BLOOD; PLASMA; MECHANISMS; CELLS; 5-HT; ACID AB Mastocytosis is a clonal disorder associated with an increased mast cell burden. We have recently demonstrated the ability of human mast cells to express and be activated through multiple serotonin receptors; to synthesize and release serotonin; and that mastocytosis patients may have abnormal serotonin levels. As serotonin has been implicated in the genesis of clinical symptoms found in association with some chronic diseases, we have now determined the whole blood serotonin levels in 29 patients diagnosed with mastocytosis, and correlated these levels with multiple clinical and laboratory parameters. Patients with mastocytosis were categorized according to disease variant. Blood serotonin values were determined and correlated with values reported for normal subjects; and clinical and laboratory features of the disease. Total blood serotonin levels followed a bimodal distribution in line with our earlier report,unlike the normal distribution reported for normal individuals. Serotonin levels did not correlate with platelet numbers, liver function tests or serum tryptase levels. Patients with lower serotonin values had greater rates of fatigue (P = 0.0001), migraine headaches (P = 0.0028), psychiatric symptoms (P = 0.0001), diarrhoea (P = 0.0407), flushing (0.0085), and abdominal and bone pain (P = 0.0001). Our study suggests that low blood serotonin levels help define a sub-group of patients with mastocytosis that are more likely to present with neurological and gastrointestinal complaints, and suggests that the use of pharmacologic agents that alter blood serotonin levels could be explored in selected patients. Eur J Clin Invest 2008; 38 (12): 953-958. C1 [Kushnir-Sukhov, N. M.; Scott, L.; Metcalfe, D. D.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA. [Brittain, E.] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, NIH, Lab Allerg Dis, Bldg 10,Room 11C207,MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov FU Division of Intramural Research; Division of Clinical Research; Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA FX This study was funded by the Division of Intramural Research and the Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. NR 28 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD DEC PY 2008 VL 38 IS 12 BP 953 EP 958 DI 10.1111/j.1365-2362.2008.02047.x PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 375GT UT WOS:000261102800011 PM 19021721 ER PT J AU Levin, D DiPaolo, RJ Brinster, C Revilleza, MJR Boyd, LF Teyton, L Natarajan, K Mage, MG Shevach, EM Margulies, DH AF Levin, Ditza DiPaolo, Richard J. Brinster, Carine Revilleza, Maria Jamela R. Boyd, Lisa F. Teyton, Luc Natarajan, Kannan Mage, Michael G. Shevach, Ethan M. Margulies, David H. TI Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Antigen presentation/processing; Autoimmunity; TCR; Tg/knockout mice ID INHIBITOR BINDING-SITES; COMPLEX CLASS-II; MHC CLASS-II; PEPTIDE COMPLEXES; TRANSGENIC MICE; FUNCTIONAL AVIDITY; KINETIC STABILITY; ANTIGENIC PEPTIDE; DENDRITIC CELLS; H+/K+-ATPASE AB We examined TCR:MHC/peptide interactions and in vivo epitope availability to explore the Th1- or Th2-like phenotype of autoimmune disease in two TCR Tg mouse models of autoimmune gastritis (AIG). The TCR of strains A23 and A51 recognize distinct IA(d)-restricted peptides from the gastric parietal cell H/K-ATPase. Both peptides form extremely stable MHC/peptide (MHC/p) complexes. All A23 animals develop a Th1-like aggressive, inflammatory AIG early in life, while A51 mice develop indolent Th2-like AIG at 6-8wk with incomplete penetrance. A51 T cells were more sensitive than A23 to low doses of soluble antigen and to MHC/p complexes. Staining with IA(d)/peptide tetramers was only detectable on previously activated T cells from A51. Thus, despite inducing a milder AIG, the A51 TCR displays a higher avidity for its cognate IA(d)/peptide. Nonetheless, in vivo proliferation of adoptively transferred A51 CFSE-labeled T cells in the gastric lymph node was relatively poor compared with A23 T cells. Also, DC from WT gastric lymph node, presenting processed antigen available in vivo, stimulated proliferation of A23 T cells better than A51. Thus, the autoimmune potential of these TCR in their respective Tg lines is strongly influenced by the availability of the peptide epitope, rather than by differential avidity for their respective MHC/p complexes. C1 [Levin, Ditza; Revilleza, Maria Jamela R.; Boyd, Lisa F.; Natarajan, Kannan; Mage, Michael G.; Margulies, David H.] Natl Inst Allergy & Infect Dis, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD USA. [Levin, Ditza] Ort Braude Coll, Dept Biotechnol Engn, Karmiel, Israel. [DiPaolo, Richard J.; Brinster, Carine; Shevach, Ethan M.] Natl Inst Allergy & Infect Dis, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD USA. [Teyton, Luc] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Margulies, DH (reprint author), Natl Inst Allergy & Infect Dis, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD USA. EM dhm@nih.gov RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID, National Institutes of Health, Bethesda, MD [NKS5037] FX This work was supported by the Intramural Research Program of the NIAID, National Institutes of Health, Bethesda, MD and by NIH grant NKS5037 to L. Teyton. We thank Alan Cheever for evaluation of pathological specimens. NR 47 TC 3 Z9 3 U1 1 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2008 VL 38 IS 12 BP 3339 EP 3353 DI 10.1002/eji.200838584 PG 15 WC Immunology SC Immunology GA 387GY UT WOS:000261940900011 PM 19039784 ER PT J AU Gruber, SG Luciani, MG Grundtner, P Zdanov, A Gasche, C AF Gruber, Sabine G. Luciani, Maria Gloria Grundtner, Paul Zdanov, Alexander Gasche, Christoph TI Differential signaling of cmvIL-10 through common variants of the IL-10 receptor 1 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cmvIL-10; IL-10; IL-10 receptor 1; Single-nucleotide polymorphism ID INTERLEUKIN-10 RECEPTOR; CRYSTAL-STRUCTURE; PHOSPHATIDYLINOSITOL 3-KINASE; CYTOMEGALOVIRUS-INFECTION; CHRONIC ENTEROCOLITIS; CYTOKINE SYNTHESIS; G330R ALLELE; COMPLEX; HOMOLOG; BINDING AB Human IL-10 (hIL-10) signaling is mediated by receptors consisting of two subunits, IL-10 receptor I (IL-10R1) and IL-10 receptor 2. Two common variants of the IL-10R1 (Ser 138 Gly (single-nucleotide polymorphism 3, SNP3) and Gly 330 Arg (SNP4)) are associated with diverse disease phenotypes. Viral homologs to hIL-10, such as cmvIL-10, utilize the same IL-10 receptor complex as part of viral immune evasion strategies. For the present study we hypothesized that IL-10R1 variants alter the ability of viral IL-10 to utilize the IL-10R1 signaling pathway. HeLa cell clones expressing different IL-10R1 haplotypes (WT or any variant) were incubated with hIL-10 or cmvIL-10. In cells expressing IL-10R1-WT, cmvIL-10 (both non-glycosylated- and HeLa-expressed) resulted in equal or slightly stronger STAT3 phosphorylation compared with hIL-10. In clones expressing IL-10R1-SNP3, IL-10R1-SNP4 or IL-10R1-SNP3+4, the cmvIL-10 showed significantly less STAT3 phosphorylation, especially when HeLa-expressed cytokines were used. Time course experiments demonstrated a slower kinetic of cmvIL-10 STAT3 activation through the variant IL-10R1. Similarly, IL-10R1 variants decreased the cmvIL-10-induced SOCS3 and signaling lymphocytic activation molecule mRNA expression. These data suggest that the IL-10R1 variants differentially reduce the signaling activity of cmvIL-10 and thereby may affect CMV's ability to escape from the host's immune surveillance. C1 [Gruber, Sabine G.; Luciani, Maria Gloria; Grundtner, Paul; Gasche, Christoph] Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Med, Vienna, Austria. [Zdanov, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Gasche, C (reprint author), Med Univ Vienna, Div Gastroenterol & Hepatol, Dept Med, Vienna, Austria. EM christoph.gasche@meduniwien.ac.at RI Gasche, Christoph/A-5139-2013 FU Austrian Science Fund [1317943]; OeNB Anniversary Fund [OeNB10543] FX The authors are grateful to Sergei Kotenko, UMDNJ-New Jersey Medical School, NJ, USA for plasmids encoding cmvIL-10 and Christoph Campregher for technical assistance with flow cytometry. The study has been supported by the Austrian Science Fund (1317943) and the OeNB Anniversary Fund (OeNB10543). NR 46 TC 18 Z9 18 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 2008 VL 38 IS 12 BP 3365 EP 3375 DI 10.1002/eji.200837718 PG 11 WC Immunology SC Immunology GA 387GY UT WOS:000261940900013 PM 19016528 ER PT J AU Ragavendran, JV Sriram, D Kotapati, S Stables, J Yogeeswari, P AF Ragavendran, Jegadeesan Vaigunda Sriram, Dharmarajan Kotapati, Srikanth Stables, James Yogeeswari, Perumal TI Newer GABA derivatives for the treatment of epilepsy including febrile seizures: A bioisosteric approach SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Thiosemicarbazones; Anticonvulsants; GABA; Pentylenetetrazole; Picrotoxin; Strychnine; Febrile seizures ID ANTIEPILEPTIC DRUG DEVELOPMENT; ANTICONVULSANT; PHARMACOPHORE AB The present study aims at design and synthesis of newer gamma-aminobutyric acid (GABA) derivatives with the combination of thiosemicarbazone and GABA pharmacophores in order to develop newer anticonvulsants. The reported compounds were designed as bioisostefic analogues of GABA semicarbazones. The structures of the synthesized compounds were confirmed by the use of their spectral data besides elemental analysis. Initial anticonvulsant screening was performed using intraperitoneal (i.p.) maximal electroshock-induced seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and subcutaneous picrotoxin (scPIC)-induced seizure threshold tests. A model involving 22-day old rat pups was also employed to further screen the effects of the test compounds against hyperthermia-induced febrile seizures. Only compounds I and II were found to be active in the MES test. Most of the compounds were found to be effective in the scPIC and febrile seizure models and very few compounds showed protection in scPTZ and scSTY models. This is the first report on these new GABA derivatives effective in the treatment of febrile seizures. (C) 2008 Published by Elsevier Masson SAS. C1 [Ragavendran, Jegadeesan Vaigunda; Sriram, Dharmarajan; Kotapati, Srikanth; Yogeeswari, Perumal] Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. [Stables, James] NIH, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Pharm Grp, Med Chem Res Lab, Pilani 333031, Rajasthan, India. EM pyogee@bits-pilani.ac.in NR 23 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD DEC PY 2008 VL 43 IS 12 BP 2650 EP 2655 DI 10.1016/j.ejmech.2008.01.036 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 387XD UT WOS:000261984000003 PM 18403060 ER PT J AU Matsuhashi, M Hallett, M AF Matsuhashi, Masao Hallett, Mark TI The timing of the conscious intention to move SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE electroencephalography; free will; neurophysiology; point of no return; readiness potential ID SIMPLE REACTION-TIME; VOLUNTARY ACTION; BRAIN; TASK; PROBABILITY; AWARENESS; EVENTS; ONSET; WILL AB The foundation of modern neuroscience and psychology about intention for action was laid by B. Libet et al. [(1983) Brain106, 623-642]. They reported the time of awareness of wanting to move to be about 0.2 s before voluntary movement onset. However, despite repeated confirmation of the result, their method has been criticised for its dependence on self-reported timing and subjective memory, and the interpretation has been widely debated without general consensus. Here, we show that the mean time of the conscious intention to move was 1.42 s before movement, estimated based on the subject's real-time decision of whether or not there was a thought to move when a tone occurred. This event is after the onset of the bereitschaftspotential, an electroencephalographic activity preceding voluntary movement, but about 1 s earlier than the timing of intention reported previously based on the subject's recall. Our result solves some problems of the conventional method, thus giving a clearer answer to the controversies. The difference between the conventional result and our result suggests that the perception of intention rises through multiple levels of awareness, starting just after the brain initiates movement. C1 [Matsuhashi, Masao; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, 10 Ctr Dr,Bldg 10 Room 5N226, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU NIH; National Institute of Neurological Disorders and Stroke FX We thank D. M. Eagleman ( Baylor College of Medicine), A. R. Mele ( Florida State University), P. Strick ( University of Pittsburgh) and D. M. Wegner ( Harvard University) for discussion and advice for the study; S. Pirio Richardson for discussion and critically reviewing the manuscript; N. Jeffries for advice and veri. cation in statistical analysis; and S. Vorbach for technical assistance. This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 37 TC 50 Z9 50 U1 5 U2 21 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2008 VL 28 IS 11 BP 2344 EP 2351 DI 10.1111/j.1460-9568.2008.06525.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 376LJ UT WOS:000261184800019 PM 19046374 ER PT J AU Trageser, JC Monosov, IE Zhou, YF Thompson, KG AF Trageser, Jason C. Monosov, Ilya E. Zhou, Yifeng Thompson, Kirk G. TI A perceptual representation in the frontal eye field during covert visual search that is more reliable than the behavioral report SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE decision; Macaca mulatta; perception; physiology; vision ID LATERAL INTRAPARIETAL AREA; DEVELOPING OCULOMOTOR COMMANDS; SACCADE TARGET SELECTION; SUPERIOR COLLICULUS; SPATIAL ATTENTION; 2-CHOICE DECISIONS; NEURONAL-ACTIVITY; PROCESSING STAGES; NEURAL SELECTION; PREMOTOR CORTEX AB Neuronal activity in the frontal eye field (FEF) identifies locations of behaviorally important objects for guiding attention and eye movements. We recorded neural activity in the FEF of monkeys trained to manually turn a lever towards the location of a pop-out target of a visual search array without shifting gaze. We examined whether the reliability of the neural representation of the salient target location predicted the monkeys' accuracy of reporting target location. We found that FEF neurons reliably encoded the location of the target stimulus not only on correct trials but also on error trials. The representation of target location in FEF persisted until the manual behavioral report but did not increase in magnitude. This result suggests that, in the absence of an eye movement report, FEF encodes the perceptual information necessary to perform the task but does not accumulate this sensory evidence towards a perceptual decision threshold. These results provide physiological evidence that, under certain circumstances, accurate perceptual representations do not always lead to accurate behavioral reports and that variability in processes outside of perception must be considered to account for the variability in perceptual choice behavior. C1 [Trageser, Jason C.; Monosov, Ilya E.; Thompson, Kirk G.] NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. [Monosov, Ilya E.] Brown Dept Neurosci, Brown NIH Grad Partnership Program, Providence, RI USA. [Zhou, Yifeng] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China. RP Thompson, KG (reprint author), NEI, NIH, Sensorimotor Res Lab, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM kgt@nci.nih.gov FU NIH, National Eye Institute FX This work was supported by the Intramural Research Program of the NIH, National Eye Institute. We thank E. Yomtovian for help with the experiments and J. D. Schall, P. Pouget, G. Woodman and Asaf Keller for helpful discussions and valuable comments. NR 47 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2008 VL 28 IS 12 BP 2542 EP 2549 DI 10.1111/j.1460-9568.2008.06530.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 382SN UT WOS:000261625800020 PM 19032593 ER PT J AU Jesus, AA Oliveira, JB Aksentijevich, I Fujihira, E Carneiro-Sampaio, MMS Duarte, AJS Silva, CAA AF Jesus, Adriana A. Oliveira, Joao B. Aksentijevich, Ivona Fujihira, Eirka Carneiro-Sampaio, Magda M. S. Duarte, Alberto J. S. Silva, Clovis A. A. TI TNF receptor-associated periodic syndrome (TRAPS): Description of a novel TNFRSF1A mutation and response to etanercept SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Periodic fever; TNF-receptor; Hibernian fever; Mutation; TNFRSF1A ID HEREDITARY AUTOINFLAMMATORY SYNDROMES; PATHOGENESIS; FEVER; FAMILY AB TRAPS is the most common of the autosomal dominant periodic fever syndromes. It is caused by mutations in the TNFRSF1A gene, which encodes for the type 1 TNF-receptor (TNFR1). We describe here a Brazilian patient with TRAPS associated to a novel TNFRSF1A de novo mutation and the response to anti-TNF therapy. The patient is a 9-year-old girl with recurrent fevers since the age of 3 years, usually lasting 3 to 7 days, and recurring every other week. These episodes are associated with mild abdominal pain, nausea, vomiting and generalized myalgia. Recurrent conjunctivitis and erysipela-like skin lesions in the lower limbs also occur. Laboratory studies show persistent normocytic normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein. IgD levels are normal. Mutational screening of TNFRSF1A revealed the association of a novel C30F mutation with the common R92Q low-penetrance mutation. The R92Q mutation is seen in 5% of the general population and is associated with an atypical inflammatory phenotype. The patient had a very good response to etanercept, with cessation of fever and normalization of inflammatory markers. Our report expands the spectrum of TNFRSF1A mutations associated with TRAPS, adding further evidence for possible additive effects of a low-penetration R92Q and cysteine residue mutations, and confirms etanercept as an efficacious treatment alternative. C1 [Jesus, Adriana A.; Silva, Clovis A. A.] Univ Sao Paulo, Dept Pediat, Pediat Rheumatol Unit, BR-05403900 Sao Paulo, Brazil. [Oliveira, Joao B.; Fujihira, Eirka; Duarte, Alberto J. S.] Univ Sao Paulo, LIM 56, Mol Immunol & Genet Sect, BR-05403000 Sao Paulo, Brazil. [Aksentijevich, Ivona] NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. RP Oliveira, JB (reprint author), Univ Sao Paulo, Dept Pediat, Pediat Rheumatol Unit, Av Dr Eneas Carvalho Aguiar 647, BR-05403900 Sao Paulo, Brazil. EM oliveirajb@lim56.fm.usp.br RI Duarte, Alberto/D-4382-2012; OI Oliveira, Joao/0000-0001-9388-8173 NR 18 TC 27 Z9 27 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 EI 1432-1076 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD DEC PY 2008 VL 167 IS 12 BP 1421 EP 1425 DI 10.1007/s00431-008-0685-2 PG 5 WC Pediatrics SC Pediatrics GA 362FD UT WOS:000260182700011 PM 18408954 ER PT J AU Acri, JB AF Acri, Jane B. TI Introduction to a Symposium on Recent Advances in the Development of Medications for Drug Abuse Treatment in Honor of Jack H. Mendelson, MD SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID MAGNETIC-RESONANCE SPECTROSCOPY; OPERANT ANALYSIS; MOOD STATES; ALCOHOL; BUPRENORPHINE; BRAIN C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. RP Acri, JB (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, 6001 Execut Blvd,Rm 4123,MSC 9551, Bethesda, MD 20892 USA. EM jacri@nih.gov NR 30 TC 0 Z9 0 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD DEC PY 2008 VL 16 IS 6 BP 443 EP 445 DI 10.1037/a0014102 PG 3 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 384CN UT WOS:000261722000001 PM 19086765 ER PT J AU Rothman, RB Blough, BE Baumann, MH AF Rothman, Richard B. Blough, Bruce E. Baumann, Michael H. TI Dual Dopamine/Serotonin Releasers: Potential Treatment Agents for Stimulant Addiction SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Recent Advances in Medications Development for Drug Abuse Treatment CY AUG 14, 2008 CL Boston, MA SP Amer Psychol Assoc, Div 28 & Div 50 DE alcohol; amphetamine; cocaine; dopamine; serotonin; transporter ID PRIMARY PULMONARY-HYPERTENSION; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE-CELLS; SEROTONIN TRANSPORTER INHIBITORS; PROGRESSIVE-RATIO SCHEDULE; INDUCED LOCOMOTOR-ACTIVITY; COCAINE-SEEKING BEHAVIOR; D-AMPHETAMINE TREATMENT; VALVULAR HEART-DISEASE; VENTRAL TEGMENTAL AREA AB "Agonist therapy" for cocaine and methamphetamine addiction involves administration of stimulant-like medications (e.g., monoamine releasers) to reduce withdrawal symptoms and prevent relapse. A significant problem with this strategy is that many candidate medications possess abuse liability because of activation of mesolimbic dopamine (DA) neurons in the brain. One way to reduce DA-mediated abuse liability of candidate drugs is to add in serotonin (5-HT) releasing properties, since substantial evidence shows that 5-HT neurons provide an inhibitory influence over mesolimbic DA neurons. This article addresses several key issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, the authors briefly summarize the evidence supporting a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Second, the authors discuss data demonstrating that 5HT release can dampen DA-mediated stimulant effects, and the "antistimulant" role of 5-HT(2C) receptors is considered. Next, the mechanisms underlying potential adverse effects of 5-HT releasers are described. Finally, the authors discuss recently published data with PAL-287, a novel nonamphetamine DA/5-HT releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers could be useful therapeutic adjuncts for the treatment of cocaine and alcohol addictions, as well as for obesity, attention-deficit disorder, and depression. C1 [Rothman, Richard B.; Baumann, Michael H.] NIDA, Clin Psychopharmacol Sect, IRP, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Blough, Bruce E.] Res Triangle Inst Int, Chem & Life Sci Grp, Res Triangle Pk, NC USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH,Dept Hlth & Human Serv, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS [Z01 DA000119-16]; NIDA NIH HHS [R01 DA012970, R01 DA012970-08, R01 DA12970] NR 174 TC 36 Z9 39 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD DEC PY 2008 VL 16 IS 6 BP 458 EP 474 DI 10.1037/a0014103 PG 17 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 384CN UT WOS:000261722000003 PM 19086767 ER PT J AU Vocci, FJ AF Vocci, Frank J. TI Cognitive Remediation in the Treatment of Stimulant Abuse Disorders: A Research Agenda SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Recent Advances in Medications Development for Drug Abuse Treatment CY AUG 14, 2008 CL Boston, MA SP Amer Psychol Assoc, Div 28 & Div 50 DE cognitive remediation; risky decision making; impulsivity ID MEDIAL PREFRONTAL CORTEX; REACTION-TIME-TASK; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; STOP-SIGNAL INHIBITION; IOWA GAMBLING TASK; DECISION-MAKING; IMPULSIVE BEHAVIOR; NUCLEUS-ACCUMBENS; COCAINE ABUSERS AB Treatment of substance abuse disorders is often characterized by high dropout rates. Patients who fail to complete a treatment course often are worse at follow-up than those patients who received the full treatment course. Cognitive deficits, including impulsivity, have been noted as a major determinant of treatment retention and successful outcomes. This review summarizes the recent literature on cognitive deficits in stimulant users and their remediation. Cognitive deficits can be remediated through computer-assisted cognitive rehabilitation in residential settings. A few studies have shown this can be transferred to the outpatient setting although much research remains to be done in this setting. Pharmacological remediation of cognitive deficits is a new target for medications development in the treatment of substance abuse disorders. Psychiatric disorders; for example, attention deficit hyperactivity disorder, are amenable to pharmacological remediation of cognitive deficits. Several cognitive deficits (set-shifting, attentional bias, reversal learning, impulsivity, and risky decision making) and their possible remediation with pharmacological agents are presented in the review. Recommendations for the research agenda include comments on testing hierarchies, clinical trial design issues, and types of pharmacological agents. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Vocci, FJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM fvocci@mail.nih.gov NR 118 TC 39 Z9 39 U1 5 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD DEC PY 2008 VL 16 IS 6 BP 484 EP 497 DI 10.1037/a0014101 PG 14 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 384CN UT WOS:000261722000005 PM 19086769 ER PT J AU Liu, J Shi, JZ Goyer, RA Waalkes, MP AF Liu, Jie Shi, Jing-Zheng Goyer, Robert A. Waalkes, Michael P. TI The Clinical Toxicity of Cinnabar Response SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Editorial Material C1 [Liu, Jie; Goyer, Robert A.; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. [Shi, Jing-Zheng] Guiyang Tradit Med Coll, Guiyang 550004, Peoples R China. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM liu6@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2008 VL 233 IS 12 BP 1480 EP 1480 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 381UN UT WOS:000261561500003 ER PT J AU Sloand, EA Pfannes, L Scheinberg, P More, K Wu, CO Horne, M Young, NS AF Sloand, Elaine A. Pfannes, Loretta Scheinberg, Phillip More, Kenneth Wu, Colin O. Horne, McDonald Young, Neal S. TI Increased soluble urokinase plasminogen activator receptor (suPAR) is associated with thrombosis and inhibition of plasmin generation in paroxysmal nocturnal hemoglobinuria (PNH) patients SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID SINGLE-CHAIN UROKINASE; BONE-MARROW; PERIPHERAL-BLOOD; CELLS; MEMBRANE; LYSIS; CD59; MICROPARTICLES; PROUROKINASE; PROTECTION AB Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the bone marrow that produces intravascular hemolysis, proclivity to venous thrombosis, and hematopoietic failure. Mutation in the PIG-A gene of a hematopoietic stem cell abrogates synthesis of glycosylphosphoinositol (GPI) anchors and expression of all GPI-anchored proteins on the surface of progeny erythrocytes, leukocytes, and platelets. Urokinase plasminogen activator receptor (uPAR), a GPI-linked protein expressed on neutrophils, mediates endogenous thrombolysis through a urokinase-dependent mechanism. Here we show that membrane GPI-anchored uPAR is decreased or absent on granulocytes and platelets of patients with PNH, while soluble uPAR (suPAR) levels are increased in patients' plasma. Serum suPAR concentrations correlated with the number of GPI-negative neutrophils and were highest in patients who later develop thrombosis. In vitro, suPAR is released from PNH hematopoietic cells and from platelets upon activation, suggesting that these cells are the probable source of plasma suPAR in the absence of GPI anchor synthesis and trafficking of uPAR to the cell membrane. In vitro, the addition of recombinant suPAR results in a dose-dependent decrease in the activity of single-chain urokinase. We hypothesized that suPAR, prevents the interaction of urokinase with membrane-anchored uPAR on residual normal cells. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. C1 [Sloand, Elaine A.; Pfannes, Loretta; Scheinberg, Phillip; Young, Neal S.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [More, Kenneth] Bethesda Naval Hosp, Bethesda, MD USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Horne, McDonald] NIH, Pathol Sect, Off Res Serv, Off Director, Bethesda, MD 20892 USA. RP Sloand, EA (reprint author), NHLBI, Hematol Branch, MS 2490, Bethesda, MD 20892 USA. EM Sloande@nhlbi.nih.gov RI Scheinberg, Phillip/H-5251-2012; OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS [Z01 HL002315-25, Z01 HL002315-26, ZIA HL002315-27] NR 38 TC 20 Z9 24 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 2008 VL 36 IS 12 BP 1616 EP 1624 DI 10.1016/j.exphem.2008.06.016 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 379BQ UT WOS:000261370000005 PM 18954937 ER PT J AU Waisberg, M Lobo, FP Cerqueira, GC Passos, LKJ Carvalho, OS El-Sayed, NM Franco, GR AF Waisberg, M. Lobo, F. P. Cerqueira, G. C. Passos, L. K. J. Carvalho, O. S. El-Sayed, N. M. Franco, G. R. TI Schistosoma mansoni: Microarray analysis of gene expression induced by host sex SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Schistosoma mansoni; Trematode; Microarray; Gene expression; Host sex; Host-parasite interaction ID RESTORES CELLULAR-IMMUNITY; FEMALE MICE; SUSCEPTIBILITY DIFFERENCES; INFLAMMATORY REACTIONS; EGG EXCRETION; ADULT WORMS; PARASITE; TESTOSTERONE; HORMONES; INFECTION AB Schistosoma mansoni is a digenetic trematode and a human parasite responsible for high social and economic impact. Although some authors have studied the effect of host hormones on parasites, not much is known about the effects of host sex on gene expression in Schistosomes. In order to study gene transcripts associated with the host sex, we compared the gene expression profiles of both male and female unisexual adult S. mansoni parasites raised on either male or female hosts, using DNA microarrays. Our results show that host sex caused differential expression of at least 11 genes in female parasites and of 134 in male parasites. Of the differentially expressed genes in female worms, 10 were preferentially expressed in female worms from male mice, while of the 134 differentially expressed genes in male parasites, 79 (59%) were preferentially expressed in worms from female mice. Further investigation of the role of each of those genes will help understand better their importance in the pathogenesis of Schistosomiasis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Waisberg, M.; Lobo, F. P.; Franco, G. R.] Univ Fed Minas Gerais, Lab Genet Bioquim, Dept Bioquim & Imunol, Inst Ciencias Biol, Belo Horizonte, MG, Brazil. [Waisberg, M.; Cerqueira, G. C.; El-Sayed, N. M.] Inst Genom Res, Dept Parasite Genom, Rockville, MD USA. [Cerqueira, G. C.] Univ Fed Minas Gerais, Lab Genet Mol Tripanosomatideos, Dept Bioquim & Imunol, Inst Ciencias Biol, Belo Horizonte, MG, Brazil. [Passos, L. K. J.; Carvalho, O. S.] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [El-Sayed, N. M.] Univ Maryland, Dept Cell Biol & Mol Genet, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. RP Waisberg, M (reprint author), NIAID, Immunogenet Lab, Natl Inst Hlth, Rockville, MD 20852 USA. EM waisberg@gmail.com RI Lobo, Francisco/A-1295-2011; Franco, Gloria/I-3654-2013; El-Sayed, Najib/K-7266-2015 OI Franco, Gloria/0000-0001-5245-2365; El-Sayed, Najib/0000-0001-7970-3312 FU CAPES; FAPEMIG [CBB 469/04]; NIH [A148828] FX The authors thank CAPES, FAPEMIG and NIH for financial support. M.W. Work at TIGR was supported by NIH Grant A148828 to NES). M.W. Work at UFMG was supported by FAPEMIG Grant CBB 469/04 to G.R.F. M.W. work on TIGR was supported by a PDEE scholarship from CAPES and his work at UFMG was supported by a CAPES PhD scholarship. We thank Prof. Karl Hoffman for providing the arrays, Prof. Elida ML Rabelo for thoughtful suggestions, Bryan Frank for technical support with the microarray experiments and Delza de Moura Soares Reis and Sueleny Silva Ferreira Texeira for technical assistance with S. mansoni life-cycle maintenance and mouse perfusions. NR 59 TC 10 Z9 11 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 2008 VL 120 IS 4 BP 357 EP 363 DI 10.1016/j.exppara.2008.09.005 PG 7 WC Parasitology SC Parasitology GA 379LU UT WOS:000261398500010 PM 18822286 ER PT J AU Gaindh, D Jeffries, N Ohayon, J Richert, ND Pellicano, C Frank, JA McFarland, H Bagnato, F AF Gaindh, Deeya Jeffries, Neal Ohayon, Joan Richert, Nancy D. Pellicano, Clelia Frank, Joseph A. McFarland, Henry Bagnato, Francesca TI The effect of interferon beta-1b on size of short-lived enhancing lesions in patients with multiple sclerosis SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE contrast enhancing lesions; interferon beta 1b; lesion size; magnetic resonance imaging; multiple sclerosis ID DISEASE-ACTIVITY; CONTROLLED TRIAL; GADOLINIUM-DTPA; PROGRESSIVE MS; SPIN-ECHO; MRI; ENHANCEMENT; PATHOLOGY; BREAKDOWN; IMAGES AB Background: Contrast enhancing lesions (CELs) in MRI represent inflammatory events in multiple sclerosis (MS). IFN-beta-1b decreases the formation of CELs. However, the ability of IFN-beta-1b to reduce the size of CELs arising during therapy has not been extensively investigated. Methods: Thirty patients with relapsing-remitting (RR) MS were followed for a 3-month pre-therapy phase then for a 6-month therapy phase during which treatment with IFN-beta-1b at a dosage of 250 mu g subcutaneously injected every other day was employed. Each patient underwent monthly clinical and MRI examinations. For all patients, CELs were identified on postcontrast T1-weighted MRIs. CEL number, size, and volume were computed using Medx software. Results: The average number and total lesion volume of CELs visible during the therapy phase were significantly lower than the number and total lesion volume of CELs observed in the pre-therapy phase. However, there was no significant reduction between pre-therapy and therapy phases in the mean size of individual lesions arising during the respective phases. Conclusions: Since size of CELs has been related to severity of tissue damage, the lack of size decrease during therapy suggested a limited therapeutic effect of IFN-beta-1b if a blood-brain barrier breakdown has occurred. C1 [Gaindh, Deeya; Ohayon, Joan; Richert, Nancy D.; Pellicano, Clelia; McFarland, Henry; Bagnato, Francesca] NIH, Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bethesda, MD 20892 USA. [Jeffries, Neal] NIH, Natl Inst Neurol Disorders & Stroke, Off Clin Director, Bethesda, MD 20892 USA. [Frank, Joseph A.] NIH, Natl Inst Neurol Disorders & Stroke, Lab Diagnost Radiol & Res, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), NIH, Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Bldg 10,Room 5C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov RI Pellicano, Clelia/K-1062-2016 OI Pellicano, Clelia/0000-0002-3272-1094 FU NINDS, NIH FX This research was supported by the Intramural Research Program of the NINDS, NIH.; The authors state no conflict of interest and have received no payment in preparation of this manuscript. NR 29 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD DEC PY 2008 VL 8 IS 12 BP 1823 EP 1829 DI 10.1517/14712590802510629 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 379CG UT WOS:000261371800001 PM 18990070 ER PT J AU Abbas, A Roth, BL AF Abbas, Atheir Roth, Bryan L. TI Pimavanserin tartrate: a 5-HT2A inverse agonist with potential for treating various neuropsychiatric disorders SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE 5-HT(2A); 5-HT(2A); antipsychotic; inverse agonist; Parkinson's Disease; pimavanserin; psychosis; schizophrenia ID ATYPICAL ANTIPSYCHOTIC-DRUGS; POSITRON-EMISSION-TOMOGRAPHY; SLOW-WAVE SLEEP; PARKINSONS-DISEASE; CHRONIC-SCHIZOPHRENIA; CLOZAPINE TREATMENT; HEALTHY-VOLUNTEERS; RECEPTOR OCCUPANCY; ACP-103; BINDING AB Background: Pimavanserin tartrate is the first 5-HT(2A) inverse agonist to enter clinical trials as a treatment for L-dopa-induced psychosis in Parkinson's disease and for augmentation of low-dose risperidone treatment in schizophrenia. Pimavanserin is also being evaluated as a possible anti-insomnia drug. Objective: To discuss the potential of pimavanserin to fill multiple therapeutic needs. Methods: The problems with currently approved antipsychotics and sleep agents are explored to highlight how pimavanserin might address some longstanding issues in the treatment of psychosis and insomnia. Results/conclusions: In Phase II clinical trials, pimavanserin seemed to be safe, well-tolerated and efficacious in treating L-dopa-induced psychosis without worsening motor symptoms. Pimavanserin also potentiated the therapeutic effects of low-dose risperidone, reduced haloperidol-induced akathisia, and increased slow-wave sleep in older individuals. C1 [Roth, Bryan L.] Univ N Carolina, Lineberger Canc Ctr, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27516 USA. [Abbas, Atheir] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Univ N Carolina, Lineberger Canc Ctr, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27516 USA. EM aia404@case.edu; bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 FU NIMH NIH HHS [R01 MH061887, U19 MH082441] NR 47 TC 45 Z9 46 U1 2 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD DEC PY 2008 VL 9 IS 18 BP 3251 EP 3259 DI 10.1517/14656560802532707 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 388KJ UT WOS:000262018400012 PM 19040345 ER PT J AU Issaq, HJ Veenstra, TD AF Issaq, Haleem J. Veenstra, Timothy D. TI Would you prefer multiple reaction monitoring or antibodies with your biomarker validation? SO EXPERT REVIEW OF PROTEOMICS LA English DT Editorial Material ID DISCOVERY C1 [Issaq, Haleem J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov; veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 4 TC 17 Z9 17 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD DEC PY 2008 VL 5 IS 6 BP 761 EP 763 DI 10.1586/14789450.5.6.761 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 399BI UT WOS:000262775000002 PM 19086854 ER PT J AU Athirakul, K Bradbury, JA Graves, JP DeGraff, LM Ma, JX Zhao, Y Couse, JF Quigley, R Harder, DR Zhao, XY Imig, JD Pedersen, TL Newman, JW Hammock, BD Conley, AJ Korach, KS Coffman, TM Zeldin, DC AF Athirakul, Krairerk Bradbury, J. Alyce Graves, Joan P. DeGraff, Laura M. Ma, Jixiang Zhao, Yun Couse, John F. Quigley, Raymond Harder, David R. Zhao, Xueying Imig, John D. Pedersen, Theresa L. Newman, John W. Hammock, Bruce D. Conley, Alan J. Korach, Kenneth S. Coffman, Thomas M. Zeldin, Darryl C. TI Increased blood pressure in mice lacking cytochrome P450 2J5 SO FASEB JOURNAL LA English DT Article DE hypertension; estrogen; proximal tubule; vascular responsiveness; eicosanoid ID SPONTANEOUSLY HYPERTENSIVE-RATS; ESTROGEN-RECEPTOR-BETA; ARACHIDONIC-ACID; 20-HYDROXYEICOSATETRAENOIC ACID; NITRIC-OXIDE; POSTMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; ANGIOTENSIN-II; EPOXYEICOSATRIENOIC ACIDS; CARDIOVASCULAR FUNCTION AB The cytochrome P450 (CYP) enzymes participate in a wide range of biochemical functions, including metabolism of arachidonic acid and steroid hormones. Mouse CYP2J5 is abundant in the kidney where its products, the cis-epoxyeicosatrienoic acids (EETs), modulate sodium transport and vascular tone. To define the physiological role of CYP2J5 in the kidney, knockout mice were generated using a conventional gene targeting approach. Cyp2j5 (-/-) mice develop normally and exhibit no overt renal pathology. While renal EET biosynthesis was apparently unaffected by the absence of CYP2J5, deficiency of this CYP in female mice was associated with increased blood pressure, enhanced proximal tubular transport rates, and exaggerated afferent arteriolar responses to angiotensin II and endothelin I. Interestingly, plasma 17 beta-estradiol levels were reduced in female Cyp2j5 (-/-) mice and estrogen replacement restored blood pressure and vascular responsiveness to normal levels. There was no evidence of enhanced estrogen metabolism, or altered expression or activities of steroidogenic enzymes in female Cyp2j5 (-/-) mice, but their plasma levels of luteinizing hormone and follicle stimulating hormone were inappropriately low. Together, our findings illustrate a sex-specific role for CYP2J5 in regulation of blood pressure, proximal tubular transport, and afferent arteriolar responsiveness via an estrogen-dependent mechanism. C1 [Bradbury, J. Alyce; Graves, Joan P.; DeGraff, Laura M.; Ma, Jixiang; Zhao, Yun; Couse, John F.; Korach, Kenneth S.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Athirakul, Krairerk; Coffman, Thomas M.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Quigley, Raymond] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Harder, David R.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Zhao, Xueying; Imig, John D.] Med Coll Georgia, Dept Physiol, Augusta, GA 30912 USA. [Pedersen, Theresa L.; Newman, John W.; Hammock, Bruce D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Pedersen, Theresa L.; Newman, John W.; Hammock, Bruce D.] Univ Calif Davis, Canc Res Ctr, Davis, CA 95616 USA. [Conley, Alan J.] Univ Calif Davis, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, 111 T W Alexander Dr,Bldg 101,Rm D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Imig, John/0000-0002-9668-2899; Korach, Kenneth/0000-0002-7765-418X FU NIH [HL6876, DK38226, ES004699, ES02710, MH39917, DK069896]; National Institute of Environmental Health Sciences [Z01 ES025034] FX We thank Drs. Michael Fessler and Robert Langenbach for helpful comments during the preparation of this manuscript, Dr. Howard Rockman for assistance with echocardiography, and Dr. Beverly Koller for assistance with generation of the Cyp2j5 (-/-) mice. This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences Z01 ES025034 (K.S.K., D.C.Z.), and NIH grants HL6876 (D.R.H.), DK38226 (J.D.I.), ES004699 (B.D.H.), ES02710 (B.D.H.), MH39917 (A.J.C.) and DK069896 (T.M.C.). NR 70 TC 40 Z9 40 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD DEC PY 2008 VL 22 IS 12 BP 4096 EP 4108 DI 10.1096/fj.08-114413 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 377MH UT WOS:000261254800009 PM 18716027 ER PT J AU Bras, J Singleton, A Cookson, MR Hardy, J AF Bras, Jose Singleton, Andrew Cookson, Mark R. Hardy, John TI Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease SO FEBS JOURNAL LA English DT Review DE ceramide; gene; glucocerebrosidase; Lewy body; loci; mutation; pathogenesis; pathway; risk factor; susceptibility ID BRAIN IRON ACCUMULATION; CHAPERONE-MEDIATED AUTOPHAGY; HALLERVORDEN-SPATZ-SYNDROME; ALPHA-SYNUCLEIN; GLUCOCEREBROSIDASE GENE; PHOSPHOLIPASE A(2); SERINE-PALMITOYLTRANSFERASE; SENSORY NEUROPATHY; GAUCHER-DISEASE; LRRK2 MUTATION AB Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis. C1 [Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England. [Hardy, John] Inst Neurol, Reta Lila Weston Inst, London WC1N 3BG, England. [Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Bethesda, MD 20892 USA. [Bras, Jose; Singleton, Andrew] NIA, Mol Genet Unit, Bethesda, MD 20892 USA. [Bras, Jose] Univ Coimbra, Ctr Neurosci & Cell Biol, P-3000 Coimbra, Portugal. RP Hardy, J (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM j.hardy@ion.ucl.ac.uk RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Bras, Jose/A-1428-2011 FU National Institute on Aging; National Institutes of Health; Department of Health and Human Services [Z01-AG 000957-05]; Portuguese FCT [SFRH/BD/29647/2006] FX This research was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; Annual Report number Z01-AG 000957-05 and Portuguese FCT grant #SFRH/BD/29647/2006. NR 56 TC 80 Z9 81 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD DEC PY 2008 VL 275 IS 23 BP 5767 EP 5773 DI 10.1111/j.1742-4658.2008.06709.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 371HP UT WOS:000260822700004 PM 19021754 ER PT J AU Jakubovics, NS Gill, SR Vickerman, MM Kolenbrander, PE AF Jakubovics, Nicholas S. Gill, Steven R. Vickerman, M. Margaret Kolenbrander, Paul E. TI Role of hydrogen peroxide in competition and cooperation between Streptococcus gordonii and Actinomyces naeslundii SO FEMS MICROBIOLOGY ECOLOGY LA English DT Article DE oral streptococci; hydrogen peroxide; Actinomyces naeslundii; metal-catalyzed oxidation; Streptococcus gordonii; catalase ID BACTERIUM ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ESCHERICHIA-COLI; OXIDATIVE STRESS; STAPHYLOCOCCUS-AUREUS; VIRIDANS STREPTOCOCCI; ORAL STREPTOCOCCI; COLONIZATION; PNEUMONIAE; GROWTH; LACTOPEROXIDASE AB In dental plaque alpha-haemolytic streptococci, including Streptococcus gordonii, are considered beneficial for oral health. These organisms produce hydrogen peroxide (H(2)O(2)) at concentrations sufficient to kill many oral bacteria. Streptococci do not produce catalase yet tolerate H(2)O(2). We recently demonstrated that coaggregation with Actinomyces naeslundii stabilizes arginine biosynthesis in S. gordonii. Protein arginine residues are sensitive to oxidation by H(2)O(2). Here, the ability of A. naeslundii to protect S. gordonii against self-produced H(2)O(2) was investigated. Coaggregation with A. naeslundii enabled S. gordonii to grow in the absence of arginine, and promoted survival of S. gordonii following growth with or without added arginine. Arginine-replete S. gordonii monocultures contained 20-30 mu M H(2)O(2) throughout exponential growth. Actinomyces naeslundii did not produce H(2)O(2) but synthesized catalase, removed H(2)O(2) from coaggregate cultures and decreased protein oxidation in S. gordonii. On solid medium, S. gordonii inhibited growth of A. naeslundii; exogenous catalase overcame this inhibition. In coaggregate cultures, A. naeslundii cell numbers were > 90% lower than in monocultures after 24 h. These results indicate that coaggregation with A. naeslundii protects S. gordonii from oxidative damage. However, high cell densities of S. gordonii inhibit A. naeslundii. Therefore, H(2)O(2) may drive these organisms towards an ecologically balanced community in natural dental plaque. C1 [Kolenbrander, Paul E.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. [Jakubovics, Nicholas S.] Univ Newcastle, Sch Dent Sci, Newcastle Upon Tyne, Tyne & Wear, England. [Gill, Steven R.; Vickerman, M. Margaret] SUNY Buffalo, Sch Dent, Dept Oral Biol, Buffalo, NY 14260 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bldg 30,Room 310,30 Convent Dr, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov RI Jakubovics, Nicholas/B-1938-2010 OI Jakubovics, Nicholas/0000-0001-6667-0515 FU National Institute of Dental and Craniofacial Research; National Institutes of Health; National Institute of Dental and Craniofacial Research [DE11090] FX The authors thank R. J. Levine for advice and E. Ko for assistance with experimental procedures. We gratefully acknowledge the gift of the S. gordonii spxB mutant strain from R. J. Lamont. This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health and by Public Health Service grant DE11090 from the National Institute of Dental and Craniofacial Research awarded to M. M. V. NR 42 TC 50 Z9 52 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0168-6496 J9 FEMS MICROBIOL ECOL JI FEMS Microbiol. Ecol. PD DEC PY 2008 VL 66 IS 3 BP 637 EP 644 DI 10.1111/j.1574-6941.2008.00585.x PG 8 WC Microbiology SC Microbiology GA 374RE UT WOS:000261060600017 PM 18785881 ER PT J AU Hong, J Kim, KP Heu, S Lee, SJ Adhya, S Ryu, S AF Hong, Junwoo Kim, Kwang-Pyo Heu, Sunggi Lee, Sang Jun Adhya, Sankar Ryu, Sangryeol TI Identification of host receptor and receptor-binding module of a newly sequenced T5-like phage EPS7 SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE T5-like viruses; genomic analysis; lytic conversion; host-phage interaction ID ESCHERICHIA-COLI K-12; COMPLETE GENOME SEQUENCE; SHAPED TAIL FIBERS; OUTER-MEMBRANE; TERMINAL REPETITION; BACTERIOPHAGE T5; PROTEIN FHUA; DNA; LIPOPROTEIN; GENE AB The virulent bacteriophage EPS7 active against a number of Salmonella serovar and Escherichia coli strains, isolated from the local sewage in Korea, belongs to the family Siphoviridae. The ESP7 genome constitutes a linear double-stranded DNA of 111 382 bp. DNA sequencing and genomic analysis of EPS7 showed that it belongs to the phage T5 family. We identified the EPS7 genes involved in DNA repair, replication, viral structure and bacterial lysis by comparing the EPS7 genome with that of T5. In contrast, the tail genes encoding for putative host receptor-binding protein and the putative receptor-blocking lipoprotein precursor of EPS7 exhibit high homologies with the corresponding gene products of BF23, another member of the T5-family. BF23 binds to BtuB, a surface receptor in the host and involved in vitamin B(12) uptake, but its infection is independent of TonB. By constructing a series of deletion mutants in Salmonella and in E. coli and studying phage infection in the mutant hosts, we showed that BtuB is also the host receptor of the phage EPS7. Whether EPS7 infection depends on TonB needs to be further studied. C1 [Hong, Junwoo; Kim, Kwang-Pyo; Ryu, Sangryeol] Seoul Natl Univ, Ctr Agr Biomat, Dept Agr Biotechnol, Seoul 151921, South Korea. [Hong, Junwoo; Kim, Kwang-Pyo; Ryu, Sangryeol] Seoul Natl Univ, Res Inst Agr & Life Sci, Seoul 151921, South Korea. [Kim, Kwang-Pyo] Cheju Natl Univ, Sch Engn, Dept Food Engn, Cheju, South Korea. [Heu, Sunggi] Natl Inst Agr Sci & Technol, Plant Pathol Div, Suwon, South Korea. [Lee, Sang Jun; Adhya, Sankar] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ryu, S (reprint author), Seoul Natl Univ, Ctr Agr Biomat, Sch Agr Biotechnol, Dept Food & Anim Biotechnol, Gwanak Ro 599, Seoul 151921, South Korea. EM sangryu@snu.ac.kr FU BioGreen 21 Program [20070301034035]; Rural Development Administration, Republic of Korea FX J. H. has been the recipient of a graduate fellowship provided by the Ministry of Education through the Brain Korea 21 Project. This work was supported by a grant (Code # 20070301034035) from BioGreen 21 Program, Rural Development Administration, Republic of Korea. NR 36 TC 19 Z9 19 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD DEC PY 2008 VL 289 IS 2 BP 202 EP 209 DI 10.1111/j.1574-6968.2008.01397.x PG 8 WC Microbiology SC Microbiology GA 375OM UT WOS:000261123200012 PM 19025561 ER PT J AU Levens, ED Whitcom, BW Hennessy, S James, AN Yauger, BJ Larsen, FW AF Levens, Eric D. Whitcom, Brian W. Hennessy, Sasha James, Aidita N. Yauger, Belinda J. Larsen, Frederick W. TI Blastocyst development rate impacts outcome in cryopreserved blastocyst transfer cycles SO FERTILITY AND STERILITY LA English DT Article DE Frozen-thawed blastocyst cycle; embryo transfer; day 5 versus day 6 ID IN-VITRO FERTILIZATION; EMBRYO-TRANSFER; PREGNANCY RATES; CULTURE; DAY-5; SUCCESS; IMPLANTATION; NUMBER AB Objective: To assess cycle outcome among day 5 and day 6 cryopreserved frozen-thawed blastocyst embryo transfers (FBET). Design: Retrospective cohort study. Setting: Military-based assisted reproduction technology (ART) center. Patient(s): One hundred seventy-two nondonor, programmed cryopreserved embryo cycles. Intervention(s): Fully expanded blastocysts on day 5 were cryopreserved on day 5, and those achieving this state on day 6 were cryopreserved on day 6. Leuprolide acetate was given for ovulation inhibition, and endometrial supplementation was by oral and vaginal estradiol. Progesterone in oil was administered, and blastocyst transfer occurred in the morning of the sixth day of progesterone. Main Outcome Measure(s): Implantation, pregnancy, and live-birth rates. Result(s): Fresh and frozen cycle characteristics were similar between groups. Day-5 FBET had statistically significantly higher implantation rates (32.2% vs. 19.2%), which remained significant even when adjusting for covariates (odds ratio: 1.91; 95% confidence interval, 1.00, 3.67). Live-birth rates trended toward improvement after adjusting for covariates (odds ratio: 1.18; 95% confidence interval, 0.61, 2.30). Conclusion(s): Cryopreserved day-5 blastocysts have higher implantation rates and trend toward improved pregnancy outcomes compared with cryopreserved day-6 blastocysts. This suggests that embryo development rate may, in part, predict implantation and subsequent FBET outcomes, although embryos not achieving the blastocyst stage until day 6 still demonstrate acceptable outcomes. (Fertil Steril(R) 2008;90:2138-43. (C) 2008 by American Society for Reproductive Medicine.) C1 [Levens, Eric D.; Yauger, Belinda J.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Whitcom, Brian W.] NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Levens, Eric D.; Yauger, Belinda J.; Larsen, Frederick W.] Walter Reed Army Med Ctr, ART Program, Washington, DC 20307 USA. [Levens, Eric D.; Yauger, Belinda J.; Larsen, Frederick W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Levens, Eric D.; Yauger, Belinda J.; Larsen, Frederick W.] NIH, Combined Fed Fellowship Program Reprod Endocrinol, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bethesda, MD 20892 USA. [Hennessy, Sasha; James, Aidita N.] Wasington Inc, ART Inst, Washington, DC USA. RP Levens, ED (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM levense@mail.nih.gov FU Reproductive Biology and Medicine Branch, NICHD, NIH, Bethesda, MD FX Research supported, in part, by the Reproductive Biology and Medicine Branch, NICHD, NIH, Bethesda, MD. