FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rao, JS Ertley, RN Lee, HJ Rapoport, SI Bazinet, RP AF Rao, J. S. Ertley, R. N. Lee, H-J Rapoport, S. I. Bazinet, R. P. TI Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic phospholipase A(2) in rat frontal cortex SO PHARMACOGENOMICS JOURNAL LA English DT Article DE fluoxetine; brain; cPLA(2); AUF-1; arachidonic acid; depression ID SEROTONIN REUPTAKE INHIBITORS; ARACHIDONIC-ACID RELEASE; CENTRAL-NERVOUS-SYSTEM; GROUP-SPECIFIC ASSAYS; BRAIN PHOSPHOLIPIDS; GENE-EXPRESSION; DOCOSAHEXAENOIC ACID; 5-HT1A AUTORECEPTORS; PREFRONTAL CORTEX; BIPOLAR DISORDER AB Chronic lithium and carbamazepine, which are effective against mania in bipolar disorder, decrease the activity of cytosolic phospholipase A(2) (cPLA(2)) and the turnover rate of arachidonic acid in phospholipids in rat brain. Assuming that stages of bipolar disorder are related to brain arachidonic acid metabolism, we hypothesized that drugs effective in depression would increase cPLA2 activity. To test this hypothesis, adult male CDF-344 rats were administered fluoxetine (10 mg/kg intraperitoneally (i.p.) or saline (control) (i.p.) chronically for 21 days. Frontal cortex cPLA2 protein, phosphorylated cPLA2, activity and mRNA levels were increased after chronic fluoxetine. Transcription factors (activator protein-1, activator protein-2, glucocorticoid response element, polyoma enhancer element-3 and nuclear factor-kappa B) that are known to regulate cPLA2 gene expression were not significantly changed by chronic fluoxetine, but nuclear AU-rich element/poly(U)-binding/degradation factor-1 RNA-stabilizing protein was increased significantly. The results suggest that chronic fluoxetine increases brain cPLA2 gene expression post-transcriptionally by increasing cPLA2 mRNA stabilization. Chronic fluoxetine's effect on cPLA2 expression was opposite to the effect reported with chronic lithium or carbamazepine administration, and may be part of fluoxetine's mode of action. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,1s-126, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 FU Intramural NIH HHS NR 74 TC 28 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD NOV PY 2006 VL 6 IS 6 BP 413 EP 420 DI 10.1038/sj.tpj.6500391 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 110TL UT WOS:000242403500008 PM 16636684 ER PT J AU Fan, J Wu, BX Sarna, T Rohrer, B Redmond, TM Crouch, RK AF Fan, Jie Wu, Bill X. Sarna, Tadeusz Rohrer, Baerbel Redmond, T. Michael Crouch, Rosalie K. TI 9-cis retinal increased in retina of RPE65 knockout mice with decrease in coat pigmentation SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MASS-SPECTROMETRIC ANALYSIS; LEBER CONGENITAL AMAUROSIS; VERTEBRATE VISUAL CYCLE; EPITHELIAL-CELLS; BETA-CAROTENE; RHODOPSIN; MUTATIONS; ISOMEROHYDROLASE; PHOSPHORYLATION; IDENTIFICATION AB The protein RPE65 is essential for the generation of the native chromophore, 11-cis retinal, of visual pigments. However, the Rpe65 knockout (Rpe65(-/-)) mouse shows a minimal visual response due to the presence of a pigment, isorhodopsin, formed with 9-cis retinal. Isorhodopsin accumulates linearly with prolonged dark-rearing of the animals. The majority of Rpe65(-/-) mice have an agouti coat color. A tan coat color subset of Rpe65(-/-) mice was found to have an enhanced visual response as measured by electroretinograms. The enhanced response was found to be due to increased levels of 9-cis retinal and isorhodopsin pigment levels. Animals of both coat colors reared in cyclic light have minimal levels of regenerated pigment and show photoreceptor degeneration. On dark-rearing, pigment accumulates and photoreceptor degeneration is decreased. In the tan Rpe65(-/-) mice, the level of photoreceptor degeneration is less than in the agouti animals, which have an increased pigment and decreased free opsin level. Therefore, photoreceptor damage correlates with the amount of the apoprotein present, supporting findings that the activity from unregenerated opsin can lead to photoreceptor degeneration. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Jagiellonian Univ, Dept Biophys, Krakow, Poland. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Fan, J (reprint author), Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. EM fan@musc.edu OI Redmond, T. Michael/0000-0002-1813-5291 FU NEI NIH HHS [R01 EY-04939, R01 EY-13520, R01 EY-14793]; PHS HHS [C06 R015455] NR 42 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2006 VL 82 IS 6 BP 1461 EP 1467 DI 10.1562/2006-02-02-RA-793 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 122GQ UT WOS:000243214100012 PM 16553465 ER PT J AU van Benthem, K Tan, GL French, RH DeNoyer, LK Podgornik, R Parsegian, VA AF van Benthem, Klaus Tan, Guolong French, Roger H. DeNoyer, Linda K. Podgornik, Rudolf Parsegian, V. Adrian TI Graded interface models for more accurate determination of van der Waals-London dispersion interactions across grain boundaries SO PHYSICAL REVIEW B LA English DT Article ID ELECTRON-ENERGY-LOSS; PEROVSKITE-TYPE TITANATES; TOUGHENED SILICON-CARBIDE; OPTICAL-PROPERTIES; QUANTITATIVE-ANALYSIS; DIELECTRIC FUNCTION; VANDERWAALS FORCES; VACUUM-ULTRAVIOLET; HAMAKER CONSTANTS; LOSS SPECTROSCOPY AB Attractive van der Waals-London dispersion interactions between two half crystals arise from local physical property gradients within the interface layer separating the crystals. Hamaker coefficients and London dispersion energies were quantitatively determined for Sigma 5 and near-Sigma 13 grain boundaries in SrTiO3 by analysis of spatially resolved valence electron energy-loss spectroscopy (VEELS) data. From the experimental data, local complex dielectric functions were determined, from which optical properties can be locally analyzed. Both local electronic structures and optical properties revealed gradients within the grain boundary cores of both investigated interfaces. The results show that even in the presence of atomically structured grain boundary cores with widths of less than 1 nm, optical properties have to be represented with gradual changes across the grain boundary structures to quantitatively reproduce accurate van der Waals-London dispersion interactions. London dispersion energies of the order of 10% of the apparent interface energies of SrTiO3 were observed, demonstrating their significance in the grain boundary formation process. The application of different models to represent optical property gradients shows that long-range van der Waals-London dispersion interactions scale significantly with local, i.e., atomic length scale property variations. C1 Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. Univ Penn, Dept Mat Sci, Philadelphia, PA 19104 USA. DuPont Co Inc, Cent Res, Expt Stn, Wilmington, DE 19880 USA. Deconvolut & Entropy Consulting, Ithaca, NY 14850 USA. Univ Ljubljana, Dept Phys, Ljubljana 1000, Slovenia. NIH, Struct Biol Lab, Bethesda, MD 20892 USA. RP van Benthem, K (reprint author), Oak Ridge Natl Lab, 1 Bethel Valley Rd, Oak Ridge, TN 37831 USA. RI French, Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008; Tan, Guolong/A-1098-2013 OI French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637; Tan, Guolong/0000-0003-0961-5506 NR 63 TC 18 Z9 18 U1 1 U2 14 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 J9 PHYS REV B JI Phys. Rev. B PD NOV PY 2006 VL 74 IS 20 AR 205110 DI 10.1103/PhysRevB.74.205110 PG 12 WC Physics, Condensed Matter SC Physics GA 110VM UT WOS:000242409400020 ER PT J AU Singh, NJ Chen, C Schwartz, RH AF Singh, Nevil J. Chen, Chuan Schwartz, Ronald H. TI The impact of T cell intrinsic antigen adaptation on peripheral immune tolerance SO PLOS BIOLOGY LA English DT Article ID IN-VIVO; ADAPTIVE TOLERANCE; AUTOIMMUNE-DISEASE; SELF-TOLERANCE; B-CELLS; FUNCTIONAL IMPAIRMENT; ACTIVATION THRESHOLD; REGULATORY FUNCTION; CYTOSOLIC ANTIGEN; EFFECTOR FUNCTION AB Overlapping roles have been ascribed for T cell anergy, clonal deletion, and regulation in the maintenance of peripheral immunological tolerance. A measurement of the individual and additive impacts of each of these processes on systemic tolerance is often lacking. In this report we have used adoptive transfer strategies to tease out the unique contribution of T cell intrinsic receptor calibration ( adaptation) in the maintenance of tolerance to a systemic self-antigen. Adoptively transferred naive T cells stably calibrated their responsiveness to a persistent self-antigen in both lymphopenic and T cell-replete hosts. In the former, this state was not accompanied by deletion or suppression, allowing us to examine the unique contribution of adaptation to systemic tolerance. Surprisingly, adapting T cells could chronically help antigen-expressing B cells, leading to polyclonal hypergammaglobulinemia and pathology, in the form of mild arthritis. The helper activity mediated by CD40L and cytokines was evident even if the B cells were introduced after extended adaptation of the T cells. In contrast, in the T cell-replete host, neither arthritis nor autoantibodies were induced. The containment of systemic pathology required host T cell-mediated extrinsic regulatory mechanisms to synergize with the cell intrinsic adaptation process. These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Singh, NJ (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ns117r@nih.gov FU Intramural NIH HHS NR 57 TC 19 Z9 19 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2006 VL 4 IS 11 BP 1957 EP 1969 AR e340 DI 10.1371/journal.pbio.0040340 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 114EJ UT WOS:000242649200009 PM 17048986 ER PT J AU Brown, SP Cornell, SJ Sheppard, M Grant, AJ Maskell, DJ Grenfell, BT Mastroeni, P AF Brown, Sam P. Cornell, Stephen J. Sheppard, Mark Grant, Andrew J. Maskell, Duncan J. Grenfell, Bryan T. Mastroeni, Pietro TI Intracellular demography and the dynamics of Salmonella enterica infections SO PLOS BIOLOGY LA English DT Article ID IN-VIVO; TYPHIMURIUM; RESISTANCE; SYSTEM; MICE; MACROPHAGES; EVOLUTION; VIRULENCE; DEATH AB An understanding of within-host dynamics of pathogen interactions with eukaryotic cells can shape the development of effective preventive measures and drug regimes. Such investigations have been hampered by the difficulty of identifying and observing directly, within live tissues, the multiple key variables that underlay infection processes. Fluorescence microscopy data on intracellular distributions of Salmonella enterica serovar Typhimurium ( S. Typhimurium) show that, while the number of infected cells increases with time, the distribution of bacteria between cells is stationary ( though highly skewed). Here, we report a simple model framework for the intensity of intracellular infection that links the quasi-stationary distribution of bacteria to bacterial and cellular demography. This enables us to reject the hypothesis that the skewed distribution is generated by intrinsic cellular heterogeneities, and to derive specific predictions on the within-cell dynamics of Salmonella division and host-cell lysis. For within-cell pathogens in general, we show that within-cell dynamics have implications across pathogen dynamics, evolution, and control, and we develop novel generic guidelines for the design of antibacterial combination therapies and the management of antibiotic resistance. C1 Univ Cambridge, Dept Zool, Cambridge CB2 1TN, England. Univ Texas, Sect Integrat Biol, Austin, TX USA. Univ Leeds, Inst Integrat & Comparat Biol, Leeds LS2 9JT, W Yorkshire, England. Univ Cambridge, Dept Vet Med, Cambridge CB2 1TN, England. Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Brown, SP (reprint author), Univ Cambridge, Dept Zool, Cambridge CB2 1TN, England. EM sam.brown@cantab.net RI Brown, Sam/B-5234-2009 OI Brown, Sam/0000-0003-1892-9275 FU Wellcome Trust NR 26 TC 44 Z9 44 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2006 VL 4 IS 11 BP 2091 EP 2098 AR e349 DI 10.1371/journal.pbio.0040349 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 114EJ UT WOS:000242649200019 PM 17048989 ER PT J AU Dadachova, E Patel, MC Toussi, S Apostolidis, C Morgenstern, A Brechbiel, MW Gorny, MK Zolla-Pazner, S Casadevall, A Goldstein, H AF Dadachova, Ekaterina Patel, Mahesh C. Toussi, Sima Apostolidis, Christos Morgenstern, Alfred Brechbiel, Martin W. Gorny, Miroslaw K. Zolla-Pazner, Susan Casadevall, Arturo Goldstein, Harris TI Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins SO PLOS MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN MONOCLONAL-ANTIBODIES; SCID-HU MICE; RICIN-A-CHAIN; IN-VIVO; HIV-1 INFECTION; IONIZING-RADIATION; LYMPHOID-TISSUES; FUNGAL-INFECTION AB Background The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. Methods and Findings Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 (Bi-213) and rhenium 188 (Re-188) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a Bi-213- or Re-188-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the Re-188-labeled antibody to gp41 compared with those treated with the Re-188-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. Conclusions The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV. C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Jacobi Med Ctr, Bronx, NY USA. Commiss European Communities, Joint Res Ctr, Inst Transuranium Elements, D-7500 Karlsruhe, Germany. Natl Canc Inst, NIH, Bethesda, MD USA. NYU, Sch Med, New York, NY USA. Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. RP Dadachova, E (reprint author), Albert Einstein Coll Med, Bronx, NY 10467 USA. EM edadacho@aecom.yu.edu RI Dadachova, Ekaterina/I-7838-2013; OI Gorny, Miroslaw/0000-0002-2714-8780 FU Intramural NIH HHS; NHLBI NIH HHS [HL059842, R01 HL059725, R01 HL059842, HL 59725]; NIAID NIH HHS [AI033142, AI-051519, AI60507, R01 AI033142, R01 AI036085, R01 AI048466, R37 AI033142, R56 AI060507, AI 27742, AI 36085, P30 AI051519, R01 AI48466, AI033774, P30 AI027742, R01 AI033774, R01 AI060507] NR 58 TC 46 Z9 46 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2006 VL 3 IS 11 BP 2094 EP 2103 AR e427 DI 10.1371/journal.pmed.0030427 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 110JO UT WOS:000242374800014 PM 17090209 ER PT J AU Viboud, C Miller, MA Grenfell, BT Bjornstad, ON Simonsen, L AF Viboud, Cecile Miller, Mark A. Grenfell, Bryan T. Bjornstad, Ottar N. Simonsen, Lone TI Air travel and the spread of influenza: Important caveats SO PLOS MEDICINE LA English DT Letter ID PANDEMIC INFLUENZA; STRATEGIES C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov RI Bjornstad, Ottar/I-4518-2012 NR 10 TC 23 Z9 24 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2006 VL 3 IS 11 BP 2159 EP 2168 AR e503 DI 10.1371/journal.pmed.0030503 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 110JO UT WOS:000242374800020 PM 17132057 ER PT J AU Zou, ZC Sun, PD AF Zou, Zhongcheng Sun, Peter D. TI An improved recombinant mammalian cell expression system for human transforming growth factor-beta 2 and -beta 3 preparations SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE TGF-beta 2; TGF-beta 3; LAP; LTBP; Chinese hamster ovary cell; protein expression; purification; activation ID GROWTH-FACTOR-BETA; TGF-BETA; ACTIVATION; LATENCY; FACTOR-BETA-3; MECHANISMS; PROTEINS; TGF-BETA-1; SECRETION; SEQUENCE AB Transforming growth factor-beta 2 and -beta 3 (TGF-beta 2 and -beta 3) are important members of TGF-beta family which play important roles in the growth, maintenance, and repair processes of developing embryos, neonates, and adults. Preparation of large quantities of these two cytokines, which is necessary for structural studies and other applications, has proven to be extremely difficult. We have developed a novel Chinese hamster ovary cell-based expression system for high-level expression and high recovery of recombinant human TGF-beta 2 and -beta 3. In this system, we used a mammalian expression vector which contains a glutamine synthetase coding region for amplification, together with a modified TGF-beta 2 or -beta 3 open reading frame for expression. The leader peptide of TGF-beta 2 or -beta 3 was replaced by that from the V-J2-C region of a mouse immunoglobulin K-chain, and a poly-histidine tag was inserted immediately after the leader sequence to facilitate protein purification without changing the mature TGF-beta 2 or -beta 3 amino acid sequence. In addition, the extreme N-terminal cysteine residue of TGF-beta 2 or -beta 3 was replaced by a serine residue. The resulting expression constructs produced two stable cell clones expressing 10mg of TGF-beta 2 and 8mg of TGF-beta 3 per liter of spent medium. The purification scheme involved the use of two simple chromatographic steps with a typical yield of 5 mg of TGF-beta 2 and 4 mg of TGF-beta 3. This method represents a significant improvement over previously published methods and may be applicable to other TGF-beta superfamily members. We further confirmed that latent TGF-beta 2 and -beta 3 can be activated by proteolysis and glycolysis, which have not been reported before. Published by Elsevier Inc. C1 NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov FU Intramural NIH HHS NR 31 TC 11 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2006 VL 50 IS 1 BP 9 EP 17 DI 10.1016/j.pep.2006.06.022 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 108SY UT WOS:000242260700002 PM 16901717 ER PT J AU Tropea, JE Phan, J Waugh, DS AF Tropea, Joseph E. Phan, Jason Waugh, David S. TI Overproduction, purification, and biochemical characterization of the dual specificity H1 protein phosphatase encoded by variola major virus SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE smallpox; variola major; dual specificity phosphatase; H1 phosphatase; H1L; l ID VACCINIA VIRUS; SMALLPOX VACCINATION; TYROSINE-PHOSPHATASE; ESCHERICHIA-COLI; UNITED-STATES; IN-VITRO; TARGETS; KINASE; CANCER AB Smallpox, a highly contagious infectious disease caused by the variola major virus, has an overall mortality rate of about 30%. Because there currently is no specific treatment for smallpox, and the only prevention is vaccination, there is an urgent need for the development of effective antiviral drugs. The dual specificity protein phosphatase encoded by the smallpox virus (H1) is essential for the production of infectious viral particles, making it a promising molecular target for antiviral therapeutics. Here, we report the molecular cloning, overproduction, purification, and initial biochemical characterization of H1 phosphatase, thereby paving the way for the discovery of small molecule inhibitors. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Ctr Canc Res, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Waugh, DS (reprint author), NCI, Ctr Canc Res, Macromol Crystallog Lab, POB B, Frederick, MD 21701 USA. EM waughd@ncifcrf.gov FU Intramural NIH HHS NR 25 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2006 VL 50 IS 1 BP 31 EP 36 DI 10.1016/j.pep.2006.05.007 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 108SY UT WOS:000242260700005 PM 16793284 ER PT J AU Shimp, RL Martin, LB Zhang, YL Henderson, BS Duggan, P MacDonald, NJ Lebowitz, J Saul, A Narum, DL AF Shimp, Richard L., Jr. Martin, Laura B. Zhang, Yanling Henderson, Brian S. Duggan, Peter MacDonald, Nicholas J. Lebowitz, Jacob Saul, Allan Narum, David L. TI Production and characterization of clinical grade Escherichia coli derived Plasmodium falciparum 42kDa merozoite surface protein 1 (MSP1(42)) in the absence of an affinity tag SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Plasmodium falciparum; MSP1; Escherichia coli; refold; vaccine ID C-TERMINAL FRAGMENT; ANALYTICAL ULTRACENTRIFUGATION; RECOMBINANT PROTEINS; PICHIA-PASTORIS; MALARIA VACCINE; SLOT BLOT; ANTIGEN; CHALLENGE; ANTIBODIES; ISOMERASE AB The 42kDa cleavage product from the carboxyl end of the Plasmodium falciparum merozoite surface protein 1 (MSP1(42)) is an important blood-stage malaria vaccine target. Several recombinant protein expression systems have been used for production of MSP1(42) including yeast (Saccharomyces cerevisiae and Pichia pastoris), Escherichia coli, baculovirus and transgenic animals. To date, all of the reported recombinant proteins include a 6x His affinity tag to facilitate purification, including three MSP1(42) clinical grade proteins currently in human trials. Under some circumstances, the presence of the 6x His tag may not be desirable. Therefore, we were interested to produce clinical grade MSP1(42) without a 6x His affinity tag from E coli inclusion bodies. We produced a recombinant MSPI, with a P. falciparum FUP (Uganda-Palo Alto) phenotype which accounts for a substantial proportion of the MSP1(42) protein observed in African isolates. EcMSP1(42)-FUP was produced in E. coli inclusion bodies by high cell mass induction with IPTG using 5 L and 60 L bioreactors. Isolated inclusion bodies were solubilized in 8 M guanidine-HCl and the EcMSP1(42)-FUP protein refolded by rapid dilution. Refolded EcMSP1(42)-FUP was purified using hydrophobic interaction chromatography, anion exchange chromatography, and size exclusion chromatography, and subject to biochemical characterization for integrity, identity, and purity. Endotoxin and host cell protein levels were within acceptable limits for human use. The process was successfully transferred to pilot-scale production in a cGMP environment. A final recovery of 87.8 mg of clinical-grade material per liter of fermentation broth was achieved. The EcMSP1(42)-FUP clinical antigen is available for preclinical evaluation and human studies. Published by Elsevier Inc. C1 NIAID, MVDB, NIH, DHHS, Rockville, MD 20852 USA. NIAID, Div Bioengn & Phys Sci, Off Res Serv, DHHS, Bethesda, MD 20892 USA. RP Narum, DL (reprint author), NIAID, MVDB, NIH, DHHS, Rockville, MD 20852 USA. EM dnarum@niaid.nih.gov RI Saul, Allan/I-6968-2013; Martin, Laura/N-1789-2013 OI