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the Department of the Army or the Department of Defense. NR 19 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2008 VL 90 IS 6 BP 2138 EP 2143 DI 10.1016/j.fertnstert.2007.10.029 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 381WO UT WOS:000261566800015 PM 18178191 ER PT J AU Sun, WJ Stegmann, BJ Henne, M Cwherino, WH Segars, JH AF Sun, Wenjie Stegmann, Barbara J. Henne, Melinda Cwherino, Williain H. Segars, James H. TI A new approach to ovarian reserve testing SO FERTILITY AND STERILITY LA English DT Article DE Ovarian reserve; ovarian insufficiency; FSH; CC challenge test; inhibin; diminished ovarian reserve; assisted reproduction; in vitro fertilization (IVF); assisted reproductive technologies (ART) ID IN-VITRO FERTILIZATION; FOLLICLE-STIMULATING-HORMONE; ASSISTED REPRODUCTIVE TECHNOLOGY; CITRATE CHALLENGE TEST; RECURRENT PREGNANCY LOSS; ANTI-MULLERIAN HORMONE; INHIBIN-B; PREDICTIVE-VALUE; DOWNS-SYNDROME; BASAL MARKERS AB Objective: To critically examine ovarian reserve testing before assisted reproduction. Design: A PUBMED computer search to identify relevant literature. Setting: Multiple sites. Patient(s): Patients undergoing assisted reproduction. Intervention(S): Testing for ovarian reserve. Main Outcome Measure(S): Assisted reproductive technology (ART) and pregnancy outcomes. Result(S): The prevalence of ovarian insufficiency varies significantly for women aged 30-45 years. Gerieralization or averaging of threshold values across different aged women leads to very poor sensitivity, specificity, and positive predictive value for all tests of ovarian reserve. Because of the changing prevalence of ovarian insufficiency, there is no single, suitable threshold value for any screening test of ovarian reserve. Our analysis supports dividing impaired ovarian reserve into two groups: age-dependent ovarian aging (physiologic) and premature (non-physiologic) reductions in the oocyte pool. Interpretation of any screening test used requires that age is considered as a variable. To guide clinical interpretation of test results, We suggest using a nomogram of FSH values versus expected delivery rate-per-cycle-start with ART for a given age. Conclusion(s): Proper interpretation of screening tests for ovarian insufficiency in couples considering ART is important as the presence of impaired ovarian reserve is associated with a low likelihood of pregnancy. The condition of premature (nonphysiologic) ovarian insufficiency warrants additional research. (Fertil Steril(R) 2008;90:2196202. (C)2008 by American Society for Reproductive Medicine.) C1 [Stegmann, Barbara J.; Segars, James H.] NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Sun, Wenjie] Wake Forest Univ, Baptist Med Ctr, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. [Stegmann, Barbara J.; Henne, Melinda; Cwherino, Williain H.; Segars, James H.] Walter Reed Army Med Ctr, Walter Reed ART Program, Washington, DC 20307 USA. [Cwherino, Williain H.; Segars, James H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), NICHD, RBMB, NIH, Bldg 10,CRC,Room 1E-3140,MSC 1109,10 Ctr Dr, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Reproductive Biology and Medicine Branch of National Institute of Child Health and Human Development, National Institutes of Health FX Supported, in part, by the Reproductive Biology and Medicine Branch of National Institute of Child Health and Human Development, National Institutes of Health. NR 44 TC 23 Z9 28 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2008 VL 90 IS 6 BP 2196 EP 2202 DI 10.1016/j.fertnstert.2007.10.080 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 381WO UT WOS:000261566800023 PM 18433750 ER PT J AU M'ikanatha, NM Rice, DH Altekruse, SF AF M'ikanatha, Nkuchia M. Rice, Daniel H. Altekruse, Sean F. TI Strategic Use of State and Local Regulatory and Public Health Surveillance Resources to Address the Growing Demand for Food Safety Oversight in the United States SO FOODBORNE PATHOGENS AND DISEASE LA English DT Review AB Although considerable progress has been made, federal food safety oversight in the United States has not overcome challenges posed by a decentralized, rapidly expanding food supply network. To complement limitations of federal measures, we believe that state-based food safety regulatory and surveillance systems should be better leveraged and integrated. A strengthened national food safety program Would include implementation Of uniform standards of food inspection and testing, reciprocal acceptance of state and federal inspection and laboratory findings, and systematic, timely sharing of data on pathogens recovered from contaminated foods and from ill persons. C1 [M'ikanatha, Nkuchia M.] Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. [M'ikanatha, Nkuchia M.] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Rice, Daniel H.] New York State Dept Agr & Markets, Food Lab Div, Albany, NY USA. [Altekruse, Sean F.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP M'ikanatha, NM (reprint author), Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17120 USA. EM nmikanatha@state.pa.us FU Agency for Healthcare Research; Quality Centers for Education and Research on Therapeutics FX We are grateful to Kathleen G. Julian for her excellent input during revision of the manuscript. This study was supported in part by the Agency for Healthcare Research and Quality Centers for Education and Research on Therapeutics cooperative agreement (U18-HS10399). All authors declare that they have no conflict of interest. Their perspectives do not necessarily represent the official policies of their agencies. NR 24 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 EI 1556-7125 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD DEC PY 2008 VL 5 IS 6 BP 747 EP 753 DI 10.1089/fpd.2008.0131 PG 7 WC Food Science & Technology SC Food Science & Technology GA 388OF UT WOS:000262028400006 PM 18950255 ER PT J AU Price, MM Oskeritzian, CA Milstien, S Spiegel, S AF Price, Megan M. Oskeritzian, Carole A. Milstien, Sheldon Spiegel, Sarah TI Sphingosine-1-phosphate synthesis and functions in mast cells SO FUTURE LIPIDOLOGY LA English DT Review DE allergy; anaphylaxis; Inflammation; mast cells; sphingolipid metabolites; sphingosine-1-phosphate; sphingosine kinase ID SPHINGOSINE KINASE TYPE-2; PROTEIN-COUPLED RECEPTOR; AIRWAY SMOOTH-MUSCLE; IN-VIVO; EXTRACELLULAR EXPORT; CALCIUM MOBILIZATION; VASCULAR MATURATION; CYTOKINE PRODUCTION; LYMPHOCYTE EGRESS; CA2+ SIGNALS AB Sphingollpids are not only major lipid components of all eukaryotic cell membranes, but they also comprise an important family of bioactive signaling molecules that regulate a diverse array of biological responses. The sphingolipid metabolite sphingosine-1-phosphate (S1P), is a key regulator of immune responses. Cellular levels of SIP are determined by the balance between its synthesis, involving two sphingosine kinases (SphK1 and SphK2), and its degradation, involving SIP lyase and SIP phosphatases, SIP mainly signals through its cell-surface receptors and may also have intracellular functions. SIP has important functions in most cells - the major effectors of allergic responses. Antigen triggering of IgE receptors on mast cells activates both SphKs resulting in the production of S1P that is released and regulates and amplifies mast cell functions, including degranulation as well as cytokine and chemokine release. C1 [Price, Megan M.; Oskeritzian, Carole A.; Spiegel, Sarah] Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Milstien, Sheldon] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem & Mol Biol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU NCI NIH HHS [R01 CA061774]; NIAID NIH HHS [R01 AI050094, R01 AI050094-06A2, U19 AI077435, U19 AI077435-010004]; NIAMS NIH HHS [K01 AR053186]; NIGMS NIH HHS [R01 GM043880, R01 GM043880-13, R37 GM043880] NR 76 TC 11 Z9 12 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0875 J9 FUTURE LIPIDOL JI Future Lipidol. PD DEC PY 2008 VL 3 IS 6 BP 665 EP 674 DI 10.2217/17460875.3.6.665 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 381WJ UT WOS:000261566300012 PM 19802381 ER PT J AU Mishra, PJ Merlino, G AF Mishra, Prasun J. Merlino, Glenn TI A traitor in our midst: mesenchymal stem cells contribute to tumor progression and metastasis SO FUTURE ONCOLOGY LA English DT Editorial Material ID BONE-MARROW; STROMAL CELLS; DIFFERENTIATION; TRANSITIONS; TRANSPLANTATION; MYOFIBROBLAST; STIMULATION; PRECURSORS; EXPRESSION; DELIVERY C1 [Mishra, Prasun J.; Merlino, Glenn] NCI, NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Mishra, PJ (reprint author), NCI, NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM mishrapj@mail.nih.gov; gmerlino@helix.nih.gov NR 35 TC 6 Z9 8 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 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD DEC PY 2008 VL 4 IS 6 BP 745 EP 749 DI 10.2217/14796694.4.6.745 PG 5 WC Oncology SC Oncology GA 391AZ UT WOS:000262206100002 PM 19086838 ER PT J AU Chalasani, N Fontana, RJ Bonkovsky, HL Watkins, PB Davern, T Serrano, J Yang, HQ Rochon, J AF Chalasani, Naga Fontana, Robert J. Bonkovsky, Herbert L. Watkins, Paul B. Davern, Timothy Serrano, Jose Yang, Hongqiu Rochon, James CA Drug Induced Liver Injury Network TI Causes, Clinical Features, and Outcomes From a Prospective Study of Drug-induced Liver Injury in the United States SO GASTROENTEROLOGY LA English DT Article ID TEA CAMELLIA-SINENSIS; CAUSALITY ASSESSMENT; ADVERSE REACTIONS; HEPATOTOXICITY; SUPPLEMENTS; EXTRACTS; THERAPY; FAILURE AB Background & Aims: Idiosyncratic drug-induced liver injury (DILI) is among the most common causes of acute liver failure in the United States, accounting for approximately 13% of cases. A prospective study was begun in 2003 to recruit patients with suspected DILI and create a repository of biological samples for analysis. This report summarizes the causes, clinical features, and outcomes from the first 300 patients enrolled. Methods: Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months. Patients with acetaminophen liver injury were excluded. Results: DILI was caused by a single prescription medication in 73% of the cases, by dietary supplements in 9%, and by multiple agents in 18%. More than 100 different agents were associated with DILI; antimicrobials (45.5%) and central nervous system agents (15%) were the most common. Causality was considered to be definite in 32%, highly likely in 41%, probable in 14%, possible in 10%, and unlikely in 3%. Acute hepatitis C virus (HCV) infection was the final diagnosis in 4 of 9 unlikely cases. Six months after enrollment, 14% of patients had persistent laboratory abnormalities and 8% had died; the cause of death was liver related in 44%. Conclusions: DILI is caused by a wide array of medications, herbal supplements, and dietary supplements. Antibiotics are the single largest class of agents that cause DILI. Acute HCV infection should be excluded in patients with suspected DILI by HCV RNA testing. The overall 6-month mortality was 8%, but the majority of deaths were not liver related. C1 [Chalasani, Naga] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Chalasani, Naga] Clarian Indiana Univ, Ctr Digest Dis, Indianapolis, IN USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Cannon Res Ctr, Charlotte, NC 28203 USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Ctr Liver & Digest Dis, Charlotte, NC 28203 USA. [Bonkovsky, Herbert L.; Watkins, Paul B.] Univ N Carolina, Dept Internal Med, Chapel Hill, NC USA. [Bonkovsky, Herbert L.] Univ Connecticut, Dept Internal Med, Farmington, CT USA. [Davern, Timothy] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. [Serrano, Jose] NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD USA. [Yang, Hongqiu; Rochon, James] Duke Clin Res Inst, Durham, NC USA. RP Chalasani, N (reprint author), Indiana Univ, Sch Med, Dept Med, RG 4100,1050 Wishard Blvd, Indianapolis, IN 46202 USA. EM nchalasa@iupui.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [1U01DK065201, 1U01DK065193, 1U01DK065184, 1U01DK065211, 1U01DK065238, 1U01DK065176] FX DILIN is supported by the National Institute of Diabetes and Digestive and Kidney Diseases under the following cooperative agreements: 1U01DK065201, 1U01DK065193, 1U01DK065184, 1U01DK065211, 1U01DK065238, and 1U01DK065176. NR 38 TC 297 Z9 318 U1 2 U2 21 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 DEC PY 2008 VL 135 IS 6 BP 1924 EP 1934 DI 10.1053/j.gastro.2008.09.011 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384RP UT WOS:000261762200054 PM 18955056 ER PT J AU Goessling, W Massaro, JM Vasan, RS D'Agostino, RB Ellison, RC Fox, CS AF Goessling, Wolfram Massaro, Joseph M. Vasan, Ramachandran S. D'Agostino, Ralph B., Sr. Ellison, R. Curtis Fox, Caroline S. TI Aminotransferase Levels and 20-Year Risk of Metabolic Syndrome, Diabetes, and Cardiovascular Disease SO GASTROENTEROLOGY LA English DT Article ID NONALCOHOLIC FATTY LIVER; SERUM ALANINE AMINOTRANSFERASE; INSULIN-RESISTANCE ATHEROSCLEROSIS; UNITED-STATES; ASPARTATE-AMINOTRANSFERASE; HEPATIC STEATOSIS; HEART-DISEASE; PREVALENCE; FRAMINGHAM; ASSOCIATION AB Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome (MetS). Alanine aminotransferase (ALT) levels are used to detect NAFLD and have also been associated with increased risk for MetS, diabetes mellitus, and cardiovascular disease (CVD). We studied the relationship between ALT levels and these disorders in a long-term follow-up study. Methods: Framingham Offspring Heart Study participants (n = 2812; mean age, 44 years; 56% women) were followed for the development of MetS, diabetes, CVD, and all-cause mortality using logistic regression (MetS, diabetes) or Cox proportional hazards models (CVD, all-cause mortality). Results: Among individuals at baseline, per 1 standard deviation increase in log ALT level, there were increased odds of the development of MetS (odds ratio [OR] 1.21, P < .001) and diabetes (OR, 1.48; P < .0001) over 20 years of follow-up. These findings also applied to participants with ALT levels within the normal range (MetS OR, 1.17; P = .006; diabetes OR, 1.34; P =.002). There was an increased risk of CVD in age/gender-adjusted models (hazard ratio, 1.23; P < .0001), but this was attenuated in multivariable-adjusted models (hazard ratio 1.05; P = .27); no association was observed for all-cause mortality. Aspartate aminotranferase levels were found to be associated with an increased risk of only diabetes. Conclusions: Both normal and increased levels of ALT are associated with long-term development of multiple metabolic disorders. These results indicate the potential for ALT values as biomarkers for the risk of metabolic disease. C1 [Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Goessling, Wolfram; Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. [Goessling, Wolfram] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.; Ellison, R. Curtis] Boston Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Div Mol Med, Boston, MA 02118 USA. RP Goessling, W (reprint author), Brigham & Womens Hosp, Div Genet, NRB 4-058,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM wgoessling@partners.org OI Ellison, Robert Curtis/0000-0002-0582-7467; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970; Goessling, Wolfram/0000-0001-9972-1569 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; NIDDK/NIH [K08-DK071940]; NHLBI/NIH [2K24HL04334] FX Supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195). W.G. is supported by K08-DK071940 (NIDDK/NIH). R.S.V. is supported in part by 2K24HL04334 (NHLBI/NIH). W.G. and C.S.F. designed and conducted the study, analyzed and interpreted the data, and prepared the manuscript. They had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. J.M.M. performed all the statistical analyses. All authors reviewed and approved the manuscript. NR 57 TC 157 Z9 163 U1 0 U2 11 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 DEC PY 2008 VL 135 IS 6 BP 1935 EP 1944 DI 10.1053/j.gastro.2008.09.018 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384RP UT WOS:000261762200055 PM 19010326 ER PT J AU Patton, HM Lavine, JE Van Natta, ML Schwimmer, JB Kleiner, D Molleston, J AF Patton, Heather M. Lavine, Joel E. Van Natta, Mark L. Schwimmer, Jeffrey B. Kleiner, David Molleston, Jean CA Nonalcoholic Steatohepatitis Clini TI Clinical Correlates of Histopathology in Pediatric Nonalcoholic Steatohepatitis SO GASTROENTEROLOGY LA English DT Article ID FATTY LIVER-DISEASE; ORGAN-SPECIFIC AUTOANTIBODIES; CHRONIC HEPATITIS-C; INSULIN-RESISTANCE; AUTOIMMUNE HEPATITIS; HEPATOCELLULAR-CARCINOMA; GLUCOSE-TOLERANCE; SCORING SYSTEM; PREVALENCE; FIBROSIS AB Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish the requirement for liver biopsy or predict those at increased risk for progression. Methods: Data obtained prospectively from children (age, 6-17 y) enrolled in the NASH Clinical Research Network were analyzed to identify clinical-pathologic correlates of pediatric NAFLD. All participants underwent liver biopsy within 6 months of clinical data that were reviewed by a central pathology committee. Results: A total of 176 children (mean age, 12.4 y; 77% male) were eligible for inclusion. By using ordinal logistic regression analysis, increasing aspartate aminotransferase (AST) level (odds ratio [OR], 1.017 per U/L; 95% confidence interval [CI], 1.004-1.031) and gamma-glutamyltransferase level (OR, 1.016 per U/L; 95% CI, 1.000-1.033) were associated independently with increasing severity of NASH. Increasing AST level (OR, 1.015 per U/L; 95% CI, 1.006-1.024), increasing white blood cell count (OR, 1.22 per 1000/mm(3); 95% CI, 1.07-1.38), and decreasing hematocrit (OR, 0.87 per %; 95% Cl, 0.79-0.96) were associated independently with increasing severity of fibrosis. Area under the receiver operator characteristic curve for a model with AST and alanine aminotransferase was 0.75 (95% CI, 0.66-0.84) and 0.74 (95% CI, 0.63-0.85) for distinguishing steatosis from more advanced forms of NASH and bridging fibrosis from lesser degrees of fibrosis, respectively. Conclusions: Certain components of routine laboratory tests are predictive of NAFLD pattern and fibrosis severity, but do not have adequate discriminate power to replace liver biopsy in evaluating pediatric NAFLD. C1 [Lavine, Joel E.; Schwimmer, Jeffrey B.] Univ Calif San Diego, Div Pediat Gastroenterol Hepatol & Nutr, San Diego, CA 92103 USA. [Patton, Heather M.] Univ Calif San Diego, Div Gastroenterol, San Diego, CA 92103 USA. [Van Natta, Mark L.] Johns Hopkins Bloomberg Sch Publ Hlth, Data Coordinating Ctr, Baltimore, MD USA. [Kleiner, David] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Molleston, Jean] Indiana Univ, Sch Med, Div Pediat Gastroenterol Hepatol & Nutr, Indianapolis, IN USA. RP Lavine, JE (reprint author), Univ Calif San Diego, Div Pediat Gastroenterol Hepatol & Nutr, 200 W Arbor Dr, San Diego, CA 92103 USA. EM jolavine@ucsd.edu OI Kleiner, David/0000-0003-3442-4453 FU National Institutes of Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institutes of Child Health and Human Development [UL1RR024989, M01RR000750, M01RR00188, RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359]; National Institutes of Health, National Cancer Institute FX The authors disclose the following: The Nonalcoholic Steatohepatitls Clinical Research Network is supported by the National Institutes of Diabetes and Digestive and Kidney Diseases (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713), and the National Institutes of Child Health and Human Development. Several clinical centers receive support from General Clinical Research Centers or Clinical and Translational Science Awards in conduct of Nonalcoholic Steatohepatitis Clinical Research Network studies (grants UL1RR024989, M01RR000750, M01RR00188, RR02413101, M01RR000827, UL1RR02501401 M01RR000065, and M01RR020359). This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 50 TC 99 Z9 103 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2008 VL 135 IS 6 BP 1961 EP 1971 DI 10.1053/j.gastro.2008.08.050 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384RP UT WOS:000261762200058 PM 19013463 ER PT J AU Fichtner-Feigl, S Young, CA Kitani, A Geissler, EK Schlitt, HJ Strober, W AF Fichtner-Feigl, Stefan Young, Cheryl A. Kitani, Atsushi Geissler, Edward K. Schlitt, Hans-Juergen Strober, Warren TI IL-13 Signaling via IL-13R alpha(2) Induces Major Downstream Fibrogenic Factors Mediating Fibrosis in Chronic TNBS Colitis SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HVJ-ENVELOPE VECTOR; NF-KAPPA-B; IGF-I; CROHNS-DISEASE; TISSUE FIBROSIS; MURINE MODEL; APOPTOSIS; CELLS; TGF-BETA-1 AB Background & Aims: Previous studies have shown that fibrosis developing in chronic experimental colitis is driven by interleukin (IL)-13 signaling via IL-13R alpha(2) and the production of transforming growth factor (TGF)-beta 1. In the present study, we sought to determine the fibrogenic downstream events set in motion by such signaling. Metho : Experimental colitis with late-onset intestinal fibrosis was induced by weekly intrarectal administration of trinitrobenzene sulfonic acid (TNBS) to BALB/c mice. Blockade of IL-13 signaling via IL-13R alpha(2) and TGF-beta 1 signaling was achieved by the administration of small interfering RNA or decoy oligonucleotides that target promoter sequences of signaling components of these receptors. Effects of blockade were determined by enzyme-linked immunosorbent assay or Western blotting detecting specific key fibrogenic factors and by measurement of collagen production. Results: Initially, we showed that abrogation of IL-13 activity via blockade of IL-13R alpha(2) and TGF-beta 1 signaling results in severe inhibition of expression of colonic insulin-like growth factor (IGF)-I and early growth response gene (Egr)-I, factors known to initiate and sustain fibrosis. We then showed that Egr-I was necessary early in the fibrotic process for caspase-mediated apoptosis of myofibroblasts and the production of urokinase plasminogen activator, a protein that enhances TGF-beta 1 activation. Finally, we showed that IGF-I (together with TGF-beta 1) acts later in the process to stimulate myofibroblasts to deposit collagen in the colon. Conclusions: These studies establish that IL-13 signaling via the IL-13R alpha(2) is a key initiation point for a complex fibrotic program in the colon consisting of TGF-beta 1 activation, IGF-I and Egr-1 expression, myofibroblast apoptosis, and myofibroblast production of collagen. C1 [Fichtner-Feigl, Stefan; Geissler, Edward K.; Schlitt, Hans-Juergen] Univ Regensburg, Dept Surg, D-93053 Regensburg, Germany. [Fichtner-Feigl, Stefan; Young, Cheryl A.; Kitani, Atsushi; Strober, Warren] NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Fichtner-Feigl, S (reprint author), Univ Regensburg, Dept Surg, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM stefan.fichtner@klinik.uni-regensburg.de RI Geissler, Edward/R-4131-2016 NR 30 TC 70 Z9 73 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2008 VL 135 IS 6 BP 2003 EP 2013 DI 10.1053/j.gastro.2008.08.055 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384RP UT WOS:000261762200062 PM 18938165 ER PT J AU Mix, H Weiler-Normann, C Thimme, R Ahlenstiel, G Shin, EC Herkel, J David, CS Lohse, AW Rehermann, B AF Mix, Heiko Weiler-Normann, Christina Thimme, Robert Ahlenstiel, Golo Shin, Eui-Cheol Herkel, Johannes David, Chella S. Lohse, Ansgar W. Rehermann, Barbara TI Identification of CD4 T-Cell Epitopes in Soluble Liver Antigen/Liver Pancreas Autoantigen in Autoimmune Hepatitis SO GASTROENTEROLOGY LA English DT Article ID CLASS-II TETRAMERS; CHRONIC ACTIVE HEPATITIS; C VIRUS-INFECTION; EX-VIVO ANALYSIS; PERIPHERAL-BLOOD; TRANSGENIC MICE; AUTOANTIBODIES; RESPONSES; MODEL; SUSCEPTIBILITY AB Background & Aims: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with autoantibodies and liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoantigenic peptides within human AIH-specific soluble liver antigen/liver pancreas antigen (SLA/LP) that are targeted by CD4(+) T cells and restricted by the disease susceptibility gene HLA-DRB1*0301. Methods: HLADR-BI*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells. Results: All mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DR-B1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoandgen-specific T cells in AIH patients were analyzed with tetramer and interferon-gamma ELISpot assays. Conclusions: This study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies. C1 [Mix, Heiko; Weiler-Normann, Christina; Ahlenstiel, Golo; Shin, Eui-Cheol; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Weiler-Normann, Christina; Herkel, Johannes; Lohse, Ansgar W.] Univ Klinikum Hamburg Eppendorf, Med Klin 1, Hamburg, Germany. [Thimme, Robert] Med Univ Klin, Innere Med Abt 2, Freiburg, Germany. [Herkel, Johannes; Lohse, Ansgar W.] Johannes Gutenberg Univ Mainz, Med Klin 1, Mainz, Germany. [David, Chella S.] Mayo Clin, Coll Med, Dept Immunol, Rochester, MN USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bldg 10,R 9B16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011; OI Ahlenstiel, Golo/0000-0003-0026-1457 FU National Institute for Diabetes, Digestive and Kidney Diseases; National Institutes of Health; Deutsche Forschungsgerneinschaft (Bonn, Germany) [MI 677/1-1, AH 173/1-1, SFB 548] FX This study was supported by the intramural research program of the National Institute for Diabetes, Digestive and Kidney Diseases, National Institutes of Health. H.M. was supported by grant MI 677/1-1 and G.A. was supported by grant AH 173/1-1 from the Deutsche Forschungsgerneinschaft (Bonn, Germany); and J.H. and A.W.L. were supported by grant SFB 548 from the Deutsche Forschungsgemeinschaft. NR 34 TC 13 Z9 16 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2008 VL 135 IS 6 BP 2107 EP 2118 DI 10.1053/j.gastro.2008.07.029 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384RP UT WOS:000261762200072 PM 18773898 ER PT J AU Sumner, AE AF Sumner, Anne E. TI The Relationship of Body Fat to Metabolic Disease: lnfluence of Sex and Ethnicity SO GENDER MEDICINE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; LIPOPROTEIN-LIPASE; AFRICAN-AMERICANS; WAIST CIRCUMFERENCE; TRIGLYCERIDE LEVELS; WOMEN; OVERWEIGHT; OBESITY; CHOLESTEROL AB Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sumner, AE (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bldg 10 CRC,Room 6-5940,MSC 1612,9000 Rockville P, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU National Institute of Diabetes; Digestive and Kidney Diseases of the National Institutes of Health, Bethesda, Maryland. FX Dr. Sumner is supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Bethesda, Maryland. NR 26 TC 19 Z9 20 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 1550-8579 J9 GENDER MED JI Gend. Med. PD DEC PY 2008 VL 5 IS 4 BP 361 EP 371 DI 10.1016/j.genm.2008.11.003 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 391CK UT WOS:000262210500003 PM 19108808 ER PT J AU Butts, CL Bowers, E Horn, JC Shukair, SA Belyavskaya, E Tonelli, L Sternberg, EM AF Butts, Cherie L. Bowers, Eve Horn, J. Cash Shukair, Shetha A. Belyavskaya, Elena Tonelli, Leonardo Sternberg, Esther M. TI Inhibitory Effects of Progesterone Differ in Dendritic Cells from Female and Male Rodents SO GENDER MEDICINE LA English DT Article DE steroid hormone receptors; immunomodulation; cytokines; gender differences ID SEXUAL-DIMORPHISM; RAT; LYMPHOCYTES; ACTIVATION; GENERATION; EXPRESSION; PROTECTION; INCREASES; RESPONSES; DISEASE AB Background: Steroid hormones, such as progesterone, are known to have immunomodulatory effects. Our research group previously reported direct effects of progesterone on dendritic cells (DCs) from female rodents. Primarily affecting mature DC function, progesterone effects included inhibition of proinflammatory cytokine secretion, downregulation of cell surface marker (major histocompatibility complex class II, CD80) expression, and decreased T-cell proliferative capacity, and were likely mediated through progesterone receptor (PR) because the PR antagonist RU486 reversed these effects. Objective: The goal of this study was to assess differences in response to progesterone by DCs from female and male rodents. Methods: Using real-time reverse-transcriptase polymerase chain reaction, transcriptional expression of steroid hormone receptors was measured in immature bone marrow-derived DCs (BMDCs) from male and female rats. Expression of steroid hormone receptor protein was also assessed in these cells using flow cytometry and fluorescence microscopy. To evaluate functional differences between BMDCs from female and male rats in response to the steroid hormone progesterone, levels of secreted cytokines were measured using enzyme-linked immunosorbent assay. Results: Higher numbers of immature BMDCs from males expressed glucocorticoid receptor (GR) and androgen receptor (AR) proteins compared with females (males vs females, mean [SD]: GR = 68.75 [7.27] vs 43.61 [13.97], 11 = NS; AR = 75.99 [15.38] vs 8.25 [1.88], P = 0.002), whereas higher numbers of immature BMDCs from females expressed PR protein compared with males (females vs males: PR = 74.19 [12.11] vs 14.14 [4.55], P = 0.043). These differences were not found at the level of transcription (females vs males: GR = 0.088 vs 0.073, P = NS; AR = 0.076 vs 0.069, P = NS; PR = 0.075 vs 0.065, P = NS). Compared with those from females, mature BMDCs from males produced higher quantities of cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1 beta, IL-10) (females vs males: TNF-alpha = 920.0 [79.25] vs 1100.61 [107.97], P = NS; IL-1 beta = 146.60 [38.04] vs 191.10 [10.47], P = NS; IL-10 = 167.25 [4.50] vs 206.15 [23.48], P = NS). Conversely, BMDCs from females were more sensitive to progesterone, as indicated by a more dramatic reduction in proinflammatory cytokine secretion (females vs males, highest concentration of progesterone: TNF-alpha = 268.94 [28.59] vs 589.91 [100.98], P = 0.04; IL-1 beta = 119.50 [10.32] vs 154.35 [6.22], P = NS). Conclusions: These findings Suggest that progesterone effects on DCs in rodents may be more pronounced in females than in males, and this is likely Clue to differences in PR protein expression. Our observations may help elucidate disparities in the incidence and severity of autoimmune disorders between females and males, and the role specific steroid hormones play in regulating immune responses. (Gend Med. 2008;5:434-447) (C) 2008 Excerpta Medica Inc. C1 [Butts, Cherie L.; Bowers, Eve; Horn, J. Cash; Shukair, Shetha A.; Belyavskaya, Elena; Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. [Tonelli, Leonardo] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. [Bowers, Eve] Howard Hughes Med Inst, Bethesda, MD 20817 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, 5625 Fishers Lane,Room 4N15, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov OI Horn, Jeremy/0000-0003-0344-5913 FU Intramural Research Program of the National Institute of Mental Health/ National Institutes of Health (NIH), Bethesda, Maryland; National Institute of Allergy and Infectious Diseases (NIAID)/NIH Intramural Research Program, Bethesda, Maryland. FX This work was supported by the Intramural Research Program of the National Institute of Mental Health/ National Institutes of Health (NIH), Bethesda, Maryland, and by a biodefense grant from the National Institute of Allergy and Infectious Diseases (NIAID)/NIH Intramural Research Program, Bethesda, Maryland. NR 45 TC 28 Z9 28 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1550-8579 J9 GENDER MED JI Gend. Med. PD DEC PY 2008 VL 5 IS 4 BP 434 EP 447 DI 10.1016/j.genm.2008.11.001 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 391CK UT WOS:000262210500011 PM 19108816 ER PT J AU Sekiguchi, T Hayashi, N Wang, Y Kobayashi, H AF Sekiguchi Takeshi Hayashi Naoyuki Wang Yongang Kobayashi Hideki TI Genetic evidence that Ras-like GTPases, Gtr1and Gtr2, are involved in epigenetic control of gene expression in Saccharomyces cerevisiae SO GENES & GENETIC SYSTEMS LA English DT Meeting Abstract C1 [Sekiguchi Takeshi; Wang Yongang] Kyushu Univ, Dept Mol Biol, Grad Sch Med Sci, Fukuoka 812, Japan. Okayama Univ, Cent Fac Dev, Okayama 7008530, Japan. [Wang Yongang] NIH, Bethesda, MD USA. [Hayashi Naoyuki; Kobayashi Hideki] Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 9201192, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GENETICS SOC JAPAN PI SHIZUOKA-KEN PA NATIONAL INST GENETICS YATA 1111, MISHIMA, SHIZUOKA-KEN, 411-8540, JAPAN SN 1341-7568 EI 1880-5779 J9 GENES GENET SYST JI Genes Genet. Syst. PD DEC PY 2008 VL 83 IS 6 BP 509 EP 509 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 433TJ UT WOS:000265228400125 ER PT J AU Bartholin, L Cyprian, FS Vincent, D Garcia, CN Martel, S Horvat, B Berthet, C Goddard-Leon, S Treilleux, I Rimokh, R Marie, JC AF Bartholin, Laurent Cyprian, Farhan S. Vincent, David Garcia, Celine N. Martel, Sylvie Horvat, Branka Berthet, Cyril Goddard-Leon, Sophie Treilleux, Isabelle Rimokh, Ruth Marie, Julien C. TI Generation of Mice with Conditionally Activated Transforming Growth Factor Beta Signaling Through the T beta RI/ALK5 Receptor SO GENESIS LA English DT Article DE TGF beta; receptor; lymphocyte; transgenesis; mouse; Smad ID TGF-BETA; T-CELLS; MECHANISMS; EXPRESSION; MUTATION; BINDING; PROTEIN; GENE; DNA AB We generated a transgenic mouse strain (LSL-T beta RI(CA)) containing a latent constitutively active TGF beta type I receptor (T beta RI/ALK5) by using a knock-in strategy into the X chromosome-linked hypoxanthine phosphoribosyl-transferase (Hprt) locus. Transgene expression, under the control of the ubiquitous CAG (human cytomegalovirus enhancer and chicken P-actin) promoter, is repressed by a floxed transcriptional "Stop" (LSL, Lox-Stop-Lox). In the presence of crerecombinase, the "Stop" is excised to allow T beta RI(CA) transgene expression. We showed that restricted expression of T beta RI(CA) in T lymphocytes efficiently activates TGFP signaling and rescues the T-cell autoimmune disorders of TGF beta RII conditional knockouts. Unexpectedly, our study reveals that TGFP signaling upregulation controls T-cell activation but does not impair their development or their peripheral homeostasis. In addition to the information provided on TGF beta effects on T-cell biology, LSL-T beta RI(CA) mouse constitutes an attractive tool to address the effect of TGFP signaling upregulation in any cell type expressing the cre-recombinase. genesis 46:724-731, 2008. Published 2008 Wiley-Liss, Inc. C1 [Bartholin, Laurent] Ctr Leon Berard, INSERM, Avenir Grp, U590,IFR62, F-69373 Lyon 08, France. [Bartholin, Laurent; Cyprian, Farhan S.; Vincent, David; Garcia, Celine N.; Horvat, Branka; Rimokh, Ruth; Marie, Julien C.] Univ Lyon 1, F-69365 Lyon, France. [Cyprian, Farhan S.; Garcia, Celine N.; Horvat, Branka; Marie, Julien C.] INSERM, U758, IFR128, F-69008 Lyon, France. [Cyprian, Farhan S.; Garcia, Celine N.; Horvat, Branka; Marie, Julien C.] ENS, Lyon, France. [Berthet, Cyril] NIH, Ctr Canc Res, Frederick, MD USA. RP Bartholin, L (reprint author), Ctr Leon Berard, INSERM, Avenir Grp, U590,IFR62, 28 Laennec, F-69373 Lyon 08, France. EM bartholi@lyon.fnclcc.fr RI Rimokh, Ruth/G-7506-2014; Marie, Julien/I-5084-2016; Horvat, Branka/M-3504-2014; OI Vincent, David/0000-0001-6482-8040; Horvat, Branka/0000-0003-0578-7765; Cyprian, Farhan/0000-0001-8162-8673 FU INSERM "Avenir Program"; INCA; Ligue comite du Rhone [ANR-06-JC]; ARC [3989, 3891] FX Contract grant sponsor: INSERM "Avenir Program" (L.B.), ARC 3891 (L.B.), INCA (L.B., R.R. and J.C.M.) and Ligue comite du Rhone (L.B. and J.C.M.), ANR-06-JC (J.C.M.). ARC 3989 (J.C.M.). F.S.C. is a MRT fellow NR 25 TC 14 Z9 14 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD DEC PY 2008 VL 46 IS 12 BP 724 EP 731 DI 10.1002/dvg.20425 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 390HW UT WOS:000262155900003 PM 18821589 ER PT J AU Rong, YS AF Rong, Yikang S. TI Loss of the Histone Variant H2A.Z Restores Capping to Checkpoint-Defective Telomeres in Drosophila SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAK; DNA; HETEROCHROMATIN; MELANOGASTER; GENE; ATM; CHROMOSOMES; MAINTENANCE; COMPLEX; PROTEIN AB The conserved histone variant H2A.Z fulfills many functions by being an integral part of the nucleosomes placed at specific regions of the genome. Telomeres cap natural ends of chromosomes to prevent their recognition as double-strand breaks. At yeast telomeres, H2A.Z prevents the spreading of silent chromatin into proximal enchromatin. A role for H2A.Z in capping, however, has not been reported in any organism. Here, I uncover such a role for Drosophila H2A.Z. Loss of H2A.Z, through Initiations in either its gene or the domino gene For the Swr1 chromatin-remodeling protein, suppressed the fusion of telomeres that lacked the protection of checkpoint proteins: ATM, ATR, and the Mre11-Rad50-NBS complex. Loss of H2A.Z partially restores the loading of the HOAP capping protein, possibly accounting for the partial restoration in capping. I propose that, in the absence of H2A.Z, checkpoint-defective telomeres adopt alternative structures, which are permissive for the loading of the capping machinery at: Drosophila telomeres. C1 NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rong, YS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bldg 37,Room 6056,37 Convent Dr, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI rong, yikang/G-6179-2011 FU Intramural NIH HHS NR 28 TC 9 Z9 10 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 2008 VL 180 IS 4 BP 1869 EP 1875 DI 10.1534/genetics.108.095547 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 388PB UT WOS:000262030600009 PM 18845840 ER PT J AU Darcy, KM Brady, WE McBroom, JW Bell, JG Young, RC McGuire, WP Linnolia, RI Hendricks, D Bonome, T Farley, JH AF Darcy, Kathleen M. Brady, William E. McBroom, John W. Bell, Jeffrey G. Young, Robert C. McGuire, William P. Linnolia, R. Ilona Hendricks, Denver Bonome, Tomas Farley, John H. TI Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers: A Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE p53; Overexpression; IHC; Ovarian cancer; Prognostic markers ID CISPLATIN-BASED CHEMOTHERAPY; PLATINUM-BASED CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; OVER-EXPRESSION; GENE-MUTATIONS; C-MYC; CARCINOMA; PROTEIN; PACLITAXEL; SURVIVAL AB Objective. The Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC). Methods. Women were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel+carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide+cisplatin vs. paclitaxel+cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and Mutant p53-isoforms. p53 overexpression was defined as >= 10%, tumor cells exhibiting nuclear staining. Results. p53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progress ion-free survival (PFS) (logrank test: p=0.013; unadjusted Cox modeling: p=0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p=0.018) and grade (p=0.003), but not With age, stage, cell type or with tumor response and disease C1 [Farley, John H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Darcy, Kathleen M.; Brady, William E.] GOG Stat & Data Ctr, Buffalo, NY 14263 USA. [McBroom, John W.] GOG Hawaii MCCOP, Honolulu, HI 96859 USA. [Bell, Jeffrey G.] Riverside Methodist Hosp, Columbus, OH 43214 USA. [Young, Robert C.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [McGuire, William P.] Franklin Sq Hosp Ctr, Harry & Jeanette Weinberg Canc Inst, Baltimore, MD 21237 USA. [Linnolia, R. Ilona; Hendricks, Denver; Bonome, Tomas] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Farley, JH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM john.farley@us.army.mil FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group Statistical and Data Center [CA 37517]; National Institute of Health FX This study was supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical and Data Center(CA 37517), and the Intramural Research program of the National Cancer Institute of the National Institute of Health. The following Gynecologic Oncology Group (GOG) institutions participated in this Study: University of Alabama at Birmingham, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University, University of Mississippi Medical Center, Colorado Gynecologic Oncology Group P.C., University of California at Los Angeles, University of Washington, University of Pennsylvania Cancer Center, Milton S. Hershey Medical Center, University of Cincinnati, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Southwestern Medical Center of Dallas, Indiana University Medical Center, Georgetown University Hospital, Wake Forest University School of Medicine, Albany Medical College, University of California Medical Center at Irvine, Tufts-New England Medical Center, Rush-Presbyterian-St. Luke's Medical Center, SUNY Downstate Medical Center, University of Kentucky, The Cleveland Clinic Foundation, SUNY at Stony Brook, Washington University School of Medicine, Johns Hopkins Oncology Center. Eastern Pennsylvania Gyn/One Center, P.C., Cooper Hospital/University Medical Center, Columbus Cancer Council, University of Massachusetts Medical Center, Fox Chase Cancer Center, Medical University of South Carolina, Women's Cancer Center, University of Oklahoma, University of Virginia, University of Chicago, Tacoma General Hospital, Thomas Jefferson University Hospital, Mayo Clinic, Case Western Reserve University, Tampa Bay Cancer Consortium, North Shore University Hospital, and Brookview Research Inc. NR 48 TC 26 Z9 27 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 DEC PY 2008 VL 111 IS 3 BP 487 EP 495 DI 10.1016/j.ygyno.2008.08.020 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 384PZ UT WOS:000261758000018 PM 18834621 ER PT J AU Sullivan, HW Beckjord, EB Rutten, LJF Hesse, BW AF Sullivan, Helen W. Beckjord, Ellen Burke Rutten, Lila J. Finney Hesse, Bradford W. TI Nutrition-Related Cancer Prevention Cognitions and Behavioral Intentions: Testing the Risk Perception Attitude Framework SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE risk perception attitude framework; Health Information National Trends Survey; cancer prevention ID NATIONAL TRENDS SURVEY; HEALTH INFORMATION; FEAR APPEALS; PERCEIVED RISK; SELF-EFFICACY; BELIEFS; METAANALYSIS; INDIVIDUALS; MOTIVATORS; FRUIT AB This study tested whether the risk perception attitude framework predicted nutrition-related cancer prevention cognitions and behavioral intentions. Data from the 2003 Health Information National Trends Survey were analyzed to assess respondents' reported likelihood of developing cancer ( risk) and perceptions of whether they could lower their chances of getting cancer ( efficacy). Respondents with higher efficacy were more likely to report that good nutrition can prevent cancer, and they reported more preventive dietary changes, as compared to respondents with lower efficacy. Respondents with higher efficacy were more likely to report intentions to change their diets to prevent cancer, and they reported more preventive dietary changes to their own diets but only at higher levels of risk. Results suggest that to improve cognitions about the role of nutrition in cancer prevention, interventions should target cancer prevention efficacy; however, to increase intentions to change nutrition behaviors, interventions should target efficacy and risk perceptions. C1 [Sullivan, Helen W.; Rutten, Lila J. Finney; Hesse, Bradford W.] NCI, Bethesda, MD 20892 USA. [Beckjord, Ellen Burke] RAND Corp, Pittsburgh, PA USA. RP Sullivan, HW (reprint author), NCI, 6130 Executive Blvd, Bethesda, MD 20892 USA. EM helen@aya.yale.edu OI Hesse, Bradford/0000-0003-1142-1161 FU Intramural NIH HHS [NIH0012158036]; PHS HHS [NIH0012158036] NR 21 TC 6 Z9 6 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD DEC PY 2008 VL 35 IS 6 BP 866 EP 879 DI 10.1177/1090198108326164 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 372WC UT WOS:000260932000009 PM 19011220 ER PT J AU Young, DR Steckler, A Cohen, S Pratt, C Felton, G Moe, SG Pickrel, J Johnson, CC Grieser, M Lytle, LA Lee, JS Raburn, B AF Young, D. R. Steckler, A. Cohen, S. Pratt, C. Felton, G. Moe, S. G. Pickrel, J. Johnson, C. C. Grieser, M. Lytle, L. A. Lee, J. -S. Raburn, B. TI Process evaluation results from a school- and community-linked intervention: the Trial of Activity for Adolescent Girls (TAAG) SO HEALTH EDUCATION RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; AMERICAN-INDIAN SCHOOLCHILDREN; PHYSICAL-ACTIVITY; PREVENTION TRIAL; PROMOTION; EDUCATION; PROGRAMS; PATHWAYS; STUDENTS; OBESITY AB Process evaluation is a component of intervention research that evaluates whether interventions are delivered and received as intended. Here, we describe the process evaluation results for the Trial of Activity for Adolescent Girls (TAAG) intervention. The intervention consisted of four synergistic components designed to provide supportive school- and community-linked environments to prevent the decline in physical activity in adolescent girls. Process evaluation results indicate that the intervention components were delivered from intervention staff to teachers with high fidelity (84-97%) to the protocol and with lower fidelity (range: 18-93%) from teachers to students. Physical activity programs for girls, a unique feature of the TAAG intervention, increased from a mean of 10 programs per school to a mean of 16 and 15 in years 1 and 2, respectively, in intervention schools, with no change in control schools. These findings suggest that a multicomponent school- and community-based physical activity intervention can be delivered with fidelity and result in a middle school environment that supports physical activity for girls. C1 [Young, D. R.] Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. [Steckler, A.; Raburn, B.] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. [Cohen, S.] Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85719 USA. [Pratt, C.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Felton, G.] Univ S Carolina, William Brice Coll Nursing, Columbia, SC 29208 USA. [Moe, S. G.; Lytle, L. A.] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55454 USA. [Johnson, C. C.] Tulane Univ, Dept Community Hlth Sci, New Orleans, LA 70112 USA. [Grieser, M.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Lee, J. -S.] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Pickrel, J.] San Diego State Univ, Ctr Behav & Community Hlth Studies, San Diego, CA 92182 USA. RP Young, DR (reprint author), Univ Maryland, Dept Epidemiol & Biostat, College Pk, MD 20742 USA. EM dryoung@umd.edu FU NHLBI NIH HHS [U01HL66853, U01 HL066845, U01 HL066845-01, U01HL66845, U01HL66852, U01HL66855, U01HL66856, U01HL66857, U01HL66858] NR 26 TC 39 Z9 40 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 2008 VL 23 IS 6 BP 976 EP 986 DI 10.1093/her/cyn029 PG 11 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 373MA UT WOS:000260974800007 PM 18559401 ER PT J AU Frankel, A Grillo, SP Pittman, M Thomas, EJ Horowitz, L Page, M Sexton, B AF Frankel, Allan Grillo, Sarah Pratt Pittman, Mary Thomas, Eric J. Horowitz, Lisa Page, Martha Sexton, Bryan TI Revealing and Resolving Patient Safety Defects: The Impact of Leadership WalkRounds on Frontline Caregiver Assessments of Patient Safety SO HEALTH SERVICES RESEARCH LA English DT Article DE WalkRounds; patient safety; safety culture; safety climate; quality improvement; senior leader partnerships ID CLIMATE; CULTURE AB To evaluate the impact of rigorous WalkRounds on frontline caregiver assessments of safety climate, and to clarify the steps and implementation of rigorous WalkRounds. Primary outcome variables were baseline and post WalkRounds safety climate scores from the Safety Attitudes Questionnaire (SAQ). Secondary outcomes were safety issues elicited through WalkRounds. Study period was August 2002 to April 2005; seven hospitals in Massachusetts agreed to participate; and the project was implemented in all patient care areas. Prospective study of the impact of rigorously applied WalkRounds on frontline caregivers assessments of safety climate in their patient care area. WalkRounds were conducted weekly and according to the seven-step WalkRounds Guide. The SAQ was administered at baseline and approximately 18 months post-WalkRounds implementation to all caregivers in patient care areas. Two of seven hospitals complied with the rigorous WalkRounds approach; hospital A was an academic teaching center and hospital B a community teaching hospital. Of 21 patient care areas, SAQ surveys were received from 62 percent of respondents at baseline and 60 percent post WalkRounds. At baseline, 10 of 21 care areas (48 percent) had safety climate scores below 60 percent, whereas post-WalkRounds three care areas (14 percent) had safety climate scores below 60 percent without improving by 10 points or more. Safety climate scale scores in hospital A were 62 percent at baseline and 77 percent post-WalkRounds (t=2.67, p=.03), and in hospital B were 46 percent at baseline and 56 percent post WalkRounds (t=2.06, p=.06). Main safety issues by category were equipment/facility (A [26 percent] and B [33 percent]) and communication (A [24 percent] and B [18 percent]). WalkRounds implementation requires significant organizational will; sustainability requires outstanding project management and leadership engagement. In the patient care areas that rigorously implemented WalkRounds, frontline caregiver assessments of patient safety increased. SAQ results such as safety climate scores facilitate the triage of quality improvement efforts, and provide consensus assessments of frontline caregivers that identify themes for improvement. C1 [Frankel, Allan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Pittman, Mary] Inst Publ Hlth, Oakland, CA USA. [Thomas, Eric J.] Univ Texas Houston, Sch Med, Houston, TX USA. [Horowitz, Lisa] NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Page, Martha] N Shore Med Ctr, Salem, MA USA. [Sexton, Bryan] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Johns Hopkins Qual & Safety Res Grp, Baltimore, MD 21205 USA. RP Frankel, A (reprint author), 15 Whitetail Lane, Sudbury, MA 01776 USA. EM allan.frankel@lotusforum.com RI Santos, Fernando/H-3257-2011 FU AHRQ [1PO1HS1154401]; RWJ Foundation [58292] FX We would like to thank the Health Resources & Services Administration for the original WalkRounds grant, and the Health Research and Educational Trust for the opportunity to significantly refine the process and supporting materials related to WalkRounds. We would like to acknowledge Lou Woolf, Robert Norton, Alex Ferraro, Jennifer Costain, Eileen Sporing, James Mandel, and Sandra Fenwick for their participation in developing WalkRounds in their institutions, and Christine G. Holzmueller for her assistance in editing this manuscript. Dr. Eric Thomas was supported by AHRQ grant # 1PO1HS1154401, and Dr. Bryan Sexton was supported by RWJ Foundation grant 58292. NR 16 TC 46 Z9 48 U1 3 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2008 VL 43 IS 6 BP 2050 EP 2066 DI 10.1111/j.1475-6773.2008.00878.x PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 372BZ UT WOS:000260877700009 PM 18671751 ER PT J AU Ashktorab, H Dashwood, RH Dashwood, MM Zaidi, SI Hewitt, SM Green, WR Lee, EL Daremipouran, M Nouraie, M Malekzadeh, R Smoot, DT AF Ashktorab, Hassan Dashwood, Rod H. Dashwood, Mohaiza M. Zaidi, Syed I. Hewitt, Stephen M. Green, William R. Lee, Edward L. Daremipouran, Mohammadreza Nouraie, Mehdi Malekzadeh, Reza Smoot, Duane T. TI H-pylori-Induced Apoptosis in Human Gastric Cancer Cells Mediated via the Release of Apoptosis-Inducing Factor from Mitochondria SO HELICOBACTER LA English DT Article DE AIF; H; pylori; gastric cells; apoptosis; mitochondria ID ACTIVATED-RECEPTOR-GAMMA; C-INDEPENDENT PATHWAY; NECROSIS-FACTOR-ALPHA; HELICOBACTER-PYLORI; CYTOCHROME-C; EPITHELIAL-CELLS; PERMEABILITY TRANSITION; BAX TRANSLOCATION; IN-VIVO; EXPRESSION AB Our previous study of Helicobacter pylori-induced apoptosis showed the involvement of Bcl-2 family proteins and cytochrome c release from mitochondria. Here, we examine the release of other factors from mitochondria, such as apoptosis-inducing factor (AIF), and upstream events involving caspase-8 and Bid. Human gastric adenocarcinoma (AGS) cells were incubated with a cagA-positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected. Proteins were immunoblotted for AIF, Bid, polyadenosine ribose polymerase (PARP), caspase-8, and beta-catenin. H. pylori activated caspase-8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time-dependent decrease in beta-catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with a decrease in beta-actin. An increase in the cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band corresponding to full-length Bid was seen in both the cytoplasmic and the nuclear fractions of controls, but not after H. pylori exposure. Active AIF staining was markedly increased in gastric mucosa from infected persons, compared to uninfected controls. H. pylori might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase-8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin. This is consistent with AIF activation that was found in the gastric mucosa of humans infected with H. pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer. C1 [Ashktorab, Hassan; Daremipouran, Mohammadreza; Nouraie, Mehdi; Smoot, Duane T.] Howard Univ, Dept Med, Gastrointestinal Div, Washington, DC 20059 USA. [Ashktorab, Hassan; Daremipouran, Mohammadreza; Nouraie, Mehdi; Smoot, Duane T.] Howard Univ, Ctr Canc, Washington, DC 20059 USA. [Dashwood, Rod H.; Dashwood, Mohaiza M.] Univ Oregon, Linus Pauling Inst, Corvallis, OR USA. [Zaidi, Syed I.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Green, William R.; Lee, Edward L.] Howard Univ, Dept Pathol, Washington, DC 20059 USA. [Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Director Digest Dis Res Ctr, Tehran, Iran. RP Ashktorab, H (reprint author), Howard Univ Hosp, Ctr Canc, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM hashktorab@howard.edu RI Dashwood, Roderick/E-9090-2011; OI Hewitt, Stephen/0000-0001-8283-1788; Malekzadeh, Reza/0000-0003-1043-3814 FU National Institutes of Health [DK53713, DK56664] FX The first two authors contributed equally. This work was supported by Public Health Service grants from the National Institutes of Health, DK53713 and DK56664. NR 64 TC 20 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD DEC PY 2008 VL 13 IS 6 BP 506 EP 517 DI 10.1111/j.1523-5378.2008.00646.x PG 12 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 371HV UT WOS:000260823300004 PM 19166416 ER PT J AU Frankenberg, T Miloh, T Chen, FY Ananthanarayanan, M Sun, AQ Balasubramaniyan, N Arias, I Setchell, KDR Suchy, FJ Shneider, BL AF Frankenberg, Tamara Miloh, Tamir Chen, Frank Y. Ananthanarayanan, Meena Sun, An-Qiang Balasubramaniyan, Natarajan Arias, Irwin Setchell, Kenneth D. R. Suchy, Frederick J. Shneider, Benjamin L. TI The Membrane Protein ATPase Class I Type 813 Member 1 Signals Through Protein Kinase C Zeta To Activate the Farnesoid X Receptor SO HEPATOLOGY LA English DT Article ID FAMILIAL INTRAHEPATIC CHOLESTASIS; BILE-ACID TRANSPORTER; NEGATIVE FEEDBACK-REGULATION; SALT EXPORT PUMP; NUCLEAR RECEPTOR; HEREDITARY CHOLESTASIS; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; LIVER-REGENERATION; SMALL-INTESTINE; PKC-ZETA AB Prior loss-of-function analyses revealed that ATPase class I type 8B member 1 [familial intrahepatic cholestasis 1 (FICI)] posttranslationally activated the farnesoid X receptor (FXR). Mechanisms underlying this regulation were examined by gain-of-function studies in UPS cells, which lack endogenous FICI expression. FXR function was assayed in response to wild-type and mutated FICI expression constructs with a human bile salt export pump (BSEP) promoter and a variety of cellular localization techniques. FICI overexpression led to enhanced phosphorylation and nuclear localization of FXR that was associated with FXR-dependent activation of the BSEP promoter. The FICI effect was lost after mutation of the FXR response element in the BSEP promoter. Despite similar levels of FICI protein expression, Byler disease FICI mutants did not activate BSEP, whereas benign recurrent intrahepatic cholestasis mutants partially activated BSEP. The FICI effect was dependent on the presence of the FXR ligand, chenodeoxycholic acid. The effect of FICI on FXR phosphorylation and nuclear localization and its effects on BSEP promoter activity could be blocked with protein kinase C zeta (PKC zeta) inhibitors (pseudosubstrate or small interfering RNA silencing). Recombinant PKC zeta directly phosphorylated immunoprecipitated FXR. The mutation of threonine 442 of FXR to alanine yielded a dominant negative protein, whereas the phosphomimetic conversion to glutamate resulted in FXR with enhanced activity and nuclear localization. Inhibition of PKC zeta in Caco-2 cells resulted in activation of the human apical sodium-dependent bile acid transporter promoter. Conclusion: These results demonstrate that FICI signals to FXR via PKC. FICI-related liver disease is likely related to downstream effects of FXR on bile acid homeostasis. Benign recurrent intrahepatic cholestasis emanates from a partially functional FICI protein. Phosphorylation of FXR is an important mechanism for regulating its activity. (HEPATOLOGY 2008;48:1896-1905.) C1 [Frankenberg, Tamara; Miloh, Tamir; Ananthanarayanan, Meena; Sun, An-Qiang; Balasubramaniyan, Natarajan; Suchy, Frederick J.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Chen, Frank Y.; Shneider, Benjamin L.] Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Pediat Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. [Chen, Frank Y.; Shneider, Benjamin L.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. [Arias, Irwin] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. [Setchell, Kenneth D. R.] Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. [Setchell, Kenneth D. R.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. RP Shneider, BL (reprint author), Univ Pittsburgh, Med Ctr, Childrens Hosp Pittsburgh, Div Pediat Gastroenterol Hepatol & Nutr, 3705 5th Ave, Pittsburgh, PA 15213 USA. EM benjamin.shneider@chp.edu FU National Institutes of Health [DK54165, 6,9942] FX This work was supported in part by grants from the National Institutes of Health (DK54165 and 6,9942 to B.L.S. and HD 20632 to F.J.S.). NR 54 TC 54 Z9 55 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2008 VL 48 IS 6 BP 1896 EP 1905 DI 10.1002/hep.22431 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 376YP UT WOS:000261219200019 PM 18668687 ER PT J AU Voutetakis, A Zheng, CY Metzger, M Cotrim, AP Donahue, RE Dunbar, CE Baum, BJ AF Voutetakis, Antonis Zheng, Changyu Metzger, Mark Cotrim, Ana P. Donahue, Robert E. Dunbar, Cynthia E. Baum, Bruce J. TI Sorting of Transgenic Secretory Proteins in Rhesus Macaque Parotid Glands After Adenovirus-Mediated Gene Transfer SO HUMAN GENE THERAPY LA English DT Article ID RAT SUBMANDIBULAR-GLANDS; SALIVARY-GLANDS; IN-VIVO; GROWTH-HORMONE; ENDOCRINE SECRETION; NONHUMAN-PRIMATES; EPITHELIAL-CELLS; THERAPEUTICS; DELIVERY; AQUAPORIN-1 AB We have previously used viral vectors encoding either human growth hormone (hGH) or erythropoietin (hEPO) to study the sorting of transgenic proteins in mouse and minipig salivary glands. Whereas hGH (a regulated secretory pathway [RSP] protein) is secreted predominantly into saliva in both species, hEPO (a constitutive secretory pathway [CSP] protein) is found primarily in the bloodstream with mice, but overwhelmingly in saliva with minipigs. In view of the hEPO sorting difference, we have conducted a similar study in nonhuman primates. Specifically, we examined hGH and hEPO sorting after adenoviral (Ad) vector-mediated gene transfer to parotid glands of rhesus macaques, another large and important animal model. Two groups (n = 2 per dose group; total n = 8) of male macaques received either 1010 particles per gland (low-dose group) or 1011 particles per gland (high-dose group) of adenoviral (Ad) vectors encoding either hGH (AdhGH) or hEPO (AdhEPO) via intraoral cannulation of both parotid glands. All macaques tolerated administration of Ad vectors well, with no clinically significant changes observed in any hematological and serum chemistry parameters. In AdhGH-treated animals, hGH was secreted exclusively into saliva. In contrast, after AdhEPO delivery, hEPO was secreted both in serum and saliva, at levels intermediate between mice and minipigs. We conclude that RSP proteins are faithfully secreted into saliva in all model species tested, whereas patterns of CSP protein secretion are variable. C1 [Voutetakis, Antonis; Zheng, Changyu; Cotrim, Ana P.; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bethesda, MD 20892 USA. [Metzger, Mark; Donahue, Robert E.; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, Bldg 10,Room 1N113,MSC-1190,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Divisions of Intramural Research of the National Institute of Dental and Craniofacial Research; National, Heart, Lung, and Blood Institute; National Institutes of Health FX The authors thank Tatiana Usherson and Brent Gordon for assistance in vector administration and sample collection, and Earl West for performing all the complete blood counts and clinical chemistries. These studies were supported by the Divisions of Intramural Research of the National Institute of Dental and Craniofacial Research and the National, Heart, Lung, and Blood Institute, National Institutes of Health. NR 32 TC 20 Z9 20 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2008 VL 19 IS 12 BP 1401 EP 1405 DI 10.1089/hum.2008.034 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 386DR UT WOS:000261863000006 PM 18764738 ER PT J AU Lindegaard, ML Wassif, CA Vaisman, B Amar, M Wasmuth, EV Shamburek, R Nielsen, LB Remaley, AT Porter, FD AF Lindegaard, Marie L. Wassif, Christopher A. Vaisman, Boris Amar, Marcelo Wasmuth, Elizabeth V. Shamburek, Robert Nielsen, Lars B. Remaley, Alan T. Porter, Forbes D. TI Characterization of placental cholesterol transport: ABCA1 is a potential target for in utero therapy of Smith-Lemli-Opitz syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR SR-BI; FOAM CELL ACCUMULATION; LIVER-X RECEPTORS; SCAVENGER RECEPTOR; HDL RECEPTOR; NUCLEAR RECEPTORS; FETAL CIRCULATION; APOLIPOPROTEIN-E; HUMAN FETUS AB Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer by similar to 30%. In contrast, disruption of the Abcg1 had no effect. Treatment of pregnant C57Bl/6 female mice with TO901317, an LXR-agonist, increased both Abca1 expression and maternal-fetal cholesterol transfer to the fetus. In an SLOS mouse model (Dhcr7(-/-)), which is incapable of de novo synthesis of cholesterol, in utero treatment with TO901317 resulted in increased cholesterol content in Dhcr7(-/-) embryos. Our data support the hypothesis that Abca1, and possibly Sr-b1, contributes to transport maternal cholesterol to the developing fetus. Furthermore, we show, as a proof of principle, that modulating maternal-fetal cholesterol transport has potential for in utero therapy of SLOS. C1 [Lindegaard, Marie L.; Nielsen, Lars B.] Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark. [Lindegaard, Marie L.; Wassif, Christopher A.; Wasmuth, Elizabeth V.; Porter, Forbes D.] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, Bethesda, MD USA. [Vaisman, Boris; Amar, Marcelo; Shamburek, Robert; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Nielsen, Lars B.] Univ Copenhagen, Dept Biomed Sci, DK-1168 Copenhagen, Denmark. RP Lindegaard, ML (reprint author), Rigshosp, Dept Clin Biochem, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM marie.s.lindegaard@dadlnet.dk OI Wassif, Christopher/0000-0002-2524-1420 FU Eunice Kennedy Schriver National Institute of Child Health and Human Development; National Heart, Lung and Blood Institute; National Institutes of Health; Lundbeck Foundation; Danish Medical Research Council [271-06-0722] FX This work was supported by the intramural programs of Eunice Kennedy Schriver National Institute of Child Health and Human Development; National Heart, Lung and Blood Institute, National Institutes of Health; The Lundbeck Foundation and the Danish Medical Research Council (# 271-06-0722). NR 53 TC 33 Z9 34 U1 0 U2 0 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 DEC 1 PY 2008 VL 17 IS 23 BP 3806 EP 3813 DI 10.1093/hmg/ddn278 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 373OG UT WOS:000260980800018 PM 18775956 ER PT J AU McKnight, DA Hart, PS Hart, TC Hartsfield, JK Wilson, A Wright, JT Fisher, LW AF McKnight, Dianalee A. Hart, P. Suzanne Hart, Thomas C. Hartsfield, James K. Wilson, Anne Wright, J. Timothy Fisher, Larry W. TI A Comprehensive Analysis of Normal Variation and Disease-Causing Mutations in the Human DSPP Gene SO HUMAN MUTATION LA English DT Article DE dentin sialophosphoprotein; DSPP; dentinogenesis imperfecta; dentin dysplasia; CpNpG methylation; epigenetics; slip-replication ID IMPERFECTA TYPE-II; NON-CPG METHYLATION; EMBRYONIC STEM-CELLS; DENTINOGENESIS-IMPERFECTA; DNA METHYLATION; OSTEOGENESIS IMPERFECTA; DENTIN PHOSPHOPROTEIN; EXPRESSION; PROTEINS; PATTERNS AB Within nine dentin dysplasia (DD) (type II) and dentinogenesis imperfecta (type II and III) patient/families, seven have 1 of 4 net -1 deletions within the similar to 2-kb coding repeat domain of the DSPP gene while the remaining two patients have splice-site mutations. All frameshift mutations are predicted to change the highly soluble DSPP protein into proteins with long hydrophobic amino acid repeats that could interfere with processing of normal DSPP and/or other secreted matrix proteins. We propose that all previously reported missense, nonsense, and splice-site DSPP mutations (all associated with exons 2 and 3) result in dominant phenotypes due to disruption of signal peptide-processing and/or related biochemical events that also result in interference with protein processing. This would bring the currently known dominant forms of the human disease phenotype in agreement with the normal phenotype of the heterozygous null Dspp (-/+) mice. A study of 188 normal human chromosomes revealed a hypervariable DSPP repeat domain with extraordinary rates of change including 20 slip-replication indel events and 37 predominantly C-to-T transition SNPs. The most frequent transition in the primordial 9-basepair (bp) DNA repeat was a sense-strand CpG site while a CpNpG (CAG) transition was the second most frequent SNP Bisulfite-sequencing of genomic DNA showed that the DSPP repeat can be methylated at both motifs. This suggests that, like plants and some animals, humans methylate some CpNpG sequences. Analysis of 37 haplotypes of the highly variable DSPP gene from geographically diverse people suggests it may be a useful autosomal marker in human migration studies. Hum Mutat 29(12), 1392-1404, 2008. Published 2008, Wiley-Liss, Inc. C1 [McKnight, Dianalee A.; Fisher, Larry W.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Hart, P. Suzanne] NHGRI, Off Clin Director, NIH, DHHS, Bethesda, MD 20892 USA. [Hart, Thomas C.] NIDCR, Sect Human & Craniofacial Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Hartsfield, James K.] Indiana Univ, Sch Dent, Dept Orthodont & Oral Facial Genet, Indianapolis, IN USA. [Wilson, Anne] Univ Colorado, Sch Dent Med, Dept Pediat Dent, Aurora, CO USA. [Wright, J. Timothy] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC USA. RP Fisher, LW (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bldg 30,Room 228,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU Division of Intramural Research (DIR); NIH, DHHS; NIDCR; NHGRI FX Division of Intramural Research (DIR), Intramural Research Program (IRP), NIH, DHHS: NIDCR, Intramural Research Program (IRP), NIH, DHHS; NHGRI, Intramural Research Program (IRP), NIH, DHHS. NR 56 TC 46 Z9 49 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD DEC PY 2008 VL 29 IS 12 BP 1392 EP 1404 DI 10.1002/humu.20783 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 383JZ UT WOS:000261671200003 PM 18521831 ER PT J AU Lasota, J Kuban, W Wardelmann, E Debiec-Rychter, M Merkelbach-Bruse, S Sciot, R Rys, J Steigen, SE Iwanik, K Holden, JA Dobosz, AJV Schildhaus, HU Miettinen, M AF Lasota, Jerzy Kuban, Wojciech Wardelmann, Eva Debiec-Rychter, Maria Merkelbach-Bruse, Sabine Sciot, Raf Rys, Janusz Steigen, Sonja E. Iwanik, Katarzyna Holden, Joseph A. Dobosz, Anna Jerzak vel Schildhaus, Hans-Ulrich Miettinen, Markku TI KIT codon 558 insertions in gastrointestinal stromal tumors. Analysis of 17 rare KIT mutants SO HUMAN PATHOLOGY LA English DT Article DE GIST; KIT; Exon 11; Insertion; Mutation ID TERM-FOLLOW-UP; C-KIT; PDGFRA MUTATIONS; TYROSINE KINASE; JUXTAMEMBRANE DOMAIN; INTERSTITIAL-CELLS; POOR-PROGNOSIS; GENE MUTATION; PRIMARY SITE; IMATINIB AB Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of gastrointestinal tract often driven by oncogenic KIT exon I I Mutations. Although deletions and substitutions are most frequent KIT exon I I mutations, duplications and insertions have been reported as well. In contrast to duplications, which cluster in 3'KIT exon 11, insertions affect 5'KIT particularly codon 558. Clinicopathologic profile of gastrointestinal stromal tumors with insertions in codon 558 is not known. In this study, 17 gastrointestinal stromal tumors with codon 558 insertions are reported. Fifteen (88.2%) KIT codon 558 insertions consisted of 1694_1695insTCC leading to Lys558delin-sAsnPro. However, 2 variant mutants Lys558delinsAsnGIn and Lys558delinsAsnAsn were also identified. Based on analysis of inserted and flanking sequences, the insertions contain inverted DNA sequences of the opposite strand. Therefore, these insertions may develop due to a DNA strand switch during replication by DNA polymerases and by the effects of several different DNA repair processes. Patient median age was 61 years, and male-to-female ratio was 1:1.8. gastrointestinal stromal tumors were diagnosed in stomach (n = 4), small intestine (n = 7), and rectum (n = 3). Three tumors were disseminated and primary location could not be established. Fourteen tumors had spindle cell morphology, and epithelioid cell features were seen in 2 intestinal and I disseminated gastrointestinal stromal tumor. Based on size and mitotic activity, 2 (50%) of 4 gastric and 3 (48.9%) of 7 small intestinal gastrointestinal stromal tumors had more than 50% risk of metastases according to previous studies of gastrointestinal stromal tumor prognosis. All 3 rectal gastrointestinal stromal tumors were malignant. Metastases were verified in 8 (66.7%) of 12 patients with known clinical and follow-tip data. In summary, KIT codon 558 insertions are rare mutations accounting for less than 1% of all KIT mutants. Gastrointestinal stromal tumors with these mutations appear to have predilection to female patients and intestinal location. Moreover, KIT codon 558 insertions might indicate an increased risk of malignant behavior for gastric gastrointestinal stromal tumors. (C) 2008 Published by Elsevier Inc. C1 [Lasota, Jerzy; Miettinen, Markku] Armed Forces Inst Pathol, Dept Soft Tissue Pathol, Washington, DC 20306 USA. [Kuban, Wojciech] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. [Wardelmann, Eva; Merkelbach-Bruse, Sabine; Schildhaus, Hans-Ulrich] Univ Bonn, Med Ctr, Dept Pathol, D-53127 Bonn, Germany. [Debiec-Rychter, Maria] Catholic Univ Louvain, Dept Human Genet, B-3000 Louvain, Belgium. [Sciot, Raf] Catholic Univ Louvain, Dept Pathol, B-3000 Louvain, Belgium. [Rys, Janusz] M Sklodowska Curie Mem Canc Ctr, Dept Pathol, PL-31115 Krakow, Poland. [Steigen, Sonja E.] Univ Tromso, Dept Pathol, N-9037 Tromso, Norway. [Rys, Janusz] Inst Oncol, PL-31115 Krakow, Poland. [Iwanik, Katarzyna] Karol Marcinkowski Med Univ, Dept Pathomorphol, PL-60355 Poznan, Poland. [Holden, Joseph A.] Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84112 USA. [Dobosz, Anna Jerzak vel] M Sklodowska Curie Mem Canc Ctr, Dept Mol Biol, PL-02784 Warsaw, Poland. [Dobosz, Anna Jerzak vel] Inst Oncol, PL-02784 Warsaw, Poland. RP Lasota, J (reprint author), Armed Forces Inst Pathol, Dept Soft Tissue Pathol, 6825 16th St NW, Washington, DC 20306 USA. EM lasota@afip.osd.mil RI Schildhaus, Hans-Ulrich/J-3094-2012 FU American Registry of Pathology (Washington, DC) [PBZ-KBN091/P05/2003]; Polish Ministry of Science (Warszawa, Poland) FX This study was partially supported by the American Registry of Pathology (Washington, DC), and by grant PBZ-KBN091/P05/2003 from the Polish Ministry of Science (Warszawa, Poland). NR 42 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 2008 VL 39 IS 12 BP 1728 EP 1736 DI 10.1016/j.humpath.2008.05.011 PG 9 WC Pathology SC Pathology GA 375LY UT WOS:000261116600003 PM 18715619 ER PT J AU Kim, HH Cannata, JM Liu, RB Chang, JH Silverman, RH Shung, KK AF Kim, Hyung Ham Cannata, Jonathan M. Liu, Ruibin Chang, Jin Ho Silverman, Ronald H. Shung, K. Kirk TI 20 MHz/40 MHz Dual Element Transducers for High Frequency Harmonic Imaging SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ULTRASOUND; DESIGN AB Concentric annular type dual element transducers for second harmonic imaging at 20 MHz / 40 MHz were designed and fabricated to improve spatial resolution and depth of penetration for ophthalmic imaging applications. The outer ring element was designed to transmit the 20 MHz signal and the inner circular element; was designed to receive the 40 MHz second harmonic signal. Lithium niobate (LiNbO(3)), With its low dielectric constant, was used as the piezoelectric material to achieve good electrical impedance matching. Double matching layers and conductive backing were used and optimized by KLM modeling to achieve high sensitivity and wide bandwidth for harmonic imaging and superior time-domain characteristics. Prototype transducers were fabricated and evaluated quantitatively and clinically. The average measured center frequency for the transmit ring element was 21 MHz and the one-way -3 dB bandwidth was greater than 50%. The 40 MHz receive element functioned at 31 MHz center frequency with acceptable bandwidth to receive attenuated and frequency downshifted harmonic signal. The lateral beam profile for the 20 MHz ring elements at the focus matched the Field 14 simulated results well, and the effect of outer ring diameter was also examined. Images of a posterior segment of an excised pig eye and a choroidal nevus of human eye were obtained both for single element and dual element; transducers and compared to demonstrate the advantages of dual element harmonic imaging. C1 [Kim, Hyung Ham; Cannata, Jonathan M.; Liu, Ruibin; Chang, Jin Ho; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, NIH, Resource Ctr Med Ultrason Transducer Technol, Los Angeles, CA 90036 USA. [Silverman, Ronald H.] Riverside Res Inst, New York, NY 10038 USA. [Silverman, Ronald H.] Weill Cornell Med Coll, New York, NY 10021 USA. RP Kim, HH (reprint author), Univ So Calif, Dept Biomed Engn, NIH, Resource Ctr Med Ultrason Transducer Technol, Los Angeles, CA 90036 USA. EM hyungham.kim@use.edu FU NIH [P41-EB002182, EB00238]; Research to Prevent Blindness; Dyson Foundation FX This work was supported by NIH grants P41-EB002182 and EB00238 and grants from Research to Prevent Blindness,and from the Dyson Foundation. NR 14 TC 17 Z9 17 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD DEC PY 2008 VL 55 IS 12 BP 2683 EP 2691 DI 10.1109/TUFFC.2008.983 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 391GM UT WOS:000262221800015 PM 19126492 ER PT J AU Single, RM Martin, MP Meyer, D Gao, XJ Carrington, M AF Single, Richard M. Martin, Maureen P. Meyer, Diogo Gao, Xiaojiang Carrington, Mary TI Methods for assessing gene content diversity of KIR with examples from a global set of populations SO IMMUNOGENETICS LA English DT Review DE Population genetics; Statistical methods; Selection; Coevolution; KIR; HLA ID IMMUNOGLOBULIN-LIKE RECEPTOR; KILLER-CELL RECEPTOR; LINKAGE DISEQUILIBRIUM; NATURAL-SELECTION; MAXIMUM-LIKELIHOOD; GENOMIC DIVERSITY; HAPLOTYPES; POLYMORPHISM; ALGORITHM; EVOLUTION AB A number of statistical methods are widely used to describe allelic variation at specific genetic loci and its implication on the evolutionary history of these loci. Although the methods were developed primarily to study allelic variation at loci that are virtually always present in the genome, they are often applied to data of gene content variation (i.e., presence/absence of multiple homologous genes) at the killer cell immunoglobulin-like receptor (KIR) gene cluster. In this paper, we discuss methodological issues involved in the analysis of gene content variation data in the KIR region and also its covariation with polymorphism at the human leukocyte antigen class I loci, which encode ligands for KIR. A comparison of several statistical methods and measures (gene frequency, haplotype frequency, and linkage disequilibrium estimation) using the Centre d'Etude du Polymorphisme Humain data will be provided using KIR haplotypes that have been determined by segregation analysis, noting the strengths and weaknesses of the methods when only the presence/absence data is considered. Finally, application of these methods to a set of globally distributed populations is described (see Single et al., Nat Genet 39:1114-1119, 2007) in order to illustrate the challenges faced when inferring the joint effects of natural selection and demographic history on these immune-related genes. C1 [Martin, Maureen P.; Gao, Xiaojiang; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Single, Richard M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Meyer, Diogo] Univ Sao Paulo, Dept Genet & Biol Evolut, BR-05608900 Sao Paulo, SP, Brazil. RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. EM carringt@ncifcrf.gov RI Meyer, Diogo/A-1868-2008 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH; National Cancer Institute; Center for Cancer Research; NIH/NIAID [HHSN266200400076C, ABD N01-AI-40076]; NASA [NNX 06AC88G]; FAPESP [03/01583-8] FX We thank G. Thomson for her comments on the manuscript, J. Hollenbach for the helpful discussions, and H. Rajeevan and M. Osier for their assistance with the ALFRED database. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This publication was supported in part by NIH/NIAID contract number HHSN266200400076C, ABD N01-AI-40076 ( R. M. S). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The computational resources provided by the Vermont Advanced Computing Center, which is supported by NASA (NNX 06AC88G), are gratefully acknowledged. D. M. was supported by FAPESP grant 03/01583-8. NR 49 TC 39 Z9 39 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2008 VL 60 IS 12 BP 711 EP 725 DI 10.1007/s00251-008-0331-1 PG 15 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 374RW UT WOS:000261062400001 PM 18797862 ER PT J AU Martin, MP Single, RM Wilson, MJ Trowsdale, J Carrington, M AF Martin, M. P. Single, R. M. Wilson, M. J. Trowsdale, J. Carrington, M. TI KIR haplotypes defined by segregation analysis in 59 Centre d'Etude Polymorphisme Humain (CEPH) families SO IMMUNOGENETICS LA English DT Article DE KIR haplotypes; CEPH; Linkage disequilibrium ID NATURAL-KILLER-CELLS; 3 ETHNIC-GROUPS; RECEPTOR GENES; GENOMIC DIVERSITY; CRYSTAL-STRUCTURE; HLA; POPULATIONS; SEQUENCES; EVOLUTION; SELECTION AB The killer cell immunoglobulin-like receptor (KIR) gene cluster exhibits extensive allelic and haplotypic diversity. Variation at the locus is associated with an increasing number of human diseases, reminiscent of the HLA loci. Characterization of diversity at the KIR locus has progressed over the past several years, particularly since the sequence of entire KIR haplotypes have become available. To determine the extent of KIR haplotypic variability among individuals of northern European descent, we genotyped 59 CEPH families for presence/absence of all KIR genes and performed limited allelic subtyping at several KIR loci. A total of 20 unique haplotypes differing in gene content were identified, the most common of which was the previously defined A haplotype (f=0.52). Several unusual haplotypes that probably arose as a consequence of unequal crossing over events were also identified. Linkage disequilibrium (LD) analysis indicated strong negative and positive LD between several pairs of genes, values that may be useful in determining haplotypic structure when family data are not available. These data provide a resource to aid in the interpretation of disease association data involving individuals of European descent. C1 [Martin, M. P.; Carrington, M.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Single, R. M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Wilson, M. J.] CSL Ltd, Inst Bio21, Parkville, Vic 3010, Australia. [Trowsdale, J.] Univ Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, England. RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400]; Center for Cancer Research; NIH/NIAID [HHSN266200400076C, ABD N01-AI40076]; NASA [NNX 06AC88G] 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 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. This Research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This publication was supported in part by NIH/NIAID contract number HHSN266200400076C, ABD N01-AI40076 (R. M. S). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The computational resources provided by the Vermont Advanced Computing Center which is supported by NASA (NNX 06AC88G) are gratefully acknowledged. J. T. and M. W. were supported by grants from MRC and Wellcome. We thank Arman Bashirova for her assistance with Fig. NR 52 TC 33 Z9 34 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 2008 VL 60 IS 12 BP 767 EP 774 DI 10.1007/s00251-008-0334-y PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 374RW UT WOS:000261062400006 PM 18972110 ER PT J AU Lyakh, L Trinchieri, G Provezza, L Carra, G Gerosa, F AF Lyakh, Lyudmila Trinchieri, Giorgio Provezza, Lisa Carra, Giuseppe Gerosa, Franca TI Regulation of interleukin-12/interleukin-23 production and the T-helper 17 response in humans SO IMMUNOLOGICAL REVIEWS LA English DT Review DE interleukin-12; interleukin-17; interleukin-23; T-helper 17; Mycobacterium tuberculosis; zymosan ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; ACTIVATED PROTEIN-KINASE; CELL STIMULATORY FACTOR; HUMAN DENDRITIC CELLS; GROWTH-FACTOR-BETA; COLLAGEN-INDUCED ARTHRITIS; SEQUENCE-BINDING-PROTEIN; INTERLEUKIN-12 P35 GENE AB Interleukin-12 (IL-12) and IL-23 share a common chain. Yet, their production in response to pathogens is differentially regulated, and their functions are distinct and often antithetic. IL-12 is involved in the induction or amplification of the T-helper (Th) type 1 response, whereas IL-23 has been associated with the generation of the Th17 response and IL-17 production. Mycobacterium tuberculosis and yeast zymosan induce IL-23, but in the absence of other stimuli, no IL-12 is induced in human dendritic cells (DCs). The stimulation of IL-23 by M. tuberculosis was mostly explained by the triggering of Toll-like receptor (TLR2) and the cytoplasmic receptor nucleotide oligomerization domain (NOD)-containing protein 2, whereas zymosan induces IL-23 primarily by stimulating the beta-glucan receptor dectin-1 alone or in combination with TLR2. IL-23, IL-6, transforming growth factor (TGF-beta 1), and IL-1 beta in supernatants from activated human DCs induce human naive CD4(+) T cells to produce IL-17. These data are consistent with various recent reports that TGF-beta is an inducer of IL-17 production both in human and in mouse cells. However, IL-1 is necessary in combination with some or all of the other cytokines to induce IL-17 production in human T cells. The ability of various stimuli to induce Th17 cells depends not only on their induction of IL-23, IL-6, and TGF-beta production in DCs but also on their ability to activate directly or indirectly the inflammasome and to induce IL-1 beta. C1 [Provezza, Lisa; Carra, Giuseppe; Gerosa, Franca] Univ Verona, Dept Pathol, Immunol Sect, I-37100 Verona, Italy. [Lyakh, Lyudmila; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Trinchieri, G (reprint author), NCI, Canc Inflammat Program, Ctr Canc Res, NIH, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM trinchig@mail.nih.gov FU Intramural NIH HHS [Z01 BC010793-01, Z99 CA999999] NR 196 TC 101 Z9 104 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 2008 VL 226 BP 112 EP 131 PG 20 WC Immunology SC Immunology GA 367FO UT WOS:000260538100010 PM 19161420 ER PT J AU Germain, RN Huang, AYC Qi, H Egen, JG Castellino, F Chieppa, M Rothfuchs, A Sher, A Peters, N Sacks, D Bajenoff, M Glaichenhaus, N Rescigno, M Cannons, J Schwartzberg, P AF Germain, R. N. Huang, A. Y. C. Qi, H. Egen, J. G. Castellino, F. Chieppa, M. Rothfuchs, A. Sher, Alan Peters, N. Sacks, D. Bajenoff, M. Glaichenhaus, N. Rescigno, M. Cannons, J. Schwartzberg, P. TI Lymphocyte Migration, Territoriality, Interaction, and Function Assessed by Intravital 2-photon Microscopy SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY NOV 17-21, 2008 CL Glasgow, SCOTLAND SP British Soc Immunol C1 [Germain, R. N.; Huang, A. Y. C.; Qi, H.; Egen, J. G.; Castellino, F.; Chieppa, M.; Bajenoff, M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Rothfuchs, A.; Sher, Alan; Peters, N.; Sacks, D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Cannons, J.; Schwartzberg, P.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Huang, A. Y. C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Sch Med, Div Pediat Hematol Oncol, Cleveland, OH 44106 USA. [Castellino, F.] Novartis Vaccines, I-53100 Siena, Italy. [Bajenoff, M.; Glaichenhaus, N.] Univ Nice Sophia Antipolis, INSERM, Valbonne, France. [Chieppa, M.; Rescigno, M.] European Inst Oncol, Dept Expt Oncol, Milan, Italy. RI Qi, Hai/A-3955-2009; Rescigno, Maria/J-9704-2012 OI Rescigno, Maria/0000-0002-6464-509X NR 0 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2008 VL 125 BP 43 EP 44 PG 2 WC Immunology SC Immunology GA 398XL UT WOS:000262764800140 ER PT J AU Tai, X Singer, A AF Tai, X. Singer, A. TI Persistent in vivo costimulation is required to maintain regulatory T cell function SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY NOV 17-21, 2008 CL Glasgow, SCOTLAND SP British Soc Immunol C1 [Tai, X.; Singer, A.] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2008 VL 125 BP 64 EP 64 PG 1 WC Immunology SC Immunology GA 398XL UT WOS:000262764800203 ER PT J AU Alter, G Carrington, M Altfeld, M AF Alter, G. Carrington, M. Altfeld, M. TI Genetically determined differences in NK cell function in HIV-1 infection SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-of-Immunology CY NOV 17-21, 2008 CL Glasgow, SCOTLAND SP British Soc Immunol C1 [Alter, G.; Altfeld, M.] MGH, Partners AIDS Res Ctr, Boston, MA USA. [Carrington, M.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2008 VL 125 BP 67 EP 68 PG 2 WC Immunology SC Immunology GA 398XL UT WOS:000262764800214 ER PT J AU Chattopadhyay, PK Hogerkorp, CM Roederer, M AF Chattopadhyay, Pratip K. Hogerkorp, Carl-Magnus Roederer, Mario TI A chromatic explosion: the development and future of multiparameter flow cytometry SO IMMUNOLOGY LA English DT Review DE flow cytometry; T cells; tetramers; fluorochromes; data analysis ID T-CELL RESPONSES; 2-COLOR FLUORESCENCE ANALYSIS; SIGNALING NETWORKS; MARGINAL ZONE; ICP-MS; POPULATIONS; CLASSIFICATION; DISEASE; IMMUNOFLUORESCENCE; HETEROGENEITY AB Multiparameter flow cytometry has matured tremendously since the 1990s, giving rise to a technology that allows us to study the immune system in unprecedented detail. In this article, we review the development of hardware, reagents, and data analysis tools for multiparameter flow cytometry and discuss future advances in the field. Finally, we highlight new applications that use this technology to reveal previously unappreciated aspects of cell biology and immunity. C1 [Chattopadhyay, Pratip K.; Hogerkorp, Carl-Magnus; Roederer, Mario] NIAID, ImmunoTechnol Sect, Immunol Lab, Vaccine Res Ctr,NIH, Bethesda, MD 20892 USA. RP Chattopadhyay, PK (reprint author), NIAID, ImmunoTechnol Sect, Immunol Lab, Vaccine Res Ctr,NIH, 40 Convent Dr,Room 5612,Bldg 40, Bethesda, MD 20892 USA. EM pchattop@mail.nih.gov; roederer@mail.nih.gov RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999] NR 76 TC 87 Z9 92 U1 0 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2008 VL 125 IS 4 BP 441 EP 449 DI 10.1111/j.1365-2567.2008.02989.x PG 9 WC Immunology SC Immunology GA 369CJ UT WOS:000260670500001 PM 19137647 ER PT J AU Chong, A Wehrly, TD Nair, V Fischer, ER Barker, JR Klose, KE Celli, J AF Chong, Audrey Wehrly, Tara D. Nair, Vinod Fischer, Elizabeth R. Barker, Jeffrey R. Klose, Karl E. Celli, Jean TI The Early Phagosomal Stage of Francisella tularensis Determines Optimal Phagosomal Escape and Francisella Pathogenicity Island Protein Expression SO INFECTION AND IMMUNITY LA English DT Article ID LISTERIA-MONOCYTOGENES; INTRACELLULAR GROWTH; MURINE MACROPHAGES; ACID-PHOSPHATASE; SECRETION SYSTEM; CYTOPLASM; VIRULENCE; IDENTIFICATION; PHAGOLYSOSOME; ACIDIFICATION AB Francisella tularensis is an intracellular pathogen that can survive and replicate within macrophages. Following phagocytosis and transient interactions with the endocytic pathway, F. tularensis rapidly escapes from its original phagosome into the macrophage cytoplasm, where it eventually replicates. To examine the importance of the nascent phagosome for the Francisella intracellular cycle, we have characterized early trafficking events of the F. tularensis subsp. tularensis strain Schu S4 in a murine bone marrow-derived macrophage model. Here we show that early phagosomes containing Schu S4 transiently interact with early and late endosomes and become acidified before the onset of phagosomal disruption. Inhibition of endosomal acidification with the vacuolar ATPase inhibitor bafilomycin A1 or concanamycin A prior to infection significantly delayed but did not block phagosomal escape and cytosolic replication, indicating that maturation of the early Francisella-containing phagosome (FCP) is important for optimal phagosomal escape and subsequent intracellular growth. Further, Francisella pathogenicity island (FPI) protein expression was induced during early intracellular trafficking events. Although inhibition of endosomal acidification mimicked the early phagosomal escape defects caused by mutation of the FPI-encoded IgICD proteins, it did not inhibit the intracellular induction of FPI proteins, demonstrating that this response is independent of phagosomal pH. Altogether, these results demonstrate that early phagosomal maturation is required for optimal phagosomal escape and that the early FCP provides cues other than intravacuolar pH that determine intracellular induction of FPI proteins. C1 [Chong, Audrey; Wehrly, Tara D.; Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Nair, Vinod; Fischer, Elizabeth R.] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Barker, Jeffrey R.; Klose, Karl E.] Univ Texas San Antonio, S Texas Ctr Emerging Infect Dis, San Antonio, TX 78249 USA. [Barker, Jeffrey R.; Klose, Karl E.] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA. RP Celli, J (reprint author), NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM jcelli@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases FX We are grateful to Anders Sjostedt and Francis Nano for the gift of strains and antibodies and to Leigh Knodler and Jessica Edwards for critical reading of the manuscript and helpful discussions. This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 31 TC 101 Z9 101 U1 0 U2 2 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 DEC PY 2008 VL 76 IS 12 BP 5488 EP 5499 DI 10.1128/IAI.00682-08 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373WJ UT WOS:000261003900006 PM 18852245 ER PT J AU Londono, D Marques, A Hornung, RL Cadavid, D AF Londono, Diana Marques, Adriana Hornung, Ronald L. Cadavid, Diego TI Relapsing Fever Borreliosis in Interleukin-10-Deficient Mice SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE; TRANSENDOTHELIAL MIGRATION; PERSISTENT INFECTION; NEUROTROPIC STRAIN; ENDOTHELIAL-CELLS; DUAL ROLE; IN-VITRO; BURGDORFERI; TURICATAE; SPIROCHETE AB Relapsing fever (RF) is a spirochetal infection characterized by periods of sickness with fever at time of high bacteremia that alternate with afebrile periods of relative well being during low bacteremia. Patients with epidemic RF who are doing relatively well have extraordinarily high levels of interleukin-10 (IL-10) in the circulation. We investigated the possibility that IL-10 plays an important protective role in this infection using wild-type and IL-10-deficient mice inoculated with virulent serotype 2 of the RF spirochete Borrelia turicatae. During peak bacteremia there was increased systemic production of IL-10 that quickly resolved in the postpeak period; in contrast, IL-6 and CXCL13 production increased during the peak but remained elevated during postpeak bacteremia. IL-10 deficiency resulted in lower bacteremia, increased specific antibody production, higher production of CXCL13 and IL-6, and thrombotic and hemorrhagic complications affecting multiple organs with secondary tissue injury. Our results revealed that production of IL-10 is highly regulated during RF and plays an important protective role in the prevention of hemorrhagic and thrombotic complications at the cost of reduced pathogen control. C1 [Londono, Diana; Cadavid, Diego] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Londono, Diana; Cadavid, Diego] Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Emerging Pathogens, Newark, NJ 07103 USA. [Marques, Adriana] NIAID, Clin Studies Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hornung, Ronald L.] SAIC Frederick Inc, NCI Frederick, Clin Serv Program, Frederick, MD 21702 USA. RP Cadavid, D (reprint author), Massachusetts Gen Hosp, Ctr Immun & Inflammatory Dis, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM dcadavid@partners.org FU NIH [R21NS053997-01]; UMDNJ Foundation; National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This study was supported by grants from NIH (R21NS053997-01) and the UMDNJ Foundation to Diego Cadavid. This project has been funded in part with federal funds from the intramural research program of the National Institute of Allergy and Infectious Diseases and from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400.; The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government.; We thank Alan G. Barbour from UC Irvine for critically reviewing the manuscript. None of the authors have any conflict of interest to disclose. NR 38 TC 6 Z9 6 U1 0 U2 0 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 DEC PY 2008 VL 76 IS 12 BP 5508 EP 5513 DI 10.1128/IAI.00587-08 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373WJ UT WOS:000261003900008 PM 18794280 ER PT J AU Noland, GS Hendel-Paterson, B Min, XM Moormann, AM Vulule, JM Narum, DL Lanar, DE Kazura, JW John, CC AF Noland, Gregory S. Hendel-Paterson, Brett Min, Xinan M. Moormann, Ann M. Vulule, John M. Narum, David L. Lanar, David E. Kazura, James W. John, Chandy C. TI Low Prevalence of Antibodies to Preerythrocytic but Not Blood-Stage Plasmodium falciparum Antigens in an Area of Unstable Malaria Transmission Compared to Prevalence in an Area of Stable Malaria Transmission SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE-ANTIGEN; CLINICAL MALARIA; CIRCUMSPOROZOITE PROTEIN; WESTERN KENYA; HIGHLAND AREA; ADHESIVE PROTEIN; ENDEMIC AREA; RESPONSES; PROTECTION; CHILDREN AB In areas where levels of transmission of Plasmodium falciparum are high and stable, the age-related acquisition of high-level immunoglobulin G (IgG) antibodies to preerythrocytic circumsporozoite protein (CSP) and liver-stage antigen 1 (LSA-1) has been associated with protection from clinical malaria. In contrast, age-related protection from malaria develops slowly or not at all in residents of epidemic-prone areas with unstable low levels of malaria transmission. We hypothesized that this suboptimal clinical and parasitological immunity may in part be due to reduced antibodies to CSP or LSA-1 and/or vaccine candidate blood-stage antigens. Frequencies and levels of IgG antibodies to CSP, LSA-1, thrombospondin-related adhesive protein ( TRAP), apical membrane antigen 1 (AMA-1), erythrocyte binding antigen 175 (EBA-175), and merozoite surface protein 1 (MSP-1) were compared in 243 Kenyans living in a highland area of unstable transmission and 210 residents of a nearby lowland area of stable transmission. Levels of antibodies to CSP, LSA-1, TRAP, and AMA-1 in the oldest age group (>40 years) in the unstable transmission area were lower than or similar to those of children 2 to 6 years old in the stable transmission area. Only 3.3% of individuals in the unstable transmission area had high levels of IgG (>2 arbitrary units) to both CSP and LSA-1, compared to 43.3% of individuals in the stable transmission area. In contrast, antibody levels to and frequencies of MSP-1 and EBA-175 were similar in adults in areas of stable and unstable malaria transmission. Suboptimal immunity to malaria in areas of unstable malaria transmission may relate in part to infrequent high-level antibodies to preerythrocytic antigens and AMA-1. C1 [John, Chandy C.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Moormann, Ann M.; Kazura, James W.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Vulule, John M.] Kenya Govt Med Res Ctr, Kisumu, Kenya. [Narum, David L.] NIH, Bethesda, MD 20892 USA. [Lanar, David E.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP John, CC (reprint author), Univ Minnesota, Dept Pediat, 717 Delaware St,SE Room 363,MC1932, Minneapolis, MN 55455 USA. EM ccj@umn.edu RI John, Chandy/B-4164-2008; Lanar, David/B-3560-2011 FU National Institutes of Allergy and Infectious Diseases [AI01572, AI056270, AI43906] FX This study was supported by grants from the National Institutes of Allergy and Infectious Diseases, AI01572 and AI056270 (C. C. J.) and AI43906 (J. W. K.).; We thank the study participants for their involvement in this study. We thank David Koech, Jackson Abuya, and Livingstone Wanyama for their work in the field collection of these samples and microscopy testing. The sample collection, field work, and initial testing for this study were performed while C. C. J. was at Case Western Reserve University.; This work is published with the permission of the Office of the Director of the Kenya Medical Research Institute. NR 33 TC 22 Z9 22 U1 1 U2 1 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 DEC PY 2008 VL 76 IS 12 BP 5721 EP 5728 DI 10.1128/IAI.00591-08 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373WJ UT WOS:000261003900030 PM 18809666 ER PT J AU Ventura, CL Higdon, R Hohmann, L Martin, D Kolker, E Liggitt, HD Skerrett, SJ Rubens, CE AF Ventura, Christy L. Higdon, Roger Hohmann, Laura Martin, Daniel Kolker, Eugene Liggitt, H. Denny Skerrett, Shawn J. Rubens, Craig E. TI Staphylococcus aureus Elicits Marked Alterations in the Airway Proteome during Early Pneumonia SO INFECTION AND IMMUNITY LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; TANDEM MASS-SPECTROMETRY; ACUTE LUNG INJURY; STREPTOCOCCUS-PNEUMONIAE; PSEUDOMONAS-AERUGINOSA; PULMONARY INFECTION; INNATE IMMUNITY; INFLAMMATORY RESPONSES; NEUTROPHIL GELATINASE; LIQUID-CHROMATOGRAPHY AB Pneumonia caused by Staphylococcus aureus is a growing concern in the health care community. We hypothesized that characterization of the early innate immune response to bacteria in the lungs would provide insight into the mechanisms used by the host to protect itself from infection. An adult mouse model of Staphylococcus aureus pneumonia was utilized to define the early events in the innate immune response and to assess the changes in the airway proteome during the first 6 h of pneumonia. S. aureus actively replicated in the lungs of mice inoculated intranasally under anesthesia to cause significant morbidity and mortality. By 6 h postinoculation, the release of proinflammatory cytokines caused effective recruitment of neutrophils to the airway. Neutrophil influx, loss of alveolar architecture, and consolidated pneumonia were observed histologically 6 h postinoculation. Bronchoalveolar lavage fluids from mice inoculated with phosphate-buffered saline (PBS) or S. aureus were depleted of overabundant proteins and subjected to strong cation exchange fractionation followed by liquid chromatography and tandem mass spectrometry to identify the proteins present in the airway. No significant changes in response to PBS inoculation or 30 min following S. aureus inoculation were observed. However, a dramatic increase in extracellular proteins was observed 6 h postinoculation with S. aureus, with the increase dominated by inflammatory and coagulation proteins. The data presented here provide a comprehensive evaluation of the rapid and vigorous innate immune response mounted in the host airway during the earliest stages of S. aureus pneumonia. C1 [Higdon, Roger; Rubens, Craig E.] Univ Washington, Sch Med, Seattle Childrens Hosp, Res Inst,BIATECH Inst, Seattle, WA 98101 USA. [Ventura, Christy L.; Rubens, Craig E.] Univ Washington, Sch Med, Div Infect Dis, Ctr Chilhood Infect & Prematur Res, Seattle, WA 98101 USA. [Higdon, Roger; Kolker, Eugene] Univ Washington, Sch Med, Ctr Dev Therapeut, Seattle, WA 98101 USA. [Hohmann, Laura; Martin, Daniel] Univ Washington, Sch Med, Inst Syst Biol, Seattle, WA 98101 USA. [Martin, Daniel] Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA 98101 USA. [Ventura, Christy L.; Rubens, Craig E.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98101 USA. [Kolker, Eugene] Univ Washington, Sch Med, Dept Med Educ & Biomed Informat, Seattle, WA 98101 USA. [Liggitt, H. Denny] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98101 USA. [Skerrett, Shawn J.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98101 USA. [Ventura, Christy L.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Rubens, CE (reprint author), Univ Washington, Sch Med, Seattle Childrens Hosp, Res Inst,BIATECH Inst, Metropolitan Pk W Bldg,1100 Olive Way,M-S MPW10, Seattle, WA 98101 USA. EM craig.rubens@seattlechildrens.org RI Kolker, Eugene/C-6711-2008; OI Ventura, Christy/0000-0002-5084-1567 FU National Institutes of Health [HL073996] FX We thank Jeannette Crisostomo, Destry Taylor, and Michele Timko for their expert technical assistance, Jimmy Eng for assistance with proteomics data analysis, William Parks for advice about MMP-9 analysis, and Amanda Jones for insightful comments and critical review of the manuscript.; This work was supported by HL073996 from the National Institutes of Health (C. E. R.). NR 70 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 2008 VL 76 IS 12 BP 5862 EP 5872 DI 10.1128/IAI.00865-08 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373WJ UT WOS:000261003900046 PM 18852243 ER PT J AU Piper, JM AF Piper, Jeanna M. TI Prevention of Sexually Transmitted Infections in Women SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID BEHAVIORAL INTERVENTION; RANDOMIZED-TRIAL; PROGRAM ARCHIVE; MINORITY WOMEN; RISK; DISEASE; HIV; BOX AB Because the acquisition of sexually transmitted infections (STIs) is based on individual sexual behaviors, the most successful STI prevention initiatives have been behavioral interventions seeking to change individual risk behaviors. This article explores systematic and community-based prevention initiatives and the seeps in development and validation of behavioral interventions to reduce STIs. Key interventions and the trials in which they were proven effective are discussed in detail. It is hoped that a greater understanding of the development and validation of behavioral interventions for STI prevention will encourage physicians to accept these interventions as additional tools to prevent disease and suffering. C1 NIAID, Microbicide Branch, Prevent Sci Program, Div AIDS, Bethesda, MD 20892 USA. RP Piper, JM (reprint author), NIAID, Microbicide Branch, Prevent Sci Program, Div AIDS, 6700 B Rockledge Dr,Room 5248, Bethesda, MD 20892 USA. EM piperj@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 18 TC 4 Z9 5 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 2008 VL 22 IS 4 BP 619 EP + DI 10.1016/j.idc.2008.05.003 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 374XO UT WOS:000261077200004 PM 18954755 ER PT J AU Zwiers, A Fuss, IJ Leijen, S Mulder, CJ Kraal, G Bouma, G AF Zwiers, Antonie Fuss, Ivan J. Leijen, Suzonne Mulder, Chris J. Kraal, Georg Bouma, Gerd TI Increased Expression of the Tight Junction Molecule Claudin-18 A1 in Both Experimental Colitis and Ulcerative Colitis SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel diseases; TNBS colitis; claudin-18; tight junction ID INFLAMMATORY-BOWEL-DISEASE; GENE-EXPRESSION; CROHNS-DISEASE; INTESTINAL PERMEABILITY; BARRIER; PATHOGENESIS; RELATIVES; PROTEIN; STRANDS; MOUSE AB Background: We previously identified a major quantitative trait locus (qtl) on mouse chromosome 9 (Tnbsl) that confers resistance/ susceptibility to trinitrobenzene sulfonic acid (TNBS) induced colitis. Here we wanted to identify possible candidate genes in this locus. Methods: We applied micro-array technology and identified clandin-18 as a plausible candidate Gene in the Tnbsl region. Subsequently we studied the expression profile of this gene by means of RT-PCR in resistant and susceptible mice as well as in human inflammatory bowel disease. Results: Expression of this gene was markedly upregulated during colitis in mice. Also in humans relative expression of claudin-18 in patients with ulcerative colitis was significantly upregulated as compared to healthy individuals undergoing surveillance endoscopy (n = 13, P < 0.0005). Expression was not related to the histological severity of the disease. Conclusions: Claudins belong to the integral membrane proteins of the tight junction, a structure that seals off the intercellular space between adjacent epithelial cells and regulates passive diffusion of solutes and macromolecules. This study demonstrates for the first time that claudin-18 is expressed in human and mouse colon. Expression is upregulated during experimental colitis and in patients with ulcerative colitis. The observation that this is unrelated to the severity of inflammation might point to a primary defect in regulation in patients with ulcerative colitis and warrants further genetic examination. C1 [Zwiers, Antonie; Mulder, Chris J.; Bouma, Gerd] Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol, NL-1081 BT Amsterdam, Netherlands. [Fuss, Ivan J.] NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Bouma, G (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Gastroenterol, Boechorststr 7,Room J393, NL-1081 BT Amsterdam, Netherlands. EM g.bouma@vumc.nl RI bouma, gerd/E-2520-2013 NR 32 TC 13 Z9 13 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD DEC PY 2008 VL 14 IS 12 BP 1652 EP 1659 DI 10.1002/ibd.20695 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 381MT UT WOS:000261541200005 PM 18831034 ER PT J AU Suomi, SJ van der Horst, FCP van der Veer, R AF Suomi, Stephen J. van der Horst, Frank C. P. van der Veer, Rene TI Rigorous Experiments on Monkey Love: An Account of Harry F. Harlow's Role in the History of Attachment Theory SO INTEGRATIVE PSYCHOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Article DE Attachment theory; Affectional systems; Ethology; Animal research; Harlow; Hinde; Spitz; Suomi; History of psychology; Biography ID PITUITARY-ADRENAL RESPONSE; RHESUS-MONKEYS; SEPARATION; MOTHER AB On the basis of personal reminiscences an account is given of Harlow's role in the development of attachment theory and key notions of attachment theory are being discussed. Among other things, it is related how Harlow arrived at his famous research with rhesus monkeys and how this made Harlow a highly relevant figure for attachment theorist Bowlby. C1 [van der Horst, Frank C. P.; van der Veer, Rene] Leiden Univ, Ctr Child & Family Studies, NL-2300 RB Leiden, Netherlands. [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, DHHS, Bethesda, MD USA. RP van der Horst, FCP (reprint author), Leiden Univ, Ctr Child & Family Studies, POB 9555, NL-2300 RB Leiden, Netherlands. EM fhorst@fsw.leidenuniv.nl NR 26 TC 14 Z9 14 U1 11 U2 32 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-4502 J9 INTEGR PSYCHOL BEHAV JI Integr. Psychol. Behav. Sci. PD DEC PY 2008 VL 42 IS 4 BP 354 EP 369 DI 10.1007/s12124-008-9072-9 PG 16 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 358II UT WOS:000259910000004 PM 18688688 ER PT J AU D'Agostini, F Balansky, R Steele, VE Ganchev, G Pesce, C De Flora, S AF D'Agostini, Francesco Balansky, Roumen Steele, Vernon E. Ganchev, Gancho Pesce, Carlo De Flora, Silvio TI Preneoplastic and neoplastic lesions in the lung, liver and urinary tract of mice exposed to environmental cigarette smoke and UV light since birth SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE environmental cigarette smoke; UV light; neonatal mice; tumorigenicity ID TOBACCO-SMOKE; MOUSE LUNG; A/J MOUSE; INHALATION EXPOSURE; SIDESTREAM SMOKE; CARCINOGENICITY; TUMOR; MAINSTREAM; MODEL; TUMORIGENESIS AB It is difficult to reproduce the carcinogenicity of cigarette smoke (CS) in animal models. Recently. we showed that exposure or mice to mainstream CS (MCS) For 120 days, starting immediately after birth. resulted in an early and potent carcinogenic response, In parallel. we implemented studies evaluating intermediate biomarkers and tumors in mice exposed to environmental CS (ECS). To this purpose. we used 263 newborn CD-I mice born from 27 dams. The whole-body. exposure to ECS for 120 days, starting within 12 hr after birth, resulted in an earls, appearance of preneoplastic lesions in lung. which however ended to attenuate after discontinuing exposure. When the experiment was stopped, after 330 days. the number of lung adenomas was higher in ECS-exposed mice as compared to sham-exposed mice, but such I in mice co-exposed to increase was statistically significant only smoke and halogen light mimicking solar irradiation. Moreover, exposure to ECS produced extensive histopathological changes, mainly parenchymatous degeneration, in liver. The alterations produced in both lung and liver require that exposure to ECS starts immediately after birth, no effect being observed when exposure started 8 days later. In contrast, induction by ECS of alterations in the urinary tract, such as microadenomas and adenomas in renal pelvis and kidney, papillary hyperplasia of urothelium, and urinary bladder papillomas, were er unrelated to the exposure time after birth. The results obtained with ECS cannot be directly compared to those previously obtained with MCS, since the latter involved Shorter daily exposures to more massive CS doses. (C) 2008 Wiley-Liss. Inc. C1 [D'Agostini, Francesco; Balansky, Roumen; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Balansky, Roumen; Ganchev, Gancho] Natl Oncol Ctr, BU-1157 Sofia, Bulgaria. [Steele, Vernon E.] NCI, Rockville, MD USA. [Pesce, Carlo] Univ Genoa, Dept Biophys Med & Odontostomatol, Genoa, Italy. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it FU The U.S. National Cancer Institute [N01-CN53301]; Bulgarian Ministry of Education and Science FX Grant sponsor: The U.S. National Cancer Institute: Grant number: N01-CN53301. Grant sponsor Bulgarian Ministry of Education and Science. NR 32 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2008 VL 123 IS 11 BP 2497 EP 2502 DI 10.1002/ijc.23836 PG 6 WC Oncology SC Oncology GA 371PT UT WOS:000260844100004 PM 18770867 ER PT J AU Stevens, VL Hsing, AW Talbot, JT Zheng, SL Sun, JL Chen, JB Thun, MJ Xu, JF Calle, EE Rodriguez, C AF Stevens, Victoria L. Hsing, Ann W. Talbot, Jeffrey T. Zheng, Siqun Lilly Sun, Jielin Chen, Jinbo Thun, Michael J. Xu, Jianfeng Calle, Eugenia E. Rodriguez, Carmen TI Genetic variation in the toll-like receptor gene cluster (TLR10-TLR1-TLR6) and prostate cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate cancer; inflammation; genetic variation ID GENOME-WIDE ASSOCIATION; SEQUENCE VARIANTS; POLYMORPHISM; INFLAMMATION; TLR1; TOLL-LIKE-RECEPTOR-4; SUSCEPTIBILITY; PATHWAY AB Toll-like receptors (TLRs) are key players in the innate immune system and initiate the inflammatory response to foreign pathogens such as bacteria, fungi and viruses. The proposed role of chronic inflammation in prostate carcinogenesis has prompted investigation into the association of common genetic variation in TLRs with the risk of this cancer. We investigated the role of common SNPs in a gene cluster encoding the TLR10, TLR6 and TLR1 proteins in prostate cancer etiology among 1.414 cancer cases and 1,414 matched controls from the Cancer Prevention Study 11 Nutrition Cohort. Twenty-eight SNPs, which included the majority of the common nonsynonymous SNPs in the 54-kb gene region and haplotype-tagging SNPs that defined 5 specific haplotype blocks, were genotyped and their association with prostate cancer risk determined. Two SNPs in TLR10 [1369L (rs11096955) and N241H (rs11096957)] and 4 SNPs in TLRI [N248S (rs4833095), S26L (rs5743596), rs5743595 and rs5743551] were associated with a statistically, significant reduced risk of prostate cancer of 29-38% (for the homozygous variant genotype). The association of these SNPs was similar when the analysis was limited to cases with advanced prostate cancer. Haplotype analysis and linkage disequilibrium findings revealed that the 6 associated SNPs were not independent and represent a single association with reduced prostate cancer risk (OR = 0.55, 95% CI: 0.33, 0.90). Our study suggest that a common haplotype in the TLR10-TLR1-TLR6 gene cluster influences prostate cancer risk and clearly supports the need for further investigation of TLR genes in other populations. (C) 2008 Wiley-Liss, Inc. C1 [Stevens, Victoria L.; Talbot, Jeffrey T.; Thun, Michael J.; Calle, Eugenia E.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zheng, Siqun Lilly; Sun, Jielin; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Stevens, VL (reprint author), Amer Canc Soc, Dept Epidemiol & Surveillance Res, 250 Williams St NW, Atlanta, GA 30303 USA. EM victoria.stevens@cancer.org NR 30 TC 47 Z9 50 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2008 VL 123 IS 11 BP 2644 EP 2650 DI 10.1002/ijc.23826 PG 7 WC Oncology SC Oncology GA 371PT UT WOS:000260844100021 PM 18752252 ER PT J AU Ogwang, MD Bhatia, K Biggar, RJ Mbulaiteye, SM AF Ogwang, Martin D. Bhatia, Kishor Biggar, Robert J. Mbulaiteye, Sam M. TI Incidence and geographic distribution of endemic Burkitt lymphoma in northern Uganda revisited SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Africa; cancer malaria; Epstein-Barr virus; clustering; epidemiology ID WEST NILE DISTRICT; EPSTEIN-BARR-VIRUS; C-MYC; EPIDEMIOLOGIC EVIDENCE; AFRICAN CHILDREN; MALARIA; AIDS; CANCER; KENYA; RISK AB Endemic Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus and ecologically linked to Plsmodium falciparum malaria. However, these infections imperfectly correlate with BL epidemiology. To obtain recent epidemiological data, we studied district- and county-specific B1. incidence and standardized incidence ratios using data collected from 1997 to 2006 at Lacor Hospital in northern Uganda, where studies were last done more than 30 years ago. Among 501) patients, median age was 6 Years (interquartile range 5-8) and male-to-female ratio was 1.8:1, Among those known, most presented with abdominal (56%, M:F 1.4:1) vs. only facial tumors (35%. M:F 3.0:1). Abdominal tumors occurred in older (mean age: 7.0 vs. 6.0 years; p < 0.001) and more frequantly in female children (68% vs. 50%, OR 2.2, 95% Cl 1.5-3.5). The age-standardized incidence was J.4 per 100,000, being 0.6 in 1-4, year olds, 4.1 in 5-9 year olds and 2.8 in 10-14 year olds and varied 3- to 4-fold across districts. The incidence was lower in districts that were far from Lacor and higher in districts that were close to Lacor. Although districts close to Lacor were also more urbanized, the incidence was higher in the nearby, perirural areas. We highlight high-BL incidence and geographic variation in neighboring districts in northern Uganda. Although distance from Lacor clearly influenced the patterns, the incidence was lower in municipal than in surrounding rural areas. Jaw tumors were characterized by young age and male gender, but presentation shifted away from facial to mostly abdominal. (C) 2008 Wiley-Liss, Inc. This article is a US Goverment work and as such is in the public domain in the United States of America. C1 [Ogwang, Martin D.] St Marys Hosp, Dept Surg, Lacor, Gulu, Uganda. [Bhatia, Kishor; Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Biggar, Robert J.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S,Rm 7080, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU Department of Health and Human Services, Intramural Research Program of the National Cancer Institute. National Institutes of Health [N02-CP-31003, N01-CO-12400] FX Grant sponsor Department of Health and Human Services, Intramural Research Program of the National Cancer Institute. National Institutes of Health: Grant numbers: N02-CP-31003. N01-CO-12400. NR 35 TC 27 Z9 28 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2008 VL 123 IS 11 BP 2658 EP 2663 DI 10.1002/ijc.23800 PG 6 WC Oncology SC Oncology GA 371PT UT WOS:000260844100023 PM 18767045 ER PT J AU Rajaraman, P Bhatti, P Doody, MM Simon, SL Weinstock, RM Linet, MS Rosenstein, M Stovall, M Alexander, BH Preston, DL Sigurdson, AJ AF Rajaraman, Preetha Bhatti, Parveen Doody, Michele Morin Simon, Steven L. Weinstock, Robert M. Linet, Martha S. Rosenstein, Marvin Stovall, Marilyn Alexander, Bruce H. Preston, Dale L. Sigurdson, Alice J. TI Nucleotide excision repair polymorphisms may modify ionizing radiation-related breast cancer risk in US radiologic technologists SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ionizing radiation; nucleotide excision repair; polymorphisms; breast cancer; case-control ID DNA-REPAIR; GENETIC-VARIATION; EXCINUCLEASE; POPULATION; EXPOSURE; COHORT; DAMAGE AB Exposure to ionizing radiation hits been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base-excision repair pathway, certain types of multiple-base damage can only be repaired through the nucleotide excision repair pathway. In a nested case-control study of breast cancer in US radiologic technologists exposed to low, levels of ionizing radiation (858 cases. 1.083 controls), we examined whether risk (If breast cancer conferred 1), v radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (ORGC = 1.1, ORCC = 1.3; p-trend = 0.08). with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/Gy(GG) = 1.0. 95% CI = <0, 6.0; EOR/Gy(GC/CC) = 5.9, 95% CI = 0.9, 14.4; p(het) = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation (lose on risk of breast cancer (EOR/Gy(AA) = 9.1, 95% CI = 2.1-21.3; EOR/Gy(AC/CC) = 0.6, 95% CI = <0.4.6; p(het) = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk. C1 [Rajaraman, Preetha; Bhatti, Parveen; Doody, Michele Morin; Simon, Steven L.; Linet, Martha S.; Sigurdson, Alice J.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Weinstock, Robert M.; Rosenstein, Marvin] Res Triangle Inst, Bethesda, MD USA. [Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. [Preston, Dale L.] HiroSoft Int Corp, Seattle, WA USA. RP Rajaraman, P (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS,Radiat Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM rajarama@mail.nih.gov FU Intramural Research Program; Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institute Of Health; Department of Health and Human Services FX Grant sponsors: Intramural Research Program. Division of Cancer Epidemiology and Genetics; National Cancer Institute: National Institute Of Health; Department of Health and Human Services. NR 22 TC 33 Z9 33 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2008 VL 123 IS 11 BP 2713 EP 2716 DI 10.1002/ijc.23779 PG 4 WC Oncology SC Oncology GA 371PT UT WOS:000260844100030 PM 18767034 ER PT J AU Karlsson, A Ungerback, J Rasmussen, A French, JE Soderkvist, P AF Karlsson, Anneli Ungerback, Jonas Rasmussen, Anna French, John E. Soderkvist, Peter TI Notch1 is a frequent mutational target in chemically induced lymphoma in mouse SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE TAN-1; hN1; butadiene; dideoxycytidine; phenolphthalein ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMOGENESIS; THYMIC LYMPHOMAS; GENE; P53; ACTIVATION; MICE; DELETIONS; RECEPTOR; 2,3-DIDEOXYCYTIDINE AB Activating Notch1 mutations have been reported in human T-lineage acute lymphoblastic leukemia (T-ALL) and lymphomas from genetically modified mice. We report that Notch1 is a prevalent and major mutational target in chemically induced mouse lymphoma. The regions of the gene that are frequently mutated are the hterodimerization domain and the N-terminal ligand-binding region, important for protein stability, and (he polypeptide rich in proline, glutamate, serine and threonine WEST) domains, which is critical for protein degradation. Another gene, CDC4, is also involved in Notch1 degradation and shows frequent mutations. Mutations in the heterodimerization and the ligand-binding regions may cause ligand-independent signaling. whereas mutations preventing protein degradation result in accumulation of intracellular Notch1. We analyzed 103 chemical-induced mouse lymphomas for mutations in the Notch1 gene using single strand conformation analysis (SSCA) and DNA sequencing. Genetic alterations resulting in premature truncation of Notch I were identified in 28 tumors, whereas 8 revealed alterations in the heterodimerization and 16 harbored deletions in the ligand-binding region. Dideoxycytidine-induced lymphomas displayed the highest frequency of Notch1 mutations (49%). whereas in butadiene- and phenolphthalein-indced tumors showed lower frequencies (26 10%, respectively). In total, 26 novel and 3 previously reported mutations were detected. This report shows that Notch1 is a prevalent and major mtational target for 2',3'-dideoxycytidine and butadiene-induced lymphoma.. (C) 2008 Wiley-Liss, Inc. C1 [Karlsson, Anneli; Ungerback, Jonas; Rasmussen, Anna; Soderkvist, Peter] Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. [French, John E.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. RP Karlsson, A (reprint author), Linkoping Univ, Dept Clin & Expt Med, S-58185 Linkoping, Sweden. EM annka@ibk.liu.se FU Swedish Cancer Society; Country Council of Ostergotland FX Grant sponsors: the Swedish Cancer Society, the Country Council of Ostergotland. NR 41 TC 2 Z9 2 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 2008 VL 123 IS 11 BP 2720 EP 2724 DI 10.1002/ijc.23832 PG 5 WC Oncology SC Oncology GA 371PT UT WOS:000260844100032 PM 18798262 ER PT J AU Kittappa, R Chang, WW Awatramani, RB Mckay, RDG AF Kittappa, R. Chang, W. W. Awatramani, R. B. McKay, R. D. G. TI The floor plate gene, foxa2, is required for the generation and maintenance of midbrain dopamine neurons SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 17th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 01-05, 2008 CL Asilomar, CA SP Int Soc Dev Neruosci C1 [Kittappa, R.; Chang, W. W.; McKay, R. D. G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Awatramani, R. B.] Northwestern Univ, Sch Med, Evanston, IL 60208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2008 VL 26 IS 8 BP 832 EP 833 DI 10.1016/j.ijdevneu.2008.09.028 PG 2 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 387CL UT WOS:000261929200020 ER PT J AU Welch, JM Lu, J Rodriguiz, RM Trotta, NC Peca, J Ding, JD Feliciano, C Chen, M Adams, JP Luo, J Dudek, SM Weinberg, RJ Calakos, N Wetsel, WC Feng, G AF Welch, J. M. Lu, J. Rodriguiz, R. M. Trotta, N. C. Peca, J. Ding, J-D. Feliciano, C. Chen, M. Adams, J. Paige Luo, J. Dudek, S. M. Weinberg, R. J. Calakos, N. Wetsel, W. C. Feng, G. TI Synaptic and circuitry mechanisms of obsessive compulsive-like behaviors in mice SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 17th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 01-05, 2008 CL Asilomar, CA SP Int Soc Dev Neruosci C1 [Welch, J. M.; Lu, J.; Rodriguiz, R. M.; Trotta, N. C.; Peca, J.; Feliciano, C.; Chen, M.; Calakos, N.; Wetsel, W. C.; Feng, G.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Ding, J-D.; Weinberg, R. J.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Adams, J. Paige; Dudek, S. M.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RI Peca, Joao/K-7900-2013 OI Peca, Joao/0000-0003-4989-2129 NR 0 TC 0 Z9 0 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2008 VL 26 IS 8 BP 835 EP 835 DI 10.1016/j.ijdevneu.2008.09.033 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 387CL UT WOS:000261929200024 ER PT J AU Williams, JP Wu, J Johansson, G Mukouyama, Y Cancelas, JA Ratner, N AF Williams, J. P. Wu, J. Johansson, G. Mukouyama, Y. Cancelas, J. A. Ratner, N. TI Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor population and confers tumorigenic potential SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 17th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 01-05, 2008 CL Asilomar, CA SP Int Soc Dev Neruosci C1 [Williams, J. P.; Wu, J.; Johansson, G.; Ratner, N.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Mukouyama, Y.] NIH, Bethesda, MD USA. [Cancelas, J. A.] Univ Cincinnati, Cincinnati, OH 45221 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2008 VL 26 IS 8 BP 843 EP 843 DI 10.1016/j.ijdevneu.2008.09.056 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 387CL UT WOS:000261929200042 ER PT J AU Davis, MI Hassoun, AT Lovinger, DM AF Davis, M. I. Hassoun, A. T. Lovinger, D. M. TI Ethanol enhances neuronal migration in the cerebellum SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 17th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 01-05, 2008 CL Asilomar, CA SP Int Soc Dev Neruosci C1 [Davis, M. I.; Hassoun, A. T.; Lovinger, D. M.] NIH, Bethesda, MD USA. RI Davis, Margaret/F-4165-2010; OI Davis, Margaret/0000-0002-0489-8351 NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2008 VL 26 IS 8 BP 853 EP 853 DI 10.1016/j.ijdevneu.2008.09.085 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 387CL UT WOS:000261929200071 ER PT J AU Miquelajauregui, A Sandoval, MT Carabez, A Zhao, Y Varela-Echavarria, A AF Miquelajauregui, A. Sandoval, M. T. Carabez, A. Zhao, Y. Varela-Echavarria, A. TI LIM homeobox protein 5 (Lhx5) is essential for mammillary body development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Meeting Abstract CT 17th Biennial Meeting of the International-Society-for-Developmental-Neuroscience CY JUN 01-05, 2008 CL Asilomar, CA SP Int Soc Dev Neruosci C1 [Miquelajauregui, A.; Sandoval, M. T.; Carabez, A.; Varela-Echavarria, A.] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Zhao, Y.] NICHHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD DEC PY 2008 VL 26 IS 8 BP 856 EP 856 DI 10.1016/j.ijdevneu.2008.09.093 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 387CL UT WOS:000261929200079 ER PT J AU Brown, J AF Brown, J. TI Indexing Infectious Disease Information with an Intelligent Database SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Brown, J.] Natl Lib Med, Tacoma, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD DEC PY 2008 VL 12 BP E190 EP E191 DI 10.1016/j.ijid.2008.05.474 PG 2 WC Infectious Diseases SC Infectious Diseases GA 406II UT WOS:000263287800473 ER PT J AU DeLeo, F AF DeLeo, F. TI Evasion of Innate Host Defense by Staphylococcus aureus SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [DeLeo, F.] NIAID, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD DEC PY 2008 VL 12 BP E30 EP E30 DI 10.1016/j.ijid.2008.05.122 PG 1 WC Infectious Diseases SC Infectious Diseases GA 406II UT WOS:000263287800081 ER PT J AU Glass, R AF Glass, R. TI Rotavirus and Rotavirus Vaccines: Are We There Yet? SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Glass, R.] Fogarty Int Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD DEC PY 2008 VL 12 BP E6 EP E6 DI 10.1016/j.ijid.2008.05.054 PG 1 WC Infectious Diseases SC Infectious Diseases GA 406II UT WOS:000263287800013 ER PT J AU Nogueira, ML Mondini, A Bronzoni, RVM Alonso, WJ MAssad, E Lazaro, E Zanotto, P Chiaravalotti, F AF Nogueira, M. L. Mondini, A. Bronzoni, R. V. M. Alonso, W. J. MAssad, E. Lazaro, E. Zanotto, P. Chiaravalotti-Neto, F. TI Spatio-Temporal and Molecular Analyses of a DENV3 Outbreak Show the Dynamics of Dengue Infection (Viral Spread) SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Nogueira, M. L.; Mondini, A.; Bronzoni, R. V. M.; Chiaravalotti-Neto, F.] FAMERP, Sao Jose Do Rio Preto, Brazil. [Alonso, W. J.] Fogarty Int Ctr, Bethesda, MD USA. [MAssad, E.; Zanotto, P.] Univ Sao Paulo, BR-09500900 Sao Paulo, Brazil. [Lazaro, E.] PMSJRP, Sao Jose Do Rio Preto, Brazil. RI Massad, Eduardo/H-6143-2011; Nogueira, Mauricio/B-7599-2012; Massad, Eduardo/B-1169-2012; OI Nogueira, Mauricio/0000-0003-1102-2419; Massad, Eduardo/0000-0002-7200-2916; Bronzoni, Roberta/0000-0002-9403-5284 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD DEC PY 2008 VL 12 BP E333 EP E333 DI 10.1016/j.ijid.2008.05.890 PG 1 WC Infectious Diseases SC Infectious Diseases GA 406II UT WOS:000263287800835 ER PT J AU Alves, S Woods, A Delvolve, A Tabet, JC AF Alves, Sandra Woods, Amina Delvolve, Alice Tabet, Jean Claude TI Influence of salt bridge interactions on the gas-phase stability of DNA/peptide complexes SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE Noncovalent DNA-Peptide complex; Salt bridge interaction; ESI mass spectrometry; Orbitrap ID ASSISTED-LASER-DESORPTION/IONIZATION; IONIZATION MASS-SPECTROMETRY; QUADRUPOLE ION-TRAP; DOUBLE-STRANDED OLIGODEOXYNUCLEOTIDES; COLLISION-INDUCED DISSOCIATION; NONCOVALENT COMPLEXES; PROTON AFFINITY; DNA DUPLEXES; MALDI-TOF; HYDROGEN/DEUTERIUM EXCHANGE AB Negative ion mode electrospray ionization mass spectrometry was used to study DNA duplexes-peptide interaction. In the present study, we show that peptides that contain two adjacent basic residues interact noncovalently with DNA single strand or duplex. Fragmentation of the complexes between peptides containing basic residues and DNA were studied under collisions and showed unexpected dissociation pathways, as previously reported for peptide-peptide interactions. The binary complexes are dissociated either along fragmentation of the covalent bonds of the peptide backbone and/or along the single DNA strand backbone cleavage without disruption of noncovalent interaction, which demonstrates the strong binding of peptide to the DNA strand. Sequential MS/MS and MSn were further performed on ternary complexes formed between duplexes and peptides to investigate the nature of interaction. The CID spectra showed as major pathway the disruption of the noncovalent interactions and the formation of binary complexes and single-strand ions, directed by the nucleic acid gas-phase acidity. Indeed, a preferential formation of complexes with thymidine containing single strands is observed. An alternative pathway is also detected, in which complexes are dissociated along the covalent bond of the peptide and/or DNA according to the basicity. Our experimental data suggest the presence of strong salt bridge interactions between DNA and peptides containing basic residues. (c) 2008 Elsevier B.V. All rights reserved. C1 [Alves, Sandra; Delvolve, Alice; Tabet, Jean Claude] Univ Paris 06, Lab Chim Struct Organ & Biol, UMR 76137, F-75252 Paris, France. [Woods, Amina] NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Tabet, JC (reprint author), Univ Paris 06, Lab Chim Struct Organ & Biol, UMR 76137, BP45,4 Pl Jussieu, F-75252 Paris, France. EM tabet@ccr.jussieu.fr NR 62 TC 12 Z9 12 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD DEC 1 PY 2008 VL 278 IS 2-3 BP 122 EP 128 DI 10.1016/j.ijms.2008.04.023 PG 7 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 378EM UT WOS:000261304000005 ER PT J AU Wang, HYJ Post, SNJJ Woods, AS AF Wang, Hay-Yan J. Post, Shelley N. Jackson Jeremy Woods, Amina S. TI A minimalist approach to MALDI imaging of glycerophospholipids and sphingolipids in rat brain sections SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE Imaging; Phophatidylcholine; Phosphatidylinositol; Sulfatides; Sample preparation ID ASSISTED-LASER-DESORPTION/IONIZATION; SITU STRUCTURAL-CHARACTERIZATION; TANDEM MASS-SPECTROMETRY; FATTY ACID COMPOSITION; TISSUE-SECTIONS; IONIZATION; SPHINGOMYELIN; LOCALIZATION; MOLECULES; PEPTIDES AB Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that has allowed researchers to directly probe tissue molecular structure and drug content with minimal manipulations,while maintaining anatomical integrity. In the present work glycerophospholipids and sphingolipids images were acquired from 16-mu m thick coronal rat brain sections using MALDI-MS. Images of phosphatidylinositol 38:4 (PI 38:4), sulfatide 24:1 (ST 24:1), and hydroxyl sulfatide 24:1 (ST 24:1 (CH)) were acquired in negative ion mode, while the images of phosphatidylcholine 34:1 (PC 34:1), potassiated phosphatidycholines 32:0 (PC 32:0 + K(+)) and 36:1 (PC 36:1 + K(+)) were acquired in positive ion mode. The images of PI 38:4 and PC 36:1 + K+ show the preferential distribution of these two lipids in gray matter; and the images of two sulfatides and PC 32:0 + K(+) show their preferential distribution in white matter. In addition, the gray cortical band and its adjacent anatomical structures were also identified by contrasting their lipid makeup. The resulting images were compared to lipid images acquired by secondary ion mass spectrometry (SIMS). The suitability of TLC sprayers, Collison Nebulizer, and artistic airbrush were also evaluated as means for matrix deposition. Published by Elsevier B.V. C1 [Wang, Hay-Yan J.; Post, Shelley N. Jackson Jeremy; Woods, Amina S.] NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 333 Cassell Dr,Triad Bldg,Room 1120, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH; Office of National Drug Control Policy (ONDCP) FX This research was supported by the Intramural Research Program of National Institute on Drug Abuse, NIH. The authors thank the Office of National Drug Control Policy (ONDCP) for instrumentation funding, without which this and other projects could not have been accomplished. We also would like to thank Dr. Patricia Tagliaferro and Dr. Marisela Morales for their assistance in light microscope photography. NR 38 TC 46 Z9 47 U1 0 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD DEC 1 PY 2008 VL 278 IS 2-3 BP 143 EP 149 DI 10.1016/j.ijms.2008.04.005 PG 7 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 378EM UT WOS:000261304000008 PM 19956342 ER PT J AU Newton, TF Reid, MS De La Garza, R Mahoney, JJ Abad, A Condos, R Palamar, J Halkitis, PN Mojisak, J Anderson, A Li, SH Elkashef, A AF Newton, Thomas F. Reid, Malcolm S. De La Garza, Richard, II Mahoney, James J., III Abad, Antonio Condos, Rany Palamar, Joseph Halkitis, Perry N. Mojisak, Jurji Anderson, Ann Li, Shou-Hua Elkashef, Ahmed TI Evaluation of subjective effects of aripiprazole and methamphetamine in methamphetamine-dependent volunteers SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Aripiprazole; methamphetamine; subjective effects ID PLACEBO-CONTROLLED TRIAL; CENTER INVENTORY ARCI; ABSTINENT METHAMPHETAMINE; DOPAMINE TRANSPORTERS; COCAINE DEPENDENCE; D-AMPHETAMINE; RATING-SCALE; ABUSERS; BUPROPION; HUMANS AB A variety of neuropharmacological strategies are being pursued in the search for an effective treatment for methamphetamine (Meth) addiction. In this study, we investigated the safety and potential efficacy of aripiprazole, an antipsychotic agent acting on both dopamine and serotonin systems. We conducted a double-blind in-patient clinical pharmacology study to assess potential interactions between intravenous (i.v.) Meth (15 mg and 30 mg) and oral aripiprazole (15 mg). In addition, the effects of aripiprazole treatment on abstinence-related craving and cue-induced craving were evaluated. Participants included non-treatment-seeking, Meth-dependent patients (n = 16), aged 18-45 yr, currently using Meth. Following baseline Meth dosing (15 mg and 30 mg), participants received 2 wk treatment with aripiprazole (n = 8) or placebo (n = 8). Participants then completed cue exposure sessions using neutral and Meth-related cues. Meth dosing (15 mg and 30 mg) was then repeated. Aripiprazole treatment had no effect on cue-induced Meth craving, or on daily baseline craving assessed over the course of medication treatment, although aripiprazole treatment was associated with increased craving independent of Meth dosing. Aripiprazole treatment was associated with significantly higher ratings on Addiction Research Center Inventory (ARCI) subscales reflecting euphoria and amphetamine-like effects following Meth dosing, Aripiprazole treatment was also associated with significant reductions in ratings of 'bad effects' and reductions on the ARCI subscale for sedation effects following Meth dosing. Aripiprazole treatment reduced the increase in systolic blood pressure following Meth dosing, but had no other effects on cardiovascular responses to Meth. Aripiprazole treatment did not alter the pharmacokinetics of Meth. These findings indicate that aripiprazole treatment appears to be safe in volunteers with Meth dependence, although the finding that aripiprazole increased some of the rewarding and stimulatory effects produced by acute Meth suggests that 15 mg aripiprazole is unlikely to be efficacious for the treatment of Meth dependence. Further research with lower doses of aripiprazole, possibly using study designs aimed at evaluating efficacy for relapse prevention, are needed before ruling out aripiprazole as a treatment for Meth dependence. C1 [Newton, Thomas F.; De La Garza, Richard, II; Mahoney, James J., III] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77056 USA. [Reid, Malcolm S.; Abad, Antonio; Condos, Rany; Palamar, Joseph] NYU, Sch Med, Dept Psychiat, New York, NY USA. [Reid, Malcolm S.; Abad, Antonio; Condos, Rany; Palamar, Joseph] NYU, Sch Med, Dept Pulm Med, New York, NY USA. [Halkitis, Perry N.] NYU, Steinhardt Sch Culture Educ & Human Dev, New York, NY USA. [Mojisak, Jurji; Anderson, Ann; Li, Shou-Hua; Elkashef, Ahmed] NIDA, Rockville, MD USA. RP Newton, TF (reprint author), Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Bldg 110,2002 Holcombe Blvd, Houston, TX 77056 USA. EM tnewton@bcm.edu RI De La Garza, Richard/B-2489-2014; Mahoney, James/I-2753-2014; OI De La Garza, Richard/0000-0003-1943-4469; Mahoney, James/0000-0003-0824-1776; newton, thomas/0000-0002-3198-5901; Palamar, Joseph/0000-0002-8565-9415 FU National Institutes of Health [RR-00865, M01RR00096, NO1DA-3-8838] FX The authors thank Ellie DeCandia, R.N., Timothy Fong, M.D., Roger Donovick, M.D. and Gilles Fleury, M.D. for medical supervision of participants during this study. This work was supported by the National Institutes of Health (RR-00865 to UCLA, M01RR00096 to NYU, and contract NO1DA-3-8838). NR 32 TC 30 Z9 31 U1 4 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 2008 VL 11 IS 8 BP 1037 EP 1045 DI 10.1017/S1461145708009097 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 375KH UT WOS:000261112100002 PM 18664303 ER PT J AU Wu, XF Chen, PS Dallas, S Wilson, B Block, ML Wang, CC Kinyamu, H Lu, N Gao, X Leng, Y Chuang, DM Zhang, WQ Lu, RB Hong, JS AF Wu, Xuefei Chen, Po See Dallas, Shannon Wilson, Belinda Block, Michelle L. Wang, Chao-Chuan Kinyamu, Harriet Lu, Nick Gao, Xi Leng, Yan Chuang, De-Maw Zhang, Wanqin Lu, Ru Band Hong, Jau-Shyong TI Histone deacetylase inhibitors up-regulate astrocyte GDNF and BDNF gene transcription and protect dopaminergic neurons SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Astrocytes; BDNF; dopaminergic neurons; GDNF; histone acetylation; neurotrophic ID C6 GLIOMA-CELLS; NEUROTROPHIC FACTOR GDNF; VALPROIC ACID; MOOD STABILIZER; PARKINSONS-DISEASE; GLIOBLASTOMA CELLS; MESSENGER-RNA; INDUCED DEGENERATION; ALZHEIMERS-DISEASE; APOPTOTIC DEATH AB Parkinson's disease (PD) is characterized by the selective and progressive loss of dopaminergic (DA) neurons in the midbrain substantia nigra. Currently, available treatment is unable to alter PD progression. Previously, we demonstrated that valproic acid (VPA), a mood stabilizer, anticonvulsant and histone deacetylase (HDAC) inhibitor, increases the expression of glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in astrocytes to protect DA neurons in midbrain neuron-glia cultures. The present study investigated whether these effects are due to HDAC inhibition and histone acetylation. Here, we show that two additional HDAC inhibitors, sodium butyrate (SB) and trichostatin A (TSA), mimic the survival-promoting and protective effects of VPA on DA neurons in neuron-glia cultures. Similar to VPA, both SB and TSA increased GDNF and BDNF transcripts in astrocytes in a time-dependent manner. Furthermore, marked increases in GDNF promoter activity and promoter-associated histone H3 acetylation were noted in astrocytes treated with all three compounds, where the time-course for acetylation was similar to that for gene transcription. Taken together, our results indicate that HDAC inhibitors up-regulate GDNF and BDNF expression in astrocytes and protect DA neurons, at least in part, through HDAC inhibition. This study indicates that astrocytes may be a critical neuroprotective mechanism of HDAC inhibitors, revealing a novel target for the treatment of psychiatric and neurodegenerative diseases. C1 [Wu, Xuefei; Chen, Po See; Dallas, Shannon; Wilson, Belinda; Block, Michelle L.; Wang, Chao-Chuan; Gao, Xi; Hong, Jau-Shyong] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Kinyamu, Harriet] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Lu, Nick] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Wu, Xuefei; Gao, Xi; Zhang, Wanqin] Dalian Med Univ, Dept Physiol, Dalian, Peoples R China. [Chen, Po See; Lu, Ru Band] Natl Cheng Kung Univ, Med Coll & Hosp, Inst Basic Med Sci, Tainan 70101, Taiwan. [Chen, Po See; Lu, Ru Band] Natl Cheng Kung Univ, Med Coll & Hosp, Dept Psychiat, Tainan 70101, Taiwan. [Wang, Chao-Chuan] Kaohsiung Med Univ, Coll Med, Dept Anat, Kaohsiung, Taiwan. [Leng, Yan; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA. RP Hong, JS (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov FU National Institute of Health; National Institute of Environmental Health Sciences [R00ES015409]; National Science Council of Taiwan [NSC96-2314-B-006-056-MY3]; Intramural Research Program; NIMH FX We are grateful to Dr Jie Liu and Maggie Humble for excellent technical assistance; Dr Deborah Thompson and Dr Dixie-Ann Sawin for careful reading of the manuscript. This work was supported in part by the Intramural Research Program of the National Institute of Health, the National Institute of Environmental Health Sciences. M.L.B. was supported by grant no. R00ES015409 from the National Institute of Environmental Health Sciences. The content is solely the responsibility of the authors and does not represent necessarily represent the official views of NIEHS or NIH. P.S.C. was supported by the National Science Council of Taiwan (NSC96-2314-B-006-056-MY3). D.M.C. was supported by the Intramural Research Program, NIMH, NIH. NR 55 TC 121 Z9 129 U1 4 U2 18 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD DEC PY 2008 VL 11 IS 8 BP 1123 EP 1134 DI 10.1017/S1461145708009024 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 375KH UT WOS:000261112100009 PM 18611290 ER PT J AU Gaynutdinov, TI Neumann, RD Panyutin, IG AF Gaynutdinov, Timur I. Neumann, Ronald D. Panyutin, Igor G. TI Iodine-125 radioprobing of intramolecular quadruplex conformation of human telomeric DNA in the presence of cationic porphyrin TMPyP4 SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Biophysical Aspects of Auger Processes CY JUL 05-07, 2007 CL Harvard Med Sch, Boston, MD HO Harvard Med Sch DE Radioprobing; quadruplex; cationic porphyrin TMPyP4; telomeric DNA ID TRIPLEX-FORMING OLIGONUCLEOTIDE; HUMAN-CHROMOSOMES; STRAND BREAKS; K+ SOLUTION; SEQUENCE; DECAY; END AB Purpose: A repeated, non-coding, DNA sequence d(17AGGG), is present in the telomeric ends of all human chromosomes. These repeats can adopt multiple inter- and intra-molecular non-B-DNA conformations that may play an important role in biological processes. We applied (125)I-radioprobing to assess the conformation of the human telomeric DNA fragment in a complex with the quadruplex-specific drug - cationic porphyrin TMPyP4. Material and methods: Synthetic DNA oligonucleotides containing the telomeric sequence were labeled with (125)I. The probability of DNA breaks caused by decay of 125 1 is inversely related to the distance between the radionuclide and the sugar unit of the DNA backbone, hence, the conformation of the DNA backbone can be deduced from the distribution of breaks. Results: The obtained data indicate that the telomeric oligonucleotides predominantly fold into an intramolecular quadruplex conformation in the presence of TMPyP4. We propose a mixed-type (3 + 1) conformation of telomeric quadruplex in a complex with the cationic porphyrin TMPyP4 in solution. Binding of the porphyrin overrides the counterion effect on quadruplex conformation. Conclusions: We have demonstrated that (125)I radioprobing can be successfully applied not only to determine folding in G-quadruplexes, but also to reveal the mode of quadruplex interaction with small ligands. C1 [Gaynutdinov, Timur I.; Neumann, Ronald D.; Panyutin, Igor G.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gaynutdinov, TI (reprint author), NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM gaynutdinovt@mail.nih.gov FU Intramural NIH HHS [Z01 CL060001-12, NIH0012037052] NR 34 TC 1 Z9 1 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD DEC PY 2008 VL 84 IS 12 BP 984 EP 990 DI 10.1080/09553000802415747 PG 7 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 405KG UT WOS:000263221300004 PM 19061122 ER PT J AU Aboud, S Msamanga, G Read, JS Mwatha, A Chen, YQ Potter, D Valentine, M Sharma, U Hoffmann, I Taha, TE Goldenberg, RL Fawzi, WW AF Aboud, S. Msamanga, G. Read, J. S. Mwatha, A. Chen, Y. Q. Potter, D. Valentine, M. Sharma, U. Hoffmann, I. Taha, T. E. Goldenberg, R. L. Fawzi, W. W. TI Genital tract infections among HIV-infected pregnant women in Malawi, Tanzania and Zambia SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article DE sexually transmitted infections; genital tract infections; pregnant women; human immunodeficiency virus; Africa ID SEXUALLY-TRANSMITTED-DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; 4 AFRICAN CITIES/; EPIDEMIOLOGIC SYNERGY; BACTERIAL VAGINOSIS; TRANSMISSION; TRIAL; SYPHILIS; WORKERS; UGANDA AB The aim of this study was to compare the prevalence and factors associated with genital tract infections among HIV-infected pregnant women from African sites. Participants were recruited from Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. Genital tract infections were assessed at baseline. Of 2627 eligible women enrolled, 2292 were HIV-infected. Of these, 47.8% had bacterial vaginosis (BV), 22.4% had vaginal candidiasis, 18.8% had trichomoniasis, 8.5% had genital warts, 2.6% had chlamydia infection, 2.2% had genital ulcers and 1.7% had gonorrhoea. The main factors associated with genital tract infections included genital warts (adjusted odds ratio [AOR] 1.8, 95% CI 1.2-2.7), genital ulcers (AOR 2.4, 95% CI 1.2-5.1) and abnormal vaginal discharge (AOR 2.5, 95% CI 1.9-3.3) for trichomoniasis. BV was the most common genital tract infection followed by candidiasis and trichomoniasis. Differences in burdens and risk factors call for enhanced interventions for identification of genital tract infections among HIV-infected women. C1 [Aboud, S.] Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. [Read, J. S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA. [Chen, Y. Q.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Potter, D.] Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. [Valentine, M.] Family Hlth Int, Res Triangle Pk, NC 27709 USA. [Sharma, U.] NIAID, Prevent Sci Program, NIH, Bethesda, MD 20892 USA. [Hoffmann, I.] Univ N Carolina, Chapel Hill, NC USA. [Taha, T. E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Goldenberg, R. L.] Drexel Univ, Dept Obstet & Gynaecol, Philadelphia, PA 19104 USA. [Fawzi, W. W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Fawzi, W. W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Aboud, S (reprint author), Muhimbili Univ Hlth & Allied Sci, Dept Microbiol & Immunol, Dar Es Salaam, Tanzania. EM aboudsaid@yahoo.com FU FIC NIH HHS [D43 TW001035, D43TW01035-07]; NIAID NIH HHS [N01 AI045200, N01-AI-045200, U01-AI-047972, U01-AI-048005, U01 AI047972, U01-AI-048006, N01-AI-035173, U01 AI048005, N01-AI-035173-117/412, U01 AI048006, N01 AI035173]; NIDDK NIH HHS [P30 DK040561-13, P30 DK040561] NR 21 TC 24 Z9 24 U1 0 U2 3 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD DEC PY 2008 VL 19 IS 12 BP 824 EP 832 DI 10.1258/ijsa.2008.008067 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 387PU UT WOS:000261964900008 PM 19050213 ER PT J AU FitzGerald, MP Richter, HE Bradley, CS Ye, W Visco, AC Cundiff, GW Zyczynski, HM Fine, P Weber, AM AF FitzGerald, M. P. Richter, H. E. Bradley, C. S. Ye, W. Visco, A. C. Cundiff, G. W. Zyczynski, H. M. Fine, P. Weber, A. M. CA Pelv Floor Disorders Network TI Pelvic support, pelvic symptoms, and patient satisfaction after colpocleisis SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Pelvic organ prolapse; Urinary incontinence; Pelvic floor disorders; Colpocleisis; Quality of life; Surgical outcomes ID QUALITY-OF-LIFE; ORGAN PROLAPSE; WOMEN AB The objective was to study the effect of colpocleisis on pelvic support, symptoms, and quality of life and report-associated morbidity and postoperative satisfaction. Women undergoing colpocleisis for treatment of pelvic organ prolapse (POP) were recruited at six centers. Baseline measures included physical examination, responses to the Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire. Three and 12 months after surgery we repeated baseline measures. Of 152 patients with mean age 79 (+/- 6) years, 132 (87%) completed 1 year follow-up. Three and 12 months after surgery, 90/110 (82%) and 75/103 (73%) patients following up had POP stage <= 1. All pelvic symptom scores and related bother significantly improved at 3 and 12 months, and 125 (95%) patients said they were either 'very satisfied' or 'satisfied' with the outcome of their surgery. Colpocleisis was effective in resolving prolapse and pelvic symptoms and was associated with high patient satisfaction. C1 [FitzGerald, M. P.] Loyola Univ, Div Female Pelv Med & Reconstruct Surg, Med Ctr, Maywood, IL 60153 USA. [Richter, H. E.] Univ Alabama, Birmingham, AL USA. [Bradley, C. S.] Univ Iowa, Iowa City, IA USA. [Ye, W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Visco, A. C.] Univ N Carolina, Chapel Hill, NC USA. [Cundiff, G. W.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Zyczynski, H. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Fine, P.] Baylor Coll Med, Houston, TX 77030 USA. [Weber, A. M.; Pelv Floor Disorders Network] NICHHD, Bethesda, MD 20892 USA. RP FitzGerald, MP (reprint author), Loyola Univ, Div Female Pelv Med & Reconstruct Surg, Med Ctr, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA. EM Mfitzg8@lumc.edu FU National Institute of Child Health and Human Development [U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, U10 HD41267]; National Institute of Diabetes, Digestive and Kidney Diseases [K24 DK068389] FX Supported by grants from the National Institute of Child Health and Human Development (U01 HD41249, U10 HD41268, U10 HD41248, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41269, and U10 HD41267) and the National Institute of Diabetes, Digestive and Kidney Diseases (K24 DK068389). NR 7 TC 45 Z9 57 U1 0 U2 3 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD DEC PY 2008 VL 19 IS 12 BP 1603 EP 1609 DI 10.1007/s00192-008-0696-6 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 367AQ UT WOS:000260525300003 PM 18690402 ER PT J AU Tennstedt, SL Litman, HJ Zimmern, P Ghetti, C Kusek, JW Nager, CW Mueller, ER Kraus, SR Varner, E AF Tennstedt, S. L. Litman, H. J. Zimmern, P. Ghetti, C. Kusek, J. W. Nager, C. W. Mueller, E. R. Kraus, S. R. Varner, E. CA Urinary Incontinence Treatment Net TI Quality of life after surgery for stress incontinence SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Quality of life; Surgery; Urinary incontinence ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; WOMEN AB This study investigated changes in condition-specific quality of life (QOL) after surgery for stress urinary incontinence. Data from 655 women in a clinical trial comparing the Burch and fascial sling were examined. Improvement in QOL, measured with the Incontinence Impact Questionnaire (mean decrease 133.1; SD 109.8), was observed 6 months after surgery and persisted at 24 months. Women for whom surgery was successful (regardless of surgery type) had greater improvement in QOL (mean decrease 160.0; SD 103.9) than did women for whom surgery was not successful (mean decrease 113.6; SD 110.9; p < 0.0001), although not statistically significant after adjusting for covariates. Multivariable analysis showed that QOL improvement was related to decreased urinary incontinence (UI) symptom bother, greater improvement in UI severity, younger age, Hispanic ethnicity, and receiving Burch surgery. Among sexually active women, worsening sexual function had a negative impact on QOL. Improved QOL was explained most by UI symptom improvement. C1 [Tennstedt, S. L.; Litman, H. J.] New England Res Inst, Watertown, MA 02472 USA. [Zimmern, P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ghetti, C.] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. [Kusek, J. W.] NIDDK, NIH, Bethesda, MD USA. [Nager, C. W.] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. [Mueller, E. R.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Kraus, S. R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Varner, E.] Univ Alabama, Birmingham, AL USA. RP Tennstedt, SL (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM stennstedt@neriscience.com FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Child Health and Human Development; Office of Research on Women's Health; National Institutes of Health FX This work was supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases with additional support from the National Institute of Child Health and Human Development and the Office of Research on Women's Health, National Institutes of Health. NR 12 TC 18 Z9 18 U1 1 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD DEC PY 2008 VL 19 IS 12 BP 1631 EP 1638 DI 10.1007/s00192-008-0700-1 PG 8 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 367AQ UT WOS:000260525300007 PM 18682875 ER PT J AU Austein, T Badge, S Kerstan, H von Bloh, J Aue, G Losekann, M Pacholik, L AF Austein, T. Badge, S. Kerstan, H. von Bloh, J. Aue, G. Loesekann, M. Pacholik, L. TI A 62 year old woman with spontaneous onset of distinct walking disorder and pancytopenia SO INTERNIST LA German DT Article DE Subacute combined degeneration of the spinal cord (SACD) Pancytopenia; Megaloblastic anemia; Cobalamin deficiency; Vegetarism ID SUBACUTE COMBINED DEGENERATION; VITAMIN-B12 DEFICIENCY AB Our case-report presents a 62 year old woman with spontaneous onset of a distinct walking disorder and pancytopenia. The diagnosis showed a sub-acute combined degeneration of the spinal cord (SACD) and a megaloblastic anemia as a result of a cobalamin deficiency. This was caused by a strict vegetarian nutrition since 18 years. Once on therapy with cobalamin substitutes the clinical and laboratory test results improved within 3 months. C1 [Austein, T.; Badge, S.; Kerstan, H.; von Bloh, J.; Loesekann, M.; Pacholik, L.] St Bernhard Hosp, Med Klin 2, Abt Hamatol Intern Onkol, D-26919 Brake, Germany. [Aue, G.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Austein, T (reprint author), St Bernhard Hosp, Med Klin 2, Abt Hamatol Intern Onkol, Claussenstr 3, D-26919 Brake, Germany. EM dr.austein@sbhospital.de NR 13 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0020-9554 J9 INTERNIST JI Internist PD DEC PY 2008 VL 49 IS 12 BP 1512 EP 1515 DI 10.1007/s00108-008-2248-z PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 379NF UT WOS:000261402600013 PM 18979078 ER PT J AU Lorenz, B Poliakov, E Schambeck, M Friedburg, C Preising, MN Redmond, TM AF Lorenz, Birgit Poliakov, Eugenia Schambeck, Maria Friedburg, Christoph Preising, Markus N. Redmond, T. Michael TI A Comprehensive Clinical and Biochemical Functional Study of a Novel RPE65 Hypomorphic Mutation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LEBERS CONGENITAL AMAUROSIS; RETINAL-PIGMENT EPITHELIUM; THERAPY RESTORES VISION; GENE-THERAPY; VISUAL CYCLE; LIPOFUSCIN FLUOROPHORES; MOUSE MODEL; DYSTROPHY; LIGHT; DEGENERATION AB PURPOSE. Later onset and progression of retinal dystrophy occur with some RPE65 missense mutations. The functional consequences of the novel P25L RPE65 mutation was correlated with its early-childhood phenotype and compared with other pathogenic missense mutations. METHODS. In addition to typical clinical tests, fundus autofluorescence (FAF), optical coherence tomography (OCT), and two-color threshold perimetry (2CTP) were measured. RPE65 mutations were screened by SSCP and direct sequencing. Isomerase activity of mutant RPE65 was assayed in 293F cells and quantified by HPLC analysis of retinoids. RESULTS. A very mild phenotype was detected in a now 7-year-old boy homozygous for the P25L mutation in RPE65. Although abnormal dark adaptation was noticed early, best corrected visual acuity was 20/20 at age 5 years and 20/30 at age 7 years. Nystagmus was absent. Cone electroretinogram (ERG) was measurable, rod ERG severely reduced, and FAF very low. 2CTP detected mainly cone-mediated responses in scotopic conditions, and light-adapted cone responses were approximately 1.5 log units below normal. High-resolution spectral domain OCT revealed morphologic changes. Isomerase activity in 293F cells transfected with RPE65/P25L was reduced to 7.7% of wild-type RPE65-transfected cells, whereas RPE65/ L22P-transfected cells had 13.5%. CONCLUSIONS. The mild clinical phenotype observed is consistent with the residual activity of a severely hypomorphic mutant RPE65. Reduction to <10% of wild-type RPE65 activity by homozygous P25L correlates with almost complete rod function loss and cone amplitude reduction. Functional survival of cones is possible in patients with residual RPE65 isomerase activity. This patient should profit most from gene therapy. (Invest Ophthalmol Vis Sci. 2008; 49: 5235-5242) DOI: 10.1167/iovs.07-1671 C1 [Lorenz, Birgit; Friedburg, Christoph; Preising, Markus N.] Univ Giessen, Dept Ophthalmol, Univ Giessen Klinikum, D-35385 Giessen, Germany. [Lorenz, Birgit; Friedburg, Christoph; Preising, Markus N.] Marburg GmbH, Giessen, Germany. [Lorenz, Birgit; Schambeck, Maria; Friedburg, Christoph; Preising, Markus N.] Univ Regensburg, Med Ctr, Dept Paediat Ophthalmol Strabismol & Ophthalmogen, Regensburg, Germany. [Poliakov, Eugenia; Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lorenz, B (reprint author), Univ Giessen, Dept Ophthalmol, Univ Giessen Klinikum, Giessen Campus,Friedrichstr 18, D-35385 Giessen, Germany. EM birgit.lorenz@uniklinikum-giessen.de OI Redmond, T. Michael/0000-0002-1813-5291 FU DFG (German Research Foundation) [LO 457/5]; Pro Retina Deutschland e.V.; National Eye Institute, NIH FX Supported by DFG (German Research Foundation) Grant LO 457/5, Pro Retina Deutschland e.V., and the Intramural Research Program of the National Eye Institute, NIH (TMR, EP). NR 47 TC 37 Z9 37 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2008 VL 49 IS 12 BP 5235 EP 5242 DI 10.1167/iovs.07-1671 PG 8 WC Ophthalmology SC Ophthalmology GA 376OW UT WOS:000261193900010 PM 18599565 ER PT J AU Resnik, DB AF Resnik, David B. TI Freedom of speech in government science SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Article C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM resnlkd@nlehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD WIN PY 2008 VL 24 IS 2 BP 31 EP 34 PG 4 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 249PT UT WOS:000252241900017 PM 19295665 ER PT J AU Gabay, O Hall, DJ Berenbaum, F Henrotin, Y Sanchez, C AF Gabay, Odile Hall, David J. Berenbaum, Francis Henrotin, Yves Sanchez, Christelle TI Osteoarthritis and obesity: Experimental models SO JOINT BONE SPINE LA English DT Review DE Osteoarthritis; Obesity; Cartilage; Bone; Mechanical stress; Adipokines ID ARTICULAR-CARTILAGE; PROTEOGLYCAN SYNTHESIS; BIOMECHANICAL SIGNALS; MECHANICAL-STRESS; UP-REGULATION; CHONDROCYTES; OSTEOBLASTS; COMPRESSION; ACTIVATION; EXPRESSION AB Osteoarthritis (OA) is a multifactorial disease. Different risk factors have been identified such as aging and obesity and different models have been used to study the impact of obesity and overweight in this pathology. The field the more studied is in vitro cartilage submitted to mechanical stresses. Four different stresses can be applied on this tissue: shear stress, loading, tensile stress (stretching) and hydrostatic pressure. The signal transduction to the chondrocyte and to the nucleus of the cell is a large field of investigation named mechano-transduction. The response of cartilage depends on quality of subchondral bone as well. So, more and more teams are studying the impact of mechanical stresses on bone, mainly by stretching osteoblasts or by submitting them to a fluid shear stress. Recently, a new model of bone compression has been set up, with osteoblasts in their own extracellular matrix. Finally the third field studied is the role of adipokines, mediators playing a key role in obesity, on the aetiology of OA. Adipokines like leptin, resistin, adiponectin and visfatin, seems to play a pro-inflammatory role in arthritis. Studying the role of obesity in OA could be more complex than expected. The link between OA and obesity may not simply be due to high mechanical stresses applied on the tissues, but soluble mediators may play an important role in the onset of OA in obese patients. (C) 2008 Elsevier Masson SAS. All rights reserved. C1 [Gabay, Odile; Hall, David J.] NIAMS, Cartilage Biol & Orthopaed Branch, Cartilage Mol Genet Grp, NIH, Bethesda, MD 20892 USA. [Berenbaum, Francis] Univ Paris 06, UPMC, Physiol & Physiopathol Lab, F-75252 Paris 5, France. [Berenbaum, Francis] CNRS, UMR 7079, F-75252 Paris 5, France. [Berenbaum, Francis] Hop St Antoine, AP HP, Dept Rheumatol, F-75012 Paris, France. [Henrotin, Yves; Sanchez, Christelle] Univ Liege, Inst Pathol, Bone & Cartilage Res Unit, B-4000 Liege, Belgium. RP Gabay, O (reprint author), NIAMS, Cartilage Biol & Orthopaed Branch, Cartilage Mol Genet Grp, NIH, 50 S Dr,Bldg 50,Room 1314, Bethesda, MD 20892 USA. EM gabayo@mail.nih.gov FU Intramural NIH HHS [Z01 AR041141-05, Z99 AR999999] NR 40 TC 36 Z9 38 U1 2 U2 15 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1297-319X J9 JOINT BONE SPINE JI Joint Bone Spine PD DEC PY 2008 VL 75 IS 6 BP 675 EP 679 DI 10.1016/j.jbspin.2008.07.011 PG 5 WC Rheumatology SC Rheumatology GA 386SI UT WOS:000261902500012 PM 19022697 ER PT J AU Shearer, WT Notarangelo, LD Griffith, LM AF Shearer, William T. Notarangelo, Luigi D. Griffith, Linda M. TI Treatment of immunodeficiency: Long-term outcome and quality of life SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material DE Hematoietic stem cell transplantation; severe combined immunodeficiency; long-term follow-up; quality of life ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; IMMUNE RECONSTITUTION; EXPERIENCE; DEFICIENCY C1 [Shearer, William T.] Texas Childrens Hosp, Allergy Immunol Serv, Houston, TX 77030 USA. [Shearer, William T.