Saul, Allan/0000-0003-0665-4091; Martin, Laura/0000-0002-4431-4381 FU Intramural NIH HHS NR 30 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2006 VL 50 IS 1 BP 58 EP 67 DI 10.1016/j.pep.2006.06.018 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 108SY UT WOS:000242260700009 PM 16884920 ER PT J AU Gutierrez-Lugo, MT Newton, GL Fahey, RC Bewley, CA AF Gutierrez-Lugo, Maria-Teresa Newton, Gerald L. Fahey, Robert C. Bewley, Carole A. TI Cloning, expression and rapid purification of active recombinant mycothiol ligase as B1 immunoglobulin binding domain of streptococcal protein G, glutathione-S-transferase and maltose binding protein fusion proteins in Mycobacterium smegmatis SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE MshC; mycothiol; fusion proteins; affinity purification; mycothiol ligase; complementation; Mycobacterium tuberculosis; shuttle vector ID ESCHERICHIA-COLI; ACETAMIDASE GENE; TUBERCULOSIS; ANTIBIOTICS; GROWTH AB Mycothiol ligase (MshC) is a key enzyme in the biosynthesis of mycothiol, a small molecular weight thiol found in Mycobacteria spp. and other actinomycetes. Mycothiol plays a fundamental role in these organisms by helping to provide protection from the effects of reactive oxygen species and electrophiles, including many antibiotics. It has recently been demonstrated that the MshC gene and more generally the production of mycothiol are essential to Mycobacterium tuberculosis, indicating that MshC may represent a novel target for new classes of antituberculars. Because MshC cannot be expressed heterologously in Escherichia coli and isolation from Mycobacterium smegmatis is impractical, we have optimized the E. coli-M. smegmatis shuttle vector pACE for cloning and recombinant expression of MshC (under control of an acetamidase-inducible promoter). To improve expression levels and simplify purification, we further constructed three N-terminal-MshC fusion proteins where N-terminal tags included the B 1 domain of streptococcal protein G (to give GB1-MshC), glutathione-S-transferase (to give GST-MshC) and maltose binding protein (to give MBP-MshC), for expression in M. smegmatis. By expressing all three fusion proteins in a mutant strain of M. smegmatis mc(2)155, namely I64 L205P MshC M. smegmatis which lacks mycothiol ligase activity, we demonstrate in vivo mycothiol ligase activity for each construct. Recombinant GST-MshC and MBP-MshC were isolated in one step by affinity chromatography in a yield of 0.7 and 1.2 mg fusion protein/L and exhibited specific activities of 9 nmol min(-1) mg-(1) and 25 nmol min(-1) mg(-1), respectively. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, 9000 Rockville Pike,Bldg 8,Room 1A-02, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI49174] NR 24 TC 8 Z9 8 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD NOV PY 2006 VL 50 IS 1 BP 128 EP 136 DI 10.1016/j.pep.2006.07.005 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 108SY UT WOS:000242260700017 PM 16908186 ER PT J AU Ahn, HC Le, YTH Nagchowdhuri, PS Derose, EF Putnam-Evans, C London, RE Markley, JL Lim, KH AF Ahn, Hee-Chul Le, Yen T. H. Nagchowdhuri, Partha S. Derose, Eugene F. Putnam-Evans, Cindy London, Robert E. Markley, John L. Lim, Kwang Hun TI NMR characterizations of an amyloidogenic conformational ensemble of the PI3KSH3 domain SO PROTEIN SCIENCE LA English DT Article DE amyloids; PI3KSH3; NMR; dynamics; amyloidogenic intermediate; long-range interactions; PRE ID 8 M UREA; FIBRIL FORMATION; SH3 DOMAIN; PROTEIN AGGREGATION; ALPHA-SYNUCLEIN; PI3-SH3 DOMAIN; UNFOLDED STATE; DYNAMICS; BETA(2)-MICROGLOBULIN; INTERMEDIATE AB Amyloid formation is associated with structural changes of native polypeptides to monomeric intermediate states and their self-assembly into insoluble aggregates. Characterizations of the amyloidogenic intermediate state are, therefore, of great importance in understanding the early stage of amyloidogenesis. Here, we present NMR investigations of the structural and dynamic properties of the acid-unfolded amyloidogenic intermediate state of the phosphatidylinositol 3-kinase (PI3K) SH3 domain-a model peptide. The monomeric amyloidogenic state of the SH3 domain studied at pH 2.0 (35 degrees C) was shown to be substantially disordered with no secondary structural preferences. N-15 NMR relaxation experiments indicated that the unfolded polypeptide is highly flexible on a subnanosecond timescale when observed under the amyloidogenic condition (pH 2.0, 35 degrees C). However, more restricted motions were detected in residues located primarily in the beta-strands as well as in a loop in the native fold. In addition, nonnative long-range interactions were observed between the residues with the reduced flexibility by paramagnetic relaxation enhancement (PRE) experiments. These indicate that the acid-unfolded state of the SH3 domain adopts a partly folded conformation through nonnative long-range contacts between the dynamically restricted residues at the amyloid-forming condition. C1 E Carolina Univ, Dept Chem, Greenville, NC 27858 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. E Carolina Univ, Dept Biol, Greenville, NC 27858 USA. RP Lim, KH (reprint author), E Carolina Univ, Dept Chem, Greenville, NC 27858 USA. EM limk@ecu.edu FU NCRR NIH HHS [P41 RR002301, P41RR02301]; NIGMS NIH HHS [P41 GM066326, P41GM66326] NR 35 TC 13 Z9 13 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2006 VL 15 IS 11 BP 2552 EP 2557 DI 10.1110/ps.062154306 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100KC UT WOS:000241666600010 PM 17001038 ER PT J AU Zhou, Z Feng, HQ Bai, YW AF Zhou, Zheng Feng, Hanqiao Bai, Yawen TI Detection of a hidden folding intermediate in the focal adhesion target domain: Implications for its function and folding SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE native-state hydrogen exchange; partially unfolded forms; FAT domain; functional intermediates; hidden intermediate ID STATE HYDROGEN-EXCHANGE; CYTOCHROME-C; PROTEIN; KINASE; PATHWAYS; PEPTIDE; MODEL AB The focal adhesion target (FAT) domain of focal adhesion kinase has a four-helix bundle structure. Based on a hydrogen exchange-constrained computer simulation study and some indirect experimental results, it has been suggested that a partially unfolded state of the FAT domain with the N-terminal helix unfolded plays an important role in its biological function. Here, using a native-state hydrogen exchange method, we directly detected an intermediate with the N-terminal helix unfolded in a mutant (Y925E) of the FAT domain. In addition, kinetic folding studies on the FAT domain suggest that this intermediate exists on the native side of the rate-limiting transition state for folding. These results provide more direct evidence of the existence of the proposed intermediate and help to understand the folding mechanism of small single domain proteins. C1 NCI, Biochem Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov FU Intramural NIH HHS NR 26 TC 18 Z9 18 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 2006 VL 65 IS 2 BP 259 EP 265 DI 10.1002/prot.21107 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 087NI UT WOS:000240748700001 PM 16909417 ER PT J AU Alfano, CM McGregor, BA Kuniyuki, A Reeve, BB Bowen, DJ Baumgartner, KB Bernstein, L Ballard-Barbash, R Malone, KE Ganz, PA McTiernan, A AF Alfano, Catherine M. McGregor, Bonnie A. Kuniyuki, Alan Reeve, Bryce B. Bowen, Deborah J. Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel Malone, Kathleen E. Ganz, Patricia A. McTiernan, Anne TI Psychometric properties of a tool for measuring hormone-related symptoms in breast cancer survivors SO PSYCHO-ONCOLOGY LA English DT Article DE breast cancer; hormone symptoms; psychometrics; oncology; survivorship; cancer ID QUALITY-OF-LIFE; SURGICAL ADJUVANT BREAST; CARCINOMA IN-SITU; MENOPAUSAL SYMPTOMS; IMPACT; RISK; HEALTH; TRIAL; PREVENTION; DIAGNOSIS AB Hormone-related symptoms are common in breast cancer survivors and many aspects of these symptoms are currently under study. Reliable and valid assessment tools are needed to successfully study hormone-related symptoms in breast cancer survivors; however, no gold standard currently exists for measuring these symptoms. This study evaluated the psychometric properties of a shortened version of the Breast Cancer Prevention Trial (BCPT) symptom checklist in a sample of 803 breast cancer survivors. Principal factor analysis with Promax oblique rotation revealed a five-factor structure, identifying five separate hormone-related symptoms scales: vasomotor symptoms, urinary incontinence, cognitive/mood changes, vaginal symptoms, and weight gain/appearance concern. Hormone-related symptom scale scores differed by demographic and clinical characteristics according to expectations, suggesting that these five scales from the shortened BCPT checklist are reasonably reliable and valid. Symptom scale scores were only weakly correlated with health-related quality of life scores; however, the pattern of results generally supported the validity of the symptom scales. This study adds to the evidence that breast cancer survivors experience a significant number of hormone-related symptoms. Future clinical trials and quality of life and symptom management intervention studies would benefit from accurate assessment of hormone-related symptoms with the five scales from the shortened BCPT checklist. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NCI, Outcomes Res Branch, ARP, DCCPS, Bethesda, MD 20892 USA. Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,M4-B402, Seattle, WA 98109 USA. EM amctiern@fhcrc.org FU NCI NIH HHS [CA92408, N01 PC035138-22, R25 CA092408] NR 26 TC 23 Z9 24 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD NOV PY 2006 VL 15 IS 11 BP 985 EP 1000 DI 10.1002/pon.1033 PG 16 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 107QZ UT WOS:000242187400005 PM 16470891 ER PT J AU Epstein, DH Preston, KL Stewart, J Shaham, Y AF Epstein, David H. Preston, Kenzie L. Stewart, Jane Shaham, Yavin TI Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure SO PSYCHOPHARMACOLOGY LA English DT Review DE conditioned drug cues; drug priming; construct validity; incubation; criterion validity; reinstatement; relapse; review; stress ID COCAINE-SEEKING BEHAVIOR; CORTICOTROPIN-RELEASING-FACTOR; STRESS-INDUCED REINSTATEMENT; CONDITIONED PLACE PREFERENCE; EXTRACELLULAR DOPAMINE LEVELS; SELF-ADMINISTERED COCAINE; CUE-INDUCED REINSTATEMENT; TIME-DEPENDENT CHANGES; HEROIN-SEEKING; ALCOHOL DEPENDENCE AB Background and rationale The reinstatement model is widely used to study relapse to drug addiction. However, the model's validity is open to question. Objective We assess the reinstatement model in terms of criterion and construct validity. Research highlights and conclusions We find that the reinstatement model has adequate criterion validity in the broad sense of the term, as evidenced by the fact that reinstatement in laboratory animals is induced by conditions reported to provoke relapse in humans. The model's criterion validity in the narrower sense, as a medication screen, seems promising for relapse to heroin, nicotine, and alcohol. For relapse to cocaine, criterion validity has not yet been established primarily because clinical studies have examined medication's effects on reductions in cocaine intake rather than relapse during abstinence. The model's construct validity faces more substantial challenges and is yet to be established, but we argue that some of the criticisms of the model in this regard may have been overstated. C1 NIDA, Clin Pharmacol & Therapeut Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. Concordia Univ, Dept Psychol, Ctr Studies Behav Neurobiol, Montreal, PQ H3G 1M8, Canada. NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA. RP Epstein, DH (reprint author), NIDA, Treatment Sect, Clin Pharmacol & Therapeut Branch, IRP,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM depstein@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013; shaham, yavin/G-1306-2014 OI Preston, Kenzie/0000-0003-0603-2479; FU Intramural NIH HHS NR 198 TC 333 Z9 337 U1 9 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2006 VL 189 IS 1 BP 1 EP 16 DI 10.1007/s00213-006-0529-6 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 096TY UT WOS:000241400900001 PM 17019567 ER PT J AU Duncan, EA Tamashiro, KLK Nguyen, MMN Gardner, SR Woods, SC Sakai, RR AF Duncan, Elizabeth A. Tamashiro, Kellie L. K. Nguyen, Mary M. N. Gardner, Stacy R. Woods, Stephen C. Sakai, Randall R. TI The impact of moderate daily alcohol consumption on aggression and the formation of dominance hierarchies in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE alcohol; sucrose; social stress; aggression; subordinate; dominant ID CORTICOTROPIN-RELEASING-FACTOR; CHRONIC SOCIAL STRESS; ETHANOL-CONSUMPTION; ANXIETY DISORDERS; INCREASES ALCOHOL; RECEPTOR-BINDING; PREFERENCE; BEHAVIOR; SHOCK; TESTOSTERONE AB Rationale and objective Group-housed male rats form social hierarchies, and under these conditions, it has been reported that subordinate ( SUB) rats consume more alcohol than dominant (DOM) rats. We tested the hypothesis that a history of drinking alcohol would cause SUB rats to consume even greater amounts of alcohol. Methods Male Long-Evans rats were trained to drink 10% alcohol or a sucrose/quinine solution equal in calories for 1 h/day using a sucrose-fading procedure. Subsequently, rats were housed in colonies ( four males, two females) in a visible burrow system (VBS) for 14 days. Individual control male rats were housed in a tub cage with one female. Rats were removed from the VBS ( or control environment) daily and given 1 h to drink alcohol or sucrose/quinine. Results Colonies given daily access to sucrose/quinine formed clear DOM/SUB relationships in all measured parameters. Alcohol-drinking colonies failed to establish a dominance hierarchy and displayed little aggression, with an average of 14.6 +/- 6.1 offensive attacks compared with 58.5 +/- 12.3 attacks carried out by DOM sucrose/quinine rats. During VBS housing, alcohol and sucrose/quinine intake decreased independent of housing environment or social status. Conclusions Contrary to prior reports of the effect of alcohol on aggressive behavior, moderate daily alcohol intake before and during VBS housing reduced aggression and precluded the formation of a dominance hierarchy in rats. C1 Natl Inst Drug Abuse, Baltimore, MD 21236 USA. Univ Cincinnati, Program Neurosci, Cincinnati, OH USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. RP Duncan, EA (reprint author), Natl Inst Drug Abuse, Room 434,Bldg C,5500 Nathan Shock Dr, Baltimore, MD 21236 USA. EM duncanel@mail.nih.gov OI Duncan-Vaidya, Elizabeth/0000-0003-3622-8819 FU NIDDK NIH HHS [DK 17844, DK 66596, T32 DK59803, R01 DK017844, R01 DK066596]; NINDS NIH HHS [F31 NS047791, F31 NS047791-01, F31 NS047791-02] NR 53 TC 11 Z9 13 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2006 VL 189 IS 1 BP 83 EP 94 DI 10.1007/s00213-006-0536-7 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 096TY UT WOS:000241400900008 PM 16972102 ER PT J AU Mintzer, MZ Kuwabara, H Alexander, M Brasic, JR Ye, WG Ernst, M Griffiths, RR Wong, DF AF Mintzer, Miriam Z. Kuwabara, Hiroto Alexander, Mohab Brasic, James R. Ye, Weiguo Ernst, Monique Griffiths, Roland R. Wong, Dean F. TI Dose effects of triazolam on brain activity during episodic memory encoding: a PET study SO PSYCHOPHARMACOLOGY LA English DT Article DE benzodiazepine; memory; PET; cerebral blood flow ID POSITRON-EMISSION-TOMOGRAPHY; MEDIAL TEMPORAL-LOBE; DRUG-INDUCED AMNESIA; BENZODIAZEPINE RECEPTORS; RECOGNITION MEMORY; ATTENTIONAL PROCESSES; ANTERIOR CINGULATE; PREFRONTAL CORTEX; WORKING-MEMORY; FRONTAL-CORTEX AB Rationale Although it is well established that acute benzodiazepine administration impairs episodic memory encoding, little is known about the neuroanatomical substrates of this effect. Objective The objective was to examine the acute dose effects of the benzodiazepine hypnotic triazolam on brain activity during episodic memory encoding. Methods After oral capsule administration (placebo, 0.1, 0.2, and 0.4 mg/70 kg triazolam), regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with O-15-H2O during performance of semantic categorization and orthographic categorization tasks in a double-blind, within-subject design in 12 healthy volunteers. The rCBF associated with episodic memory encoding was measured by subtracting the rCBF during orthographic categorization from that during semantic categorization and by examining correlations between brain activity during encoding and subsequent recognition memory performance. Results Results in the placebo condition replicated those of nonpharmacological encoding studies, including activation in left ventrolateral prefrontal cortex. Correlations between brain activity and subsequent memory performance additionally showed medial temporal activation. Triazolam produced dose-related impairment in memory performance and dose-related deactivation in encoding-associated areas including right prefrontal cortex, left parahippocampal gyrus, and left anterior cingulate cortex. Conclusions Results are consistent with behavioral evidence that benzodiazepines impair prefrontal control processes as well as contextual memory and episodic binding processes thought to be controlled by the medial temporal lobe. In addition to elucidating the brain mechanisms underlying these benzodiazepine-induced behavioral deficits, results of this study also help validate hypotheses generated in nonpharmacological neuroimaging studies regarding the processes controlled by these brain regions. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Mintzer, MZ (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mmintzer@jhmi.edu RI Brasic, James/B-3503-2008 OI Brasic, James/0000-0002-3948-4853 FU NIDA NIH HHS [K24 DA-00412, R01 DA-14101] NR 86 TC 10 Z9 10 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2006 VL 188 IS 4 BP 445 EP 461 DI 10.1007/s00213-006-0446-8 PG 17 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 097NT UT WOS:000241455400005 PM 16847681 ER PT J AU Birbaumer, N AF Birbaumer, Niels TI Breaking the silence: Brain-computer interfaces (BCI) for communication and motor control SO PSYCHOPHYSIOLOGY LA English DT Review DE brain-computer interface; brain-machine interface; EEG; invasive brain measures; locked-in syndrome ID SLOW CORTICAL POTENTIALS; RESONANCE-IMAGING FMRI; FOREBRAIN INHIBITORY MECHANISMS; AMYOTROPHIC-LATERAL-SCLEROSIS; THOUGHT-TRANSLATION DEVICE; SELF-REGULATION; MOVEMENT SIGNAL; HASTENED DEATH; TIME; BIOFEEDBACK AB Brain-computer interfaces (BCI) allow control of computers or external devices with regulation of brain activity alone. Invasive BCIs, almost exclusively investigated in animal models using implanted electrodes in brain tissue, and noninvasive BCIs using electrophysiological recordings in humans are described. Clinical applications were reserved with few exceptions for the noninvasive approach: communication with the completely paralyzed and locked-in syndrome with slow cortical potentials, sensorimotor rhythm and P300, and restoration of movement and cortical reorganization in high spinal cord lesions and chronic stroke. It was demonstrated that noninvasive EEG-based BCIs allow brain-derived communication in paralyzed and locked-in patients but not in completely locked-in patients. At present no firm conclusion about the clinical utility of BCI for the control of voluntary movement can be made. Invasive multielectrode BCIs in otherwise healthy animals allowed execution of reaching, grasping, and force variations based on spike patterns and extracellular field potentials. The newly developed fMRI-BCIs and NIRS-BCIs, like EEG BCIs, offer promise for the learned regulation of emotional disorders and also disorders of young children. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, MEG Ctr, D-72074 Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Birbaumer, N (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, MEG Ctr, Gartenstr 29, D-72074 Tubingen, Germany. EM niels.birbaumer@uni-Tuebingen.de NR 123 TC 226 Z9 245 U1 8 U2 91 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2006 VL 43 IS 6 BP 517 EP 532 DI 10.1111/j.1469-8986.2006.00456.x PG 16 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 099VV UT WOS:000241626200001 PM 17076808 ER PT J AU Christian, LM Stoney, CM AF Christian, Lisa M. Stoney, Catherine M. TI Social support versus social evaluation: Unique effects on vascular and myocardial response patterns SO PSYCHOSOMATIC MEDICINE LA English DT Article DE cardiovascular reactivity; social support; evaluation; vascular resistance; impedance cardiography ID CARDIOVASCULAR REACTIVITY; BLOOD-PRESSURE; PSYCHOLOGICAL CHALLENGE; IMPEDANCE CARDIOGRAPHY; BEHAVIORAL STRESSORS; HYPERTENSIVE MEN; LABORATORY MODEL; SEX-DIFFERENCES; FOLLOW-UP; DISEASE AB Objectives: This study examined the effects of companion presence and evaluation on cardiovascular reactivity to an acute stressor. Methods: Eighty-two women completed a speech task in one of four conditions: with an evaluative companion present, with a nonevaluative companion present, alone while being evaluated by a companion with a video camera, or alone while the companion waited outside. Results: A significant interaction between companion condition and evaluative condition on systolic blood pressure was found; women who were evaluated while alone demonstrated significantly greater reactivity than did women who were in the nonevaluative alone condition. Furthermore, both potential for evaluation and the presence of a companion had important influences on hemodynamic parameters underlying the blood pressure response. Specifically, those in evaluative conditions showed greater myocardial responding than those in nonevaluative conditions and those in alone conditions showed greater vascular responding than did those with companions present. Taken together, those in the evaluative alone condition demonstrated systolic blood pressure responses reflecting both myocardial and vascular contributions. Conclusions: Social support and social evaluation have unique effects on vascular and myocardial responding. The implications for future research include focus on the stress-buffering model of social support and the value of including impedance cardiography measures in investigations of cardiovascular functioning. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Stoney, CM (reprint author), NIH, Natl Ctr Complementary & Alternat Med, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM stoneyc@mail.nih.gov RI Christian, Lisa/E-2892-2011 OI Christian, Lisa/0000-0001-5571-050X FU NHLBI NIH HHS [R01 HL068956, HL068956, R01 HL068956-02]; NIAID NIH HHS [T32 AI055411, T32AI55411, T32 AI055411-02] NR 59 TC 9 Z9 9 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2006 VL 68 IS 6 BP 914 EP 921 DI 10.1097/01.psy.0000244023.20755.cf PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 108SK UT WOS:000242259300015 PM 17079702 ER PT J AU Morasco, BJ Pietrzak, RH Blanco, C Grant, BF Hasin, D Petry, NM AF Morasco, Benjamin J. Pietrzak, Robert H. Blanco, Carlos Grant, Bridget F. Hasin, Deborah Petry, Nancy M. TI Health problems and medical utilization associated with gambling disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOSOMATIC MEDICINE LA English DT Article DE pathologic gambling; health functioning; medical utilization; epidemiology; psychiatric disorder; mental health ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; QUALITY-OF-LIFE; UNITED-STATES; OLDER-ADULTS; PSYCHIATRIC-DISORDERS; SOCIOECONOMIC-STATUS; FAMILY-HISTORY; DRUG MODULES; SELF-REPORT AB Objective: Pathologic gambling is believed to be associated with adverse health consequences, but no prior studies have rigorously evaluated these relationships. We sought to examine medical disorders and health service utilization associated with problem and pathologic gambling. Method: A total of 43,093 adults aged 18 years and older were evaluated in the 2001 to 2002 National Epiderniologic Survey on Alcohol and Related Conditions. Self-reported medical diagnoses and past-year medical services used were assessed. Results: Pathologic gamblers were more likely than low-risk individuals to have been diagnosed with tachycardia (odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.05-2.97), angina (OR = 2.35; 95% Cl = 1.33-4.15), cirrhosis (OR = 3.90; 95% CI = 1.11-13.72), and other liver disease (OR = 2.98; 95% Cl = 1.07-8.26). Gambling severity was also associated with higher rates of medical utilization with pathologic gamblers more likely than low-risk individuals to have been treated in the emergency room in the year before the survey (OR = 1.98; 95% Cl = 1.27-3.09). Significant effects of gambling severity remained even after controlling for demographic characteristics (age, gender, ethnicity, marital status, education, income, and region of the country) and behavioral risk factors such as body mass index, alcohol abuse and dependence, nicotine dependence, and mood and anxiety disorders. Conclusions: A lifetime diagnosis of pathologic gambling is associated with several medical disorders and increased medical utilization, perhaps leading to a burden on healthcare costs in the United States. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Columbia Univ, Dept Psychiat, New York, NY USA. NIAAA, Lab Epidemiol & Biometry, Div Intramural Chem & Biol Res, NIH, Bethesda, MD 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 Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU NIAAA NIH HHS [P50-AA03510]; NIDA NIH HHS [R01-DA14618, P50-DA09241, R01-DA016855, R01-DA018883, R01-DA13444]; NIMH NIH HHS [R01-MH60417, R01-MH60417-SUPP] NR 54 TC 82 Z9 83 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2006 VL 68 IS 6 BP 976 EP 984 DI 10.1097/01.psy.0000238466.76172.cd PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 108SK UT WOS:000242259300022 PM 17132843 ER PT J AU Mushkacheva, G Rabinovich, E Privalov, V Povolotskaya, S Shorokhova, V Sokolova, S Turdakova, V Ryzhova, E Hall, P Schneider, AB Preston, DL Ron, E AF Mushkacheva, G. Rabinovich, E. Privalov, V. Povolotskaya, S. Shorokhova, V. Sokolova, S. Turdakova, V. Ryzhova, E. Hall, P. Schneider, A. B. Preston, D. L. Ron, E. TI Thyroid abnormalities associated with protracted childhood exposure to I-131 from atmospheric emissions from the Mayak weapons facility in Russia SO RADIATION RESEARCH LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; HIGH BACKGROUND-RADIATION; POWER-STATION ACCIDENT; HANFORD NUCLEAR SITE; CANCER-RISK; CHERNOBYL ACCIDENT; NODULARITY; NEOPLASIA; BYELARUS; CHILDREN AB Between 1948 and 1960, the Mayak nuclear weapons facility in Ozyorsk, Russia discharged relatively high levels of radionuclides, primarily I-131, into the atmosphere, resulting in appreciable exposure to the residents of Ozyorsk. To evaluate the association between thyroid diseases and childhood exposure to radioiodines, we screened 894 Ozyorsk residents born between 1952 and 1953. The study population was comprised of 581 exposed individuals living in Ozyorsk during the years of heaviest exposure and 313 nonexposed individuals who moved to Ozyorsk when radiation exposure from Mayak largely had ended. The screening protocol included a patient interview, palpation of the thyroid, cervical lymph nodes and salivary glands, an ultrasound examination, and measurement of fT4, TSH and TPOAb. Twenty-eight percent of the study group was diagnosed with a thyroid abnormality. The prevalence of nodular disease was significantly higher in the exposed group (20.7%) compared with the nonexposed (14.4%) group (relative risk = 1.4, 95% CI = 1.1; 1.9). Risks were larger for solitary nodules and for nodules >= 10 mm in diameter. Expansion of the study to increase the number of persons screened as well as detailed dose estimation would offer an unique opportunity to evaluate thyroid disease in relation to chronic exposure to radioiodines during childhood. (c) 2006 by Radiation Research Society. C1 NCI, DCEG, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. So Urals Biophys Inst, Ozyorsk, Russia. Chelyabinsk State Med Acad, Chelyabinsk, Russia. Karolinska Inst, Stockholm, Sweden. Univ Illinois, Chicago, IL 60680 USA. Hirosoft Int, Eureka, CA USA. RP Ron, E (reprint author), NCI, DCEG, Radiat Epidemiol Branch, EPS 7054, Bethesda, MD 20892 USA. EM cron@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CP-11014] NR 49 TC 5 Z9 7 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2006 VL 166 IS 5 BP 715 EP 722 DI 10.1667/RR0410.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 099UM UT WOS:000241621700002 PM 17067203 ER PT J AU Datta, K Jaruga, P Dizdaroglu, M Neumann, RD Winters, TA AF Datta, Kamal Jaruga, Pawel Dizdaroglu, Miral Neumann, Ronald D. Winters, Thomas A. TI Molecular analysis of base damage clustering associated with a site-specific radiation-induced DNA double-strand break SO RADIATION RESEARCH LA English DT Article ID COLI ENDONUCLEASE-III; DEPENDENT PROTEIN-KINASE; ESCHERICHIA-COLI; IONIZING-RADIATION; SYNTHETIC OLIGODEOXYNUCLEOTIDE; I-125 DECAY; MAMMALIAN-CELLS; SUBSTRATE-SPECIFICITY; OXIDATIVE DAMAGE; EXCISION-REPAIR AB Base damage flanking a radiation-induced DNA double-strand break (DSB) may contribute to DSB complexity and affect break repair. However, to date, an isolated radiation-induced DSB has not been assessed for such structures at the molecular level. In this study, an authentic site-specific radiation-induced DSB was produced in plasmid DNA by triplex forming oligonucleotide-targeted I-125 decay. A restriction fragment terminated by the DSB was isolated and probed for base damage with the E. coli DNA repair enzymes endonuclease III and formamidopyrimidine-DNA glycosylase. Our results demonstrate base damage clustering within 8 bases of the I-125-targeted base in the DNA duplex. An increased yield of base damage (purine > pyrimidine) was observed for DSBs formed by irradiation in the absence of DMSO. An internal control fragment 1354 bp upstream from the targeted base was insensitive to enzymatic probing, indicating that the damage detected proximal to the DSB was produced by the I-125 decay that formed the DSB. Gas chromatography-mass spectrometry identified three types of damaged bases in the similar to 32-bp region proximal to the DSB. These base lesions were 8-hydroxyguanine, 8-hydroxyadenine and 5-hydroxycytosine. Finally, evidence is presented for base damage > 24 bp upstream from the I-125-decay site that may form via a charge migration mechanism. (c) 2006 by Radiation Research Society. C1 NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21228 USA. RP Winters, TA (reprint author), NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 1C401,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twinters@mail.cc.nih.gov RI Jaruga, Pawel/M-4378-2015 FU Intramural NIH HHS [Z01 CL060001-13, Z99 CL999999] NR 59 TC 24 Z9 24 U1 1 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2006 VL 166 IS 5 BP 767 EP 781 DI 10.1667/RR0628.1 PG 15 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 099UM UT WOS:000241621700007 PM 17067210 ER PT J AU Krestinina, LY Preston, DL Ostroumova, EV Degteva, MO Ron, E Olga, VV Startsev, NV Akleyev, AV AF Krestinina, Ludmila Yu. Preston, Dale L. Ostroumova, Evgenia V. Degteva, Marina O. Ron, Elaine Olga, V. Vyushkova Startsev, Nicholas V. Akleyev, Alexander V. TI Comments on "protracted radiation exposure and cancer mortality in the Techa River cohort" by Krestinina et al. - Reply SO RADIATION RESEARCH LA English DT Letter C1 URCRM, Chelyabinsk 454076, Russia. Hirsoft Int Corp, Res & Dev, Eureka, CA 95501 USA. NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Krestinina, LY (reprint author), URCRM, Chelyabinsk 454076, Russia. NR 4 TC 1 Z9 1 U1 2 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2006 VL 166 IS 5 BP 814 EP 815 DI 10.1667/0033-7587(2006)166[814b:RTCOPR]2.0.CO;2 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 099UM UT WOS:000241621700013 ER PT J AU Choyke, PL AF Choyke, Peter L. TI Common and uncommon histologic subtypes of renal cell carcinoma: Imaging spectrum with pathologic correlation - Commentary SO RADIOGRAPHICS LA English DT Editorial Material ID TOMOGRAPHY C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2006 VL 26 IS 6 BP 1806 EP 1809 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 102QQ UT WOS:000241828200016 ER PT J AU O'Connor, SD Summers, RM Yao, JH Pickhardt, PJ Choi, JR AF O'Connor, Stacy D. Summers, Ronald M. Yao, Jianhua Pickhardt, Perry J. Choi, J. Richard TI CT Colonography with computer-aided polyp detection: Volume and attenuation thresholds to reduce false-positive findings owing to the ileocecal valve SO RADIOLOGY LA English DT Article ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONIC POLYPS; SCREENING MAMMOGRAPHY; LUNG NODULES; DIAGNOSIS; LESIONS; FEASIBILITY; POPULATION; PITFALLS; FEATURES AB Purpose: To retrospectively identify volume and average attenuation thresholds for differentiating between ileocecal valve (ICV) and polyp at computed tomographic (CT) colonography with computer-aided detection (CAD). Materials and Methods: Informed consent (with consent for future retrospective research) and institutional review board (IRB) approval were obtained for the original prospective study. This retrospective study had IRB approval, as well, and was HIPAA-compliant. A total of 496 patients were selected from a larger screening population. CT colonographic images from 394 patients (227 men, 167 women; mean age, 58.0 years; range, 40-79 years) were used as a training set, and images from 102 patients (76 men, 26 women; mean age, 59.8 years; range, 46-79 years) were used as a test set. A series of 2742 volume and attenuation thresholds, for which segmented findings both larger in volume and lower in average attenuation were labeled as ICVs and remaining findings were labeled polyps, were applied to the training set to determine settings with 100% sensitivity for polyp detection and the highest specificity for ICV detection. The optimal settings were then applied to the test set. Significance was assessed with the Fisher exact test, and 95% confidence intervals (CIs) were computed for sensitivity and specificity. Results: A total of 386 ICVs and 67 adenomatous polyps from the training set and 102 ICVs and 138 adenomatous polyps from the test set could be segmented with a three-dimensional segmentation algorithm. When supine and prone images were counted individually, 746 nonunique ICVs from the training set and 191 from the test set were segmentable. In the training set, a volume of 600 mm(3) and an attenuation of 36 HU provided 100% sensitivity (67 polyps; 95% CI: 93%, 100%) and the optimal 83% specificity (618 of 746 ICVs; 95% CI: 80%, 85%). When applied to the test set, this combination provided 97% sensitivity (134 of 138 polyps; 95% CI: 92%, 99%) and 84% specificity (160 of 191 ICVs; 95% CI: 78%, 89%). Differences in sensitivity and specificity in the detection of polyps between the sets were not significant. Conclusion: Volume and average CT attenuation thresholds can help differentiate most ICVs from true polyps. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Summers, RM (reprint author), NIH, Dept Radiol, 10 Ctr Dr,Bldg 10,Rm 1C351,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 38 TC 15 Z9 15 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2006 VL 241 IS 2 BP 426 EP 432 DI 10.1148/radiol.2412051223 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098KM UT WOS:000241519400013 PM 17005773 ER PT J AU Cid, MC Hoffman, MP Hernandez-Rodriguez, J Segarra, M Elkin, M Sanchez, M Vilardell, C Garcia-Martinez, A Pla-Campo, M Grau, JM Kleinman, HK AF Cid, M. C. Hoffman, M. P. Hernandez-Rodriguez, J. Segarra, M. Elkin, M. Sanchez, M. Vilardell, C. Garcia-Martinez, A. Pla-Campo, M. Grau, J. M. Kleinman, H. K. TI Association between increased CCL2 (MCP-1) expression in lesions and persistence of disease activity in giant-cell arteritis SO RHEUMATOLOGY LA English DT Article DE vasculitis; inflammation; chemokines ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SYSTEMIC INFLAMMATORY RESPONSE; POLYMYALGIA-RHEUMATICA; CORTICOSTEROID REQUIREMENTS; ISCHEMIC COMPLICATIONS; ANGIOGENIC ACTIVITY; TEMPORAL ARTERITIS; SERUM CHEMOKINES; IFN-GAMMA; TNF-ALPHA AB Objective. Patients with giant-cell arteritis (GCA) usually respond dramatically to corticosteroid treatment. However, recurrences are frequent and corticosteroid requirements are highly variable among patients. The aim of our study was to identify genes potentially involved in disease persistence. Methods. Gene expression was explored with cDNA arrays in temporal artery biopsies from six GCA patients with relapsing disease and six patients who easily achieved sustained remission. Differentially expressed genes of interest were subsequently analysed by quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry in temporal artery biopsies from 35 patients with biopsy-proven GCA and nine controls. Results. CCL2 (MCP-1) was up-regulated in temporal artery samples from relapsing individuals. In the extended series of patients, CCL2 mRNA concentration in lesions was significantly higher than in controls (31 +/- 15.6 vs 0.44 +/- 0.10, P = 0.0001). In addition, CCL2 was more abundant in patients who experienced two or more relapses during the first year compared with those who endured sustained remission (127 +/- 82 vs 11 +/- 5.5, P = 0.0233) and correlated with the cumulated prednisolone dose (R = 0.533, P = 0.0024). CCL2 mRNA concentration correlated with IL-1 beta (R = 0.45, P = 0.02), tumour necrosis factor-alpha (TNF-alpha) (R = 0.47, P = 0.013) and IL-6 (R = 0.52, P = 0.0053) mRNA. However, circulating CCL2 determined by ELISA was decreased in patients with strong systemic inflammatory response, suggesting that reduction in circulating CCL2 may reinforce the local gradient in lesions. Conclusion. Increased CCL2 (MCP-1) expression in lesions is associated with persistence of disease activity in GCA. C1 Hosp Clin Barcelona, Dept Internal Med, E-08036 Barcelona, Spain. Univ Barcelona, Dept Pathol, Vasculitis Res Unit,IDIBAPS, Hosp Clin Barcelona, Barcelona, Spain. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA. RP Cid, MC (reprint author), Hosp Clin Barcelona, Dept Internal Med, Villarroel 170, E-08036 Barcelona, Spain. EM mccid@clinic.ub.es OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 41 TC 28 Z9 28 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2006 VL 45 IS 11 BP 1356 EP 1363 DI 10.1093/rheumatology/ke1128 PG 8 WC Rheumatology SC Rheumatology GA 097EZ UT WOS:000241431000007 PM 16621921 ER PT J AU Miller, JH Kramer, BS AF Miller, Jennifer H. Kramer, Barnett S. TI Proteomics: Promise and problems SO SCIENTIST LA English DT Editorial Material ID OVARIAN-CANCER; NEUROBLASTOMA C1 NIH, Off Dis Prevent, Bethesda, MD 20892 USA. RP Miller, JH (reprint author), NIH, Off Dis Prevent, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV PY 2006 VL 20 IS 11 BP 34 EP 35 PG 2 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 100MT UT WOS:000241673900021 ER PT J AU Poodry, CA AF Poodry, Clifton A. TI The scientific approach SO SCIENTIST LA English DT Article C1 Natl Inst Gen Med Sci, Div Minor Opportun Res, NIH, Bethesda, MD 20892 USA. RP Poodry, CA (reprint author), Natl Inst Gen Med Sci, Div Minor Opportun Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV PY 2006 SU S BP 8 EP 9 PG 2 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 102HB UT WOS:000241800500004 ER PT J AU Norton, A AF Norton, Amy TI Juan Rivera - Profile SO SCIENTIST LA English DT Biographical-Item C1 NIAMSD, Mol Imflammat Sect, NIH, Bethesda, MD USA. RP Norton, A (reprint author), NIAMSD, Mol Imflammat Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV PY 2006 SU S BP 29 EP 29 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 102HB UT WOS:000241800500015 ER PT J AU Aiba, K Carter, MG Matoba, R Ko, MSH AF Aiba, Kazuhiro Carter, Mark G. Matoba, Ryo Ko, Minoru S. H. TI Genomic approaches to early embryogenesis and stem cell biology SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Review DE microarray; stem cells; preimplantation embryos; embryogenomics; large-scale analysis ID GENE-EXPRESSION ANALYSIS; PREIMPLANTATION MOUSE DEVELOPMENT; SUPPRESSION SUBTRACTIVE HYBRIDIZATION; EQUALIZED CDNA LIBRARY; MATCHED HUMAN HOMOLOGS; IN-SITU HYBRIDIZATION; RNA INTERFERENCE; LARGE-SCALE; GERM-CELLS; MICROARRAY PLATFORMS AB Large-scale systematic gene expression analyses of early embryos and stem cells provide useful information to identify genes expressed differentially or uniquely in these cells. We review the current status of various approaches applied to preimplantation embryos and stem cells: expressed sequence tag, serial analysis of gene expression, differential display, massively parallel signature sequencing, DNA microarray (DNA chip) analysis, and chromatin-immunoprecipitation microarrays. We also discuss the biological questions that can only be addressed by the analysis of global gene expression patterns, such as so-called sternness and developmental potency. As the emphasis now shifts from expression profiling to functional studies, we review the genome-scale functional studies of genes: expression cloning, gene trapping, RNA interference, and gene disruptions. Finally, we discuss the future clinical application of such methodologies. C1 NIA, Dev Genom & Aging Sect, Lab Genet, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Lab Genet, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU Intramural NIH HHS NR 114 TC 11 Z9 11 U1 0 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD NOV PY 2006 VL 24 IS 5 BP 330 EP 339 DI 10.1055/s-2006-952155 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 111TE UT WOS:000242476800008 PM 17123228 ER PT J AU Miura, Y Gao, ZG Miura, M Seo, BM Sonoyama, W Chen, WJ Gronthos, S Zhang, L Shi, ST AF Miura, Yasuo Gao, Zhigang Miura, Masako Seo, Byoung-Moo Sonoyama, Wataru Chen, WanJun Gronthos, Stan Zhang, Li Shi, Songtao TI Mesenchymal stem cell-organized bone marrow elements: An alternative hematopoietic progenitor resource SO STEM CELLS LA English DT Article DE mesenchymal stem cell; hematopoietic stem cell; platelet-derived growth factor; bone marrow organ system ID STROMAL CELLS; IN-VIVO; DENTAL-PULP; NICHE; OSTEOGENESIS; FIBROBLASTS; EXPRESSION; TISSUES; INVIVO; REPAIR AB Bone marrow-derived mesenchymal stem cells (BMMSCs) are multipotent postnatal stem cells that have been used for the treatment of bone defects and graft-versus-host diseases in clinics. In this study, we found that subcutaneously transplanted human BMMSCs are capable of organizing hematopoietic progenitors of recipient origin. These hematopoietic cells expressed multiple lineages of hematopoietic cell associated markers and were able to rescue lethally irradiated mice, with successful engraftment in the recipient, suggesting a potential bone marrow (BM) resource for stem cell therapies. Furthermore, we found that platelet-derived growth factor (PDGF) promotes the formation of BMMSC-generated BM niches through upregulation of beta-catenin, implying that the PDGF pathway contributes to the formation of ectopic BM. These results indicate that the BMMSC-organized BM niche system represents a unique hematopoietic progenitor resource possessing potential clinical value. C1 Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. Univ Maryland, Sch Med, Dept Physiol, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Johns Hopkins Sch Med, Sidney Kimmel Oncol Ctr, Div Hematol Immunol, Baltimore, MD USA. Inst Med & Vet Sci, Div Haematol, Mesenchymal Stem Cell Grp, Adelaide, SA 5000, Australia. RP Shi, ST (reprint author), Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. EM lizhang@som.umaryland.edu; songtaos@usc.