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Shearer, William T.] Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. [Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Allergy Immunol Serv, 6621 Fannin St,MF FC330-01, Houston, TX 77030 USA. EM wtsheare@TexasChildrensHospital.org RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU NCRR NIH HHS [RR0188]; NHLBI NIH HHS [HL079533, HL72705, HL78522]; NIAID NIH HHS [AI036211, AI069441]; NICHD NIH HHS [HD052102]; PHS HHS [RAT003084A] NR 38 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2008 VL 122 IS 6 BP 1065 EP 1068 DI 10.1016/j.jaci.2008.10.033 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 383ZA UT WOS:000261711800003 PM 19084107 ER PT J AU Griffith, LM Cowan, MJ Kohn, DB Notarangelo, LD Puck, JM Schultz, KR Buckley, RH Eapen, M Kamani, NR O'Reilly, RJ Parkman, R Roifman, CM Sullivan, KE Filipovich, AH Fleisher, TA Shearer, WT AF Griffith, Linda M. Cowan, Morton J. Kohn, Donald B. Notarangelo, Luigi D. Puck, Jennifer M. Schultz, Kirk R. Buckley, Rebecca H. Eapen, Mary Kamani, Naynesh R. O'Reilly, Richard J. Parkman, Robertson Roifman, Chaim M. Sullivan, Kathleen E. Filipovich, Alexandra H. Fleisher, Thomas A. Shearer, William T. CA Workshop Participants TI Allogeneic hematopoietic cell transplantation for primary immune deficiency diseases: Current status and critical needs SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Allogeneic hematopoietic cell transplantation; primary immune deficiency; clinical trial ID SEVERE COMBINED IMMUNODEFICIENCY; BONE-MARROW-TRANSPLANTATION; WISKOTT-ALDRICH-SYNDROME; CHRONIC GRANULOMATOUS-DISEASE; TERM-FOLLOW-UP; EUROPEAN EXPERIENCE; CLINICAL-FEATURES; IMPROVED SURVIVAL; RECONSTITUTION; BLOOD AB Allogeneic hematopoietic cell transplantation (HCT) has been used for 40 years to ameliorate or cure primary immune deficiency (PID) diseases, including severe combined immunodeficiency (SCID) and non-SCID PID. There is a critical need for evaluation of the North American experience of different HCT approaches for these diseases to identify best practices and plan future investigative clinical trials. Our survey of incidence and prevalence of PID in North American practice sites indicates that such studies are feasible. A conference of experts in HCT treatment of PID has recommended (1) a comprehensive cross-sectional and retrospective analysis of HCT survivors with SCID; (2) a prospective study of patients with SCID receiving HCT, with comparable baseline and follow-up testing across participating centers; (3) a pilot study of newborn screening for SCID to identify affected infants before compromise by infection; and (4) studies of the natural history of disease in patients who do or do not receive RCT for the non-SCID diseases of Wiskott-Aldrich syndrome and chronic granulomatous disease. To accomplish these goals, collaboration by a consortium of institutions in North America is proposed. Participation of immunologists and HCT physicians having interest in PID and experts in laboratory methods, clinical outcomes assessment, databases, and analysis will be required for the success of these studies. (J Allergy Clin Immunol 2008; 122:1087-96.) C1 [Shearer, William T.] Texas Childrens Hosp, Baylor Coll Med, Dept Allergy & Immunol, Houston, TX 77030 USA. [Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Cowan, Morton J.] UCSF Childrens Hosp, Pediat Blood & Marrow Transplant Div, San Francisco, CA USA. [Kohn, Donald B.] Univ So Calif, Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplantat, Los Angeles, CA 90089 USA. [Notarangelo, Luigi D.] Harvard Univ, Childrens Hosp, Sch Med, Div Immunol, Boston, MA 02115 USA. [Puck, Jennifer M.] Univ Calif San Francisco, Inst Human Genet, Dept Pediat, San Francisco, CA 94143 USA. [Schultz, Kirk R.] Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. [Buckley, Rebecca H.] Duke Univ, Sch Med, Durham, NC 27706 USA. [Eapen, Mary] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Kamani, Naynesh R.] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. [O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Immunol, New York, NY 10021 USA. [Parkman, Robertson] Childrens Hosp Los Angeles, Div Immunol Res, BMT, Los Angeles, CA 90027 USA. [Roifman, Chaim M.] Univ Toronto, Hosp Sick Children, Div Immunol & Allergy, Toronto, ON M5S 1A1, Canada. [Sullivan, Kathleen E.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Filipovich, Alexandra H.] Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH USA. [Fleisher, Thomas A.] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, Baylor Coll Med, Dept Allergy & Immunol, MC FC330-01,6621 Fannin St,Ste A-380, Houston, TX 77030 USA. EM wtsheare@texaschildrenshospital.org RI Notarangelo, Luigi/F-9718-2016; Kohn, Donald/N-5085-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Kohn, Donald/0000-0003-1840-6087; Sullivan, Kathleen/0000-0003-4018-1646 FU March of Dimes; Enzo Therapeutics; USIDNET; National Cancer Institute; Leukemia and Lymphoma Society; National Institutes of Health; Pediatric Blood and Marrow Transplant Consortium/Children's Oncology Group FX M. J. Cowan has received research support from the March of Dimes and Enzo Therapeutics, J. NI. Puck has received research support from USIDNET and has provided legal consultation on primary immunodeficiency. K. R. Schultz has received research support from the National Cancer Institute and the Leukemia and Lymphoma Society and has served as an expert witness for DOIL BioPharma. R. H. Buckley has received research support from the National Institutes of Health. N. R. Kamani has received research Support from the Pediatric Blood and Marrow Transplant Consortium/Children's Oncology Group and has served as a member of the National Marrow Donor Program. R. J. O'Reilly has received research support from the National Institutes of Health and owns stock in Calibrant. R. Parkman has received research support from the National Institutes of Health. K. E. Sullivan has received research support front the National Institutes of Health and USIDNET, has served as an expert witness for Contocor-Psorusis, and has consulting arrangements with the Immune Deficiency Foundation. The rest of the authors have declared that they have no conflict of interest. NR 40 TC 42 Z9 43 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2008 VL 122 IS 6 BP 1087 EP 1096 DI 10.1016/j.jaci.2008.09.045 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 383ZA UT WOS:000261711800007 PM 18992926 ER PT J AU De Ravin, SS Naumann, N Cowen, EW Friend, J Hilligoss, D Marquesen, M Balow, JE Barron, KS Turner, ML Gallin, JI Malech, HL AF De Ravin, Suk See Naumann, Nora Cowen, Edward W. Friend, Julia Hilligoss, Dianne Marquesen, Martha Balow, James E. Barron, Karyl S. Turner, Maria L. Gallin, John I. Malech, Harry L. TI Chronic granulomatous disease as a risk factor for autoimmune disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Chronic granulomatous disease; autoimmune; antiphospholipid syndrome; IgA nephropathy; lupus; juvenile idiopathic nephropathy ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IGA NEPHROPATHY; PERICARDIAL-EFFUSIONS; CLINICAL-FEATURES; PATIENT; ARTHRITIS; CRITERIA; MODEL; CGD AB Chronic granulomatous disease (CGD) is characterized by recurrent infections and granuloma formation. In addition, we have observed a number of diverse autoimmune conditions in our CGD population, suggesting that patients with CGD are at an elevated risk for development of autoimmune disorders. In this report, we describe anti phospholipid syndrome, recurrent pericardial effusion, juvenile idiopathic arthritis, IgA nephropathy, cutaneous lupus erythematosus, and autoimmune pulmonary disease in the setting of CGD. The presence and type of autoimmune disease have important treatment implications for patients with CGD. (J Allergy Clin Immunol 2008;122:1097-103.) C1 [De Ravin, Suk See; Naumann, Nora; Friend, Julia; Hilligoss, Dianne; Marquesen, Martha; Barron, Karyl S.; Gallin, John I.; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. [Balow, James E.] NIDDKD, Bethesda, MD 20892 USA. [Cowen, Edward W.; Turner, Maria L.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP De Ravin, SS (reprint author), NIAID, Host Def Lab, NIH, Bldg 10-CRC,Room 5-3816,10 Ctr Dr, Bethesda, MD 20892 USA. EM sderavin@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Intramural NIH HHS [Z01 AI000645-16, Z01 AI000645-17] NR 32 TC 81 Z9 83 U1 0 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2008 VL 122 IS 6 BP 1097 EP 1103 DI 10.1016/j.jaci.2008.07.050 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 383ZA UT WOS:000261711800008 PM 18823651 ER PT J AU Jacobs, M Snow, J Geraci, M Vythilingam, M Blair, RJR Charney, DS Pine, DS Blair, KS AF Jacobs, Madeline Snow, Joseph Geraci, Marilla Vythilingam, Meena Blair, R. J. R. Charney, Dennis S. Pine, Daniel S. Blair, Karina S. TI Association between level of emotional intelligence and severity of anxiety in generalized social phobia SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Generalized social phobia; Emotional responding; Emotional intelligence; MSCEIT ID AMYGDALA ACTIVATION; TEST MSCEIT; FACES; VALIDITY; INDIVIDUALS; ABILITIES; RESPONSES; RATINGS; QUALITY; CORTEX AB Generalized social phobia (GSP) is characterized by a marked fear of most social situations. It is associated with an anomalous neural response to emotional stimuli, and individuals with the disorder frequently show interpretation bias in social situations. From this it might be suggested that GSP involves difficulty in accurately perceiving, using, understanding and managing emotions. Here we applied the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) to medication-free GSP (n = 28) and no pathology (n = 21) individuals. Patients with GSP performed within the normal range on the measure however severity of social anxiety significantly correlated with emotional intelligence (EI). Specifically, there was a negative correlation between social anxiety severity and Experiential (basic-level emotional processing) EI. In contrast, there was no significant correlation between social anxiety severity and Strategic (higher-level conscious emotional processing) EI. These results suggest that El may index emotional processing systems that mitigate the impact of systems causally implicated in GSP. Published by Elsevier Ltd. C1 [Jacobs, Madeline; Snow, Joseph; Geraci, Marilla; Vythilingam, Meena; Blair, R. J. R.; Pine, Daniel S.; Blair, Karina S.] NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Charney, Dennis S.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Blair, KS (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 43 TC 18 Z9 18 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD DEC PY 2008 VL 22 IS 8 BP 1487 EP 1495 DI 10.1016/j.janxdis.2008.03.003 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 361TV UT WOS:000260150900024 PM 18439799 ER PT J AU Ghitza, UE Epstein, DH Schmittner, J Vahabzadeh, M Lin, JL Preston, KL AF Ghitza, Udi E. Epstein, David H. Schmittner, John Vahabzadeh, Massoud Lin, Jia-Ling Preston, Kenzie L. TI EFFECT OF REINFORCEMENT PROBABILITY AND PRIZE SIZE ON COCAINE AND HEROIN ABSTINENCE IN PRIZE-BASED CONTINGENCY MANAGEMENT SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE computer automation; contingency management; methadone; operant conditioning; opiate; substance abuse ID VOUCHER-BASED REINFORCEMENT; CLINICAL-TRIALS NETWORK; METHADONE PATIENTS; CIGARETTE-SMOKING; SUBSTANCE-ABUSERS; RANDOMIZED-TRIAL; USE DISORDERS; THERAPY; DRUG; INCENTIVES AB Although treatment outcome in prize-based contingency management has been shown to depend on reinforcement schedule, the optimal schedule is still unknown. Therefore, we conducted a retrospective analysis of data from a randomized clinical trial (Ghitza et al., 2007) to determine the effects of the probability of winning a prize (low vs. high) and the size of the prize won (small, large, or jumbo) on likelihood of abstinence until the next urine-collection day for heroin and cocaine Users (N = 116) in methadone maintenance. Higher probability of winning, but not the size of individual prizes, was associated with a greater percentage of cocaine-negative, but not opiate-negative, urines. C1 [Ghitza, Udi E.] NIDA, IRP, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, IRP, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM ghitzau@nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS NR 37 TC 11 Z9 11 U1 3 U2 4 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD WIN PY 2008 VL 41 IS 4 BP 539 EP 549 DI 10.1901/jaba.2008.41-539 PG 11 WC Psychology, Clinical SC Psychology GA 390LH UT WOS:000262165300006 PM 19192858 ER PT J AU Preston, KL Ghitza, UE Schmittner, JP Schroeder, JR Epstein, DH AF Preston, Kenzie L. Ghitza, Udi E. Schmittner, John P. Schroeder, Jennifer R. Epstein, David H. TI RANDOMIZED TRIAL COMPARING TWO TREATMENT STRATEGIES USING PRIZE-BASED REINFORCEMENT OF ABSTINENCE IN COCAINE AND OPIATE USERS SO JOURNAL OF APPLIED BEHAVIOR ANALYSIS LA English DT Article DE cocaine abuse; community settings; contingency management; heroin abuse; opiate ID VOUCHER-BASED REINFORCEMENT; DRUG-ABUSE TREATMENT; CONTINGENCY MANAGEMENT; METHADONE-MAINTENANCE; CIGARETTE-SMOKING; PROGRAM; HEROIN; ADDICTION; THERAPY; MODELS AB We compared two strategies of prize-based contingency management (CM) in methadone-maintained outpatients. Urine was tested thrice weekly, for 5 weeks pre-CM, 12 weeks GM, and 8 weeks post-CM. Participants were randomly assigned to a cocaine contingency (four prize draws for each cocaine-negative urine, N = 29) or an opiate-cocaine contingency (one draw for each urine negative for opiates or cocaine, four draws if negative for both, N = 38). There Were no group differences in cocaine abstinence during CM or post-CM and no differences in opiate abstinence during CM, Opiate abstinence was greater in the opiate-cocaine group post-CM, and heroin craving was reduced in this group during and post-CM. Draws earned per cocaine-negative wine (four vs. one) did not affect cocaine use. C1 [Ghitza, Udi E.] NIDA, IRP, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, Baltimore, MD 21224 USA. RP Ghitza, UE (reprint author), NIDA, IRP, Clin Pharmacol & Therapeut Res Branch, Treatment Sect, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM ghitzau@nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS NR 39 TC 10 Z9 10 U1 2 U2 4 PU JOURNAL APPL BEHAV ANAL PI LAWRENCE PA DEPT HUMAN DEVELOPMENT, UNIV KANSAS, LAWRENCE, KS 66045 USA SN 0021-8855 J9 J APPL BEHAV ANAL JI J. Appl. Behav. Anal. PD WIN PY 2008 VL 41 IS 4 BP 551 EP 563 DI 10.1901/jaba.2008.41-551 PG 13 WC Psychology, Clinical SC Psychology GA 390LH UT WOS:000262165300007 PM 19192859 ER PT J AU Ma, JC Xia, D AF Ma, Jichun Xia, Di TI The use of blue native PAGE in the evaluation of membrane protein aggregation states for crystallization SO JOURNAL OF APPLIED CRYSTALLOGRAPHY LA English DT Article ID CYTOCHROME BC(1) COMPLEX; FULGIDUS CU+-ATPASE; CRYSTAL-STRUCTURE; ARCHAEOGLOBUS-FULGIDUS; INTERMOLECULAR INTERACTIONS; BINDING DOMAIN; CLPAP PROTEASE; MENKES-DISEASE; BOVINE HEART; COPPER AB Crystallization has long been one of the bottlenecks in obtaining structural information at atomic resolution for membrane proteins. This is largely due to difficulties in obtaining high-quality protein samples. One frequently used indicator of protein quality for successful crystallization is the monodispersity of proteins in solution, which is conventionally obtained by size exclusion chromatography ( SEC) or by dynamic light scattering (DLS). Although useful in evaluating the quality of soluble proteins, these methods are not always applicable to membrane proteins either because of the interference from detergent micelles or because of the requirement for large sample quantities. Here, the use of blue native polyacrylamide gel electrophoresis (BN-PAGE) to assess aggregation states of membrane protein samples is reported. A strong correlation is demonstrated between the monodispersity measured by BN-PAGE and the propensity for crystallization of a number of soluble and membrane protein complexes. Moreover, it is shown that there is a direct correspondence between the oligomeric states of proteins as measured by BN-PAGE and those obtained from their crystalline forms. When applied to a membrane protein with unknown structure, BN-PAGE was found to be useful and efficient for selecting well behaved proteins from various constructs and in screening detergents. Comparisons of BN-PAGE with DLS and SEC are provided. (C) 2008 International Union of Crystallography Printed in Singapore - all rights reserved C1 [Ma, Jichun; Xia, Di] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Xia, D (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Bldg 37,Room 2122C, Bethesda, MD 20892 USA. EM dixia@helix.nih.gov FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research FX The authors wish to thank Drs Lothar Esser and Robert M. Rutledge for their critical comments and George Leiman for editorial assistance. We also thank Dr Chang-An Yu for providing cytochrome bc1 complexes from bovine heart mitochondria and from R. sphaeroides and the staff at the SER-CAT beamline at the Advanced Photon Source, Argonne National Laboratory, for assistance with the X-ray diffraction experiments. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 41 TC 13 Z9 14 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-8898 J9 J APPL CRYSTALLOGR JI J. Appl. Crystallogr. PD DEC PY 2008 VL 41 BP 1150 EP 1160 DI 10.1107/S0021889808033797 PN 6 PG 11 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA 373WM UT WOS:000261004200021 ER PT J AU Rickard, AH Campagna, SR Kolenbrander, PE AF Rickard, A. H. Campagna, S. R. Kolenbrander, P. E. TI Autoinducer-2 is produced in saliva-fed flow conditions relevant to natural oral biofilms SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE Actinomyces naeslundii; autoinducer-2; cell-cell signalling; communication; dual-species biofilm; oral bacteria; Streptococcus oralis ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; VIBRIO-HARVEYI; INTERSPECIES COMMUNICATION; ACTINOMYCES-VISCOSUS; BACTERIAL BIOFILMS; ESCHERICHIA-COLI; LUXS MUTANT; SIGNAL; MOLECULES; GROWTH AB We evaluated the ability of a dual-species community of oral bacteria to produce the universal signalling molecule, autoinducer-2 (AI-2), in saliva-fed biofilms. Streptococcus oralis 34, S. oralis 34 luxS mutant and Actinomyces naeslundii T14V were grown as single- and dual-species biofilms within sorbarods fed with 25% human saliva. AI-2 concentration in biofilm effluents was determined by the Vibrio harveyi BB170 bioluminescence assay. After homogenizing the sorbarods to release biofilm cells, cell numbers were determined by fluorometric analysis of fluorescent antibody-labelled cells. After 48 h, dual-species biofilm communities of interdigitated S. oralis 34 and A. naeslundii T14V contained 3.2 x 10(9) cells: fivefold more than single-species biofilms. However, these 48-h dual-species biofilms exhibited the lowest concentration ratio of AI-2 to cell density. Oral bacteria produce AI-2 in saliva-fed biofilms. The decrease of more than 10-fold in concentration ratio seen between 1 and 48 h in S. oralis 34-A. naeslundii T14V biofilms suggests that peak production of AI-2 occurs early and is followed by a very low steady-state level. High oral bacterial biofilm densities may be achieved by inter-species AI-2 signalling. We propose that low concentrations of AI-2 contribute to the establishment of oral commensal biofilm communities. C1 [Rickard, A. H.; Kolenbrander, P. E.] Natl Inst Dent & Craniofacial Res, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. [Campagna, S. R.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Oral Infect & Immun Branch, Bldg 30,Room 310,30 Convent Dr,MSC4350, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov OI Campagna, Shawn/0000-0001-6809-3862 FU National Institute of Dental and Craniofacial Research; National Institutes of Health FX This research was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. The authors thank R.J. Palmer, Jr., R. Levine, J. Kolenbrander and J. Thompson for suggestions. The DPD was a kind gift from B. Bassler and M. Semmelhack. NR 35 TC 28 Z9 28 U1 1 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD DEC PY 2008 VL 105 IS 6 BP 2096 EP 2103 DI 10.1111/j.1365-2672.2008.03910.x PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 375PH UT WOS:000261125300039 PM 19120655 ER PT J AU Jennings, P Chan, A Schwartzberg, P Wakeland, EK Yuan, D AF Jennings, Paula Chan, Alice Schwartzberg, Pamela Wakeland, Edward K. Yuan, Dorothy TI Antigen-specific responses and ANA production in B6.Sle1b mice: A role for SAP SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE ANA; Antigen-specific responses; SAP; SLE ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SLAM-ASSOCIATED PROTEIN; CONGENIC MOUSE STRAINS; MEMORY CD4 CELLS; B-CELLS; NK CELLS; T-CELL; SUSCEPTIBILITY LOCUS; IMMUNE-RESPONSES; IN-VIVO AB B6.Sle1b mice, which contain the Sle1b gene interval derived from lupus prone NZM2410 mice on a C57BL/6 background, present with gender-biased, highly penetrant anti-nuclear antibody (ANA) production. To obtain some insight into the possible induction mechanism of autoantibodies in these mice we compared antigen-specific T dependent (TD) and T independent (TI-II) responses between B6.Sle1b and B6 mice before the development of high ANA titers. Our results show that B6.Sle1b mice mount enhanced responses to a TI-II antigen. Additionally, the memory T cell response generated by a TD antigen also increased. This enhancement correlates with the greater ability of B cells from B6.Sle1b mice to present antigen to T cells. The SLAM Associated Protein (SAP) is critical for signaling of many of the molecules encoded by the SLAM/CD2 gene cluster, candidates for mediating the Sle1b phenotype; therefore, we also investigated the effect of sap deletion in these strains on the TD and TI-II responses as well as on ANA production. The results of these studies of responses to non-self-antigens provide further insight into the mechanism by which responses to self-antigens might be initiated in the context of specific genetic alterations. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Jennings, Paula; Yuan, Dorothy] Univ Texas SW Med Ctr Dallas, Dept Mol Pathol, Dallas, TX 75390 USA. [Chan, Alice; Wakeland, Edward K.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA. [Schwartzberg, Pamela] NHGRI, NIH, Bethesda, MD 20892 USA. RP Yuan, D (reprint author), Univ Texas SW Med Ctr Dallas, Dept Mol Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM dorothy.yuan@utsouthwestern.edu RI Jennings, Paula/H-2046-2011 FU National Institutes of Health [R01: AI69253] FX The study was supported by The National Institutes of Health grant: R01: AI69253. NR 38 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 2008 VL 31 IS 4 BP 345 EP 353 DI 10.1016/j.jaut.2008.08.002 PG 9 WC Immunology SC Immunology GA 385UP UT WOS:000261839400005 PM 18845419 ER PT J AU Lee, SJ Lewis, DEA Adhya, S AF Lee, Sang Jun Lewis, Dale E. A. Adhya, Sankar TI Induction of the Galactose Enzymes in Escherichia coli Is Independent of the C-1-Hydroxyl Optical Configuration of the Inducer D-Galactose SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GAL OPERON; RECEPTOR PROTEIN; CYCLIC-AMP; 2 PROMOTERS; TRANSCRIPTION; REPRESSOR; GENE; DNA; MUTATIONS; ACID AB The two optical forms of aldohexose galactose differing at the C-1 position, alpha-D-galactose and beta-D-galactose, are widespread in nature. The two anomers also occur in di- and polysaccharides, as well as in glycoconjugates. The anomeric form of D-galactose, when present in complex carbohydrates, e. g., cell wall, glycoproteins, and glycolipids, is specific. Their interconversion occurs as monomers and is effected by the enzyme mutarotase (aldose-1-epimerase). Mutarotase and other D-galactose-metabolizing enzymes are coded by genes that constitute an operon in Escherichia coli. The operon is repressed by the repressor GalR and induced by D-galactose. Since, depending on the carbon source during growth, the cell can make only one of the two anomers of D-galactose, the cell must also convert one anomer to the other for use in specific biosynthetic pathways. Thus, it is imperative that induction of the gal operon, specifically the mutarotase, be achievable by either anomer of D-galactose. Here we report in vivo and in vitro experiments showing that both alpha-D-galactose and beta-D-galactose are capable of inducing transcription of the gal operon with equal efficiency and kinetics. Whereas all substitutions at the C-1 position in the alpha configuration inactivate the induction capacity of the sugar, the effect of substitutions in the beta configuration varies depending upon the nature of the substitution; methyl and phenyl derivatives induce weakly, but the glucosyl derivative does not. C1 [Lee, Sang Jun; Lewis, Dale E. A.; Adhya, Sankar] NCI, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Natl Inst Hlth, Bldg 37, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank S. Busby for providing plasmid pJW-4* and B. Wanner for providing pKD46 and pCP20. We are also grateful to the Keio Collection for mutant strains. We thank M. Yarmolinsky for critical reading of the manuscript. We thank our colleagues in the laboratory for discussions and technical help.; This research was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, the Center for Cancer Research. NR 38 TC 5 Z9 5 U1 1 U2 1 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 DEC PY 2008 VL 190 IS 24 BP 7932 EP 7938 DI 10.1128/JB.01008-08 PG 7 WC Microbiology SC Microbiology GA 376YC UT WOS:000261217900010 PM 18931131 ER PT J AU Zhou, YN Coleman, WG Yang, ZX Yang, Y Hodgson, N Chen, F Jin, DJ AF Zhou, Yan Ning Coleman, William G., Jr. Yang, Zhaoxu Yang, Yi Hodgson, Nathaniel Chen, Fuxiang Jin, Ding Jun TI Regulation of Cell Growth during Serum Starvation and Bacterial Survival in Macrophages by the Bifunctional Enzyme SpoT in Helicobacter pylori SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; STRINGENT RESPONSE; ESCHERICHIA-COLI; DELAYED PHAGOCYTOSIS; PROFESSIONAL PHAGOCYTES; VACUOLATING CYTOTOXIN; GENOME SEQUENCE; PPGPP SYNTHESIS; NULL MUTATIONS; STRAINS AB In Helicobacter pylori the stringent response is mediated solely by spoT. The spoT gene is known to encode (p) ppGpp synthetase activity and is required for H. pylori survival in the stationary phase. However, neither the hydrolase activity of the H. pylori SpoT protein nor the role of SpoT in the regulation of growth during serum starvation and intracellular survival of H. pylori in macrophages has been determined. In this study, we examined the effects of SpoT on these factors. Our results showed that the H. pylori spoT gene encodes a bifunctional enzyme with both a hydrolase activity and the previously described ( p) ppGpp synthetase activity, as determined by introducing the gene into Escherichia coli relA and spoT defective strains. Also, we found that SpoT mediates a serum starvation response, which not only restricts the growth but also maintains the helical morphology of H. pylori. Strikingly, a spoT null mutant was able to grow to a higher density in serum-free medium than the wild-type strain, mimicking the "relaxed" growth phenotype of an E. coli relA mutant during amino acid starvation. Finally, SpoT was found to be important for intracellular survival in macrophages during phagocytosis. The unique role of (p) ppGpp in cell growth during serum starvation, in the stress response, and in the persistence of H. pylori is discussed. C1 [Jin, Ding Jun] Natl Canc Inst, Transcript Control Sect, Regulat & Chromosome Biol Lab, Natl Inst Hlth, Ft Detrick, MD 21702 USA. [Coleman, William G., Jr.; Hodgson, Nathaniel; Chen, Fuxiang] NIDDK, Natl Inst Hlth, Bethesda, MD USA. RP Jin, DJ (reprint author), Natl Canc Inst, Transcript Control Sect, Regulat & Chromosome Biol Lab, Natl Inst Hlth, Ft Detrick, MD 21702 USA. EM djjin@helix.nih.gov FU NIH National Cancer Institute Center for Cancer Research; National Institute of Digestive Diseases, Diabetes and Kidney Diseases; NIH National Center on Minority Health and Health Disparities FX We thank the leadership of the Gene Regulation and Chromosome Biology Laboratory and the National Cancer Institute Center for Cancer Research for the support in the initiation of the H. pylori project in D.J.J.'s laboratory, and we thank colleagues in the H. pylori research community and in our laboratories for helpful discussions. We also thank Scotty Merrell, Karen Guillemin, Kevin Bourzac, Rainer Haas, Mike Cashel, and Lee-Anne Allen for providing strains, plasmids and/or protocols. Y.N.Z. thanks Susan Gottesman for her support. We are grateful for helpful comments on the manuscript from Don Court, Susan Gottesman, Mikhail Kashlev, Peter McPhie, Scotty Merrell, Herbert Tabor, and Julie Torruellas Garcia.; This research was supported by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research, by the Intramural Research Program of the National Institute of Digestive Diseases, Diabetes and Kidney Diseases, and by an intra-agency agreement with the NIH National Center on Minority Health and Health Disparities. NR 57 TC 17 Z9 17 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2008 VL 190 IS 24 BP 8025 EP 8032 DI 10.1128/JB.01134-08 PG 8 WC Microbiology SC Microbiology GA 376YC UT WOS:000261217900021 PM 18835987 ER PT J AU Chalmers, NI Palmer, RJ Cisar, JO Kolenbrander, PE AF Chalmers, Natalia I. Palmer, Robert J., Jr. Cisar, John O. Kolenbrander, Paul E. TI Characterization of a Streptococcus sp.-Veillonella sp Community Micromanipulated from Dental Plaque SO JOURNAL OF BACTERIOLOGY LA English DT Article ID VIRIDANS GROUP STREPTOCOCCI; CELL-WALL POLYSACCHARIDES; HUMAN ORAL BACTERIA; REAL-TIME PCR; GNOTOBIOTIC-RATS; SELECTIVE MEDIUM; FLOW CONDITIONS; IN-SITU; COAGGREGATION; COLONIZATION AB Streptococci and veillonellae occur in mixed-species colonies during formation of early dental plaque. One factor hypothesized to be important in assembly of these initial communities is coaggregation (cell-cell recognition by genetically distinct bacteria). Intrageneric coaggregation of streptococci occurs when a lectin-like adhesin on one streptococcal species recognizes a receptor polysaccharide (RPS) on the partner species. Veillonellae also coaggregate with streptococci. These genera interact metabolically; lactic acid produced by streptococci is a carbon source for veillonellae. To transpose these interactions from undisturbed dental plaque to an experimentally tractable in vitro biofilm model, a community consisting of RPS-bearing streptococci juxtaposed with veillonellae was targeted by quantum dot-based immunofluorescence and then micromanipulated off the enamel surface and cultured. Besides the expected antibody-reactive cell types, a non-antibodyreactive streptococcus invisible during micromanipulation was obtained. The streptococci were identified as Streptococcus oralis ( RPS bearing) and Streptococcus gordonii ( adhesin bearing). The veillonellae could not be cultivated; however, a veillonella 16S rRNA gene sequence was amplified from the original isolation mixture, and this sequence was identical to the sequence of the previously studied organism Veillonella sp. strain PK1910, an oral isolate in our culture collection. S. oralis coaggregated with S. gordonii by an RPS-dependent mechanism, and both streptococci coaggregated with PK1910, which was used as a surrogate during in vitro community reconstruction. The streptococci and strain PK1910 formed interdigitated three-species clusters when grown as a biofilm using saliva as the nutritional source. PK1910 grew only when streptococci were present. This study confirms that RPS-mediated intrageneric coaggregation occurs in the earliest stages of plaque formation by bringing bacteria together to create a functional community. C1 [Chalmers, Natalia I.; Palmer, Robert J., Jr.; Cisar, John O.; Kolenbrander, Paul E.] NIDCR, NIH, Bethesda, MD 20892 USA. [Chalmers, Natalia I.] Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov FU Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health FX We thank Nicholas Jakubovics ( Newcastle University) for his assistance with the Q-PCR.; This research was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health. NR 43 TC 72 Z9 74 U1 3 U2 17 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 DEC PY 2008 VL 190 IS 24 BP 8145 EP 8154 DI 10.1128/JB.00983-08 PG 10 WC Microbiology SC Microbiology GA 376YC UT WOS:000261217900033 PM 18805978 ER PT J AU Erickson, DL Jarrett, CO Callison, JA Fischer, ER Hinnebusch, BJ AF Erickson, David L. Jarrett, Clayton O. Callison, Julie A. Fischer, Elizabeth R. Hinnebusch, B. Joseph TI Loss of a Biofilm-Inhibiting Glycosyl Hydrolase during the Emergence of Yersinia pestis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI; STAPHYLOCOCCUS-EPIDERMIDIS; CAENORHABDITIS-ELEGANS; FLEA VECTOR; PIGMENTATION PHENOTYPE; BACTERIAL PATHOGENS; MEMBRANE-PROTEINS; EVOLUTION AB Yersinia pestis, the bacterial agent of plague, forms a biofilm in the foregut of its flea vector to produce a transmissible infection. The closely related Yersinia pseudotuberculosis, from which Y. pestis recently evolved, can colonize the flea midgut but does not form a biofilm in the foregut. Y. pestis biofilm in the flea and in vitro is dependent on an extracellular matrix synthesized by products of the hms genes; identical genes are present in Y. pseudotuberculosis. The Yersinia Hms proteins contain functional domains present in Escherichia coli and Staphylococcus proteins known to synthesize a poly-beta-1,6-N-acetyl-D-glucosamine biofilm matrix. In this study, we show that the extracellular matrices (ECM) of Y. pestis and staphylococcal biofilms are antigenically related, indicating a similar biochemical structure. We also characterized a glycosyl hydrolase (NghA) of Y. pseudotuberculosis that cleaved beta-linked N-acetylglucosamine residues and reduced biofilm formation by staphylococci and Y. pestis in vitro. The Y. pestis nghA ortholog is a pseudogene, and overexpression of functional nghA reduced ECM surface accumulation and inhibited the ability of Y. pestis to produce biofilm in the flea foregut. Mutational loss of this glycosidase activity in Y. pestis may have contributed to the recent evolution of flea-borne transmission. C1 [Erickson, David L.; Jarrett, Clayton O.; Callison, Julie A.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Fischer, Elizabeth R.] NIAID, RTS Microscopy Unit, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Erickson, DL (reprint author), Brigham Young Univ, Dept Mol Biol & Microbiol, Provo, UT 84663 USA. EM xenopsylla@gmail.com FU Division of Intramural Research, NIAID, NIH; Ellison Medical Foundation FX We thank Cuong Vuong and Michael Otto for providing the antiPIA antiserum and the S. epidermidis strains used in this study. We also thank Viveka Vadyvaloo and Frank Gherardini for critical reading of the manuscript.; This work was supported by the Division of Intramural Research, NIAID, NIH, and the Ellison Medical Foundation. NR 52 TC 31 Z9 32 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 DEC PY 2008 VL 190 IS 24 BP 8163 EP 8170 DI 10.1128/JB.01181-08 PG 8 WC Microbiology SC Microbiology GA 376YC UT WOS:000261217900035 PM 18931111 ER PT J AU Kaluzhny, DN Timoshin, VV Borisova, OF Zhurkin, VB Florentiev, VL Shchyolkina, AK AF Kaluzhny, Dmitry N. Timoshin, Vladimir V. Borisova, Olga F. Zhurkin, Victor B. Florentiev, Vladimir L. Shchyolkina, Anna K. TI Intramolecular Recombination R-Triplex in Solution: Stabilization by bis-intercalator YOYO SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article DE R-triplex DNA; Stabilization; YOYO; Melting temperature ID STRANDED DNA; ETHIDIUM-BROMIDE; NUCLEIC-ACIDS; PARALLEL; OLIGONUCLEOTIDES; STABILITY; LIGANDS; COMPLEX; BINDING; MODEL AB Recognition of double-stranded DNA with a mixed nucleotide sequence by oligonucleotide is a long-term challenge. This aim can be achieved via formation of the recombination R-triplex, accommodating two identical DNA strands in parallel orientation, and antiparallel complementary strand. In the absence of proteins the R-triplex stability is low, however, so that intermolecular R-triplex is not formed by three DNA strands in a ligand-free system. Recently, recognition of DNA with mixed base sequence by single-stranded oligonucleotide in the presence of bis-intercalator YOYO was reported. Here, we describe thermodynamic characteristics of YOYO complexes with the model oligonucleotides 5'-GT-2AP-GACTGAG TTTT CTCAGTCTACGC GAA GCCTAGACTGAG-3' (R(2AP)CW) bearing a single reporting 2-aminopurine (2AP) in place of adenine and 5'-CTCAGTCTACGC GAA GCGTAGACTGAG-3' (CW). We found that each oligonucleotide is able to bind two YOYO molecules via intercalation mode in 0.5 M LiCl. Fluorescence intensity of YOYO intercalated in triplex R(2AP)CW and in CW hairpin increased 40-fold compared to the free YOYO. Remarkably, the melting temperature of the triplex (determined using temperature dependence of the 2AP fluorescence) increased from 19 degrees C to 33 degrees C upon binding two YOYO molecules. Further increase in the YOYO concentration resulted in binding of up to five YOYO molecules to R(2AP)CW triplex and up to six YOYO molecules to CW hairpin. C1 [Kaluzhny, Dmitry N.; Borisova, Olga F.; Florentiev, Vladimir L.; Shchyolkina, Anna K.] Engelhardt Inst Mol Biol RASc, Moscow 119991, Russia. [Timoshin, Vladimir V.] Moscow Phys Tech Inst, Dolgoprudnyi 141700, Russia. [Zhurkin, Victor B.] NCI, NIH, Bethesda, MD 20892 USA. RP Shchyolkina, AK (reprint author), Engelhardt Inst Mol Biol RASc, Vavilova 32, Moscow 119991, Russia. EM ashchyolkina@gmail.com RI Kaluzhny, Dmitry/G-7256-2014 FU RFBR [07-04-00645-a, 07-04-00691-a] FX The authors appreciate helpful discussions with T. M. Jovin, D.J. Arndt-Jovin, and V A. Livshits. The Study was supported by RFBR grants 07-04-00645-a, 07-04-00691-a. NR 20 TC 2 Z9 2 U1 1 U2 6 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 2008 VL 26 IS 3 BP 301 EP 305 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 376TR UT WOS:000261206400004 PM 18808196 ER PT J AU Uveges, TE Collin-Osdoby, P Cabral, WA Ledgard, F Goldberg, L Bergwitz, C Forlino, A Osdoby, P Gronowicz, GA Marini, JC AF Uveges, Thomas E. Collin-Osdoby, Patricia Cabral, Wayne A. Ledgard, Felicia Goldberg, Leah Bergwitz, Clemens Forlino, Antonella Osdoby, Philip Gronowicz, Gloria A. Marini, Joan C. TI Cellular Mechanism of Decreased Bone in Brtl Mouse Model of OI: Imbalance of Decreased Osteoblast Function and Increased Osteoclasts and Their Precursors SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Brtl mouse; type I collagen; osteoclast; histomorphometry; RANKL/osteoprotegerin ID EHLERS-DANLOS-SYNDROME; OSTEOGENESIS IMPERFECTA; COLLAGEN GENE; MURINE MODEL; MICE; MUTATION; GROWTH; FORM; EXPRESSION; CHILDREN AB The Brtl mouse, a knock-in model for moderately severe osteogenesis imperfecta (OI), has a G349C substitution in half of type I collagen alpha 1(I) chains. We studied the cellular contribution to Brtl bone properties. Brtl cortical and trabecular bone are reduced before and after puberty, with BV/TV decreased 40-45%. Brtl ObS/BS is comparable to wildtype, and Brtl and wildtype marrow generate equivalent number of colony-forming units (CFUs) at both ages. However, OcS/BS is increased in Brtl at both ages (36-45%), as are TRACP(+) cell numbers (57-47%). After puberty, Brtl ObS/BS decreases comparably to wildtype mice, but osteoblast matrix production (MAR) decreases to one half of wildtype values. In contrast, Brtl OcS falls only moderately (similar to 16%), and Brtl TRACP staining remains significantly elevated compared with wildtype. Consequently, Brtl BFR decreases from normal at 2 mo to one half of wildtype values at 6 mo. Immunohistochemistry and real-time RT-PCR show increased RANK, RANKL, and osteoprotegerin (OPG) levels in Brtl, although a normal RANKL/OPG ratio is maintained. TRACP(+) precursors are markedly elevated in Brtl marrow cultures and form more osteoclasts, suggesting that osteoclast increases arise from more RANK-expressing precursors. We conclude that osteoblasts and osteoclasts are unsynchronized in Brtl bone. This cellular imbalance results in declining BFR as Brtl ages, consistent with reduced femoral geometry. The disparity in cellular number and function results from poorly functioning osteoblasts in addition to increased RANK-expressing precursors that respond to normal RANKL/OPG ratios to generate more bone-resorbing osteoclasts. Interruption of the stimulus that increases osteoclast precursors may lead to novel OI therapies. C1 [Uveges, Thomas E.; Cabral, Wayne A.; Bergwitz, Clemens; Forlino, Antonella; Marini, Joan C.] NICHD, NIH, BEMB, Bethesda, MD 20892 USA. [Collin-Osdoby, Patricia; Goldberg, Leah; Osdoby, Philip] Washington Univ, Dept Biol, St Louis, MO 63130 USA. [Collin-Osdoby, Patricia; Goldberg, Leah; Osdoby, Philip] Washington Univ, Div Bone & Mineral Metab, St Louis, MO 63130 USA. [Ledgard, Felicia; Gronowicz, Gloria A.] Univ Connecticut, Ctr Hlth, Dept Orthopaed Surg, Farmington, CT USA. RP Marini, JC (reprint author), NICHD, NIH, BEMB, Bldg 10,Room 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov RI Forlino, Antonella/H-5385-2015; OI Forlino, Antonella/0000-0002-6385-1182; Gronowicz, Gloria/0000-0001-7158-3598 FU NICHD Intramural Funding; Center for Histology and Histomorphometry at the University of Connecticut (GAG); NIH [RO1 DK56547, R21AR05449701] FX Dr Xiao-Dong Chen generously provided instruction in CFU assays. The authors thank Dr Weizhong Chang, BEMB, NICHD for critical reading of the manuscript. This work was supported by NICHD Intramural Funding (JCM), The Center for Histology and Histomorphometry at the University of Connecticut (GAG), and NIH Grants RO1 DK56547 (PC-O), and R21AR05449701 (PO). NR 37 TC 38 Z9 38 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2008 VL 23 IS 12 BP 1983 EP 1994 DI 10.1359/JBMR.080804 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 376AR UT WOS:000261155600013 PM 18684089 ER PT J AU Kamiya, N Ye, L Kobayashi, T Lucas, DJ Mochida, Y Yamauchi, M Kronenberg, HM Feng, JQ Mishina, Y AF Kamiya, Nobuhiro Ye, Ling Kobayashi, Tatsuya Lucas, Donald J. Mochida, Yoshiyuki Yamauchi, Mitsuo Kronenberg, Henry M. Feng, Jian Q. Mishina, Yuji TI Disruption of BMP Signaling in Osteoblasts Through Type IA Receptor (BMPRIA) Increases Bone Mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY OCT 01-05, 2004 CL Seattle, WA SP Amer Soc Bone & Mineral Res DE bone morphogenetic protein; knockout; modeling and remodeling; osteoblasts; rodent ID TAMOXIFEN-INDUCIBLE FORM; MORPHOGENETIC PROTEINS; MOUSE; EXPRESSION; CELLS; GENE; MICE; OSTEOPROTEGERIN; CRE; DIFFERENTIATION AB Bone morphogenetic proteins (BMPs) are known as ectopic bone inducers. The FDA approved BMPs (BMP2 and BMP7) for clinical use. However, direct effects of BMPs on endogenous bone metabolism are not yet well known. We conditionally disrupted BMP receptor type IA (BMPRIA) in osteoblasts during weanling and adult stages to show the impact of BMP signaling on endogenous bone modeling and remodeling. Cre recombination was detected in immature osteoblasts in the periosteum, osteoblasts, and osteocytes but not in chondrocytes and osteoclasts after tamoxifen administration. Bmpr1a conditional knockout mice (cKO) showed increased bone mass primarily in trabecular bone at P21 and 22 wk as determined by H&E staining. Vertebrae, tails, and ribs showed increased radiodensity at 22 wk, consistent with a significant increase in BMD. Both mu CT and histomorphometry showed an increase in trabecular BV/TV and thickness of cKO adult bones, whereas osteoclast number, bone formation rate, and mineral apposition rate were decreased. Expression levels of bone formation markers (Runx2 and Bsp), resorption markers (Mmp9, Ctsk, and Tracp), and Rankl were decreased, and Opg was increased in adult bones, resulting in a reduction in the ratio of Rankl to osteoprotegerin (Opg). The reduction in osteoclastogenesis through the RANKL-OPG pathway was also observed in weanling stages and reproduced in newborn calvaria culture. These results suggest that Bmpr1a cKO increased endogenous bone mass primarily in trabecular bone with decreased osteoclastogenesis through the RANKL-OPG pathway. We conclude that BMPRIA signaling in osteoblasts affects both bone formation and resorption to reduce endogenous bone mass in vivo. C1 [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. [Kamiya, Nobuhiro; Lucas, Donald J.] NIEHS, NIH, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Ye, Ling; Feng, Jian Q.] Univ Missouri, Sch Dent, Kansas City, MO USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. [Mochida, Yoshiyuki; Yamauchi, Mitsuo] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RP Mishina, Y (reprint author), Univ Michigan, Sch Dent, Dept Biol & Mat Sci, 4222A Dent,1011 N Univ Ave, Ann Arbor, MI 48108 USA. EM mishina@umich.edu OI Mochida, Yoshiyuki/0000-0002-2115-4303 FU Intramural NIH HHS; NIAMS NIH HHS [R21 AR052824, R01 AR051587]; NIDCR NIH HHS [K22 DE016977]; NIDDK NIH HHS [P01 DK56246, P01 DK056246]; NIEHS NIH HHS [Z01 ES071003] NR 34 TC 72 Z9 77 U1 1 U2 8 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 DEC PY 2008 VL 23 IS 12 BP 2007 EP 2017 DI 10.1359/JBMR.080809 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 376AR UT WOS:000261155600015 PM 18684091 ER PT J AU Daniel, JA Pellegrini, M Lee, JH Paull, TT Feigenbaum, L Nussenzweig, A AF Daniel, Jeremy A. Pellegrini, Manuela Lee, Ji-Hoon Paull, Tanya T. Feigenbaum, Lionel Nussenzweig, Andre TI Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; CLASS SWITCH RECOMBINATION; DNA-DAMAGE; ATAXIA-TELANGIECTASIA; DEFICIENT MICE; MRE11-RAD50-NBS1 COMPLEX; DOWNSTREAM EFFECTOR; KINASE-ACTIVITY; PROTEIN-KINASE; CHECKPOINT AB Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon DNA damage, an activation mechanism involving autophosphorylation has been reported to allow ATM to phosphorylate downstream targets important for cell cycle checkpoints and DNA repair. In humans, serine residues 367, 1893, and 1981 have been shown to be autophosphorylation sites that are individually required for ATM activation. To test the physiological importance of these sites, we generated a transgenic mouse model in which all three conserved ATM serine autophosphorylation sites (S367/1899/1987) have been replaced with alanine. In this study, we show that ATM-dependent responses at both cellular and organismal levels are functional in mice that express a triple serine mutant form of ATM as their sole ATM species. These results lend further support to the notion that ATM autophosphorylation correlates with the DNA damage induced activation of the kinase but is not required for ATM function in vivo. C1 [Daniel, Jeremy A.; Pellegrini, Manuela; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Pellegrini, Manuela] Univ Roma Tor Vergata, Dept Publ Hlth & Cellular Biol, I-00175 Rome, Italy. [Lee, Ji-Hoon; Paull, Tanya T.] Univ Texas Austin, Dept Mol Genet & Microbiol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Feigenbaum, Lionel] NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Daniel, Jeremy/S-4729-2016 OI Daniel, Jeremy/0000-0002-1981-5571 FU National Institutes of Health; National Cancer Institute; Center for Cancer Research; A-T Children's Project FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and the A-T Children's Project. NR 43 TC 49 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 1 PY 2008 VL 183 IS 5 BP 777 EP 783 DI 10.1083/jcb.200805154 PG 7 WC Cell Biology SC Cell Biology GA 377DN UT WOS:000261232000005 PM 19047460 ER PT J AU Narendra, D Tanaka, A Suen, DF Youle, RJ AF Narendra, Derek Tanaka, Atsushi Suen, Der-Fen Youle, Richard J. TI Parkin is recruited selectively to impaired mitochondria and promotes their autophagy SO JOURNAL OF CELL BIOLOGY LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; DOPAMINERGIC NEURON LOSS; CELL-DEATH; DISEASE; FUSION; DYSFUNCTION; DROSOPHILA; PINK1; DISRUPTION; MATURATION AB Loss-of-function mutations in Park2, the gene coding for the ubiquitin ligase Parkin, are a significant cause of early onset Parkinson's disease. Although the role of Parkin in neuron maintenance is unknown, recent work has linked Parkin to the regulation of mitochondria. Its loss is associated with swollen mitochondria and muscle degeneration in Drosophila melanogaster, as well as mitochondrial dysfunction and increased susceptibility to mitochondrial toxins in other species. Here, we show that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential in mammalian cells. After recruitment, Parkin mediates the engulfment of mitochondria by autophagosomes and the selective elimination of impaired mitochondria. These results show that Parkin promotes autophagy of damaged mitochondria and implicate a failure to eliminate dysfunctional mitochondria in the pathogenesis of Parkinson's disease. C1 [Narendra, Derek; Tanaka, Atsushi; Suen, Der-Fen; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Narendra, Derek] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU National Institutes of Health; Japan Society for the Promotion of Science Research Fellowship FX This work was supported by the National Institutes of Health intramural program and the Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers (to A. Tanaka). NR 32 TC 1413 Z9 1446 U1 57 U2 192 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 1 PY 2008 VL 183 IS 5 BP 795 EP 803 DI 10.1083/jcb.200809125 PG 9 WC Cell Biology SC Cell Biology GA 377DN UT WOS:000261232000007 PM 19029340 ER PT J AU Kriebel, PW Barr, VA Rericha, EC Zhang, GF Parent, CA AF Kriebel, Paul W. Barr, Valarie A. Rericha, Erin C. Zhang, Guofeng Parent, Carole A. TI Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CLATHRIN HEAVY-CHAIN; DICTYOSTELIUM-DISCOIDEUM; ADENYLYL-CYCLASE; UNCONVENTIONAL MYOSIN; MEMBRANE-VESICLES; PLASMA-MEMBRANE; MOLECULAR-GENETICS; GOLGI-APPARATUS; CAMP SYNTHESIS; LEADING-EDGE AB Chemoattractant signaling induces the polarization and directed movement of cells secondary to the activation of multiple effector pathways. In addition, chemotactic signals can be amplified and relayed to proximal cells via the synthesis and secretion of additional chemoattractant. The mechanisms underlying such remarkable features remain ill defined. We show that the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells, an essential determinant of their ability to migrate in a head-to-tail fashion, requires vesicular trafficking. This trafficking results in a local accumulation of ACA-containing intracellular vesicles and involves intact actin, microtubule networks, and de novo protein synthesis. We also show that migrating cells leave behind ACA-containing vesicles, likely secreted as multivesicular bodies and presumably involved in the formation of head-to-tail arrays of migrating cells. We propose that similar compartmentalization and shedding mechanisms exist in mammalian cells during embryogenesis, wound healing, neuron growth, and metastasis. C1 [Kriebel, Paul W.; Barr, Valarie A.; Rericha, Erin C.; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. [Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. [Rericha, Erin C.] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov FU Center for Cancer Research; NCI; National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Cancer Research, NCI, National Institutes of Health. NR 61 TC 57 Z9 57 U1 3 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD DEC 1 PY 2008 VL 183 IS 5 BP 949 EP 961 DI 10.1083/jcb.200808105 PG 13 WC Cell Biology SC Cell Biology GA 377DN UT WOS:000261232000018 PM 19047467 ER PT J AU Yu, C Zhang, X Sun, G Guo, X Li, H You, Y Jacobs, JL Gardner, K Yuan, D Xu, Z Du, Q Dai, C Qian, Z Jiang, K Zhu, Y Li, QQ Miao, Y AF Yu, C. Zhang, X. Sun, G. Guo, X. Li, H. You, Y. Jacobs, J. L. Gardner, K. Yuan, D. Xu, Z. Du, Q. Dai, C. Qian, Z. Jiang, K. Zhu, Y. Li, Q. Q. Miao, Y. TI RNA interference-mediated silencing of the polo-like kinase 1 gene enhances chemosensitivity to gemcitabine in pancreatic adenocarcinoma cells SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE polo-like kinase 1; RNA interference; siRNA; gemcitabine; cell cycle; G2; M arrest apoptosis; pancreatic cancer ID POLO-LIKE-KINASE; GROWTH-FACTOR RECEPTOR; MAMMALIAN-CELLS; PROGNOSTIC-SIGNIFICANCE; SPINDLE FORMATION; ADJUVANT THERAPY; TUMOR RESISTANCE; PLK EXPRESSION; CANCER-CELLS; CYCLIN-E AB Gemcitabine is the first-line chemotherapeutic agent for advanced adenocarcinoma of the pancreas; however, chemoresistance to gemcitabine remains a major cause of failure for the clinical treatment of this disease. Polo-like kinase 1 (Plk-1) is highly expressed in pancreatic cancer cell lines and pancreatic tumour tissues, and is involved in a wide variety of cell cycle processes. Nevertheless, its biological role and implication for gemcitabine resistance are not clearly defined. In this study, we used RNA-interference (RNAi)-mediated depletion of Plk-1 to determine its potential for sensitizing pancreatic tumour cells to gemcitabine. We showed that the level of Plk-1 protein was correlated significantly with gemcitabine resistance in human pancreatic adenocarcinoma cells and that overexpression of Plk-1 reduced sensitivity to gemcitabine in these cells. In addition, small interfering RNA (siRNA)-mediated knockdown of Plk-1 caused cell cycle arrest at G2/M and the reduction of cellular proliferation. More importantly, the treatment of pancreatic cancer cells with Plk-1 siRNA followed by exposure to gemcitabine dramatically decreased cell viability and increased cellular apoptosis, as compared with treatment with either agent alone. These observations indicate that down-regulation of Plk-1 expression by RNAi enhances gemcitabine sensitivity and increases gemcitabine cytotoxicity in pancreatic tumour cells. This is the first demonstration that the combination of Plk-1 gene therapy and gemcitabine chemotherapy has synergistic anti-tumour activity against pancreatic carcinoma in vitro. This combination treatment warrants further investigation as an effective therapeutic regimen for patients with resistant pancreatic cancer and other tumours. C1 [Yu, C.; Sun, G.; Li, H.; You, Y.; Xu, Z.; Du, Q.; Dai, C.; Qian, Z.; Jiang, K.; Zhu, Y.; Miao, Y.] Nanjing Med Univ, Affiliated Hosp 1, Dept Surg, Nanjing 210029, Peoples R China. [Zhang, X.; Guo, X.] Nanjing Med Univ, Inst Pediat Med, Nanjing, Peoples R China. [Yu, C.] Beijing Aerosp Gen Hosp, Dept Surg, Beijing, Peoples R China. [Jacobs, J. L.; Gardner, K.; Li, Q. Q.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Yuan, D.] Hubei Inst Nationalities, Sch Med, Lab Pathophysiol, Enshi, Peoples R China. RP Miao, Y (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Surg, Nanjing 210029, Peoples R China. EM miaoyi@njmu.edu.cn RI Guo, Xuejiang/J-9600-2014; OI Guo, Xuejiang/0000-0002-0475-5705; Jacobs, Jonathan/0000-0001-5608-4256 FU National Natural Science Foundation of China [39670265]; China Postdoctoral Science Foundation [20060390294]; Research Start-up Funds of Ministry of Education [2003-14] FX This work was supported in part by grants from the National Natural Science Foundation of China ( No. 39670265), China Postdoctoral Science Foundation ( No. 20060390294), and Research Start-up Funds of Ministry of Education for Chinese Overseas Returned Scholars ( No. 2003-14), P. R. China. NR 49 TC 16 Z9 16 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD DEC PY 2008 VL 12 IS 6A BP 2334 EP 2349 DI 10.1111/j.1582-4934.2008.00257.x PG 16 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 378OP UT WOS:000261334100018 PM 18266952 ER PT J AU Ratner, RE Christophi, CA Metzger, BE Dabelea, D Bennett, PH Pi-Sunyer, X Fowler, S Kahn, SE AF Ratner, Robert E. Christophi, Costas A. Metzger, Boyd E. Dabelea, Dana Bennett, Peter H. Pi-Sunyer, Xavier Fowler, Sarah Kahn, Steven E. CA Diabet Prevention Program Res Grp TI Prevention of Diabetes in Women with a History of Gestational Diabetes: Effects of Metformin and Lifestyle Interventions SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-TOLERANCE; MELLITUS; PREGNANCY; PROGRAM; MODELS AB Context: A past history of gestational diabetes mellitus (GDM) confers a very high risk of postpartum development of diabetes, particularly type 2 diabetes. Objective: The Diabetes Prevention Program (DPP) sought to identify individuals with impaired glucose tolerance (IGT) and intervene in an effort to prevent or delay their progression to diabetes. This analysis examined the differences between women enrolled in DPP with and without a reported history of GDM. Design: The DPP was a randomized, controlled clinical trial. Setting: The study was a multicenter, National Institutes of Health-sponsored trial carried out at 27 centers including academic and Indian Health Services sites. Patients: A total of 2190 women were randomized into the DPP and provided information for past history of GDM. This analysis addressed the differences between those 350 women providing a past history of GDM and those 1416 women with a previous live birth but no history of GDM. Interventions: Subjects were randomized to either standard lifestyle and placebo or metformin therapy or to an intensive lifestyle intervention. Main Outcomes: The primary outcome was the time to development of diabetes ascertained by semiannual fasting plasma glucose and annual oral glucose tolerance testing. Assessments of insulin secretion and insulin sensitivity were also performed. Results: Whereas entering the study with similar glucose levels, women with a history of GDM randomized to placebo had a crude incidence rate of diabetes 71% higher than that of women without such a history. Among women reporting a history of GDM, both intensive lifestyle and metformin therapy reduced the incidence of diabetes by approximately 50% compared with the placebo group, whereas this reduction was 49 and 14%, respectively in parous women without GDM. These data suggest that metformin may be more effective in women with a GDM history as compared with those without. Conclusions: Progression to diabetes is more common in women with a history of GDM compared with those without GDM history despite equivalent degrees of IGT at baseline. Both intensive lifestyle and metformin are highly effective in delaying or preventing diabetes in women with IGT and a history of GDM. (J Clin Endocrinol Metab 93: 4774-4779, 2008) C1 [Christophi, Costas A.; Fowler, Sarah] George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. [Ratner, Robert E.] Medstar Res Inst, Hyattsville, MD 20783 USA. [Metzger, Boyd E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Dabelea, Dana] Univ Colorado, Dept Prevent Med & Biometr, Denver, CO 80262 USA. [Bennett, Peter H.] NIDDKD, Phoenix, AZ 85016 USA. [Pi-Sunyer, Xavier] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY 10019 USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98108 USA. RP Ratner, RE (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. OI Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS NR 15 TC 248 Z9 260 U1 5 U2 23 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2008 VL 93 IS 12 BP 4774 EP 4779 DI 10.1210/jc.2008-0772 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 379LE UT WOS:000261396900028 PM 18826999 ER PT J AU Timmers, HJLM Pacak, K Huynh, TT Abu-Asab, M Tsokos, M Merino, MJ Baysal, BE Adams, KT Eisenhofer, G AF Timmers, Henri J. L. M. Pacak, Karel Huynh, Thanh T. Abu-Asab, Mones Tsokos, Maria Merino, Maria J. Baysal, Bora E. Adams, Karen T. Eisenhofer, Graeme TI Biochemically Silent Abdominal Paragangliomas in Patients with Mutations in the Succinate Dehydrogenase Subunit B Gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA-FREE METANEPHRINES; ELECTROCHEMICAL DETECTION; TYROSINE-HYDROXYLASE; ADRENAL-GLAND; PHEOCHROMOCYTOMA; CATECHOLAMINES; NORADRENALINE; PHENOTYPES; EXPRESSION; DIAGNOSIS AB Context: Patients with adrenal and extra-adrenal abdominal paraganglioma (PGL) almost invariably have increased plasma and urine concentrations of metanephrines, the O-methylated metabolites of catecholamines. We report four cases of biochemically silent abdominal PGL, in which metanephrines were normal despite extensive disease. Objective: Our objective was to identify the mechanism underlying the lack of catecholamine hypersecretion and metabolism to metanephrines in biochemically silent PGL. Design: This is a descriptive study. Setting: The study was performed at a referral center. Patients: One index case and three additional patients with large abdominal PGL and metastases but with the lack of evidence of catecholamine production, six patients with metastatic catecholamine-producing PGL and a mutation of the succinate dehydrogenase subunit B (SDHB) gene, and 136 random patients with catecholamine-producing PGL were included in the study. Main Outcome Measures: Plasma, urine, and tumor tissue concentrations of catecholamines and metabolites were calculated with electron microscopy and tyrosine hydroxylase immunohistochemistry. Results: All four patients with biochemically silent PGL had an underlying SDHB mutation. In the index case, the tumor tissue concentration of catecholamines (1.8 nmol/g) was less than 0.01% that of the median (20,410 nmol/g) for the 136 patients with catecholamine-producing tumors. Electron microscopy showed the presence of normal secretory granules in all four biochemically silent PGLs. Tyrosine hydroxylase immunoreactivity was negligible in the four biochemically silent PGLs but abundant in catecholamine-producing PGLs. Conclusions: Patients with SDHB mutations may present with biochemically silent abdominal PGLs due to defective catecholamine synthesis resulting from the absence of tyrosine hydroxylase. Screening for tumors in patients with SDHB mutations should not be limited to biochemical tests of catecholamine excess. (J Clin Endocrinol Metab 93: 4826-4832, 2008) C1 [Timmers, Henri J. L. M.; Pacak, Karel; Huynh, Thanh T.; Adams, Karen T.] NCI, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA. [Abu-Asab, Mones; Tsokos, Maria; Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Baysal, Bora E.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands. [Eisenhofer, Graeme] Tech Univ Dresden, Dept Med, D-01062 Dresden, Germany. [Eisenhofer, Graeme] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-01062 Dresden, Germany. RP Timmers, HJLM (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, 10 Ctr Dr,Bldg 10,CRC,Room 1-E 3140, Bethesda, MD 20892 USA. EM h.timmers@endo.umcn.nl OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural Research Program of the National Institutes of Health; National Institute of Child Health and Human Development FX Address all correspondence and requests for reprints to: Henri J. L. M. Timmers, M. D., Ph.D., Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Building 10, CRC, Room 1-E 3140, Bethesda Maryland 20892-1109. E-mail: h. timmers@endo.umcn.nl.; This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Child Health and Human Development.; Disclosure Statement: The authors have nothing to disclose. NR 25 TC 29 Z9 29 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2008 VL 93 IS 12 BP 4826 EP 4832 DI 10.1210/jc.2008-1093 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 379LE UT WOS:000261396900035 PM 18840642 ER PT J AU Charmandari, E Ichijo, T Jubiz, W Baid, S Zachman, K Chrousos, GP Kino, T AF Charmandari, Evangelia Ichijo, Takamasa Jubiz, William Baid, Smita Zachman, Keith Chrousos, George P. Kino, Tomoshige TI A Novel Point Mutation in the Amino Terminal Domain of the Human Glucocorticoid Receptor (hGR) Gene Enhancing hGR-Mediated Gene Expression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LIGAND-BINDING DOMAIN; TRANSCRIPTIONAL ACTIVITY; IN-VIVO; RESISTANCE; POLYMORPHISM; ASSOCIATION; STRESS; CARBAMAZEPINE; SENSITIVITY; RESPONSES AB Context: Interindividual variations in glucocorticoid sensitivity have been associated with manifestations of cortisol excess or deficiency and may be partly explained by polymorphisms in the human glucocorticoid receptor (hGR) gene. We studied a 43-yr-old female, who presented with manifestations consistent with tissue-selective glucocorticoid hypersensitivity. We detected a novel, single, heterozygous nucleotide (G -> C) substitution at position 1201 (exon 2) of the hGR gene, which resulted in aspartic acid to histidine substitution at amino acid position 401 in the amino-terminal domain of the hGR alpha. We investigated the molecular mechanisms of action of the natural mutant receptor hGR alpha D401H. Methods-Results: Compared with the wild-type hGR alpha, the mutant receptor hGR alpha D401H demonstrated a 2.4-fold increase in its ability to transactivate the glucocorticoid-inducible mouse mammary tumorvirus promoter in response to dexamethasone but had similar affinity for the ligand (dissociation constant = 6.2 +/- 0.6 vs. 6.1 +/- 0.6 nM) and time to nuclear translocation (14.75 +/- 0.25 vs. 14.25 +/- 1.13 min). The mutant receptor hGR alpha D401H did not exert a dominant positive or negative effect upon the wild-type receptor, it preserved its ability to bind to glucocorticoid response elements, and displayed a normal interaction with the glucocorticoid receptor-interacting protein 1 coactivator. Conclusions: The mutant receptor hGR alpha D401H enhances the transcriptional activity of glucocorticoid-responsive genes. The presence of the D401H mutation may predispose subjects to obesity, hypertension, and other manifestations of the metabolic syndrome. (J Clin Endocrinol Metab 93: 4963-4968, 2008) C1 [Charmandari, Evangelia; Chrousos, George P.] Acad Athens, Biomed Res Fdn, Div Endocrinol & Metab, Athens 11527, Greece. [Charmandari, Evangelia; Ichijo, Takamasa; Baid, Smita; Zachman, Keith; Chrousos, George P.; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Jubiz, William] Ctr Endocrinol, Cali, Colombia. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, Athens 11527, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; European Union-European Social Fund; Greek Ministry of Development-General Secretariat of Research and Technology, Athens, Greece FX This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, the European Union-European Social Fund, and the Greek Ministry of Development-General Secretariat of Research and Technology, Athens, Greece. NR 20 TC 25 Z9 27 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2008 VL 93 IS 12 BP 4963 EP 4968 DI 10.1210/jc.2008-0892 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 379LE UT WOS:000261396900054 PM 18827003 ER PT J AU Langenickel, TH Olive, M Boehm, M San, H Crook, MF Nabel, EG AF Langenickel, Thomas H. Olive, Michelle Boehm, Manfred San, Hong Crook, Martin F. Nabel, Elizabeth G. TI KIS protects against adverse vascular remodeling by opposing stathmin-mediated VSMC migration in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PACLITAXEL-ELUTING STENT; CYCLIN-DEPENDENT KINASE; RNA-RECOGNITION MOTIF; IN-VITRO; PHOSPHORYLATION; P27(KIP1); TRIAL; ONCOPROTEIN-18; IDENTIFICATION; TUBULIN AB Vascular proliferative diseases are characterized by VSMC proliferation and migration. Kinase interacting with stathmin (KIS) targets 2 key regulators of cell proliferation and migration, the cyclin-dependent kinase inhibitor P27(Kip1) and the microtubule-destabilizing protein stathmin. Phosphorylation of p27(Kip1) by KIS leads to cell-cycle progression, whereas the target sequence and the physiological relevance of KIS-mediated stathmin phosphorylation in VSMCs are unknown. Here we demonstrated that vascular wound repair in KIS(-/-) mice resulted in accelerated formation of neointima, which is composed predominantly of VSMCs. Deletion of KIS increased VSMC migratory activity and cytoplasmic tubulin destabilizing activity, but abolished VSMC proliferation through the delayed nuclear export and degradation of p27(Kip1). This promigratory phenotype resulted from increased stathmin protein levels, caused by a lack of KIS-mediated stathmin phosphorylation at serine 38 and diminished stathmin protein degradation. Downregulation of stathmin in KTS(-/-) VSMCs fuilly restored the phenotype, and stathmin-deficient mice demonstrated reduced lesion formation in response to vascular injury. These data suggest that KIS protects against excessive neointima formation by opposing stathmin-mediated VSMC migration and that VSMC migration represents a major mechanism of vascular wound repair, constituting a relevant target and mechanism for therapeutic interventions. C1 [Langenickel, Thomas H.; Olive, Michelle; Boehm, Manfred; San, Hong; Crook, Martin F.; Nabel, Elizabeth G.] NHLBI, Vasc Biol & Genom Sect, Genome Technol Branch, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Vasc Biol & Genom Sect, Genome Technol Branch, Bldg 31,Room 5A48,31 Ctr Dr, Bethesda, MD 20892 USA. EM nabele@nhlbi.nih.gov FU NHLBI Division of Intramural Research FX This study was Supported by the NHLBI Division of Intramural Research. NR 31 TC 15 Z9 15 U1 1 U2 5 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 DEC PY 2008 VL 118 IS 12 BP 3848 EP 3859 DI 10.1172/JCI33206 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 377FO UT WOS:000261237300010 PM 19033656 ER PT J AU Leyland-Jones, BR Ambrosone, CB Bartlett, J Ellis, MJC Enos, RA Raji, A Pins, MR Zujewski, JA Hewitt, SM Forbes, JF Abramovitz, M Braga, S Cardoso, F Harbeck, N Denkert, C Jewell, SD AF Leyland-Jones, Brian R. Ambrosone, Christine B. Bartlett, John Ellis, Matthew J. C. Enos, Rebecca A. Raji, Adekunle Pins, Michael R. Zujewski, Jo Anne Hewitt, Stephen M. Forbes, John F. Abramovitz, Mark Braga, Sofia Cardoso, Fatima Harbeck, Nadia Denkert, Carsten Jewell, Scott D. TI Recommendations for Collection and Handling of Specimens From Group Breast Cancer Clinical Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TISSUE MICROARRAYS; TIME AB Recommendations for specimen collection and handling have been developed for adoption across breast cancer clinical trials conducted by the Breast International Group (BIG)-sponsored Groups and the National Cancer Institute (NCI)-sponsored North American Cooperative Groups. These recommendations are meant to promote identifiable standards for specimen collection and handling within and across breast cancer trials, such that the variability in collection/handling practices that currently exists is minimized and specimen condition and quality are enhanced, thereby maximizing results from specimen-based diagnostic testing and research. Three working groups were formed from the Cooperative Group Banking Committee, BIG groups, and North American breast cancer cooperative groups to identify standards for collection and handling of (1) formalin-fixed, paraffin-embedded (FFPE) tissue; (2) blood and its components; and (3) fresh/frozen tissue from breast cancer trials. The working groups collected standard operating procedures from multiple group specimen banks, administered a survey on banking practices to those banks, and engaged in a series of discussions from 2005 to 2007. Their contributions were synthesized into this document, which focuses primarily on collection and handling of specimens to the point of shipment to the central bank, although also offers some guidance to central banks. Major recommendations include submission of an FFPE block, whole blood, and serial serum or plasma from breast cancer clinical trials, and use of one fixative and buffer type (10% neutral phosphate-buffered formalin, pH 7) for FFPE tissue across trials. Recommendations for proper handling and shipping were developed for blood, serum, plasma, FFPE, and fresh/frozen tissue. C1 [Leyland-Jones, Brian R.] Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. SW Oncol Grp, Buffalo, NY USA. Univ Edinburgh, Edinburgh Canc Res Ctr, Endocrine Canc Grp, Edinburgh, Midlothian, Scotland. Washington Univ, Sch Med, St Louis, MO USA. Canc & Leukemia Grp B, St Louis, MO USA. Amer Coll Surg, Oncol Grp, St Louis, MO USA. EMMES Corp, Rockville, MD USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. NCI, Ctr Canc Res, Pathol Lab, Tissue Array Res Program, Bethesda, MD USA. Northwestern Univ, Eastern Cooperat Oncol Grp, Pathol Coordinating Off, Evanston, IL USA. Advocate Lutheran Gen Hosp, Dept Pathol, Park Ridge, IL USA. Australian New Zealand Breast Canc Trials Group, Newcastle, NSW, Australia. Univ Newcastle, Newcastle, NSW 2308, Australia. VM Inst Res, Montreal, PQ, Canada. Inst Jules Bordet, B-1000 Brussels, Belgium. Tech Univ Munich, Munich, Germany. Kommiss Translat Forsch Arbeitgemeinschaft Gynako, Taufkirchen, Germany. Charite Univ Med Berlin, Berlin, Germany. German Breast Grp, Neu Isenburg, Germany. Canc & Leukemia Grp B Pathol Coordinating Off, Columbus, OH USA. Ohio State Univ, Cooperat Grp Banking Comm, NCI, Columbus, OH 43210 USA. RP Leyland-Jones, BR (reprint author), Emory Univ, Sch Med, Winship Canc Ctr, 1365-C Clifton Rd, Atlanta, GA 30322 USA. EM leyland@emory.edu OI Denkert, Carsten/0000-0002-2249-0982; Hewitt, Stephen/0000-0001-8283-1788; Cardoso, Fatima/0000-0002-6692-2249 FU Breast Cancer Research Foundation; National Cancer Institute (NCI); Breast International Group FX Supported by the Breast Cancer Research Foundation, the National Cancer Institute (NCI), the Breast International Group, and NCI-supported Cooperative Groups. NR 7 TC 52 Z9 52 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 1 PY 2008 VL 26 IS 34 BP 5638 EP 5644 DI 10.1200/JCO.2007.15.1712 PG 7 WC Oncology SC Oncology GA 376RC UT WOS:000261199700023 PM 18955459 ER PT J AU Huey, ED Garcia, C Wassermann, EM Tierney, MC Grafman, J AF Huey, Edward D. Garcia, Charisse Wassermann, Eric M. Tierney, Michael C. Grafman, Jordan TI Stimulant Treatment of Frontotemporal Dementia in 8 Patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 [Huey, Edward D.; Wassermann, Eric M.; Tierney, Michael C.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Garcia, Charisse] NIH, Dept Nursing, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Huey, ED (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS [Z01 NS003023-01] NR 7 TC 14 Z9 14 U1 1 U2 4 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 DEC PY 2008 VL 69 IS 12 BP 1981 EP 1982 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 388ZQ UT WOS:000262059700019 PM 19203481 ER PT J AU Sulkowski, ML Storch, EA Geffken, GR Ricketts, E Murphy, TK Goodman, WK AF Sulkowski, Michael L. Storch, Eric A. Geffken, Gary R. Ricketts, Emily Murphy, Tanya K. Goodman, Wayne K. TI Concurrent Validity of the Yale-Brown Obsessive-Compulsive Scale-Symptom Checklist SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE Obsessive-compulsive disorder; Yale-Brown Obsessive-Compulsive Scale; Obsessive-Compulsive Inventory-Revised ID DEPRESSION INVENTORY-II; TRAIT ANXIETY INVENTORY; PSYCHOMETRIC PROPERTIES; OCI-R; DIMENSIONAL STRUCTURE; NONCLINICAL SAMPLE; DISORDER SYMPTOMS; PADUA INVENTORY; CLINICAL-SAMPLE; RELIABILITY AB Despite the frequent use of the Yale-Brown Obsessive-Compulsive Scale-Symptom Checklist (Y-BOCS-SC; Goodman et al., 1989a) and the Obsessive-Compulsive Inventory-Revised (OCI-R; Foa et al., 2002), there are limited data on the psychometric properties of the two instruments. In the present research, clinician ratings on the Y-BOCS-SC for 112 patients with obsessive-compulsive disorder (OCD) were compared to their self-report ratings on the OCI-R. In addition, Y-BOCS-SC and OCI-R scores were compared to measures of OCD symptom severity and self-report measures of anxiety (State-Trait Anxiety Inventory-Trait Subscale [STAI-T]; Spielberger, Gorusch, & Lushene, 1970) and depression (Beck Depression Inventory-II [BDI-II]; Beck, Steer, & Brown, 1996). The six symptom scales of the OCI-R had good internal consistency reliabilities (alpha s). For the Y-BOCS-SC, three of five scales had good reliabilities (alpha s >.80), but alpha s for symmetry/ordering and sexual/religious symptom scales were inadequate. Total scores for the two instruments were strongly correlated with their corresponding "checking'' scales, but no individual symptoms scales were identified as indices of overall OCD symptom presence. Scales assessing washing/contamination, symmetry/ordering, and hoarding from the two OCD instruments correlated well, but lower correlations for the other scales suggested differences in symptom coverage by the two instruments. Most symptom scales from the Y-BOCS-SC and OCI-R had low correlations with the BDI-II and STAI-T, but the OCI-R obsessing scale was well correlated (r=.54) with the STAI-T. These findings reveal some of the strengths and weaknesses of these two OCD instruments, and the results provide guidance for selecting scales that are suitable for measuring OCD symptoms. (C) 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1338-1351, 2008. C1 [Storch, Eric A.] Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA. [Sulkowski, Michael L.; Geffken, Gary R.; Ricketts, Emily] Univ Florida, Gainesville, FL 32611 USA. [Goodman, Wayne K.] Natl Inst Hlth, Bethesda, MD 20892 USA. RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, 800 6th St S,Box 7523, St Petersburg, FL 33701 USA. EM estorch@health.usf.edu RI Storch, Eric/I-4935-2012 NR 58 TC 19 Z9 20 U1 3 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD DEC PY 2008 VL 64 IS 12 BP 1338 EP 1351 DI 10.1002/jclp.20525 PG 14 WC Psychology, Clinical SC Psychology GA 378TN UT WOS:000261346900004 PM 18942133 ER PT J AU Petry, NM Roll, JM Rounsaville, BJ Ball, SA Stitzer, M Peirce, JM Blaine, J Kirby, KC McCarty, D Carroll, KM AF Petry, Nancy M. Roll, John M. Rounsaville, Bruce J. Ball, Samuel A. Stitzer, Maxine Peirce, Jessica M. Blaine, Jack Kirby, Kimberly C. McCarty, Dennis Carroll, Kathleen M. TI Serious Adverse Events in Randomized Psychosocial Treatment Studies: Safety or Arbitrary Edicts? SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE human subjects protection; serious adverse events; psychosocial treatments; good clinical practice; participant safety ID MOTIVATIONAL ENHANCEMENT THERAPY; CLINICAL-TRIALS NETWORK; DRUG-ABUSE; MENTAL-HEALTH; DEPENDENCE; OUTCOMES; ALCOHOL; INDIVIDUALS; INCENTIVES; MANAGEMENT AB Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials, of the National Institute on Drug Abuse Clinical Trials Network. Substance-abusing participants (N = 1.687) were randomized to standard care or standard care plus either contingency management or motivational enhancement. Twelve percent of participants experienced I or more SAEs during the 27.198 person-weeks of follow-up. Of the 260 SAEs recorded. none were judged by the data safety monitoring board to be study related, and there were no significant differences between experimental and control conditions in SAE incidence rates. These data underscore the need to reconsider the rationale behind, and appropriate methods for. monitoring safety during psychosocial therapy trials. C1 [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Dept Med, Calhoun Cardiol Ctr, Farmington, CT 06030 USA. [Roll, John M.] Washington State Univ, Intercollegiate Coll Nursing, Pullman, WA 99164 USA. [Rounsaville, Bruce J.; Ball, Samuel A.; Carroll, Kathleen M.] Yale Univ, Dept Psychiat, West Haven, CT 06520 USA. [Rounsaville, Bruce J.; Ball, Samuel A.; Carroll, Kathleen M.] Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. [Stitzer, Maxine; Peirce, Jessica M.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. [Blaine, Jack] Natl Inst Drug Abuse, Rockville, MD USA. [Kirby, Kimberly C.] Treatment Res Inst, Philadelphia, PA USA. [Kirby, Kimberly C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [McCarty, Dennis] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA. EM petry@psychiatry.uchc.edu RI Carroll, Kathleen/A-7526-2009; Peirce, Jessica/E-7790-2013; OI Peirce, Jessica/0000-0002-1192-3965; Carroll, Kathleen/0000-0003-3263-3374; Kirby, Kimberly/0000-0001-6745-3854 FU NIAAA NIH HHS [P60-AA03510]; NIDA NIH HHS [R01 DA018883, DA13034, DA13036, DA13038, DA13046, DA13716, P30 DA023918, P30 DA023918-01A1, P50 DA009241, P50 DA009241-06, P50-DA09241, R01 DA013444, R01 DA013444-08, R01 DA014618, R01 DA016855, R01 DA016855-05, R01 DA018883-05, R01 DA021567, R01 DA021567-03, R01 DA022739, R01 DA022739-02, R01-DA016855, R01-DA018883, R01-DA021567, R01-DA022739, R01-DA13444, R01-DA14618, U10 DA013034, U10 DA013034-03, U10 DA013038, UG1 DA013034]; NIMH NIH HHS [R01-MH60417] NR 27 TC 18 Z9 18 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X EI 1939-2117 J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2008 VL 76 IS 6 BP 1076 EP 1082 DI 10.1037/a0013679 PG 7 WC Psychology, Clinical SC Psychology GA 375KP UT WOS:000261113000016 PM 19045975 ER PT J AU McKnight, DA Simmer, JP Hart, PS Hart, TC Fisher, LW AF McKnight, D. A. Simmer, J. P. Hart, P. S. Hart, T. C. Fisher, L. W. TI Overlapping DSPP Mutations Cause Dentin Dysplasia and Dentinogenesis Imperfecta SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE DSPP; dentinogenesis imperfecta; dentin dysplasia; DPP ID SIALOPROTEIN; PROTEIN; PHOSPHOPROTEIN; PHOSPHOPHORYN; MATRIX; GENE AB Dentinogenesis imperfecta (DGI) and dentin dysplasia ( DD) are allelic disorders due to mutations in DSPP. Typically, the phenotype breeds true within a family. Recently, two reports showed that 3 different net -1 bp frameshift mutations early in DSPP's repeat domain caused DD, whereas 6 more 3' frameshift mutations were associated with DGI. Here we identify a DD kindred with a novel -1 bp frameshift (c.3141de1C) that falls within the portion of the DSPP repeat domain previously associated solely with the DGI phenotype. This new frameshift mutation shows that overlapping DSPP mutations can give rise to either DGI or DD phenotypes. Furthermore, the consistent kindred presentation of the DD or DGI phenotype appears to be dependent on an as-yet-ndescribed genetic modifier closely linked to DSPP. C1 [McKnight, D. A.; Fisher, L. W.] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Simmer, J. P.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Dent Res Lab, Ann Arbor, MI 48108 USA. [Hart, P. S.] NHGRI, Off Clin Director, NIH, DHHS, Bethesda, MD 20892 USA. [Hart, T. C.] NIDCR, Sect Human & Craniofacial Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Fisher, LW (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, DHHS, 9000 Rockville Pike,Bldg 30,Room 228, Bethesda, MD 20892 USA. EM lfisher@dir.nidcr.nih.gov FU USPHS [DE15846]; NIH; NIDCR FX This research was supported by the Intramural Research Program of the NIH, NIDCR and in part (for JPS) by USPHS Research Grant DE15846, also from the NIH, NIDCR. NR 14 TC 37 Z9 39 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2008 VL 87 IS 12 BP 1108 EP 1111 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 376KX UT WOS:000261183600006 PM 19029076 ER PT J AU Saha, A Liang, HY Vogel, R Badano, A AF Saha, Anindita Liang, Hongye Vogel, Rebecca Badano, Aldo TI Assessment of Mobile Technologies for Displaying Medical Images SO JOURNAL OF DISPLAY TECHNOLOGY LA English DT Article DE Displays; medical display; radiology; mobile display; portable display ID LIQUID-CRYSTAL DISPLAYS AB We compared the characteristics of state-of-the-art mobile display systems based on reflective and transmissive liquid crystal displays (LCDs) and an organic light-emitting display with respect to physical characterization metrics and observer studies. Physical performance factors provided information on the differences among display technologies. Observer studies resulted in different system ranking between the task-based performance and user-preference approaches. The results of the physical characterization and preference study showed that the reflective LCD ranked lower. We also found that ambient illumination played a lesser role than previously seen in large-format workstation displays. The methodology developed in this study provides an initial insight into the comparison of alternative technologies for display of diagnostic images in small portable devices. C1 [Saha, Anindita; Liang, Hongye; Vogel, Rebecca; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math,CDRH NIBIB Lab Assessment, Silver Spring, MD 20993 USA. RP Saha, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math,CDRH NIBIB Lab Assessment, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 14 TC 2 Z9 2 U1 4 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1551-319X J9 J DISP TECHNOL JI J. Disp. Technol. PD DEC PY 2008 VL 4 IS 4 BP 415 EP 423 DI 10.1109/JDT.2008.924157 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 376YR UT WOS:000261219400010 ER PT J AU Wu, ZJ Zhou, HY Peng, XT Jia, N Wang, YH Yuan, LX AF Wu, Zijun Zhou, Huaiyang Peng, Xiaotong Jia, Nan Wang, Yuhong Yuan, Linxi TI Anaerobic oxidation of methane in coastal sediment from Guishan Island (Pearl River Estuary), South China Sea SO JOURNAL OF EARTH SYSTEM SCIENCE LA English DT Article DE Anaerobic oxidation of methane (AOM); sulfate reduction; pore-water; South China Sea ID COUPLED SULFATE REDUCTION; CARBON ISOTOPIC EVIDENCE; MARINE-SEDIMENTS; ORGANIC-MATTER; BIOGENIC METHANE; SAANICH INLET; BAY; CONSORTIUM; DELTA-C-13; MODEL AB The concentrations of CH(4 center dot) SO(4)(2-), Sigma CO(2) and the carbon isotope compositions of Sigma CO(2) and CH(4) in the pore-water of the GS sedimentary core collected from Guishan Island (Pearl River Estuary). South China Sea, were determined. The methane concentration in the pore-water shows dramatic changes and sulfate concentration gradients are linear at the base of the sulfate reduction zone for the station. The carbon isotope of methane becomes heavier at the sulfate-methane transition (SMT) likely because of the Raleigh distillation effect; (12)CH(4) was oxidized faster than (13)CH(4 center dot) and this caused the enrichment of residual methane delta(13)C and delta(13)C-Sigma CO(2) minimum. The geochemical profiles of the pore-water support the existence of anaerobic oxidation of methane (AOM), which is mainly controlled by the quality and quantity of the sedimentary organic matter. As inferred from the index of delta(13)C-TOC value and TOC/TN ratio, the organic matter is a mix of mainly refractory terrestrial component plus some labile alga marine-derived in the study area. A large amount of labile organic matter (mainly labile alga marine-derived) is consumed via the process of sedimentary organic matter diagenesis, and this reduces the amount of labile organic matter incorporated into the base of the sulfate reduction zone. Due to the scarcity of labile organic matter, the sulfate will in turn be consumed by its reaction with methane and therefore AOM takes place. Based on a diffussion model, the portion of pore-water sulfate reduction via AOM is 58.6%, and the percentage of Sigma CO(2) in the pore-water derived from AOM is 41.4%. Thus, AOM plays an important role in the carbon and sulfur cycling in the marine sediments of Pearl River Estuary. C1 [Wu, Zijun; Zhou, Huaiyang; Peng, Xiaotong] Tongji Univ, State Key Lab Marine Geol, Shanghai 200092, Peoples R China. [Wu, Zijun; Jia, Nan; Yuan, Linxi] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. RP Wu, ZJ (reprint author), Tongji Univ, State Key Lab Marine Geol, Shanghai 200092, Peoples R China. EM wuzj@tongji.edu.cn FU National Basic Research Project [G200007850]; National Natural Science Foundation of China [40803020]; Opening Foundation of State Key Laboratory of Marine Geology; Tongji University [MG0807] FX We thank the shipboard scientists, captain, and crew of the R/V Haijian 83 for their excellent support during the South China Sea cruise in March, 2006. We thank Dr Liu Jinzhong for his assistance in analyzing the stable carbon isotopes of methane and CO2. We would also like to thank Dr Tina Treude and an anonymous reviewer for their very helpful comments on the manuscript. This research was supported by the National Basic Research Project (Grant No. G200007850), National Natural Science Foundation of China (Grant No. 40803020) and the Opening Foundation of State Key Laboratory of Marine Geology, Tongji University (Grant No. MG0807). NR 38 TC 2 Z9 3 U1 1 U2 12 PU INDIAN ACAD SCIENCES PI BANGALORE PA C V RAMAN AVENUE, SADASHIVANAGAR, P B #8005, BANGALORE 560 080, INDIA SN 0253-4126 J9 J EARTH SYST SCI JI J. Earth Syst. Sci. PD DEC PY 2008 VL 117 IS 6 BP 935 EP 943 PG 9 WC Geosciences, Multidisciplinary; Multidisciplinary Sciences SC Geology; Science & Technology - Other Topics GA 405KH UT WOS:000263221400004 ER PT J AU Clennell, S Kuh, D Guralnik, JM Patel, KV Mishra, GD AF Clennell, S. Kuh, D. Guralnik, J. M. Patel, K. V. Mishra, G. D. TI Characterisation of smoking behaviour across the life course and its impact on decline in lung function and all-cause mortality: evidence from a British birth cohort SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID CIGARETTE-SMOKING; RESPIRATORY SYMPTOMS; ADOLESCENT SMOKING; WOMEN; CESSATION; HEALTH; RISK; MEN; TRAJECTORIES; DISEASE AB Objectives: To describe smoking trajectories from early adolescence into mid-life and to examine the effects of these trajectories on health and all-cause mortality. Methods: A nationally representative birth cohort study including 3387 men and women followed up since their birth in 1946 in England, Scotland and Wales. The main outcome measure is all-cause mortality by age 60 years and rate of decline in forced expiratory volume in 1 second (FEV(1)). Results: Eighteen per cent of the sample were categorised as lifelong smokers (smokers at all six waves at ages 20, 25, 31, 36, 43, 53 years), of whom 90% had begun smoking by age 18 years. By age 60 years, 10% of all lifelong smokers had died. They had a threefold increase in mortality rate compared with never smokers (hazard ratio (HR) 3.2, 95% confidence interval (CI) 2.1 to 4.8). For predominantly smokers ( smokers for at least four of the six data collections), mortality rate remained higher than never smokers (HR 1.6, 95% CI 1.0 to 2.5). Predominantly non-smokers did not differ from those who never smoked (HR 1.3, 95% CI 0.9 to 2.0). Using the most recent smoking status available, current smokers had more than double the risk of mortality compared with never smokers (HR 2.4, 95% CI 1.6 to 3.5). Lifelong smokers and predominantly smokers had a greater rate of decline in lung function than never smokers (regression coefficients 218 ml/year, 95% CI 222 to 213; 26, 95% CI -10.3 to -1.7 respectively). For current smokers, the decline was 8.4 ml/year (95% CI -12.0 to -5.0) faster than never smokers. Conclusions: The strength and differentiation of adverse effects identified by using simplified smoking behaviours has highlighted the advantages of obtaining further information on lifelong smoking behaviour from former smokers, rather than just current smoking status. C1 [Clennell, S.; Kuh, D.; Mishra, G. D.] Univ Coll & Royal Free Med Sch, MRC Natl Survey Hlth & Dev, London WC1B 5JU, England. [Guralnik, J. M.; Patel, K. V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Mishra, GD (reprint author), Univ Coll & Royal Free Med Sch, MRC Natl Survey Hlth & Dev, 33 Bedford Pl, London WC1B 5JU, England. EM g.mishra@nshd.mrc.ac.uk RI Mishra, Gita/F-8052-2011 OI Mishra, Gita/0000-0001-9610-5904 FU Medical Research Council; National Institute on Aging, NIH FX The Medical Research Council provided funding for the National Survey of Health and Development and financial support for GM and DK. Supported in part by the Intramural Research Program, National Institute on Aging, NIH. NR 38 TC 17 Z9 17 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD DEC PY 2008 VL 62 IS 12 BP 1051 EP 1056 DI 10.1136/jech.2007.068312 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 372FD UT WOS:000260886600007 PM 18450766 ER PT J AU de Graaf, M Osterhaus, ADME Fouchier, RAM Holmes, EC AF de Graaf, Miranda Osterhaus, Albert D. M. E. Fouchier, Ron A. M. Holmes, Edward C. TI Evolutionary dynamics of human and avian metapneumoviruses SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; AMINO-ACID-SEQUENCE; SUBGROUP-C; PROTECTIVE IMMUNITY; G-GLYCOPROTEIN; RNA VIRUSES; INDIVIDUAL CONTRIBUTIONS; EPIDEMIOLOGIC DYNAMICS; MOLECULAR EVOLUTION; TRACT DISEASE AB Human (HMPV) and avian (AMPV) metapneumoviruses are closely related viruses that cause respiratory tract illnesses in humans and birds, respectively. Although HMPV was first discovered in 2001, retrospective studies have shown that HMPV has been circulating in humans for at least 50 years. AMPV was first isolated in the 1970s, and can be classified into four subgroups, A-D. AMPV subgroup C is more closely related to HMPV than to any other AMPV subgroup, suggesting that HMPV has emerged from AMPV-C upon zoonosis. Presently, at least four genetic lineages of HMPV circulate in human populations - A1, A2, B1 and B2 - of which lineages A and B are antigenically distinct. We used a Bayesian Markov Chain Monte Carlo (MCMC) framework to determine the evolutionary and epidemiological dynamics of HMPV and AMPV-C. The rates of nucleotide substitution, relative genetic diversity and time to the most recent common ancestor (TMRCA) were estimated using large sets of sequences of the nucleoprotein, the fusion protein and attachment protein genes. The sampled genetic diversity of HMPV was found to have arisen within the past 119-133 years, with consistent results across all three genes, while the TMRCA for HMPV and AMPV-C was estimated to have existed around 200 years ago. The relative genetic diversity observed in the four HMPV lineages was low, most likely reflecting continual population bottlenecks, with only limited evidence for positive selection. C1 [de Graaf, Miranda; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.] Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands. [Holmes, Edward C.] Penn State Univ, Dept Biol, Mueller Lab, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Fouchier, RAM (reprint author), Erasmus MC, Dept Virol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM r.fouchier@erasmusmc.nl RI Fouchier, Ron/A-1911-2014; OI Fouchier, Ron/0000-0001-8095-2869; Osterhaus, Albert/0000-0002-6074-1172; Holmes, Edward/0000-0001-9596-3552 NR 53 TC 48 Z9 48 U1 1 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2008 VL 89 BP 2933 EP 2942 DI 10.1099/vir.0.2008/006957-0 PN 12 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 381HY UT WOS:000261527800002 PM 19008378 ER PT J AU Sundling, C Schon, K Morner, A Forsell, MNE Wyatt, RT Thorstensson, R Hedestam, GBK Lycke, NY AF Sundling, Christopher Schon, Karin Morner, Andreas Forsell, Mattias N. E. Wyatt, Richard T. Thorstensson, Rigmor Hedestam, Gunilla B. Karlsson Lycke, Nils Y. TI CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; ADP-RIBOSYLTRANSFERASE ACTIVITY; 2ND HYPERVARIABLE REGION; NEUTRALIZING ANTIBODIES; CHOLERA-TOXIN; VACCINE DEVELOPMENT; INFLUENZA VACCINE; PARTIAL DELETION; HIV-1 VACCINE; GENITAL-TRACT AB Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env. C1 [Sundling, Christopher; Morner, Andreas; Thorstensson, Rigmor; Hedestam, Gunilla B. Karlsson] Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Mucosal Immunobiol & Vaccine Ctr MIVAC, Gothenburg, Sweden. [Sundling, Christopher; Forsell, Mattias N. E.; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. [Sundling, Christopher; Morner, Andreas; Thorstensson, Rigmor; Hedestam, Gunilla B. Karlsson] Swedish Inst Infect Dis Control, S-17182 Solna, Sweden. [Forsell, Mattias N. E.; Wyatt, Richard T.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Lycke, NY (reprint author), Univ Gothenburg, Dept Microbiol & Immunol, Inst Biomed, Mucosal Immunobiol & Vaccine Ctr MIVAC, Gothenburg, Sweden. EM nils.lycke@microbio.gu.se OI Morner, Andreas/0000-0002-3654-1728; Sundling, Christopher/0000-0002-6138-690X FU Swedish Research Council; Swedish Cancer Foundation; LUA-ALF; EU [QLK2-CT-2001-01702, QLK2-CT-199-00228, LSHP-CT-2003-503240, COOPT-CT-2005-017749]; Swedish Foundation for Strategic Research (MIVAC) FX We thank the staff at the Mucosal Immunobiology & Vaccine Center (MIVAC), the Department of Microbiology, Tumor and Cell Biology and Mats Spangberg and Helene Fredlund and their staff ill the Astrid Fagraeus Laboratory at the Swedish Institute for Infectious Disease Control (SMI), for expert assistance. We also thank Sofia Dahlberg at SMI and Yuxing Li at the Vaccine Research Center at the National Institutes of Health for helpful contributions. This study was generously supported by grants from Sida/SAREC (N. L., G. K. H. and R.T.), the Swedish Research Council, the Swedish Cancer Foundation, the LUA-ALF, EU grants QLK2-CT-2001-01702, QLK2-CT-199-00228, LSHP-CT-2003-503240, COOPT-CT-2005-017749 and the Swedish Foundation for Strategic Research (MIVAC). NR 75 TC 28 Z9 28 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2008 VL 89 BP 2954 EP 2964 DI 10.1099/vir.0.2008/005470-0 PN 12 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 381HY UT WOS:000261527800004 PM 19008380 ER PT J AU Maria, OM Kim, JWM Gerstenhaber, JA Baum, BJ Tran, SD AF Maria, Ola M. Kim, Jung-Wan Martin Gerstenhaber, Jonathan A. Baum, Bruce J. Tran, Simon D. TI Distribution of Tight Junction Proteins in Adult Human Salivary Glands SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE salivary gland; tight junction; claudins; occludin; junctional adhesion molecules; zonula occludens; epithelial barriers ID GRAFT CELL-LINE; EPITHELIAL-CELLS; ADHESION MOLECULE; IN-VIVO; EXPRESSION; CLAUDINS; STRANDS; ZO-1; OCCLUDIN; IDENTIFICATION AB Tight junctions (TJs) are an essential structure of fluid-secreting cells, such as those in salivary glands. Three major families of integral membrane proteins have been identified as components of the TJ: claudins, occludin, and junctional adhesion molecules (JAMs), plus the cytosolic protein zonula occludens (ZO). We have been working to develop an orally implantable artificial salivary gland that would be suitable for treating patients lacking salivary parenchymal tissue. To date, little is known about the distribution of TJ proteins in adult human salivary cells and thus what key molecular components might be desirable for the cellular component of an artificial salivary gland device. Therefore, the aim of this study was to determine the distribution of TJ proteins in human salivary glands. Salivary gland samples were obtained from 10 patients. Frozen and formalin-fixed paraffin-embedded sections were stained using IHC methods. Claudin-1 was expressed in ductal, endothelial, and similar to 25% of serous cells. Claudins-2, -3, and -4 and JAM-A were expressed in both ductal and acinar cells, whereas claudin-5 was expressed only in endothelial cells. Occludin and ZO-1 were expressed in acinar, ductal, and endothelial cells. These results provide new information on TJ proteins in two major human salivary glands and should serve as a reference for future studies to assess the presence of appropriate TJ proteins in a tissue-engineered human salivary gland. (J Histochem Cytochem 56:1093-1098,2008) C1 [Maria, Ola M.; Kim, Jung-Wan Martin; Tran, Simon D.] McGill Univ, Fac Dent, Montreal, PQ, Canada. [Gerstenhaber, Jonathan A.; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Tran, SD (reprint author), 3640 Univ St,Room M43, Montreal, PQ H3A 2B2, Canada. EM simon.tran@mcgill.ca FU Intramural NIH HHS NR 40 TC 21 Z9 21 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 2008 VL 56 IS 12 BP 1093 EP 1098 DI 10.1369/jhc.2008.951780 PG 6 WC Cell Biology SC Cell Biology GA 374KF UT WOS:000261041500005 PM 18765838 ER PT J AU Fedorova, OV Simbirtsev, AS Kolodkin, NI Kotov, AY Agalakova, NI Kashkin, VA Tapilskaya, NI Bzhelyansky, A Reznik, VA Frolova, EV Nikitina, ER Budny, GV Longo, DL Lakatta, EG Bagrov, AY AF Fedorova, Olga V. Simbirtsev, Andrey S. Kolodkin, Nikolai I. Kotov, Alexander Y. Agalakova, Natalia I. Kashkin, Vladimir A. Tapilskaya, Natalia I. Bzhelyansky, Anton Reznik, Vitaly A. Frolova, Elena V. Nikitina, Elena R. Budny, Georgy V. Longo, Dan L. Lakatta, Edward G. Bagrov, Alexei Y. TI Monoclonal antibody to an endogenous bufadienolide, marinobufagenin, reverses preeclampsia-induced Na/K-ATPase inhibition and lowers blood pressure in NaCl-sensitive hypertension SO JOURNAL OF HYPERTENSION LA English DT Article DE marinobufagenin; monoclonal antibody; Na/K-ATPase; preeclampsia; salt-sensitive hypertension ID SODIUM-PUMP; OUABAIN; DIGITALIS; PLASMA; RATS; BUFODIENOLIDE; ALDOSTERONE; PREGNANCY; STEROIDS; FAILURE AB Background Levels of marinobufagenin (MBG), an endogenous bufadienolide Na/K-ATPase (NKA) inhibitor, increase in preeclampsia and in NaCl-sensitive hypertension. Methods We tested a 3E9 monoclonal anti-MBG antibody (mAb) for the ability to lower blood pressure (BP) in NaCl-sensitive hypertension and to reverse the preeclampsia-induced inhibition of erythrocyte NKA. Measurements of MBG were performed via immunoassay based on 4G4 anti-MBG mAb. Results In hypertensive Dahl-S rats, intraperitoneal administration of 50 mu g/kg 3E9 mAb lowered BP by 32 mmHg and activated the Na/K-pump in the thoracic aorta by 51%. NaCl supplementation of pregnant rats (n = 16) produced a 37 mmHg increase in BP, a 3.5-fold rise in MBG excretion, and a 25% inhibition of the Na/K-pump in the thoracic aorta, compared with pregnant rats on a normal NaCl intake. In eight pregnant hypertensive rats, 3E9 mAb reduced the BP (21 mmHg) and restored the vascular Na/K-pump. In 14 patients with preeclampsia (mean BP, 126 +/- 3 mmHg; 26.9 +/- 1.4 years; gestational age, 37 +/- 0.8 weeks), plasma MBG was increased three-fold and erythrocyte NKA was inhibited compared with that of 12 normotensive pregnant women (mean BP, 71 +/- 3 mmHg) (1.5 +/- 0.1 vs. 3.1 +/- 0.2 mu mol Pi/ml/h, respectively; P<0.01). Ex-vivo 3E9 mAb restored NKA activity in erythrocytes from patients with preeclampsia. As compared with 3E9 mAb, Digibind, an affinity-purified antidigoxin antibody, was less active with respect to lowering BP in both hypertensive models and to restoration of NKA from erythrocytes from patients with preeclampsia. Conclusion Anti-MBG mAbs may be a useful tool in studies of MBG in vitro and in vivo and may offer treatment of preeclampsia. J Hypertens 26: 2414-2425 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [Fedorova, Olga V.; Agalakova, Natalia I.; Kashkin, Vladimir A.; Bzhelyansky, Anton; Lakatta, Edward G.; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Simbirtsev, Andrey S.; Kolodkin, Nikolai I.; Kotov, Alexander Y.; Budny, Georgy V.] State Inst Highly Pure Biopreparat, St Petersburg, Russia. [Agalakova, Natalia I.; Frolova, Elena V.; Nikitina, Elena R.; Budny, Georgy V.] IM Sechenov Evolut Physiol & Biochem Inst, St Petersburg 194223, Russia. [Tapilskaya, Natalia I.; Reznik, Vitaly A.] Sch Pediat Med, Dept Obstet & Gynecol, St Petersburg, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov RI Simbirtsev, Andrei/K-5061-2014; Bzhelyansky, Anton/J-8302-2014; OI Simbirtsev, Andrei/0000-0002-8228-4240; Bzhelyansky, Anton/0000-0001-6184-9284; Kashkin, Vladimir/0000-0002-7202-0233 FU Intramural Research Program, National Institute on Aging, NIH; Russian Foundation for Fundamental Science [06-04-48956] FX These studies were supported by Intramural Research Program, National Institute on Aging, NIH. Fragments of the studies were supported by Russian Foundation for Fundamental Science (grant 06-04-48956). Authors gratefully acknowledge excellent technical assistance by Irina V. Averina, MD, Ekaterina P. Fadeeva, MD, Alexandra (Namikas) Newman, Danielle Joseph, and Chad Boily. NR 32 TC 35 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD DEC PY 2008 VL 26 IS 12 BP 2414 EP 2425 DI 10.1097/HJH.0b013e328312c86a PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 379NT UT WOS:000261404100023 PM 19008721 ER PT J AU Rochman, Y Leonard, WJ AF Rochman, Yrina Leonard, Warren J. TI The Role of Thymic Stromal Lymphopoietin in CD8(+) T Cell Homeostasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; INTESTINAL IMMUNE HOMEOSTASIS; AIRWAY EPITHELIAL-CELLS; IGM(+) B-CELLS; INTERLEUKIN-7 RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; DENDRITIC CELLS; CUTTING EDGE; IN-VITRO; IL-7 AB Thymic stromal lymphopoietin (TSLP) is a cytokine produced by stromal cells, epithelial cells, and basophils that acts on dendritic cells, mast cells, and CD4(+) T cells. The receptor for TSLP contains a TSLP-specific receptor chain (TSLPR) and the IL-7R a-chain. Although IL-7 critically controls the expansion and survival of naive and memory CD8(+) T cells, an action for TSLP on CD8(+) T cells has not been reported. We now demonstrate that CD8(+) T cells express TSLPR and that TSLP activates both STAT5 and Akt and induces Bcl-2 in these cells. Correspondingly, TSLP increases CD8(+) T cell survival in vitro as well as in wild-type and T-depleted mice in vivo, without altering the homeostatic proliferation of these cells. Moreover, TSLP can maintain CD8(+) T cells even in the absence of IL-7. Thus, our data reveal that TSLP contributes to CD8(+) T cell homeostasis in both normal and lymphopenic conditions. The Journal of Immunology, 2008, 181: 7699-7705. C1 [Rochman, Yrina; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Division of Intramural Research; National Heart, Lung, and Blood Institute,; National Institutes of Health FX This work Was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 41 TC 51 Z9 51 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 DEC 1 PY 2008 VL 181 IS 11 BP 7699 EP 7705 PG 7 WC Immunology SC Immunology GA 376YX UT WOS:000261220000031 PM 19017958 ER PT J AU Kuehn, HS Swindle, EJ Kim, MS Beaven, MA Metcalfe, DD Gilfillan, AM AF Kuehn, Hye Sun Swindle, Emily J. Kim, Mi-Sun Beaven, Michael A. Metcalfe, Dean D. Gilfillan, Alasdair M. TI The Phosphoinositide 3-Kinase-Dependent Activation of Btk Is Required for Optimal Eicosanoid Production and Generation of Reactive Oxygen Species in Antigen-Stimulated Mast Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATOR RELEASE; ARACHIDONIC-ACID; NADPH OXIDASE; PATHWAYS; PHOSPHOLIPASE-A(2); PROSTAGLANDINS; IMMUNITY; RECEPTOR; KINASES; DOMAIN AB Activated mast cells are a major source of the eicosanoids PGD(2) and leukotriene C(4) (LTC(4)), which contribute to allergic responses. These eicosanoids are produced following the ERK1/2-dependent activation of cytosolic phospholipase A(2), thus liberating arachidonic acid, which is subsequently metabolized by the actions of 5-lipoxygenase and cyclooxygenase to form LTC(4) and PGD(2), respectively. These pathways also generate reactive oxygen species (ROS), which have been proposed to contribute to Fc epsilon RI-mediated signaling in mast cells. In this study, we demonstrate that, in addition to ERK1/2-dependent pathways, ERK1/2-independent pathways also regulate Fc epsilon RI-mediated eicosanoid and ROS production in mast cells. A role for the Tee kinase Btk in the ERK1/2-independent regulatory pathway was revealed by the significantly attenuated Fc epsilon RI-dependent PGD(2), LTC(4), and ROS production in bone marrow-derived mast cells of Btk(-/-) mice. The Fc epsilon RI-dependent activation of Btk and eicosanoid and ROS generation in bone marrow-derived mast cells and human mast cells were similarly blocked by the PI3K inhibitors, Wortmannin and LY294002, indicating that Btk-regulated eicosanoid and ROS production occurs downstream of PI3K. In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase A(2) phosphorylation but rather appears to regulate the generation of ROS, LTC(4), and PGD(2) by contributing to the necessary Ca(2+) signal for the production of these molecules. These data demonstrate that strategies to decrease mast cell production of ROS and eicosanoids would have to target both ERK1/2- and PI3K/Btk-dependent pathways. The Journal of Immunology, 2008, 181: 7706-7712. C1 [Kuehn, Hye Sun; Swindle, Emily J.; Kim, Mi-Sun; Metcalfe, Dean D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,Mail Stop Code 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Heart, Lung. and Blood Institute Divisions; National Institutes of Health FX This work was supported by the National Institute of Allergy and Infectious Diseases and National Heart, Lung. and Blood Institute Divisions of intramural Research within the National Institutes of Health. NR 31 TC 28 Z9 29 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 7706 EP 7712 PG 7 WC Immunology SC Immunology GA 376YX UT WOS:000261220000032 PM 19017959 ER PT J AU Longo, NS Grundy, GJ Lee, J Gellert, M Lipsky, PE AF Longo, Nancy S. Grundy, Gabrielle J. Lee, Jisoo Gellert, Martin Lipsky, Peter E. TI An Activation-Induced Cytidine Deaminase-Independent Mechanism of Secondary V(H) Gene Rearrangement in Preimmune Human B Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHAIN VARIABLE REGION; RECOMBINATION SIGNAL SEQUENCE; CLASS-SWITCH RECOMBINATION; J-LAMBDA REPERTOIRE; V(D)J RECOMBINATION; SOMATIC HYPERMUTATION; 12/23 RULE; IMMUNOGLOBULIN GENES; RECEPTOR REVISION; HAIRPIN FORMATION AB V(H) replacement is a form of IgH chain receptor editing that is believed to be mediated by recombinase cleavage at cryptic recombination signal sequences (cRSS) embedded in V(H) genes. Whereas there are several reports of V(H) replacement in primary and transformed human B cells and murine models, it remains unclear whether V(H) replacement contributes to the normal human B cell repertoire. We identified V(H)-> V(H)(D)J(H) compound rearrangements front fetal liver, fetal bone marrow, and naive peripheral blood, all of which involved invading and recipient V(H)4 genes that contain a cryptic heptamer, a 13-bp spacer, and nonamer in the 5' portion of framework region 3. Surprisingly, all pseudohybrid joins lacked the molecular processing associated with typical V(H)(D)J(H) recombination or nonhomologous end joining. Although inefficient compared with a canonical recombination signal sequences, the V(H)4 cRSS was a significantly better substrate for in vitro RAG-mediated cleavage than the V(H)3 cRSS. It has been suggested that activation-induced cytidine deamination (AICDA) may contribute to V(H) replacement. However, we found similar secondary rearrangements using V(H)4 genes in AICDA-deficient human B cells. The data suggest that V(H)4 replacement in preimmune human B cells is mediated by an AICDA-independent mechanism resulting from inefficient but selective RAG activity. The Journal of Immunology, 2008, 181: 7825-7834. C1 [Longo, Nancy S.; Lee, Jisoo; Lipsky, Peter E.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Grundy, Gabrielle J.; Gellert, Martin] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, NIH, Bldg 10,Room 6D47C, Bethesda, MD 20892 USA. EM peterlipsky@comcast.net FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Bethesda, MD FX This research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Diabetes and Digestive and Kidney Diseases intramural research programs of the National Institutes of Health, Bethesda, MD. NR 62 TC 4 Z9 4 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 DEC 1 PY 2008 VL 181 IS 11 BP 7825 EP 7834 PG 10 WC Immunology SC Immunology GA 376YX UT WOS:000261220000045 PM 19017972 ER PT J AU Robila, V Ostankovitch, M Altrich-VanLith, ML Theos, AC Drover, S Marks, MS Restifo, N Engelhard, VH AF Robila, Valentina Ostankovitch, Marina Altrich-VanLith, Michelle L. Theos, Alexander C. Drover, Sheila Marks, Michael S. Restifo, Nicholas Engelhard, Victor H. TI MHC Class II Presentation of gp100 Epitopes in Melanoma Cells Requires the Function of Conventional Endosomes and Is Influenced by Melanosomes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYSOSOME-RELATED ORGANELLES; HLA-DR MOLECULES; CD4(+) T-CELLS; ENDOCYTIC COMPARTMENTS; ENDOPLASMIC-RETICULUM; CYTOPLASMIC ANTIGENS; PROCESSING PATHWAY; CD4+T CELLS; PROTEIN; TYROSINASE AB Many human solid tumors express MHC class II (MHC-II) molecules, and proteins normally localized to melanosomes give rise to MHC-II-restricted epitopes in melanoma. However, the pathways by which this response occurs have not been defined. We analyzed the processing of one such epitope, gp100(44-59), derived from gp100/Pmel17. In melanomas that have down-regulated components of the melanosomal pathway, but constitutively express HLA-DR*0401, the majority of gp100 is sorted to LAMP-1(high)/MHC-II(+) late endosomes. Using mutant gp100 molecules with altered intracellular trafficking, we demonstrate that endosomal localization is necessary for gp100(44-59) presentation. By depletion of the AP-2 adaptor protein using small interfering RNA, we demonstrate that gp100 protein internalized from the plasma membrane to such endosomes is a major source for gp100(44-59) epitope production. The gp100 trapped in early endosomes gives rise to epitopes that are indistinguishable from those produced in late endosomes but their production is less sensitive to inhibition of lysosomal proteases. In melanomas containing melanosomes, gp100 is underrepresented in late endosomes, and accumulates in stage 11 melanosomes devoid of MHC-II molecules. The gp100(44-59) presentation is dramatically reduced, and processing occurs entirely in early endosomes or stage I melanosomes. This occurrence suggests that melanosomes are inefficient Ag-processing compartments. Thus, melanoma de-differentiation may be accompanied by increased presentation of MHC-II restricted epitopes from gp100 and other melanosome-localized proteins, leading to enhanced immune recognition. The Journal of Immunology, 2008, 181: 7843-7852. C1 [Robila, Valentina; Ostankovitch, Marina; Altrich-VanLith, Michelle L.; Engelhard, Victor H.] Univ Virginia, Sch Med, Carter Immunol Ctr, Charlottesville, VA 22908 USA. [Robila, Valentina; Ostankovitch, Marina; Altrich-VanLith, Michelle L.; Engelhard, Victor H.] Univ Virginia, Sch Med, Dept Microbiol, Charlottesville, VA 22908 USA. [Drover, Sheila] Mem Univ Newfoundland, Div Biomed Sci, St John, NF, Canada. [Theos, Alexander C.; Marks, Michael S.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Restifo, Nicholas] NCI, NIH, Bethesda, MD 20892 USA. RP Engelhard, VH (reprint author), Univ Virginia, Sch Med, Carter Immunol Ctr, Box 801386, Charlottesville, VA 22908 USA. EM vhe@virginia.edu RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580; Marks, Michael/0000-0001-7435-7262 FU U.S. Public Health Service [A120963, A133134, AR041855, EY015625]; Canadian Institutes for Health Research [ROP-38369] FX This work was supported by Grants A120963 and A133134 from the U.S. Public Health Service (to V.H.E.), Grants AR041855 and EY015625 (to M.S.M.), and Grant ROP-38369 from Canadian Institutes for Health Research (to S.D). NR 72 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 7843 EP 7852 PG 10 WC Immunology SC Immunology GA 376YX UT WOS:000261220000047 PM 19017974 ER PT J AU Venturi, V Chin, HY Asher, TE Ladell, K Scheinberg, P Bornstein, E van Bockel, D Kelleher, AD Douek, DC Price, DA Davenport, MP AF Venturi, Vanessa Chin, Hui Yee Asher, Tedi E. Ladell, Kristin Scheinberg, Phillip Bornstein, Ethan van Bockel, David Kelleher, Anthony D. Douek, Daniel C. Price, David A. Davenport, Miles P. TI TCR beta-Chain Sharing in Human CD8(+) T Cell Responses to Cytomegalovirus and EBV SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; COMPLEX CLASS-I; LARGE CLONAL EXPANSIONS; PRIMARY IMMUNE-RESPONSE; INFECTIOUS-MONONUCLEOSIS; ANTIGEN RECEPTOR; STRUCTURAL BASIS; VIRAL-INFECTION; CTL RESPONSE; V-ALPHA AB The CD8(+) TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCR beta chains between individuals is strongly associated with TCR beta production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCRP sequences. In this study, we analyzed a total of 2836 TCR beta sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCR beta sequences in the CD8(+) T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCR beta amino acid sequences were found to have two features that indicate efficient TCR beta production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCR beta production frequency was predictive of the extent to which both TCR beta nucleotide and amino acid sequences were shared in vivo. These results suggest that TCR beta production frequency plays an important role in the interindividual sharing of TCR beta sequences within CD8(+) T cell responses specific for CMV and EBV. The Journal of Immunology, 2008, 181: 7853-7862. C1 [Venturi, Vanessa; Chin, Hui Yee; Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia. [Asher, Tedi E.; Scheinberg, Phillip; Bornstein, Ethan; Douek, Daniel C.; Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Ladell, Kristin; Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales. [van Bockel, David; Kelleher, Anthony D.] Univ New S Wales, St Vincents Hosp, Ctr Immunol, Sydney, NSW, Australia. [van Bockel, David; Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Davenport, MP (reprint author), Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia. EM priced6@cardiff.ac.uk; rn.davenport@unsw.edu.au RI Scheinberg, Phillip/H-5251-2012; Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013; OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938; Scheinberg, Phillip/0000-0002-9047-4538 FU James S. McDonnell Foundation; Australian Research Council; National Health and Medical Research Council; National Institutes of Health FX This work was support by the James S. McDonnell Foundation 21st Century Research Award/Studying Complex Systems, the Australian Research Council, the National Health and Medical Research Council, and the National Institutes of Health. M.P.D. is a Sylvia and Charles Viertel Senior Medical Research Fellow, and D.A.P. is a Medical Research Council (U.K.) Senior Clinical Fellow. NR 50 TC 46 Z9 47 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 DEC 1 PY 2008 VL 181 IS 11 BP 7853 EP 7862 PG 10 WC Immunology SC Immunology GA 376YX UT WOS:000261220000048 PM 19017975 ER PT J AU Bansal, G DiVietro, JA Kuehn, HS Rao, S Nocka, KH Gilfillan, AM Druey, KM AF Bansal, Geetanjali DiVietro, Jeffrey A. Kuehn, Hye Sun Rao, Sudhir Nocka, Karl H. Gilfillan, Alasdair M. Druey, Kirk M. TI RGS13 Controls G Protein-Coupled Receptor-Evoked Responses of Human Mast Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL-REGULATED KINASE; PHOSPHOLIPASE-C; B-LYMPHOCYTES; IN-VITRO; T-CELLS; ACTIVATION; PATHWAYS; ROLES; CHEMOTAXIS; EXPRESSION AB IgE-mediated mast cell degranulation and release of vasoactive mediators induced by allergens elicits allergic responses. Although G protein-coupled receptor (GPCR)-induced signals may amplify IgE-dependent degranulation, how GPCR signaling in mast cells is regulated remains incompletely defined. We investigated the role of regulator of G protein signaling (RGS) proteins in the modulation of these pathways in human mast cells. Several RGS proteins were expressed in mast cells including RGS13, which we previously showed inhibited IgE-mediated mast cell degranulation and anaphylaxis in mice. To characterize how RGS13 affects GPCR-mediated functions of human mast cells, we analyzed human mast cell lines (HMC-1 and LAD2) depleted of RGS13 by specific small interfering RNA or short hairpin RNA and HMC-1 cells overexpressing RGS13. Transient RGS13 knockdown in LAD2 cells lead to increased degranulation to sphingosine-1-phosphate but not to IgE-Ag or C3a. Relative to control cells, HMC-1 cells stably expressing RGS13-targeted short hairpin RNA had greater Ca(2+) mobilization in response to several natural GPCR ligands such as adenosine, C5a, sphingosine-1-phosphate, and CXCL12 than wild-type cells. Akt phosphorylation, chemotaxis, and cytokine (IL-8) secretion induced by CXCL12 were also greater in short hairpin RGS13-HMC-1 cells compared with control. RGS13 overexpression inhibited CXCL12-evoked Ca(2+) mobilization, Akt phosphorylation and chemotaxis. These results suggest that RGS13 restricts certain GPCR-mediated biological responses of human mast cells. The Journal of Immunology, 2008, 181: 7882-7890. C1 [Bansal, Geetanjali; DiVietro, Jeffrey A.; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Kuehn, Hye Sun; Gilfillan, Alasdair M.] NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Rao, Sudhir; Nocka, Karl H.] UCB Pharma Inc, Cambridge, MA 02139 USA. RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM kdrucy@niaid.nih.gov RI Bansal, Geetanjali/C-3854-2009 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 65 TC 21 Z9 24 U1 3 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 DEC 1 PY 2008 VL 181 IS 11 BP 7882 EP 7890 PG 9 WC Immunology SC Immunology GA 376YX UT WOS:000261220000051 PM 19017978 ER PT J AU Thio, CL Astemborski, J Thomas, R Mosbruger, T Witt, MD Goedert, JJ Hoots, K Winkler, C Thomas, DL Carrington, M AF Thio, Chloe L. Astemborski, Jacquie Thomas, Rasmi Mosbruger, Timothy Witt, Mallory D. Goedert, James J. Hoots, Keith Winkler, Cherie Thomas, David L. Carrington, Mary TI Interaction between RANTES Promoter Variant and CCR5 Delta 32 Favors Recovery from Hepatitis B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENETIC-VARIANTS; IMMUNE-RESPONSE; INFECTION; CCR5; POLYMORPHISM; POPULATION; TYPE-1; HEMOPHILIA; DEFICIENCY AB Recovery from acute hepatitis B virus (HBV) infection occurs in 95% of adult-acquired infections. A 32-bp deletion in CCR5 (CCR5 Delta 32), which encodes for a nonfunctional receptor, increases the likelihood of recovery. Using 181 subjects with persistent HBV infection and 316 who had recovered, we tested the hypothesis that an epistatic interaction between functional polymorphisms in RANTES (a CCR5 ligand) and CCR5 impacts recovery. Specific models designed to assess individual contributions of compound genotypes demonstrated that the only combination associated with recovery from an HBV infection was RANTES -403A with CCR5 Delta 32 (odds ratio 0.36, p = 0.02). Because the phenotypic consequence of -403A is reported to be higher levels of RANTES, we propose a model in which excess RANTES in combination with low CCR5 favors recovery from an HBV infection, which will require validation through functional testing. The Journal of Immunology, 2008, 181: 7944-7947. C1 [Thomas, Rasmi; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Thio, Chloe L.; Astemborski, Jacquie; Mosbruger, Timothy; Thomas, David L.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. [Witt, Mallory D.] Univ Calif Med Ctr, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90509 USA. [Witt, Mallory D.] David Geffen Sch Med, Los Angeles, CA 90509 USA. [Goedert, James J.] NCI, Viral Epidemiol Branch, Div Cancer Epidemiol & Genet, Rockville, MD 20852 USA. [Hoots, Keith] Univ Texas Hlth Sci Ctr Houston, Gulf States Hemophilia Ctr, Houston, TX 77030 USA. [Winkler, Cherie] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Carrington, M (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU National Institutes of Health [DA00441, N01-CO-12400, MO1-RR06020]; Burroughs Wellcome Fund; National Cancer Institute [N02-CP-55504, UO1-AI-35042, 5-MO1-RR-00722, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; Bureau of Maternal and Mid Health and Resources Development [MCJ-060570]; National Institute of Child Health and Human Development [N01-HD-4-3200]; Centers for Disease Control and Prevention; National Institute of Mental Health; Mount Sinai General Clinical Research Center, New York [MO1-RR00071]; University of Iowa Clinical Research Center [MO1-RR00059]; University of Texas Health Science Center, Houston [MO1-RR02558, RO1-HD-4-1224] FX This work was supported by National Institutes of Health Grant DA00441 mid by the investigators in the Pathogenesis of Infectious Diseases Award front the Burroughs Wellcome Fund (to C.L.T.). This project has been funded in whole or in pail with federal funds from tire National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Multicenter Hemophilia Cohort Study is supported by National Cancer Institute Contract N02-CP-55504 with RTI International. Hemophilia Growth and Development Study is supported by the Bureau of Maternal and Mid Health and Resources Development (MCJ-060570), the National Institute of Child Health and Human Development (N01-HD-4-3200), die Centers for Disease Control and Prevention, and the National Institute of Mental Health. Additional support has been provided by grants from the National Center for Research Resources of the National Institutes of Health to the New York Hospital-Cornell Medical Center Clinical Research Center (MO1-RR06020); Mount Sinai General Clinical Research Center, New York (MO1-RR00071); University of Iowa Clinical Research Center (MO1-RR00059); University of Texas Health Science Center, Houston (MO1-RR02558) and RO1-HD-4-1224.; Data in this manuscript were collected by the Multicenter AIDS Cohort Study. with centers (principal investigators) at The Johns Hopkins University Bloomberg School of Public Health (Joseph B. Margolick, Lisa Jacobson); Howard Brown Health Center and Northwestern University Medical School (John Phair); University of California, Los Angeles (Roger Detels); and University of Pittsburgh (Charles Rinaldo). 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 and the National Heart, Lung, and Blood Institute (UO1-AI-35042,5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041). Website located at http://www.statepi.jhsph.edu/macs/macs.html NR 24 TC 14 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 7944 EP 7947 PG 4 WC Immunology SC Immunology GA 376YX UT WOS:000261220000058 PM 19017985 ER PT J AU Geldmacher, C Schuetz, A Ngwenyama, N Casazza, JP Sanga, E Saathoff, E Boehme, C Geis, S Maboko, L Singh, M Minja, F Meyerhans, A Koup, RA Hoelscher, M AF Geldmacher, Christof Schuetz, Alexandra Ngwenyama, Njabulo Casazza, Joseph P. Sanga, Erica Saathoff, Elmar Boehme, Catharina Geis, Steffen Maboko, Leonard Singh, Mahavir Minja, Fred Meyerhans, Andreas Koup, Richard A. Hoelscher, Michael TI Early Depletion of Mycobacterium tuberculosis-Specific T Helper 1 Cell Responses after HIV-1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY VIRUS-1 REPLICATION; CD4(+) T-CELLS; ANTIRETROVIRAL THERAPY; INTRACELLULAR BACTERIA; M. TUBERCULOSIS; IMMUNE-RESPONSE; FLOW-CYTOMETRY; ACTIVATION; CYTOKINES; SIV AB Background. The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis-specific pathogenicity early after onset of HIV infection. Methods. M. tuberculosis-specific T helper 1 (Th1) cells were studied in HIV negative (n = 114) and chronically HIV infected (n = 68) Tanzanian subjects by using early secreted antigenic target 6 (ESAT6) protein or tuberculin (purified protein derivative) with interferon-gamma ELISPOT and intracellular cytokine staining. In a longitudinal study, the effect of acute HIV infection on M. tuberculosis-specific Th1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent M. tuberculosis infection who became infected with HIV. Results. In tuberculosis (TB)-asymptomatic subjects (i.e., subjects with unknown TB status who did not show clinical signs suggestive of TB), chronic HIV infection was associated with a decreased percentage of subjects with detectable M. tuberculosis-specific Th1 cells (P < .001), a decrease which was not observed among subjects with active TB. Acute HIV infection induced a rapid depletion of M. tuberculosis-specific Th1 cells in 4 subjects remained TB asymptomatic, whereas the population of these cells remained stable in subjects who remained HIV negative (P < .01). Conclusions. Taken together, these data suggest a mechanism of rapid M. tuberculosis-specific Th1 cell depletion that may contribute to the early onset of TB in individuals with latent M. tuberculosis infection who become HIV infected. C1 [Saathoff, Elmar; Boehme, Catharina; Geis, Steffen; Hoelscher, Michael] Klinikum Ludwig Maximilians Univ, Dept Infect Dis & Trop Med, D-80802 Munich, Germany. [Geldmacher, Christof; Ngwenyama, Njabulo; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Minja, Fred] Mbeya Reg Med Off, Natl TB & Leprosy Programme, Mbeya, Tanzania. [Schuetz, Alexandra; Sanga, Erica; Geis, Steffen; Maboko, Leonard] Referral Hosp, Mbeya Med Res Programme, Natl Inst Med Res, Mbeya, Tanzania. [Meyerhans, Andreas] Univ Saarland, Inst Virol, D-6650 Homburg, Germany. [Singh, Mahavir] Lionex Diagnost & Therapeut, Braunschweig, Germany. [Boehme, Catharina] Fdn Innovat New Diagnost, Cointrin, Switzerland. RP Geldmacher, C (reprint author), Klinikum Ludwig Maximilians Univ, Dept Infect Dis & Trop Med, Leopoldsstr 5, D-80802 Munich, Germany. EM geldmacher@lrz.uni-muenchen.de RI Hoelscher, Michael/D-3436-2012; Meyerhans, Andreas/D-3382-2014 OI Meyerhans, Andreas/0000-0003-0620-5317 FU European Commission, Directorate General XII, International Cooperation-Developing Countries [ICA-CT-2002-10048] FX Financial support: European Commission, Directorate General XII, International Cooperation-Developing Countries (grant ICA-CT-2002-10048 to M. H.). NR 39 TC 76 Z9 77 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2008 VL 198 IS 11 BP 1590 EP 1598 DI 10.1086/593017 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 374NY UT WOS:000261052200004 PM 19000013 ER PT J AU Dowd, KA Hershow, RC Yawetz, S LaRussa, P Diaz, C Landesman, SH Paul, ME Read, JS Lu, M Thomas, DL Netski, DM Ray, SC AF Dowd, Kimberly A. Hershow, Ronald C. Yawetz, Sigal LaRussa, Philip Diaz, Clemente Landesman, Sheldon H. Paul, Mary E. Read, Jennifer S. Lu, Ming Thomas, David L. Netski, Dale M. Ray, Stuart C. TI Maternal Neutralizing Antibody and Transmission of Hepatitis C Virus to Infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERINATAL TRANSMISSION; INFECTION; RESPONSES; PSEUDOPARTICLES; MOTHERS AB To determine whether lower levels of hepatitis C virus (HCV) specific neutralizing antibodies (nAb) are associated with an increased risk of mother-to-child transmission (MTCT) of HCV, HCV nAb titers were assessed in 63 mothers coinfected with HCV and human immunodeficiency virus (HIV) type 1. Of the mothers, 16 transmitted HCV to their infant, but no difference was detected between the ability of maternal plasma from transmitters and nontransmitters to neutralize heterologous HCV pseudoparticles (median nAb titer, 1: 125 vs. 1: 100; P = .23). In the setting of HIV/HCV coinfection, we found no evidence that HCV nAbs are associated with the prevention of MTCT of HCV. C1 [Dowd, Kimberly A.; Thomas, David L.; Netski, Dale M.; Ray, Stuart C.] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Thomas, David L.] Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Hershow, Ronald C.] Univ Illinois, Sch Publ Hlth, Chicago, IL USA. [Yawetz, Sigal] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Yawetz, Sigal] Harvard Univ, Sch Med, Boston, MA USA. [LaRussa, Philip] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Landesman, Sheldon H.] Brookdale Hosp, Dept Med, Brooklyn, NY USA. [Diaz, Clemente] Univ Puerto Rico, San Juan, PR 00936 USA. [Paul, Mary E.] Baylor Coll Med, Houston, TX 77030 USA. RP Ray, SC (reprint author), Johns Hopkins Univ, Sch Med, 855 N Wolfe St,Suite 530, Baltimore, MD 21205 USA. EM sray@jhmi.edu RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU National Institutes of Health [DK-068555] FX Financial support: National Institutes of Health (grant DK-068555 to D.M.N.). Funding sources for the Women and Infants Transmission Study are listed at the end of the text, along with additional members of the study group. NR 15 TC 14 Z9 14 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 1 PY 2008 VL 198 IS 11 BP 1651 EP 1655 DI 10.1086/593067 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 374NY UT WOS:000261052200011 PM 18928374 ER PT J AU Couce, ML Boveda, MD Castineiras, DE Corrales, FJ Mora, MI Fraga, JM Mudd, SH AF Couce, M. L. Boveda, M. D. Castineiras, D. E. Corrales, F. J. Mora, M. I. Fraga, J. M. Mudd, S. H. TI Hypermethioninaemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency: Diagnosis in an expanded neonatal screening programme SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article AB The Expanded Newborn Screening Program (MS/MS) in the region of Galicia (NW Spain) was initiated in 2000 and includes the measurement of methionine levels in dried blood spots. Between June 2000 and June 2007, 140 818 newborns were analysed, and six cases of persistent hypermethioninaemia were detected: one homocystinuria due to cystathionine beta-synthase (CbS) deficiency, and five methionine adenosyltransferase I/III (MAT I/III) deficiencies. The five cases of MAT I/III deficiency represent an incidence of 1/28 163 newborns. In these five patients, methionine levels in dried blood spots ranged from 50 to 147 mu mol/L. At confirmation of the persistence of the hypermethioninaemia in a subsequent plasma sample, plasma methionine concentrations were moderately elevated in 4 of the 5 patients (mean 256 mmol/L), while total homocysteine (tHcy) was normal; the remaining patient showed plasma methionine of 573 mu mol/L and tHcy of 22.8 mu mol/L. All five patients were heterozygous for the same dominant mutation, R264H in the MAT1A gene. With a diet not exceeding recommended protein requirements for their age, all patients maintained methionine levels below 300 mu mol/L. Currently, with a mean of 2.5 years since diagnosis, the patients are asymptomatic and show developmental quotients within the normal range. Our results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency in the Galician neonatal population, indicating a need for further studies to evaluate the impact of persistent isolated hypermethioninaemia in neonatal screening programmes. C1 [Boveda, M. D.] Hosp Clin Univ, Lab Metabolopatias, Santiago De Compostela 15706, Spain. [Couce, M. L.; Boveda, M. D.; Castineiras, D. E.; Fraga, J. M.] Hosp Clin Univ, Dept Pediat, Unidad Trastornos Metab, Santiago De Compostela 15706, Spain. [Corrales, F. J.; Mora, M. I.] Univ Navarra, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain. [Mudd, S. H.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Boveda, MD (reprint author), Hosp Clin Univ, Lab Metabolopatias, Planta 0,Trav Choupana S-N, Santiago De Compostela 15706, Spain. EM maria.boveda.fontan@sergas.es OI fraga, jose m/0000-0001-8897-3621 NR 26 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD DEC PY 2008 VL 31 SU 2 BP S233 EP S239 DI 10.1007/s10545-008-0811-3 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA V20QV UT WOS:000208155400009 PM 18500573 ER PT J AU Hjalgrim, H Engels, EA AF Hjalgrim, H. Engels, E. A. TI Infectious aetiology of Hodgkin and non-Hodgkin lymphomas: a review of the epidemiological evidence SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE epidemiology; Epstein-Barr virus; hepatitis C; HIV; infections; malignant lymphomas ID EPSTEIN-BARR-VIRUS; HEPATITIS-C VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; CHILDHOOD SOCIAL-ENVIRONMENT; T-CELL LYMPHOMAS; HLA-CLASS-I; KAPOSIS-SARCOMA; BURKITTS-LYMPHOMA; UNITED-STATES; YOUNG-ADULTS AB Lymphomas constitute a heterogeneous group of malignant disorders with different clinical behaviours, pathological features and epidemiological characteristics. For some lymphoma subtypes, epidemiological evidence has long pointed to infectious aetiologies. A subset of Hodgkin lymphoma is strongly linked to Epstein-Barr virus (EBV) infection. In addition, infectious agents can directly infect and transform lymphocytes (e.g. EBV, human herpesvirus 8), induce immunosuppression (human immunodeficiency virus), or cause chronic immune stimulation (hepatitis C virus, Helicobacter pylori), all of which may play a role in the development of various non-Hodgkin lymphoma subtypes. Here, we review the epidemiological evidence linking infections with malignant lymphoma. C1 [Hjalgrim, H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Engels, E. A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Hjalgrim, H (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen, Denmark. EM hhj@ssi.dk FU Intramural NIH HHS NR 70 TC 76 Z9 79 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD DEC PY 2008 VL 264 IS 6 BP 537 EP 548 DI 10.1111/j.1365-2796.2008.02031.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 371IA UT WOS:000260823800005 PM 19017178 ER PT J AU Pietroni, V Di Giorgi, S Paradisi, A Ahvazi, B Candi, E Melino, G AF Pietroni, Valentina Di Giorgi, Sabrina Paradisi, Andrea Ahvazi, Bijan Candi, Eleonora Melino, Gerry TI Inactive and Highly Active, Proteolytically Processed Transglutaminase-5 in Epithelial Cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID COAGULATION FACTOR-XIII; CROSS-LINKING ENZYMES; EPIDERMAL-KERATINOCYTES; GUANINE-NUCLEOTIDES; STRUCTURAL BASIS; IN-VITRO; EXPRESSION; IDENTIFICATION; ACTIVATION; ENVELOPE AB Transglutaminases (TGs) are Ca2+ -dependent enzymes capable of catalyzing transamidation of glutamine residues to form intermolecular isopeptide bonds. These enzymes are involved in various biological phenomena, including blood coagulation, wound healing, cell death, tissue repair, and terminal differentiation of keratinocytes. Among the TG-family members, TG5 is one of the latest identified enzymes and therefore the less characterized at the functional level. In this work, we reported that TG5 is proteolytically processed in the baculovirus expression system and in mammal epithelial cells. Similar to other members of the TG family-TG1, TG3, and factor XIIIa -, TG5 full-length enzyme has very low enzymatic activity, while the 53-kDa proteolytically processed form is highly active. C1 [Pietroni, Valentina; Di Giorgi, Sabrina; Paradisi, Andrea; Candi, Eleonora; Melino, Gerry] Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Biochem Lab, I-00133 Rome, Italy. [Ahvazi, Bijan] NIAMS, Xray Crystallog Facil, Off Sci & Technol, NIH, Bethesda, MD USA. RP Candi, E (reprint author), Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, Biochem Lab, Via Tor Vergata 135, I-00133 Rome, Italy. EM candi@uniroma2.it; melino@uniroma2.it FU Telethon [GGPO6048, FIRB-2001-RBNE01KJHT_004 (Marino)]; PRIN 2006; MIUR, PRIN, MinSan; NIH-NIAMS FX This work was supported by grants from Telethon (GGPO6048) to EC; FIRB-2001-RBNE01KJHT_004 (Marino) to GM; PRIN 2006 to EC; and MIUR, PRIN, MinSan to GM. This work was also supported partially by the Intramural Research Program of the NIH-NIAMS to BA. We are indebted to Dr Karen Boeshans for editorial support of this paper. NR 32 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2008 VL 128 IS 12 BP 2760 EP 2766 DI 10.1038/jid.2008.146 PG 7 WC Dermatology SC Dermatology GA 374RX UT WOS:000261062500005 PM 18509357 ER PT J AU Purdue, MP Freeman, LEB Anderson, WF Tucker, MA AF Purdue, Mark P. Freeman, Laura E. Beane Anderson, William F. Tucker, Margaret A. TI Recent Trends in Incidence of Cutaneous Melanoma among US Caucasian Young Adults SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID UNITED-STATES; MALIGNANT-MELANOMA; ADOLESCENTS; ATTITUDES; CANCER; RATES C1 [Purdue, Mark P.; Freeman, Laura E. Beane; Anderson, William F.; Tucker, Margaret A.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA. EM purduem@mail.nih.gov RI Tucker, Margaret/B-4297-2015; Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS [Z01 CP010183-05] NR 16 TC 139 Z9 141 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2008 VL 128 IS 12 BP 2905 EP 3908 DI 10.1038/jid.2008.159 PG 4 WC Dermatology SC Dermatology GA 374RX UT WOS:000261062500024 PM 18615112 ER PT J AU Thurber, KR Tycko, R AF Thurber, Kent R. Tycko, Robert TI Biomolecular solid state NMR with magic-angle spinning at 25 K SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Signal-to-noise; Amyloid structure; Villin HP35; Spin-lattice relaxation; Paramagnetic relaxation; Dynamic nuclear polarization ID NUCLEAR-MAGNETIC-RESONANCE; OPTICALLY PUMPED NMR; ROTATING SOLIDS; CONFORMATIONAL DISTRIBUTIONS; MOLECULAR-STRUCTURE; LATTICE RELAXATION; VILLIN HEADPIECE; AMYLOID FIBRILS; QUANTUM-WELLS; HIV-1 GP120 AB A magic-angle spinning (MAS) probe has been constructed which allows the sample to be cooled with helium, while the MAS bearing and drive gases are nitrogen. The sample can be cooled to 25 K using roughly 3 L/h of liquid helium, while the 4-mm diameter rotor spins at 6.7 kHz with good stability (+/- 5 Hz) for many hours. Proton decoupling fields up to at least 130 kHz can be applied. This helium-cooled MAS probe enables a variety of one-dimensional and two-dimensional NMR experiments on biomolecular solids and other materials at low temperatures, with signal-to-noise proportional to 1/T. We show examples of low-temperature C-13 NMR data for two biomolecular samples, namely the peptide A beta(14-23) in the form of amyloid fibrils and the protein HP35 in frozen glycerol/water solution. Issues related to temperature calibration, spin-lattice relaxation at low temperatures, paramagnetic doping of frozen solutions, and C-13 MAS NMR linewidths are discussed. Published by Elsevier Inc. C1 [Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH) FX We thank Bernie Howder for machining many of the parts for the love-temperature MAS probe, David Callaway for providing the A beta14-23 fibril sample, and Wai-Ming Yau for synthesizing the HP35 protein. This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a component of the National Institutes of Health (NIH), and by a grant from the NIH Intramural AIDS Targeted Antiviral Program. NR 44 TC 62 Z9 62 U1 2 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD DEC PY 2008 VL 195 IS 2 BP 179 EP 186 DI 10.1016/j.jmr.2008.09.015 PG 8 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 374KZ UT WOS:000261043600008 PM 18922715 ER PT J AU Qin, SL Sui, YJ Murphey-Corb, MA Reinhart, TA AF Qin, Shulin Sui, Yongjun Murphey-Corb, Michael A. Reinhart, Todd A. TI Association between decreased CXCL12 and CCL25 expression and increased apoptosis in lymphoid tissues of cynomolgus macaques during SIV infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Symposium on Nonhuman Primate Models for Aids CY SEP 10-13, 2007 CL Monterey, CA DE activated caspase-3; apoptosis; chemokine; SIV ID IMMUNODEFICIENCY-VIRUS-INFECTION; RECEPTOR 9/TECK INTERACTION; CD4(+) T-CELLS; SIMIAN-IMMUNODEFICIENCY; DENDRITIC CELLS; CHEMOKINE; NODES; AIDS; PROGRESSION; INFLAMMATION AB Chemokines likely play multiple roles in HIV-1 and SIV pathogenesis. To examine potential associations between chemokine expression levels and apoptosis of cells in lymphoid tissues during SIV infection, we measured chemokine and cytokine mRNA levels in multiple lymphoid tissues compartments from uninfected and SIV-infected cynomolgus macaques (Macaca fascicularis). Real-time RT-PCR was used to measure host mRNA levels in macaque lymphoid tissues. Proliferating or apoptotic cells were identified in lymphoid tissues by immunohistochemistry. We found that CXCL12 and CCL25 mRNAs in SIV-infected lymphoid tissues were decreased and their levels were negatively correlated with the numbers of proliferating and apoptotic cells. In vitro analyses revealed that CXCL12 and CCL25 were capable of reducing apoptosis induced by SIV infection. These findings suggest that increased apoptosis in lymphoid tissues due to reduced levels of anti-apoptotic chemokines might be a mechanism that contributes to loss of immune function following pathogenic SIV infection. C1 [Qin, Shulin; Sui, Yongjun; Reinhart, Todd A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. [Sui, Yongjun] NCI, Vaccine Branch, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. [Murphey-Corb, Michael A.] Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Reinhart, TA (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, 606 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM reinhar@pitt.edu FU NIAID NIH HHS [R01 AI060422, AI060422] NR 34 TC 7 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD DEC PY 2008 VL 37 SU 2 BP 46 EP 54 DI 10.1111/j.1600-0684.2008.00327.x PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 397OK UT WOS:000262671800007 PM 19187430 ER PT J AU Bokhari, A Solomon, T Desai, S AF Bokhari, Abdullah A. B. Solomon, Tsione Desai, Sanjay A. TI Two Distinct Mechanisms of Transport Through the Plasmodial Surface Anion Channel SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE Plasmodial surface anion channel; Malaria; Plasmodium falciparum; Ion channel selectivity; Furosemide; Solute permeability; Erythrocyte; Antimalarial target ID RED-BLOOD-CELLS; FALCIPARUM-INFECTED ERYTHROCYTES; MALARIA PARASITE; OMPF PORIN; CONDUCTANCE; DANTROLENE; RESISTANCE; MEMBRANE; SUM AB The plasmodial surface anion channel (PSAC) is a voltage-dependent ion channel on erythrocytes infected with malaria parasites. To fulfill its presumed function in parasite nutrient acquisition, PSAC is permeant to a broad range of charged and uncharged solutes; it nevertheless excludes Na(+) as required to maintain erythrocyte osmotic stability in plasma. Another surprising property of PSAC is its small single-channel conductance (< 3 pS in isotonic Cl(-)) in spite of broad permeability to bulky solutes. While exploring the mechanisms underlying these properties, we recently identified interactions between permeating solutes and PSAC inhibitors that suggest the channel has more than one route for passage of solutes. Here, we explored this possibility with 22 structurally diverse solutes and found that each could be classified into one of two categories based on effects on inhibitor affinity, the temperature dependence of these effects and a clear pattern of behavior in permeant solute mixtures. The clear separation of these solutes into two discrete categories suggests two distinct mechanisms of transport through this channel. In contrast to most other broad-permeability channels, selectivity in PSAC appears to be complex and cannot be adequately explained by simple models that invoke sieving through rigid, noninteracting pores. C1 [Bokhari, Abdullah A. B.; Solomon, Tsione; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, S (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Room 3 W-01, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; Medicines for Malaria Venture FX We thank Wang Nguitragool and Ajay Pillai for helpful comments. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases and by the Medicines for Malaria Venture. NR 25 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD DEC PY 2008 VL 226 IS 1-3 BP 27 EP 34 DI 10.1007/s00232-008-9136-2 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 383DT UT WOS:000261655000004 PM 19050955 ER PT J AU Currey, KM Zielke, HR Khaitovich, P Nickel, B Kleinman, JE Hyde, TM Lipska, BK AF Currey, Kathleen M. Zielke, H. Ronald Khaitovich, Philipp Nickel, Birgit Kleinman, Joel E. Hyde, Thomas M. Lipska, Barbara K. TI International scope of the NICHD brain and tissue bank for developmental disorders SO JOURNAL OF NEURAL TRANSMISSION LA English DT Meeting Abstract CT BrainNet Europe 2nd International Conference on Human Brain Tissue Research CY DEC 10-12, 2008 CL Munich, GERMANY C1 [Currey, Kathleen M.; Zielke, H. Ronald] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Kleinman, Joel E.; Hyde, Thomas M.; Lipska, Barbara K.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 EI 1435-1463 J9 J NEURAL TRANSM JI J. Neural Transm. PD DEC PY 2008 VL 115 IS 12 BP 1728 EP 1728 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 376JQ UT WOS:000261180300061 ER PT J AU Dobolyi, A Bago, AG Seress, L Usdin, TB Palkovits, M AF Dobolyi, Arpad Bago, Attila G. Seress, Laszlo Usdin, Ted B. Palkovits, Miklos TI Parathyroid hormone 2 receptor in the human brain-a combined RT-PCR and fluorescent amplification immunocytochemistry study SO JOURNAL OF NEURAL TRANSMISSION LA English DT Meeting Abstract CT BrainNet Europe 2nd International Conference on Human Brain Tissue Research CY DEC 10-12, 2008 CL Munich, GERMANY C1 [Dobolyi, Arpad] Hungarian Acad Sci, Human Brain Tissue Bank, Budapest, Hungary. [Dobolyi, Arpad; Palkovits, Miklos] Hungarian Acad Sci, Neuromorphol & Neuroendocrine Res Lab, Budapest, Hungary. [Dobolyi, Arpad] Semmelweis Univ, H-1085 Budapest, Hungary. [Bago, Attila G.] Natl Inst Neurosurg, Budapest, Hungary. [Seress, Laszlo] Univ Pecs, Cent Electron Microscop Lab, Pecs, Hungary. [Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 2008 VL 115 IS 12 BP 1730 EP 1730 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 376JQ UT WOS:000261180300067 ER PT J AU Shaikh, AG Ramat, S Optican, LM Miura, K Leigh, RJ Zee, DS AF Shaikh, Asef G. Ramat, Stefano Optican, Lance M. Miura, Kenichiro Leigh, R. John Zee, David S. TI Saccadic Burst Cell Membrane Dysfunction Is Responsible for Saccadic Oscillations SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID THALAMIC RELAY NEURONS; TRANSCRANIAL MAGNETIC STIMULATION; ACTIVATED CATION CURRENT; EYE-MOVEMENTS; OCULAR OSCILLATIONS; OPSOCLONUS; EXCITABILITY; DISORDERS; SYSTEM; PHYSIOLOGY AB Saccadic oscillations threaten clear vision by causing image motion on the retina. They are either purely horizontal (ocular flutter) or multidimensional (opsoclonus). We propose that ion channel dysfunction in the burst cell membrane is the underlying abnormality. We have tested this hypothesis by simulating a neuromimetic computational model of the burst neurons. This biologically realistic model mimics the physiologic properties and anatomic connections in the brainstem saccade generator. A rebound firing after sustained inhibition, called post-inhibitory rebound (PIR), and reciprocal inhibition between premotor saccadic burst neurons are the key features of this conceptual scheme. PIR and reciprocal inhibition make the circuits that generate the saccadic burst inherently unstable and can lead to oscillations unless stabilized by external inhibition. Our Simulations suggest that alterations in membrane properties that lead to an increase in PIR, a reduction in external glycinergic inhibition, or both can cause saccadic oscillations. C1 [Shaikh, Asef G.; Zee, David S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Ramat, Stefano] Univ Pavia, I-27100 Pavia, Italy. [Optican, Lance M.] NEI, NIH, Bethesda, MD 20892 USA. [Leigh, R. John] Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. [Miura, Kenichiro] Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Kyoto, Japan. RP Shaikh, AG (reprint author), Johns Hopkins Univ, Dept Neurol, 600 N Wolfe St,Path 2-210, Baltimore, MD 21287 USA. EM ashaikh@dizzy.med.jhu.edu RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU National Institutes of Health [EY01849, EY06717]; Department of Veterans Affairs; Intramural Research Program of the National Eye Institute (National Institutes of Health, Department of Health and Human Services) FX The work was Supported by grants from the National Institutes of Health (EY01849 and EY06717). Department of Veterans Affairs, Intramural Research Program of the National Eye Institute (National Institutes of Health, Department of Health and Human Services). Gustavus and Louise Pfeiffer Foundation and Ataxia Telangiectasia Children's Project. NR 42 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2008 VL 28 IS 4 BP 329 EP 336 PG 8 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 380BI UT WOS:000261440100015 PM 19145136 ER PT J AU Lathia, JD Mattson, MP Cheng, A AF Lathia, Justin D. Mattson, Mark P. Cheng, Aiwu TI Notch: from neural development to neurological disorders SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE brain ischemia and neurodegeneration; development; neural stem cells; notch; synaptic plasticity ID FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; MOUSE CORTICAL NEUROGENESIS; TERM SYNAPTIC PLASTICITY; TUMOR-INITIATING CELLS; RADIAL GLIAL-CELLS; STEM-LIKE CELLS; SUBVENTRICULAR ZONE; IN-VITRO; ASYMMETRIC DISTRIBUTION AB Notch is an integral membrane protein that functions as receptor for ligands such as jagged and delta that are associated with the surface of neighboring cells. Upon ligand binding, notch is proteolytically cleaved within its transmembrane domain by presenilin-1 (the enzymatic component of the gamma-secretase complex) resulting in the release of a notch intracellular domain which translocates to the nucleus where it regulates gene expression. Notch signaling plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. Notch is also present in post-mitotic neurons in the adult CNS wherein its activation influences structural and functional plasticity including processes involved in learning and memory. Recent findings suggest that notch signaling in neurons, glia, and NSCs may be involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Studies of animal models suggest the potential of agents that target notch signaling as therapeutic interventions for several different CNS disorders. C1 [Cheng, Aiwu] Natl Inst Aging Intramural Res Program, Lab Neurosciences, GRC, Baltimore, MD 21224 USA. [Lathia, Justin D.] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Lathia, Justin D.] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 1QP, England. RP Cheng, A (reprint author), Natl Inst Aging Intramural Res Program, Lab Neurosciences, GRC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM chengai@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU NIA Intramural Research Program; NIH-Cambridge Graduate Partnership Program FX This work was supported by the NIA Intramural Research Program. J.D.L. is supported by the NIH-Cambridge Graduate Partnership Program. NR 130 TC 82 Z9 88 U1 2 U2 13 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 DEC PY 2008 VL 107 IS 6 BP 1471 EP 1481 DI 10.1111/j.1471-4159.2008.05715.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 376TF UT WOS:000261205200001 PM 19094054 ER PT J AU Yin, P Mishkin, M Sutter, M Fritz, JB AF Yin, Pingbo Mishkin, Mortimer Sutter, Mitchell Fritz, Jonathan B. TI Early Stages of Melody Processing: Stimulus-Sequence and Task-Dependent Neuronal Activity in Monkey Auditory Cortical Fields A1 and R SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID SINGLE-UNIT-ACTIVITY; SPECTROTEMPORAL RECEPTIVE-FIELDS; INTERMODAL SELECTIVE ATTENTION; RHESUS-MONKEY; STREAM SEGREGATION; MACAQUE MONKEYS; MULTISENSORY CONVERGENCE; BEHAVIORAL DEPENDENCY; PHYSIOLOGICAL MEMORY; SENSITIVE NEURONS AB To explore the effects of acoustic and behavioral context on neuronal responses in the core of auditory cortex (fields A1 and R), two monkeys were trained on a go/no-go discrimination task in which they learned to respond selectively to a four-note target (S+) melody and withhold response to a variety of other nontarget (S-) sounds. We analyzed evoked activity from 683 units in A1/R of the trained monkeys during task performance and from 125 units in A1/R of two naive monkeys. We characterized two broad classes of neural activity that were modulated by task performance. Class I consisted of tone-sequence-sensitive enhancement and suppression responses. Enhanced or suppressed responses to specific tonal components of the S+ melody were frequently observed in trained monkeys, but enhanced responses were rarely seen in naive monkeys. Both facilitatory and suppressive responses in the trained monkeys showed a temporal pattern different from that observed in naive monkeys. Class II consisted of nonacoustic activity, characterized by a task-related component that correlated with bar release, the behavioral response leading to reward. We observed a significantly higher percentage of both Class I and Class II neurons in field R than in A1. Class I responses may help encode a long-term representation of the behaviorally salient target melody. Class II activity may reflect a variety of nonacoustic influences, such as attention, reward expectancy, somatosensory inputs, and/or motor set and may help link auditory perception and behavioral response. Both types of neuronal activity are likely to contribute to the performance of the auditory task. C1 [Yin, Pingbo; Mishkin, Mortimer; Fritz, Jonathan B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Yin, Pingbo; Sutter, Mitchell] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. RP Fritz, JB (reprint author), Univ Maryland, Syst Res Inst, Ctr Acoust & Auditory Res, College Pk, MD 20742 USA. EM ripple@isr.umd.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD); Intramural Research Program; National Institute of Mental Health; National Institutes of Health FX Much of this research was conducted while P. B. Yin and J. B. Fritz were supported by postdoctoral fellowships from the Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and it was continued and completed with the assistance of additional separate grant support to J. B. Fritz, to M. Sutter, and to S. Shamma from the National Institute on Deafness and Other Communication Disorders (NIDCD). NR 142 TC 24 Z9 24 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2008 VL 100 IS 6 BP 3009 EP 3029 DI 10.1152/jn.00828.2007 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 380EQ UT WOS:000261449400004 PM 18842950 ER PT J AU Song, DK Lonser, RR AF Song, Debbie K. Lonser, Russell R. TI Pathological satiety caused by brainstem hemangioblastoma Case report SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE appetite disturbance; brainstem; developmental arrest; hemangioblastoma; satiety; von Hippell-Lindau disease ID CENTRAL-NERVOUS-SYSTEM; HIPPEL-LINDAU-DISEASE; ANOREXIA-NERVOSA; FOOD-INTAKE; NATURAL-HISTORY AB Because of the multiplicity and saltatory growth pattern associated with central nervous system hemangioblastomas in von Hippel-Lindau (VHL) disease, resection of individual tumors is usually reserved until symptoms occur, to avoid unnecessary surgery over the lifetime of a patient. Brainstem hemangioblastomas in VHL typically cause lower cranial nerve dysfunction, long-tract signs, sensory impairment, and gait abnormalities. The authors report oil a 16-year-old girl with VHL who presented with abnormal early satiety resulting in growth and developmental arrest associated with a growing obex hemangioblastoma. Tumor resection resulted in restoration of appetite, with rapid weight gain, growth in statute, and onset of menses. These findings indicate that caudal brainstem-mediated mechanisms have a profound effect on satiety. Moreover, brainstem hemangioblastomas may present with abnormalities ill satiety and feeding that call be effectively reversed with resection. (DOI: 10.3171/PED.2008.2.12.397) C1 [Song, Debbie K.; Lonser, Russell R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Song, Debbie K.] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov FU Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program, National Institute of Neurological Disorders and Stroke, National Institutes of Health. The funding organization did not participate in the design and conduct of the study: collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. NR 17 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROS-PEDIATR JI J. Neurosurg.-Pediatr. PD DEC PY 2008 VL 2 IS 6 BP 397 EP 401 DI 10.3171/PED.2008.2.12.397 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 376TJ UT WOS:000261205600005 PM 19035684 ER PT J AU Wright, EJ Nunn, M Joseph, J Robertson, K Lal, L Brew, BJ AF Wright, Edwina J. Nunn, Michael Joseph, Jeymohan Robertson, Kevin Lal, Luxshimi Brew, Bruce J. TI NeuroAIDS in the Asia Pacific Region SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE Asia Pacific; Clade; neuroAIDS; HAD; HIV; host genotype ID CENTRAL-NERVOUS-SYSTEM; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 INFECTION; SOUTH-AFRICA; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; NEURAL PROGENITORS; SUBTYPE-C; CHILDREN; RISK AB Over 8.3 million people living in the Asia Pacific region are human immunodeficiency virus (HIV) positive and up to 40% of these individuals have had prior acquired immunodeficiency syndrome (AIDS) illnesses. Recently endeavors have been made to better characterize the burden of HIV-related neurological disease within the Asia Pacific region and, with this in mind, the NeuroAIDS in Asia and the Pacific Rim workshop was held in Sydney, Australia, as an affiliated event of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention. The workshop was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) of the United States National Institutes of Health and the Australian Government overseas AID program, AusAID. HIV neurologists, infectious disease physicians, pediatricians, psychiatrists, immunologists, virologists,and researchers from 12 countries of the Asia Pacific region (including Australia), the United States, and the United Kingdom attended the meeting. A broad range of topics were addressed, including common HIV neurological disorders, the lack of diagnostic, management, and research infrastructure, central nervous system (CNS) immune restoration disease, pediatric neuroAIDS, and current clinical and laboratory research projects being undertaken within the Asia Pacific region. Journal of NeuroVirology (2008) 14, 465-473. C1 [Wright, Edwina J.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Wright, Edwina J.; Lal, Luxshimi] Burnet Inst, Dept Neurovirol, Melbourne, Vic, Australia. [Wright, Edwina J.; Lal, Luxshimi] Monash Univ, Dept Med, Clayton, Vic, Australia. [Nunn, Michael] Salk Inst, San Diego, CA 92186 USA. [Joseph, Jeymohan] NIMH, NIH, Bethesda, MD 20892 USA. [Robertson, Kevin] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Brew, Bruce J.] St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia. [Brew, Bruce J.] Univ New S Wales, Dept Med, Sydney, NSW, Australia. RP Wright, EJ (reprint author), Alfred Hosp, Dept Infect Dis, Commercial Rd Melbourne, Melbourne, Vic 3004, Australia. EM e.wright@alfred.org.au RI Brew, Bruce/J-6513-2012 NR 41 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2008 VL 14 IS 6 BP 465 EP 473 DI 10.1080/13550280802235932 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 400ES UT WOS:000262851400001 PM 19031289 ER PT J AU Lewis, SD Butchi, NB Khaleduzzaman, M Morgan, TW Du, M Pourciau, S Baker, DG Akira, S Peterson, KE AF Lewis, Stephanie D. Butchi, Niranjan B. Khaleduzzaman, Mohammed Morgan, Tim W. Du, Min Pourciau, Susan Baker, David G. Akira, Shizuo Peterson, Karin E. TI Toll-like receptor 7 is not necessary for retroviral neuropathogenesis but does contribute to virus-induced neuroinflammation SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE retrovirus; Toll-like receptor 7; chemokines; tumor necrosis factor; brain; mouse ID PLASMACYTOID DENDRITIC CELLS; POLYTROPIC MURINE RETROVIRUSES; INTERFERON-PRODUCING CELLS; CHEMOKINE RESPONSES; LETHAL ENCEPHALITIS; ENVELOPE PROTEIN; BACTERIAL-DNA; RECOGNITION; INFECTION; BRAIN AB Toll-like receptor 7 (TLR7) recognizes guanidine-rich single-stranded (ss) viral RNA and is an important mediator of peripheral immune responses to several ssRNA viruses. However, the role that TLR7 plays in regulating the innate immune response to ssRNA virus infections in specific organs is not as clear. This is particularly true in the central nervous system (CNS) where microglia and astrocytes are often the first cells responding to virus infection instead of dendritic cells. In the current study, we examined the mechanism by which TLR7 contributes to ssRNA virus-induced neuroinflammation using a mouse model of polytropic retrovirus infection. The authors found that TLR7 was necessary for the early production of certain cytokines and chemokines, including CCL2 and tumor necrosis factor (TNF) and was also involved in the early activation of astrocytes. However, TLR7 was not necessary for cytokine production and astrocyte activation at later stages of infection and did not alter viral pathogenesis or viral replication in the brain. This suggests that other pathogen recognition receptors may be able to compensate for the lack of TLR7 during retrovirus infection in the CNS. Journal of NeuroVirology (2008) 14, 492-502. C1 [Lewis, Stephanie D.; Butchi, Niranjan B.; Khaleduzzaman, Mohammed; Morgan, Tim W.; Du, Min; Pourciau, Susan; Baker, David G.; Peterson, Karin E.] Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. [Akira, Shizuo] Osaka Univ & Solut Oriented Res Sci & Technol, Res Inst Microbial Dis, Dept Host Def, Osaka, Japan. RP Peterson, KE (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM petersonka@niaid.nih.gov RI Akira, Shizuo/C-3134-2009; Peterson, Karin/D-1492-2016; OI Peterson, Karin/0000-0003-4177-7249; Khaledian, Hossein/0000-0002-4082-2987 FU National Institutes of Health [K22AI57118-2]; National Center for Research Resources [IP20RR020159] FX The authors would like to thank Marilyn Dietrich for her assistance with flow cytometry. This work was supported by grants from the National Institutes of Health (K22AI57118-2) and the National Center for Research Resources (IP20RR020159). NR 30 TC 13 Z9 13 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2008 VL 14 IS 6 BP 492 EP 502 DI 10.1080/13550280802345723 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 400ES UT WOS:000262851400005 PM 19016073 ER PT J AU Brown, AK Kimura, Y Zoghbi, SS Simeon, FG Liow, JS Kreisl, WC Tau, A Fujita, M Pike, VW Innis, RB AF Brown, Amira K. Kimura, Yasuyuki Zoghbi, Sami S. Simeon, Fabrice G. Liow, Jeih-San Kreisl, William C. Tau, Andrew Fujita, Masahiro Pike, Victor W. Innis, Robert B. TI Metabotropic Glutamate Subtype 5 Receptors Are Quantified in the Human Brain with a Novel Radioligand for PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE molecular imaging; glutamate neurotransmission; PET ID IN-VITRO; RADIOTRACERS; C-11-ABP688; TOMOGRAPHY; BINDING; LIGANDS AB We developed a radioligand, 3-fluoro-5-(2-(2-(18)F-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile ((18)F-SP203), for metabotropic glutamate subtype 5 (mGluR5) receptors that showed both promising (high specific binding) and problematic (defluorination) imaging characteristics in animals. The purposes of this initial evaluation in human subjects were to determine whether (18)F-SP203 is defluorinated in vivo (as measured by uptake of radioactivity in the skull) and to determine whether the uptake in the brain can be quantified as distribution volume relative to concentrations of (18)F-SP203 in plasma. Methods: Seven healthy subjects were injected with (18)F-SP203 (323 +/- 87 MBq) and scanned over 5h, with rest periods outside the camera. The concentrations of (18)F-SP203, separated from radiometabolites, were measured in arterial plasma. Results: The skull was difficult to visualize on PET images in the initial 2 h, because of high radioactivity in the brain. Although radioactivity in the skull and adjacent cortex showed some cross-contamination, the concentration of radioactivity in the skull was less than half of that in the adjacent cortex during the initial 2 h. Modeling of regional brain and plasma data showed that a 2-tissue-compartment model was superior to a 1-tissue-compartment model, consistent with measurable amounts of both receptor-specific and nonspecific binding. The concentrations of activity in the brain measured with PET were consistently greater than the modeled values at late but not early time points and may well have been caused by the slow accumulation of radiometabolites in the brain. To determine an adequate time for more accurate measurement of distribution volume, we selected a scan duration (i.e., 2 h) associated with maximal or near-maximal identifiability. Distribution volume was well identified (similar to 2%) by only 2 h (and even just 1) of image acquisition. Conclusion: This initial evaluation of (18)F-SP203 in healthy human subjects showed that defluorination is relatively small and that brain uptake can be robustly calculated as distribution volume. The values of distribution volume were well identified and had relatively small variation in this group of 7 subjects. These results suggest that (18)F-SP203 will have good sensitivity to measure mGluR5 receptors for both within-subject studies (e.g., receptor occupancy) and between-subject studies (e.g., patients vs. healthy subjects). C1 [Brown, Amira K.; Kimura, Yasuyuki; Zoghbi, Sami S.; Simeon, Fabrice G.; Liow, Jeih-San; Kreisl, William C.; Tau, Andrew; Fujita, Masahiro; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr,Room B2-B37, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Kimura, Yasuyuki/D-4459-2016 OI Kimura, Yasuyuki/0000-0002-7927-9483 FU Intramural Program of NIMH [Z01 MH-002795-04] FX We thank Maria Desiree Ferraris Araneta, Amanda Farris, Ed Tuan, Pavitra Kannan, and the staff of the PET department for successful completion of the studies, and we thank PMOD Technologies (Adliswil, Switzerland) for providing its image analysis and modeling software. This research was supported by the Intramural Program of NIMH (project Z01 MH-002795-04). NR 16 TC 39 Z9 39 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 DEC PY 2008 VL 49 IS 12 BP 2042 EP 2048 DI 10.2967/jnumed.108.056291 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 381KV UT WOS:000261535800028 PM 19038998 ER PT J AU Lichtenstein, AH Yetley, EA Lau, J AF Lichtenstein, Alice H. Yetley, Elizabeth A. Lau, Joseph TI Application of Systematic Review Methodology to the Field of Nutrition SO JOURNAL OF NUTRITION LA English DT Review ID RANDOMIZED CONTROLLED-TRIALS; CARDIOVASCULAR-DISEASE; PREVENTIVE-SERVICES; CONSORT STATEMENT; HEALTH CLAIMS; QUALITY; FOOD; SUPPLEMENTATION; RECOMMENDATIONS; METAANALYSES AB Systematic reviews represent a rigorous and transparent approach to synthesizing scientific evidence that minimizes bias. They evolved within the medical community to support development of clinical and public health practice guidelines, set research agendas, and formulate scientific consensus statements. The use of systematic reviews for nutrition-related topics is more recent. Systematic reviews provide independently conducted comprehensive and objective assessments of available information addressing precise questions. This approach to summarizing available data is a useful tool for identifying the state of science including knowledge gaps and associated research needs, supporting development of science-based recommendations and guidelines, and serving as the foundation for updates as new data emerge. Our objective is to describe the steps for performing systematic reviews and highlight areas unique to the discipline of nutrition that are important to consider in data assessment. The steps involved in generating systematic reviews include identifying staffing and planning for outside expert input, forming a research team, developing an analytic framework, developing and refining research questions, defining eligibility criteria, identifying search terms, screening abstracts according to eligibility criteria, retrieving articles for evaluation, constructing evidence and summary tables, assessing methodological quality and applicability, and synthesizing results including performing meta-analysis, if appropriate. Unique and at times challenging, nutrition-related considerations include baseline nutrient exposure, nutrient status, bioequivalence of bioactive compounds, bioavailability, multiple and interrelated biological functions, undefined nature of some interventions, and uncertainties in intake assessment. Systematic reviews are a valuable and independent component of decision-making processes by groups responsible for developing science-based recommendations and policies. J. Nutr. 138. 2297-2306, 2008. C1 [Lichtenstein, Alice H.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. [Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Lau, Joseph] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Tufts Evidence Based Practice Ctr, Boston, MA 02111 USA. RP Lichtenstein, AH (reprint author), Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA. EM alice.lichtenstein@tufts.edu FU Agency for Healthcare Research and Quality [290-02-0022]; U.S. Department of Health and Human Service; Office of Dietary Supplements; NIH FX Supported by Contract No. 290-02-0022 from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, with funding from the Office of Dietary Supplements, the NIH. The authors of this report are responsible for its content. Statements in the report should not be construed as an endorsement by the Agency for Healthcare Research and Quality, the NIH, or the U.S. Department of Health and Human Services. NR 45 TC 40 Z9 40 U1 2 U2 10 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD DEC PY 2008 VL 138 IS 12 BP 2297 EP 2306 DI 10.3945/jn.108.097154 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 374IZ UT WOS:000261038300002 PM 19022948 ER PT J AU Rapoport, SI AF Rapoport, Stanley I. TI Arachidonic Acid and the Brain SO JOURNAL OF NUTRITION LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; DOCOSAHEXAENOIC ACID; RAT-BRAIN; PHOSPHOLIPASE A(2); NUTRITIONAL DEPRIVATION; SIGNAL-TRANSDUCTION; FRONTAL-CORTEX; TURNOVER; N-3 AB Kinetic methods in unanesthetized rodents have shown that turnover rates of arachidonic acid (AA) and docosahexaenoic acid (DHA) in brain membrane phospholipids are rapid and energy consuming and that phospholipase A(2) (PLA(2)) and acyl-CoA synthetase enzymes that regulate turnover are specific for one or the other PUFA. Thus, AA turnover in brain phospholipids was reduced, and AA-selective cytosolic cPLA(2) or acyl-CoA synthetase, as well as cyclooxygenase (COX)-2, were downregulated in brains of rats given drugs effective against bipolar disorder, whereas DHA turnover and expression of DHA-selective calcium-independent iPLA(2) were unchanged. Additionally, the brain AA and DHA cascades can be altered reciprocally by dietary or genetic conditions. Thus, following 15 wk of dietary (n-3) PUFA deprivation, DHA loss from rat brain was slowed because of reduced iPLA(2) and COX-1 expression, whereas AA-selective cPLA(2), sPLA(2), and COX-2 were upregulated, as were AA and docosapentaenoic acid concentrations. Measured rates of AA and DHA incorporation into brain represent their respective rates of metabolic consumption, because these PUFA are not synthesized de novo or converted significantly from their precursors in brain. In healthy human volunteers, positron emission tomography (PET) was used to show that the brain consumes AA and DHA at respective rates of 17.8 and 4.6 mg/d, whereas in patients with Alzheimer disease, AA consumption is elevated. In the future, PET could be used to relate human brain rates of AA and DHA consumption to liver PUFA metabolism and dietary PUFA intake. J. Nutr. 138: 2515-2520, 2008. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM sir@helix.nih.gov FU Intramural NIH HHS NR 35 TC 71 Z9 73 U1 0 U2 6 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2008 VL 138 IS 12 BP 2515 EP 2520 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 374IZ UT WOS:000261038300035 PM 19022981 ER PT J AU Miller, S Tudor, C Thorsten, V Nyima Sonam Droyoung Wright, L Varner, M AF Miller, Suellen Tudor, Carrie Thorsten, Vanessa Nyima Sonam Droyoung Wright, Linda Varner, Michael TI Comparison of maternal and newborn outcomes of Tibetan and Han Chinese delivering in Lhasa, Tibet SO JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH LA English DT Article DE gestational hypertension; high altitude; low birthweight; postpartum hemorrhage; pre-eclampsia; small for gestational age; Tibet ID INTRAUTERINE GROWTH RESTRICTION; PREGNANCY-INDUCED HYPERTENSION; HIGH-ALTITUDE; BIRTH-WEIGHT; OXYGEN-TRANSPORT; FETAL-GROWTH; PREECLAMPSIA; COMMUNITIES; PROTECTION; COLORADO AB Aim: To compare maternal and neonatal outcomes of Tibetan and Han Chinese women delivering vaginally at high altitude (3650 meters) in Lhasa, Tibet Autonomous Region, People's Republic of China. Method: Comparative analysis of data from a prospective observational study of Tibetan (n = 938) and Han Chinese (n = 146) women delivering at three hospitals between January 2004 and May 2005. Results: Han Chinese women had higher rates of pre-eclampsia/gestational hypertension than Tibetan women, (10.3% vs 5.9%, P = 0.04). There was no difference in rates of postpartum hemorrhage between Tibetan and Han women (12.8% vs 17.1%, P = 0.15). Han newborns weighed significantly less than Tibetan newborns (P < 0.01), and were twice as likely to be small for gestational age, (24.5% vs 11.6%, P < 0.01). Tibetan newborns were less likely to have poor neonatal outcomes than Han newborns (P < 0.01). Conclusion: In high altitude deliveries in Tibet, adverse outcomes were significantly more common among Han Chinese. C1 [Miller, Suellen] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Bixby Ctr Global Reprod Hlth, San Francisco, CA 94105 USA. [Thorsten, Vanessa] RTI Int, Res Triangle Pk, NC USA. [Nyima] Lhasa Municipal Hosp, Womens Div, Lhasa, Peoples R China. [Sonam] Mentsikhang Tradit Tibetan Med & Astrol Hosp, Womens Div, Lhasa, Peoples R China. [Droyoung] Lhasa Maternal Child Hlth Hosp, Womens Div, Lhasa, Peoples R China. [Wright, Linda] NICHHD, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. [Varner, Michael] Univ Utah, Sch Med, Salt Lake City, UT USA. RP Miller, S (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Bixby Ctr Global Reprod Hlth, 50 Beale St,Suite 1200, San Francisco, CA 94105 USA. EM suellenmiller@gmail.com RI Varner, Michael/K-9890-2013 OI , Carrie/0000-0003-4502-309X; Varner, Michael/0000-0001-9455-3973 FU National Institute for Child Health and Human Development (NICHD) [U01-HD40613]; Bill and Melinda Gates Foundation; Mentzikhang Traditional Tibetan Medicine and Astrology Hospital FX This study is part of the Global Network for Women's and Children's Health Research supported by the National Institute for Child Health and Human Development (NICHD) (grant U01-HD40613) and the Bill and Melinda Gates Foundation.; The authors gratefully acknowledge Ngawang Drolma, TAR Health Bureau and Dr Dromdul, Director of the Mentzikhang Traditional Tibetan Medicine and Astrology Hospital for their continued support and assistance to make this project possible. The authors are also indebted to the staff at the three project hospitals in Lhasa: Mentzikhang Traditional Tibetan Medicine and Astrology Hospital, Lhasa Municipal Hospital and the Lhasa Maternal and Child Health Hospital for their work and dedication to this project. NR 27 TC 5 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1341-8076 J9 J OBSTET GYNAECOL RE JI J. Obstet. Gynaecol. Res. PD DEC PY 2008 VL 34 IS 6 BP 986 EP 993 DI 10.1111/j.1447-0756.2008.00804.x PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367IB UT WOS:000260544600011 PM 19012697 ER PT J AU Wiener, L Ballard, E Brennan, T Haven, B Martinez, P Pao, M AF Wiener, Lori Ballard, Elizabeth Brennan, Tara Haven, Battles Martinez, Pedro Pao, Maryland TI How I Wish to be Remembered: The Use of an Advance Care Planning Document in Adolescent and Young Adult Populations SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PALLIATIVE CARE; CHILDREN; COMMUNICATION; DIRECTIVES; CANCER; DEATH; LIFE; END AB Background: Discussing end-of-life (EOL) issues is difficult with any population. These conversations are even more challenging with adolescents and young adults due to the poignancy of the situation and the need for developmentally appropriate language. Objective: To explore whether adolescents and young adults living with a life-limiting illness find it acceptable and helpful to have a planning document to share their wishes and thoughts regarding EOL care. If so, to learn about specific concerns adolescents and young adults feel are important to include in such a document. Methods: Adolescents and young adults with metastatic cancer or pediatric human immunodeficiency virus (HIV)-1 infection were presented Five Wishes, an advance directive document for adults. Each participant was asked to critically evaluate each wish in terms of whether the concepts within were considered (1) appropriate to ask individuals the participant's age; (2) helpful for other people the participant's age to think about; (3) helpful to the participant to think about; (4) stressful to contemplate. Participants were also asked to suggest modifications and additions to the document. Results: Twenty patients completed the survey. Ninety-five percent of the participants reported that an advance directive like Five Wishes would be "helpful" or "very helpful" to themselves, 90% stated that the document would be helpful to others, and no patients found talking about the issues in Five Wishes "stressful" or "very stressful." Participants were more interested in items concerning how they wanted to be treated and remembered than items concerning medical decision-making. Conclusions: An advance care planning document may be appropriate and helpful for adolescents and young adults living with a serious illness. Future research should further validate the preferences identified by participants and explore whether an age-appropriate document can improve communication with family and staff in EOL care. C1 [Wiener, Lori; Brennan, Tara; Haven, Battles] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ballard, Elizabeth; Martinez, Pedro; Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA. RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr,Room 1-6466, Bethesda, MD 20892 USA. EM wienerl@mail.nih.gov FU Center for Cancer Research; National Cancer Institute; National Institute of Mental Health FX The opinions expressed in the article are the views of the authors and do not necessarily reflect the views of the Department of Health and Human Services or the United States government. NR 15 TC 41 Z9 41 U1 1 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD DEC PY 2008 VL 11 IS 10 BP 1309 EP 1313 DI 10.1089/jpm.2008.0126 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 389IK UT WOS:000262085900009 PM 19115889 ER PT J AU Shively, SB Beltaifa, S Gehrs, B Duong, H Smith, J Edwards, NA Lonser, RR Raffeld, M Vortmeyer, AO AF Shively, S. B. Beltaifa, S. Gehrs, B. Duong, H. Smith, J. Edwards, N. A. Lonser, R. R. Raffeld, M. Vortmeyer, A. O. TI Protracted haemangioblastic proliferation and differentiation in von Hippel-Lindau disease SO JOURNAL OF PATHOLOGY LA English DT Article DE VHL; haemangioblastoma; HIF1 alpha; HIF2 alpha; VEGF; von Hippel-Lindau; neoplasia; development ID CEREBELLAR HEMANGIOBLASTOMA; RETICULAR VARIANTS; BLOOD-VESSELS; STROMAL CELLS; GENE; TUMORIGENESIS; HISTOGENESIS; PRECURSOR; BRAIN; TUMOR AB Von Hippel-Lindau (VHL) disease is caused by germline mutation of the VHL tumour suppressor gene. Patients frequently develop multiple nervous system tumours, denominated haemangioblastomas. Analysis of affected autopsy tissues suggests that tumourigenesis propagates from developmentally arrested, embryonic cells and progresses with consistent architectural, cytological, and molecular sequences similar to haemangioblastic formation and differentiation in the embryo. In this study, we analysed 156 nervous system tumours, 139 of which had been surgically resected from 83 VHL patients. We demonstrate that large tumours consistently contain epithelioid components characteristic of haemangioblastic differentiation in comparison to small tumours that solely display a poorly differentiated, mesenchymal structure. We further show exclusive activation of HIF2 alpha in both small mesenchymal tumours and the mesenchymal component of large tumours, whereas activation of HIF1 alpha is associated with epithelioid structure. We also show that the MIBI proliferative index is variably increased in the epithelioid component of large tumours, with extramedullary haematopoiesis foci within the epithelioid component at 100%. These data provide compelling evidence that nervous system tumourigenesis in VHL disease represents a protracted process of haemangioblastic proliferation and differentiation that parallels haemangioblastic formation and differentiation in the embryo. Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Shively, S. B.; Duong, H.; Smith, J.; Edwards, N. A.; Lonser, R. R.; Raffeld, M.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Shively, S. B.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Beltaifa, S.; Gehrs, B.; Raffeld, M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Vortmeyer, AO (reprint author), Yale Univ, Sch Med, Dept Pathol, 416A Lauder Hall,310 Cedar St, New Haven, CT 06520 USA. EM alexander.vortmeyer@yale.edu FU NIH FX This research was supported, in part, by the Intramural Research Program of the NIH. SB Shively is a doctoral student in the Molecular and Cellular Oncology Program of the Institute for Biomedical Sciences at George Washington University and the Graduate Partnerships Program at the NIH. This work is from a dissertation to be presented to George Washington University in partial fulfilment of the requirements for the PhD degree. We are grateful to Cynthia Harris for skilful immunohistochemistry preparation; to Willie Young, Jim Rainey, and David Kleiner at Autopsy Service, Laboratory of Pathology, NCI; and to Travis Moncrief for work on the illustrations. NR 27 TC 13 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD DEC PY 2008 VL 216 IS 4 BP 514 EP 520 DI 10.1002/path.2435 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 381BG UT WOS:000261509200014 PM 18836991 ER PT J AU Scheinberg, P Wu, CO Nunez, O Young, NS AF Scheinberg, Phillip Wu, Colin O. Nunez, Olga Young, Neal S. TI Long-Term Outcome of Pediatric Patients with Severe Aplastic Anemia Treated with Antithymocyte Globulin and Cyclosporine SO JOURNAL OF PEDIATRICS LA English DT Article ID BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; SAA-WORKING-PARTY; IMMUNOSUPPRESSIVE THERAPY; UNRELATED DONORS; CHILDREN; MUTATIONS; EXPERIENCE; FAILURE; DISEASE AB Objective To determine the long-term outcomes in children with severe aplastic anemia (SAA) treated with antithymocyte globulin (ATG) and cyclosporine (CsA) through a retrospective analysis of the pediatric patients treated at our institution in all protocols that included horse ATG (h-ATG) and CsA. Study design Between 1989 and 2006, a total of 406 patients. 20% of whom were children under age 18 years, received an initial course of immunosuppressive therapy (IST) at our institution. Here we report the outcome of 77 children who were treated with all h-ATG plus CsA-based regimen during this period. Results The overall response rate at 6 months was 74% (57/77); the cumulative incidence. of relapse at 10 years was 33%. and the median time to relapse was 558 days. The cumulative incidence of evolution after IST was 8.5%; all 3 such events occurred in partial responders. Overall, there were 13 deaths (17%). with 4 occurring within the 3 months after IST in patients who had a pretreatment absolute neutrophil count of < 100/mu L and the other 9 occurring more than 6 months after initiation of IST. The median time to death was 570 days. The overall 10-year survival for the entire cohort was 80%; long-term survival in the children who responded to IST was 89%. Conclusions The long-term survival in pediatric patients who respond to IST is excellent, at about 90%. IST remains a good alternative in pediatric patients who lack an HLA-matched sibling donor and should be offered as initial therapy before possible hematopoietic stem cell transplantation from an unrelated donor. (J Pediatr 2008;153:814-9) C1 [Scheinberg, Phillip; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Rm 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@mail.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute FX Supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung and Blood Institute. The authors have no conflicts of interest to disclose. NR 25 TC 51 Z9 71 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD DEC PY 2008 VL 153 IS 6 BP 814 EP 819 DI 10.1016/j.jpeds.2008.06.004 PG 6 WC Pediatrics SC Pediatrics GA 383FK UT WOS:000261659300021 PM 18672253 ER PT J AU Zhang, SM Mada, SR Sharma, S Torch, M Mattison, D Caritis, S Venkataramanan, R AF Zhang, Shimin Mada, Sripal Reddy Sharma, Shringi Torch, Marilyn Mattison, Don Caritis, Steve Venkataramanan, Raman TI Simultaneous quantitation of 17 alpha-hydroxyprogesterone caproate, 17 alpha-hydroxyprogesterone and progesterone in human plasma using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE 17-OHPC; 17-OHP, P, MPA; Liquid chromatography-mass spectrometry; Pregnancy ID PRETERM DELIVERY; 17-HYDROXYPROGESTERONE; ASSAY; SERUM; PREVENTION; BIRTH AB A sensitive and specific assay method for the simultaneous quantitation of 17 alpha-hydroxyprogesterone caproate (17-OHPC). 17 alpha-hydroxyprogesterone (17-OHP), and progesterone (P) in human plasma using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS) was developed and validated. Plasma samples were processed by a solid phase extraction (SPE) procedure using Oasis (R) HLB extraction cartridge prior to chromatography. Medroxyprogestrone acetate (MPA) was used as the internal standard. The compounds were separated using Waters C18 Symmetry analytical column (3.5 mu m, 2.1 mm x 50 mm) using a gradient elusion with a mobile phase consisting of 5% methanol in water [A] and methanol [B], with ammonium acetate(2 mM) and formic acid (0.1%) being added to both [A] and [B], at a flow rate 0.3 ml/min. The retention times for 17-OHPC, 17-OHP, P and MPA were 4.5,1.5, 2.5 and 2.2 min. respectively, with a total run time of 7 min. The analytes were detected by a Micromass Quattro Micro triple quadrupole mass spectrometer in positive electron spray ionization (ESI) mode using multiple reaction monitoring (MRM). The extracted ions monitored following MRM transitions were m/z 429.10 -> 313.10 for 17-OHPC, m/z 331.17 -> 97.00 for 17-OHP, m/z 315.15 -> 109.00 for P and m/z 387.15 -> 327.25 for MPA (IS). The assay was linear over the range 1-200 ng/ml for 17-OHPC and 17-OHP, and 2-400 ng/ml for P, when 0.4 ml of plasma was used in the extraction. The overall intra- and inter-day assay variation was <15%. No significant variation in the concentration of 17-OHPC, 17-OHP or P was observed with different sample processing and/or storage conditions. This method is simple, allows easy, accurate and reproducible measurement of 17-OHPC, 17-OHP and P simultaneously in human plasma, and is used to evaluate the pharmacokinetics of 17-OHPC in pregnant subjects. (C) 2008 Elsevier B.V. All rights reserved. C1 [Zhang, Shimin; Mada, Sripal Reddy; Sharma, Shringi; Torch, Marilyn; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. [Venkataramanan, Raman] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. [Caritis, Steve] Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15261 USA. [Mattison, Don] NICHD, Obstet Fetal Pharmacol Res Units OPRU, Ctr Res Mothers & Children, Bethesda, MD USA. RP Venkataramanan, R (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. EM rv+@pitt.edu RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712 FU NICHD [HD-047905-2] FX This work is supported in part by NICHD grant HD-047905-2. NR 17 TC 16 Z9 18 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD DEC 1 PY 2008 VL 48 IS 4 BP 1174 EP 1180 DI 10.1016/j.jpba.2008.08.024 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 396WL UT WOS:000262622000017 PM 18947956 ER PT J AU Othman, AA Newman, AH Eddington, ND AF Othman, Ahmed A. Newman, Amy H. Eddington, Natalie D. TI The Novel N-Substituted Benztropine Analog GA2-50 Possesses Pharmacokinetic and Pharmacodynamic Profiles Favorable for a Candidate Substitute Medication for Cocaine Abuse SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE cocaine abuse; substitution therapy; pharmacokinetics; pharmacodynamics; microdialysis ID IN-VIVO MICRODIALYSIS; BRAIN DOPAMINE LEVELS; RHESUS-MONKEYS; INTRACEREBRAL MICRODIALYSIS; POPULATION PHARMACOKINETICS; AGONIST-LIKE; TRANSPORTER; RAT; METABOLISM; DEPENDENCE AB GA2-50 is a novel N-substituted benztropine analog with improved potency and selectivity for the dopamine transporter. The pharmacokinetic and pharmacodynamic properties of GA2-50 were characterized as a part of its preclinical evaluation as a substitute medication for cocaine abuse. In vitro transport and metabolism studies as well as pharmacokinetic studies in rats were conducted. Effect of GA2-50 on the extracelluar nucleus accumbens (NAc) dopamine levels and on cocaine's induced dopamine elevation was evaluated using intracerebral microdialysis. GA2-50 showed high transcellular permeability despite being a P-glycoprotein substrate. GA2-50 was a substrate of human CYP2D6, CYP2C19, CYP2E1, rat CYP2C11, CYP2D1, CYP3A1, and CYP1A2; with low intrinsic clearance values. In vivo, GA2-50 showed high brain uptake (R(i) similar to 10), large volume of distribution (V(ss) = 37 L/kg), and long elimination half-life (t(1/2) = 19 h). GA2-50 resulted in 1.6- and 2.7-fold dopamine elevation at the 5 and 10 mg/kg i.v. doses. Dopamine elevation induced by GA2-50 was significantly reduced, slower and longer lasting than previously observed for cocaine. GA2-50 had no significant effect on cocaine's induced dopamine elevation upon simultaneous administration. Results from the present study indicate that GA2-50 possesses several attributes sought after for a substitute medication for cocaine abuse. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5453-5470, 2008 C1 [Othman, Ahmed A.; Eddington, Natalie D.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. [Othman, Ahmed A.] Cairo Univ, Sch Pharm, Dept Pharmaceut & Ind Pharm, Cairo, Egypt. [Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, 20 N Pine St, Baltimore, MD 21201 USA. EM neddingt@rx.umaryland.edu FU Intramural NIH HHS [Z01 DA000389-12]; NIDA NIH HHS [R01 DA016715, R01 DA16715-03] NR 46 TC 2 Z9 2 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD DEC PY 2008 VL 97 IS 12 BP 5453 EP 5470 DI 10.1002/jps.21389 PG 18 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 378IA UT WOS:000261313200036 PM 18425847 ER PT J AU Shetty, HU Zoghbi, SS Simeon, FG Liow, JS Brown, AK Kannan, P Innis, RB Pike, VW AF Shetty, H. Umesha Zoghbi, Sami S. Simeon, Fabrice G. Liow, Jeih-San Brown, Amira K. Kannan, Pavitra Innis, Robert B. Pike, Victor W. TI Radiodefluorination of 3-Fluoro-5-(2-(2-[F-18](fluoromethyl)-thiazol-4-yl) ethynyl)benzonitrile ([F-18]SP203), a Radioligand for Imaging Brain Metabotropic Glutamate Subtype-5 Receptors with Positron Emission Tomography, Occurs by Glutathionylation in Rat Brain SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 55th Annual Conference of the American-Society-for-Mass-Spectrometry CY JUN 03-07, 2007 CL Indianapolis, IN SP Amer Soc Mass Spectrometry ID IN-VITRO; 5-HT1A RECEPTORS; LIVER CYTOSOL; S-TRANSFERASE; DEFLUORINATION; IDENTIFICATION; ANTAGONIST; METABOLISM; MICE; FLUOROACETATE AB Metabotropic glutamate subtype-5 receptors (mGluR5) are implicated in several neuropsychiatric disorders. Positron emission tomography (PET) with a suitable radioligand may enable monitoring of regional brain mGluR5 density before and during treatments. We have developed a new radioligand, 3-fluoro-5-(2-(2[F-18](fluoromethyl)thiazol-4-yl) ethynyl) benzonitrile ([F-18]SP203), for imaging brain mGluR5 in monkey and human. In monkey, radioactivity was observed in bone, showing release of [F-18]fluoride ion from [F-18] SP203. This defluorination was not inhibited by disulfiram, a potent inhibitor of CYP2E1. PET confirmed bone uptake of radioactivity and therefore defluorination of [F-18] SP203 in rats. To understand the biochemical basis for defluorination, we administered [F-18] SP203 plus SP203 in rats for ex vivo analysis of metabolites. Radio-high-performance liquid chromatography detected [F-18] fluoride ion as a major radiometabolite in both brain extract and urine. Incubation of [F-18] SP203 with brain homogenate also generated this radiometabolite, whereas no metabolism was detected in whole blood in vitro. Liquid chromatography-mass spectrometry analysis of the brain extract detected m/z 548 and 404 ions, assignable to the [M + H](+) of S-glutathione (SP203Glu) and N-acetyl-S-L-cysteine (SP203Nac) conjugates of SP203, respectively. In urine, only the [M + H](+) of SP203Nac was detected. Mass spectrometry/mass spectrometry and multi-stage mass spectrometry analyses of each metabolite yielded product ions consistent with its proposed structure, including the former fluoromethyl group as the site of conjugation. Metabolite structures were confirmed by similar analyses of SP203Glu and SP203Nac, prepared by glutathione S-transferase reaction and chemical synthesis, respectively. Thus, glutathionylation at the 2-fluoromethyl group is responsible for the radiodefluorination of [F-18] SP203 in rat. This study provides the first demonstration of glutathione-promoted radiodefluorination of a PET radioligand. C1 [Shetty, H. Umesha] NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Shetty, HU (reprint author), NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C351,10 Ctr Dr,MSC 1003, Bethesda, MD 20892 USA. EM shettyu@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999]; NIMH NIH HHS [Z01 MH002795] NR 40 TC 34 Z9 34 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2008 VL 327 IS 3 BP 727 EP 735 DI 10.1124/jpet.108.143347 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 371ZM UT WOS:000260871200014 PM 18806125 ER PT J AU Gay, EA Klein, RC Melton, MA Blackshear, PJ Yakel, JL AF Gay, Elaine A. Klein, Rebecca C. Melton, Mark A. Blackshear, Perry J. Yakel, Jerrel L. TI Inhibition of Native and Recombinant Nicotinic Acetylcholine Receptors by the Myristoylated Alanine-Rich C Kinase Substrate Peptide SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID E-DERIVED PEPTIDES; XENOPUS OOCYTES; BETA-AMYLOID(1-42) PEPTIDE; HIPPOCAMPAL-NEURONS; CALMODULIN-BINDING; DRUG DISCOVERY; MARCKS FAMILY; MUTANT MICE; PROTEIN; BRAIN AB A variety of peptide ligands are known to inhibit the function of neuronal nicotinic acetylcholine receptors (nAChRs), including small toxins and brain-derived peptides such as beta-amyloid(1-42) and synthetic apolipoproteinE peptides. The myristoylated alanine-rich C kinase substrate ( MARCKS) protein is a major substrate of protein kinase C and is highly expressed in the developing and adult brain. The ability of a 25-amino acid synthetic MARCKS peptide, derived from the effector domain (ED), to modulate nAChR activity was tested. To determine the effects of the MARCKS ED peptide on nAChR function, receptors were expressed in Xenopus laevis oocytes, and two-electrode voltage-clamp experiments were performed. The MARCKS ED peptide completely inhibited acetylcholine (ACh)-evoked responses from alpha 7 nAChRs in a dose-dependent manner, yielding an IC50 value of 16 nM. Inhibition of ACh-induced responses was both activity- and voltage-independent. The MARCKS ED peptide was unable to block alpha-bungarotoxin binding. A MARCKS ED peptide in which four serine residues were replaced with aspartate residues was unable to inhibit alpha 7 nAChR-mediated currents. The MARCKS ED peptide inhibited ACh-induced alpha 4 beta 2 and alpha 2 beta 2 responses, although with decreased potency. The effects of the MARCKS ED peptide on native nAChRs were tested using acutely isolated rat hippocampal slices. In hippocampal interneurons, the MARCKS ED peptide was able to block native alpha 7 nAChRs in a dose-dependent manner. The MARCKS ED peptide represents a novel antagonist of neuronal nAChRs that has considerable utility as a research tool. C1 [Gay, Elaine A.; Klein, Rebecca C.; Melton, Mark A.; Yakel, Jerrel L.] Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Dept Hlth & Human Serv, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 37 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 2008 VL 327 IS 3 BP 884 EP 890 DI 10.1124/jpet.108.144758 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 371ZM UT WOS:000260871200030 PM 18812491 ER PT J AU Steeve, RW Moore, CA Green, JR Reilly, KJ McMurtrey, JR AF Steeve, Roger W. Moore, Christopher A. Green, Jordan R. Reilly, Kevin J. McMurtrey, Jacki Ruark TI Babbling, Chewing, and Sucking: Oromandibular Coordination at 9 Months SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE speech; development; motor control; mandible; human ID SPEECH MOTOR CONTROL; VOCAL EXPRESSION; MUSCLE-ACTIVITY; RESPONSE-MODE; JAW STIFFNESS; BRAIN-STEM; MASTICATION; PATTERNS; INFANTS; MOVEMENTS AB Purpose: The ontogeny of mandibular control is important for understanding the general neurophysiologic development for speech and alimentary behaviors. Prior investigations suggest that mandibular control is organized distinctively across speech and nonspeech tasks in 15-month-olds and adults and that, with development, these extant forms of motor control primarily undergo refinement and rescaling. The present investigation was designed to evaluate whether these coordinative infrastructures for alimentary behaviors and speech are evident during the earliest period of their co-occurrence. Method: Electromyographic (EMG) signals were obtained from the mandibular muscle groups of 15 typically developing 9-month-old children during sucking, chewing, and speech. Results: Unlike prior investigations of 12- and 15-month-olds and adults, 9-month-olds' analyses of peak correlations among agonist and antagonist comparisons of mandibular EMG data revealed weak coupling during sucking, chewing, and babble; associated lag values for antagonist muscle groups indicated greater synchrony during alimentary behaviors and less synchrony during babble. Unlike the speech data of 15-month-olds, 9-month-olds exhibited consistent results across speech subtasks. Conclusion: These findings were consistent with previous results in which mandibular coordination across behaviors was more variable for younger age groups, whereas the essential organization of each behavior closely reflected that seen in older infants and adults. C1 [Steeve, Roger W.] Univ Wyoming, Div Commun Disorders, Laramie, WY 82071 USA. [Moore, Christopher A.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. [Green, Jordan R.] Univ Nebraska, Lincoln, NE USA. [Reilly, Kevin J.] Northeastern Univ, Chicago, IL USA. [McMurtrey, Jacki Ruark] Univ Cent Arkansas, Conway, AR USA. RP Steeve, RW (reprint author), Univ Wyoming, Div Commun Disorders, 1000 E Univ Ave, Laramie, WY 82071 USA. EM rsteeve@uwyo.edu RI Green, Jordan/A-7159-2008 OI Green, Jordan/0000-0002-1464-1373 FU NCRR NIH HHS [P20 RR16474, P20 RR016474]; NIDCD NIH HHS [F31 DC000295, T32 DC00033, R01 DC000822, T32 DC000033, R01 DC000822-08, R01 DC00822, F31 DC00295] NR 53 TC 24 Z9 24 U1 1 U2 10 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC 1 PY 2008 VL 51 IS 6 BP 1390 EP 1404 DI 10.1044/1092-4388(2008/07-0046) PG 15 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 376PS UT WOS:000261196100002 PM 18664699 ER PT J AU Du, HX Yoo, T Qin, H AF Du, Haixia Yoo, Terry Qin, Hong TI PDE-Based Medial Axis Extraction and Shape Manipulation of Arbitrary Meshes SO JOURNAL OF SYSTEMS SCIENCE & COMPLEXITY LA English DT Article DE Diffusion Equation; Medial Axis Extraction; PDE techniques; Polygonal Meshes; Shape Manipulation ID DISTANCE MAPS; ALGORITHM; TRANSFORM; SURFACES; MODELS AB Shape skeletonization (i.e., medial axis extraction) is powerful in many visual computing applications, such as pattern recognition, object segmentation, registration, and animation. In this paper, the authors expand the use of diffusion equations combined with distance field information to approximate medial axes of arbitrary 3D solids represented by polygonal meshes based on their differential properties. It offers an alternative but natural way for medial axis extraction for commonly used 3D polygonal models. By solving the PDE along time axis, this system can not only quickly extract diffusion-based medial axes of input meshes, but also allow users to visualize the extraction process at each time step. In addition, the proposed model provides users a set of manipulation toolkits to sculpt extracted medial axes, then use diffusion-based techniques to recover corresponding deformed shapes according to the original input datasets. This skeleton-based shape manipulation offers a fast and easy way for animation and deformation of complicated mesh objects. C1 [Du, Haixia] Sterne Kessler Goldstein & Fox PLLC, Washington, DC 20005 USA. [Yoo, Terry] Natl Lib Med, NIH, Bethesda, MD 20894 USA. [Qin, Hong] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. RP Du, HX (reprint author), Sterne Kessler Goldstein & Fox PLLC, Washington, DC 20005 USA. EM haixia.du@gmail.com FU National Science Foundation (NSF) [IIS-0082035, IIS-0097646]; National Library of Medicine; Oak Ridge Institute for Science and Education FX This research was supported in part by the National Science Foundation (NSF) Information Technology Research under Grant No. IIS-0082035, the NSF under Grant No. IIS-0097646, Alfred P. Sloan Fellowship, Honda Initiation Award, and an appointment of Haixia du to the NLM Research Participation Program Sponsored by the National Library of Medicine and administered by the Oak Ridge Institute for Science and Education. NR 42 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1009-6124 J9 J SYST SCI COMPLEX JI J. Syst. Sci. Complex. PD DEC PY 2008 VL 21 IS 4 BP 609 EP 625 DI 10.1007/s11424-008-9138-2 PG 17 WC Mathematics, Interdisciplinary Applications SC Mathematics GA 372CD UT WOS:000260878200009 ER PT J AU Vitiello, B AF Vitiello, Benedetto TI Recent NIMH Clinical Trials and Implications for Practice SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; ADOLESCENT DEPRESSION; CHILDREN; TADS; METHYLPHENIDATE; DISORDERS; SAFETY; ADHD; MEDICATION C1 NIMH, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Dept Hlth & Human Serv, NIH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 27 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2008 VL 47 IS 12 BP 1369 EP 1374 DI 10.1097/CHI.0b013e31818960a7 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 375KI UT WOS:000261112200004 PM 19034188 ER PT J AU Witt, KL Shelby, MD Itchon-Ramos, N Faircloth, M Kissling, GE Chrisman, AK Ravi, H Murli, H Mattison, DR Kollins, SH AF Witt, Kristine L. Shelby, Michael D. Itchon-Ramos, Nilda Faircloth, Melissa Kissling, Grace E. Chrisman, Allan K. Ravi, Hima Murli, Hemalatha Mattison, Donald R. Kollins, Scott H. TI Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children With ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE stimulant drugs; micronuclei; chromosome aberrations; sister chromatid exchanges; cohort study ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERIPHERAL-BLOOD LYMPHOCYTES; SALTS EXTENDED-RELEASE; ZEIN ET-AL; STIMULANT MEDICATIONS; PRACTICE PARAMETERS; RISK; CANCER; ADULTS; ADOLESCENTS AB Objective: In response to previously published findings of methylphenidate-induced chromosomal changes in children, this study was designed to determine whether methylphenidate- or amphetamine-based drugs induce chromosomal damage (structural aberrations, micronuclei, and sister chromatid exchanges) in peripheral blood lymphocytes of children with attention-deficit/hyperactivity disorder after 3 months of continuous treatment. Method: Stimulant drug-naive subjects, 6 to 12 years of age, in good overall health, and judged to be appropriate candidates for stimulant therapy based on rigorously diagnosed ADHD using DSM-IV criteria, were randomized into two open-label treatment groups (methylphenidate or mixed amphetamine salts). Each subject provided a blood sample before initiation of treatment and after 3 months of treatment. Pretreatment and posttreatment frequencies of chromosomal aberrations, micronuclei, and sister chromatid exchanges were determined for each subject. Results: Sixty-three subjects enrolled in the study; 47 subjects completed the full 3 months of treatment, 25 in the methylphenidate group and 22 in the amphetamine group. No significant treatment-related increases were observed in any of the three measures of cytogenetic damage in the 47 subjects who completed treatment or the 16 subjects who did not. Conclusions: Earlier findings of methylphenidate-induced chromosomal changes in children were not replicated in this study. These results add to the accumulating evidence that therapeutic levels of methylphenidate do not induce cytogenetic damage in humans. Furthermore, our results indicate that amphetamine-based products do not pose a risk for cytogenetic damage in children. J. Am. Acad. Child. Adolsc. Psychiatry, 2008;47(12):1375-1383. C1 [Witt, Kristine L.; Shelby, Michael D.; Kissling, Grace E.] NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Itchon-Ramos, Nilda; Faircloth, Melissa; Chrisman, Allan K.; Ravi, Hima; Kollins, Scott H.] Duke Univ, Med Ctr, Dept Psychiat, Duke ADHD Program, Durham, NC 27706 USA. [Mattison, Donald R.] NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Witt, KL (reprint author), NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop EC 32,79 TW Alexander Dr,Suit, Res Triangle Pk, NC 27709 USA. EM witt@niehs.nih.gov RI Mattison, Donald/C-2015-2009; Kollins, Scott/G-2965-2012; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU Pfizer; New River Pharmaceuticals; Shire Pharmaceuticals; National Institute on Drug Abuse; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Environmental Protection Agency FX Dr. Kollins received research support and/or bonorarial consulting fees from the following sources during the conduct of this study: Athenagen, Eli Lilly, Psychogenics, Pfizer, New River Pharmaceuticals, Shire Pharmaceuticals, National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and Environmental Protection Agency. Dr. Chrisman received honoraria and was on the speakers' bureaus of Shire Pharmaceuticals and McNeil-PPC The other authors report no conflicts of interest. NR 38 TC 19 Z9 19 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2008 VL 47 IS 12 BP 1375 EP 1383 DI 10.1097/CHI.0b013e3181893620 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 375KI UT WOS:000261112200005 PM 18978633 ER EF