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL061589, R01 HL61589] NR 24 TC 44 Z9 47 U1 1 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2006 VL 24 IS 11 BP 2428 EP 2436 DI 10.1634/stemcells.2006-0089 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 103NM UT WOS:000241893600012 PM 17071859 ER PT J AU Lin, L Isacson, O AF Lin, Ling Isacson, Ole TI Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by Netrin-1 and Slits SO STEM CELLS LA English DT Article DE embryonic stem cell; axon guidance; dopaminergic neuron; Netrin-1; Slit ID FLOOR PLATE; GUIDANCE; TRANSPLANTATION; RECEPTOR; PROTEIN; SYSTEM; RAT; EXPRESSION; REPELLENT; LIGAND AB The physical restoration of dopamine circuits damaged or lost in Parkinson disease by implanting embryonic stem (ES)-derived cells may become a treatment. It is critical to understand responses of ES-derived dopamine (DA) neurons to guidance signals that determine axonal path and targeting. Using a collagen gel culture system, we examined effects of secreted molecules Netrin-1 and Slits on neurite outgrowth of fetal DA neurons and murine ES-differentiated DA neurons. We have previously shown that fetal DA neurons express DCC and Robo1/2 receptors and that Netrin-1 and Slit2 function as an attractant and a repellent for DA neurite outgrowth. In the present study, we observe that both Slit1 and Slit3 repel and inhibit neurite growth of fetal DA neurons. Here, we also demonstrate that ES-differentiated neurons including DA neurons express the Netrin receptor DCC and Slit receptor Robo proteins. In the gel culture system of ES cells, Netrin-1 promoted neurite outgrowth mediated by DCC receptor, and Slit1 and Slit3 were inhibitory for neurite outgrowth through Robo receptors. Slit2 appeared to exert inhibitory as well as repulsive effects in the coculture assay. However, unlike fetal DA neurites, no directed neurite outgrowth was observed in the cocultures of ES-derived DA neurons with Netrin-1-, Slit1-, and Slit3-producing cells. The findings suggest that ES-derived DA neurons generated by current protocols can respond to guidance cues in vitro in a similar manner to fetal cells but also exhibit distinct responses. This may result from developmental differences generated by present in vitro methods of cell patterning or conditioning during ES cell differentiation. C1 Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, McLean Hosp, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. RP Lin, L (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Neuroregenerat Labs, 115 Mill St, Belmont, MA 02478 USA. EM llin@mclean.harvard.edu; isacson@hms.harvard.edu FU NINDS NIH HHS [P50 NS039793, P50 NS039793-07, P50 NS39793] NR 47 TC 45 Z9 46 U1 1 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2006 VL 24 IS 11 BP 2504 EP 2513 DI 10.1634/stemcells.2006-0119 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 103NM UT WOS:000241893600020 PM 16840550 ER PT J AU Cabana, R Frolova, EG Kapoor, V Thomas, RA Krishan, A Telford, WG AF Cabana, Raquel Frolova, Ella G. Kapoor, Veena Thomas, Richard A. Krishan, Awtar Telford, William G. TI The minimal instrumentation requirements for Hoechst side population analysis: Stem cell analysis on low-cost flow cytometry platforms SO STEM CELLS LA English DT Article DE Hoechst side population; stem cell; solid state laser; laser diode; mercury arc lamp; light-emitting diode ID ULTRAVIOLET LASER-DIODES; EXCITED FLUOROCHROMES; TRANSPORTER; VIOLET; ABCG2; PHENOTYPE; MARROW; EFFLUX AB The Hoechst side population (SP) technique is a critical method of identifying stem cells and early progenitors in rodent, nonhuman primate, and human hematopoietic and nonhematopoietic tissues. In this technique, the cell-permeable DNA-binding dye Hoechst 33342 is loaded into the cell population of interest; stem cells and early progenitors subsequently pump this dye out via an ATP-binding cassette membrane pump-dependent mechanism, resulting in a low-fluorescence "tail" ( the SP) when the cells are analyzed by flow cytometry. This population contains stem cells and early progenitors. One significant drawback of this method is the requirement of an UV laser to excite the Hoechst 33342. Unfortunately, flow cytometers equipped with UV sources are expensive to own and operate and are not readily available to many laboratories or institutions. In the interests of designing a less expensive flow cytometric system for stem cell analysis, we determined the minimum UV excitation and instrumentation requirements for measuring Hoechst SP. Less than 3 mW of UV laser output was required for adequate resolution of Hoechst SP on two cuvette-based flow cytometers, one of which was a simple, inexpensive benchtop analyzer ( the Quanta Analyzer; NPE Systems). Furthermore, Hoechst SP could also be adequately resolved on this epifluorescence-based cytometer platform using two nonlaser UV sources, a mercury arc lamp with a UV bandpass filter and a UV-emitting light-emitting diode. These results suggest that an economical flow cytometric system can be designed that is capable of resolving Hoechst SP, with a cost far lower than most UV laser-equipped commercial systems. An inexpensive system of this type would make Hoechst SP analysis available to a much broader group of stem cell investigators. C1 NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NPE Syst, Pembroke Pines, FL USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Miami, FL USA. RP Telford, WG (reprint author), NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Rm 3-3297,9000 Rockville Pike, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov FU Intramural NIH HHS NR 19 TC 15 Z9 18 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2006 VL 24 IS 11 BP 2573 EP 2581 DI 10.1634/stemcells.2006-0266 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 103NM UT WOS:000241893600028 PM 16888279 ER PT J AU Fruchter, O Zoumakis, E Alesci, S De Martino, M Chrousos, G Hochberg, Z AF Fruchter, Oren Zoumakis, Emmanouil Alesci, Salvatore De Martino, Massimo Chrousos, George Hochberg, Zeev TI Intracrine modulation of gene expression by intracellular generation of active glucocorticoids SO STEROIDS LA English DT Article DE 11 beta-hydroxysteroid dehydrogenase type-1; glucocorticoids; gene expression ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; BETA-HYDROXYSTEROID DEHYDROGENASE; ADIPOSE STROMAL CELLS; INSULIN SENSITIVITY; CORTISOL METABOLISM; TISSUE SENSITIVITY; CARBENOXOLONE; PREDNISOLONE; OBESITY; DIFFERENTIATION AB Glucocorticoids (GC) by either up-regulating or down-regulating the expression of genes influence cellular processes in every tissue and organ of the body. The enzyme 11 beta-hydroxysteroid dehydrogenase Type-1 (11 beta-HSD-1) confers bioactivity upon the inactive GC cortisone (E) and prednisone (P) by converting them to cortisol (F) and prednisolone (L), respectively. We sought to investigate whether gene expression modulation by GC is under the regulation of an intracrine mechanism that determines the intracellular concentration of active GC. Human cell lines were transiently and stably co-transfected with an expression construct for 11 beta-HSD-1 and a GC-responsive reporter gene and incubated with active and inactive GC. Whereas in cells that were not transfected with the expression construct for 11 beta-HSD-1 inactive GC had no transcriptional activity, in both transiently and stably transfected cells E and P demonstrated a dose-dependent transcriptional activity. This transcriptional potency of both inactive GC was effectively abolished by carbenoxolone, an 11 beta-HSD-1 inhibitor, and was directly related to the concentration of transfected 11 beta-HSD-1. We conclude that gene expression modulation by GC is under a decisive influence of target cell 11 beta-HSD-1 that modulates the intracellular concentration of active GC. The intracrine mechanism is an under- appreciated aspect of GC activity that could be a potential target for future therapies aimed at modulating GC effects at the cellular level. Crown Copyright (C) 2006 Published by Elsevier Inc. All rights reserved. C1 Meyer Childrens Hosp, Rambam Med Ctr, IL-31096 Haifa, Israel. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Fruchter, O (reprint author), Meyer Childrens Hosp, Rambam Med Ctr, IL-31096 Haifa, Israel. EM oren_md@inter.net.il NR 34 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD NOV PY 2006 VL 71 IS 11-12 BP 1001 EP 1006 DI 10.1016/j.steroids.2006.08.002 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 105VK UT WOS:000242060200011 PM 16996097 ER PT J AU Gan, L Speir, JA Conway, JF Lander, G Cheng, NQ Firek, BA Hendrix, RW Duda, RL Liljas, L Johnson, JE AF Gan, Lu Speir, Jeffrey A. Conway, James F. Lander, Gabriel Cheng, Naiqian Firek, Brian A. Hendrix, Roger W. Duda, Robert L. Liljas, Lars Johnson, John E. TI Capsid conformational sampling in HK97 maturation visualized by X-ray crystallography and cryo-EM SO STRUCTURE LA English DT Article ID ROTATION FUNCTION; VIRUS MATURATION; VIRAL CAPSIDS; CROSS-LINKING; PROTEIN; DYNAMICS; MODEL; SYSTEM AB Maturation of the bacteriophage HK97 capsid from a precursor (Prohead II) to the mature state (Head II) involves a 60 angstrom radial expansion. The mature particle is formed by 420 copies of the major capsid protein organized on a T = 7 laevo, lattice with each subunit covalently crosslinked to two neighbors. Well-characterized pH 4 expansion intermediates make HK97 valuable for investigating quaternary structural dynamics. Here, we use X-ray crystallography and cryo-EM to demonstrate that in the final transition in maturation (requiring neutral pH), pentons in Expansion Intermediate IV (EI-IV) reversibly sample 14 angstrom translations and 6 degrees rotations relative to a fixed hexon lattice. The limit of this trajectory corresponds to the Head II conformation that is secured at this extent only by the formation of the final class of covalent crosslinks. Mutants that cannot crosslink or EI-IV particles that have been rendered incapable of forming the final crosslink remain in the EI-IV state. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Pittsburgh, Sch Med, Dept Biol Struct, Pittsburgh, PA 15260 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Bacteriophage Inst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Uppsala Univ, Dept Cell & Mol Biol, S-75124 Uppsala, Sweden. CALTECH, Div Biol, Pasadena, CA 91106 USA. RP Johnson, JE (reprint author), Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. EM jackj@scripps.edu RI Gan, Lu/F-8317-2011; Conway, James/A-2296-2010 OI Gan, Lu/0000-0002-8685-4896; Conway, James/0000-0002-6581-4748 FU NCI NIH HHS [Y1-CO-1020]; NCRR NIH HHS [RR07707]; NIAID NIH HHS [R01 AI40101]; NIGMS NIH HHS [R01 GM47795, Y1-GM-1104] NR 33 TC 48 Z9 50 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 EI 1878-4186 J9 STRUCTURE JI Structure PD NOV PY 2006 VL 14 IS 11 BP 1655 EP 1665 DI 10.1016/j.str.2006.09.006 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 106UQ UT WOS:000242127800009 PM 17098191 ER PT J AU Ammerman, JM Ammerman, MD Dambrosia, J Ammerman, BJ AF Ammerman, Joshua M. Ammerman, Matthew D. Dambrosia, James Ammerman, Bruce J. TI A prospective evaluation of the role for intraoperative x-ray in lumbar discectomy. Predictors of incorrect level exposure SO SURGICAL NEUROLOGY LA English DT Article DE x-ray; lumbar; spine; discectomy; intraoperative; incorrect level ID LOW-BACK-PAIN; DISC HERNIATION; SURGERY; COMPLICATIONS AB Background: Lumbar discectomy is among the most frequently performed procedures by spine surgeons. Among the potential difficulties encountered during this procedure, incorrect spinal level surgery remains a significant concern for surgeons and patients. Multiple groups have advocated the use of intraoperative x-ray to reduce the incidence of incorrect level surgery; however, this technique has not been prospectively evaluated. Methods: In an effort to determine the incidence of incorrect level exposure during lumbar discectomy and to define patient characteristics predictive of wrong level exposure, we examined 100 consecutive patients who underwent lumbar discectomy by a single surgeon. After exposure, the surgeon was asked to identify the level exposed, which was confirmed by intraoperative x-ray. Several patient characteristics were then examined by logistical regression to identify features predictive of a mismatch between level of exposure and level of pathology. Results: The study population was composed of 48 men and 52 women who were aged 18 to 83 years. Patient weights ranged from 105 to 410 lb. There were 51 patients who had pathology at the L5-SI level; 44 patients, L4-L5; 3 patients, L3-L4; and I patient, L2-L3. Four patients had transitional vertebrae. The intended level was initially exposed in 85% of cases. Age and level of pathology (P <.05) were identified as factors predictive of a mismatch between intraoperative level of exposure and preoperative level of pathology. Conclusions: Pathology above L5-S1 and patient age have been shown to reliably predict incorrect level exposure. Based upon the findings of this study, the routine use of intraoperative x-ray to confirm the level of exposure should be considered in all cases of lumbar discectomy. (c) 2006 Elsevier Inc. All rights reserved. C1 George Washington Univ, Sch Med, Dept Neurol Surg, Washington, DC 20037 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Ammerman, JM (reprint author), George Washington Univ, Sch Med, Dept Neurol Surg, Washington, DC 20037 USA. EM jammerm@gwu.edu NR 18 TC 29 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD NOV PY 2006 VL 66 IS 5 BP 470 EP 474 DI 10.1016/j.surneu.2006.05.069 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 106UA UT WOS:000242126000006 PM 17084188 ER PT J AU Horton, R Coggill, P Miretti, MM Sambrook, JG Traherne, JA Ward, R Sims, S Palmer, S Sehra, H Harrow, J Rogers, J Carrington, M Trowsdale, J Beck, S AF Horton, R. Coggill, P. Miretti, M. M. Sambrook, J. G. Traherne, J. A. Ward, R. Sims, S. Palmer, S. Sehra, H. Harrow, J. Rogers, J. Carrington, M. Trowsdale, J. Beck, S. TI The LRC haplotype project: a resource for killer immunoglobulin-like receptor-linked association studies SO TISSUE ANTIGENS LA English DT Article DE haplotypes; killer immunoglobulin-like receptor; leucocyte receptor complex; polymorphism; single nucleotide ID HUMAN HISTORY; ORGANIZATION; CLUSTER AB There is increasing evidence for epistatic interactions between gene products (e.g. KIR) encoded within the Leukocyte Receptor Complex (LRC) with those (e.g. HLA) of the Major Histocompatibility Complex (MHC), resulting in susceptibility to disease. Identification of such associations at the DNA level requires comprehensive knowledge of the genetic variation and haplotype structure of the underlying loci. The LRC haplotype project aims to provide this knowledge by sequencing common LRC haplotypes. C1 Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Cambridge, Dept Pathol, Dept Immunol, Cambridge CB2 1QP, England. NCI, SAIC Frederick Inc, Lab Genome Diver, Frederick, MD 21702 USA. RP Beck, S (reprint author), Wellcome Trust Sanger Inst, Genome Campus, Cambridge CB10 1SA, England. EM beck@sanger.ac.uk FU Intramural NIH HHS; Medical Research Council [G0401569, G9800943]; NCI NIH HHS [N01-CO-12400, N01CO12400]; Wellcome Trust [, 077198] NR 8 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2006 VL 68 IS 5 BP 450 EP 452 DI 10.1111/j.1399-0039.2006.00697.x PG 3 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 102RU UT WOS:000241831800012 PM 17092261 ER PT J AU Luebke, RW Holsapple, MP Ladics, GS Luster, MI Selgrade, M Smialowicz, RJ Woolhiser, MR Germolec, DR AF Luebke, Robert W. Holsapple, Michael P. Ladics, Gregory S. Luster, Michael I. Selgrade, MaryJane Smialowicz, Ralph J. Woolhiser, Michael R. Germolec, Dori R. TI Immunotoxicogenomics: The potential of genomics technology in the immunotoxicity risk assessment process SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE immunotoxicogenomics; EPA; immunotoxicity; microarray analysis; risk assessment ID GENE; TOXICOGENOMICS; MICROARRAY; ALLERGEN AB Evaluation of xenobiotic-induced changes in gene expression as a method to identify and classify potential toxicants is being pursued by industry and regulatory agencies worldwide. A workshop was held at the Research Triangle Park campus of the Environmental Protection Agency to discuss the current state-of-the-science of "immunotoxicogenomics" and to explore the potential role of genomics techniques for immunotoxicity testing. The genesis of the workshop was the current lack of widely accepted triggering criteria for Tier 1 immunotoxicity testing in the context of routine toxicity testing data, the realization that traditional screening methods would require an inordinate number of animals and are inadequate to handle the number of chemicals that may need to be screened (e.g., high production volume compounds) and the absence of an organized effort to address the state-of-the-science of toxicogenomics in the identification of immunotoxic compounds. The major focus of the meeting was on the theoretical and practical utility of genomics techniques to (1) replace or supplement current immunotoxicity screening procedures, (2) provide insight into potential modes or mechanisms of action, and (3) provide data suitable for immunotoxicity hazard identification or risk assessment. The latter goal is of considerable interest to a variety of stakeholders as a means to reduce animal use and to decrease the cost of conducting and interpreting standard toxicity tests. A number of data gaps were identified that included a lack of dose response and kinetic data for known immunotoxic compounds and a general lack of data correlating genomic alterations to functional changes observed in vivo. Participants concluded that a genomics approach to screen chemicals for immunotoxic potential or to generate data useful to risk assessors holds promise but that routine use of these methods is years in the future. However, recent progress in molecular immunology has made mode and mechanism of action studies much more practical. Furthermore, a variety of published immunotoxicity studies suggest that microarray analysis is already a practical means to explore pathway-level changes that lead to altered immune function. To help move the science of immunotoxicogenomics forward, a partnership of industry, academia, and government was suggested to address data gaps, validation, quality assurance, and protocol development. C1 US EPA, Immunotoxicol Branch, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. Hlth Environm Sci Inst, Washington, DC 20005 USA. DuPont Co Inc, Crop Genet, Wilmington, DE 19880 USA. NIOSH, Toxicol & Mol Biol Branch, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Luebke, RW (reprint author), US EPA, Immunotoxicol Branch, Expt Toxicol Div, Natl Hlth & Environm Effects Res Lab,Off Res & De, Res Triangle Pk, NC 27711 USA. EM luebke.robert@epamail.epa.gov FU Intramural NIH HHS [Z99 ES999999] NR 20 TC 23 Z9 26 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2006 VL 94 IS 1 BP 22 EP 27 DI 10.1093/toxsci/kfl074 PG 6 WC Toxicology SC Toxicology GA 092KL UT WOS:000241095300003 PM 16882865 ER PT J AU Knobloch, M Portier, CJ Levionnois, OL Theurillat, R Thormann, W Spadavecchia, C Mevissen, M AF Knobloch, M. Portier, C. J. Levionnois, O. L. Theurillat, R. Thormann, W. Spadavecchia, C. Mevissen, M. TI Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE physiologically based pharmacokinetic (PBPk) model; ketamine; norketatnine; nociceptive withdrawal reflex (NWR); enantioselective metabolism; target-controlled infusion (TCI) ID NOCICEPTIVE WITHDRAWAL REFLEX; HUMAN LIVER-MICROSOMES; TEMPORAL SUMMATION; N-DEMETHYLATION; PARTITION-COEFFICIENTS; ADMINISTERED KETAMINE; ORGANIC-CHEMICALS; CONSCIOUS HORSES; BLOOD-FLOW; PHARMACOKINETICS AB Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 wg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were detetermined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TO and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketatnine. Furthermore, biotransfornation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TO at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses). (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ Bern, Div Anesthesiol, Dept Vet Clin Med, CH-3012 Bern, Switzerland. Univ Bern, Dept Clin Pharmacol, CH-3010 Bern, Switzerland. RP Mevissen, M (reprint author), Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland. EM meike.mevissen@vpi.unibe.ch RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES048002-18] NR 69 TC 41 Z9 45 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2006 VL 216 IS 3 BP 373 EP 386 DI 10.1016/j.taap.2006.06.011 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 101MT UT WOS:000241745600002 PM 16919695 ER PT J AU Herraiz, T Guillen, H Aran, VJ Idle, JR Gonzalez, FJ AF Herraiz, Tomas Guillen, Hugo Aran, Vicente J. Idle, Jeffrey R. Gonzalez, Frank J. TI Comparative aromatic hydroxylation and N-demethylation of MPTP neurotoxin and its analogs, N-methylated beta-carboline and isoquinoline alkaloids, by human cytochrome P450 2D6 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE cytochrome P450; CYP2D6; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-methyl-4-phenylpyridinium; MPTP neurotoxin; Parkinson's disease; tetrahydro-beta-carbolines; beta-carbolines; isoquinolines; monoamine oxidase; MAO; polymorphism; N-demethylation; hydroxylation; metabolism ID MONOAMINE-OXIDASE INHIBITORS; RAT-LIVER MICROSOMES; PARKINSONS-DISEASE; HUMAN BRAIN; CYP2D6 POLYMORPHISM; BIOACTIVE ALKALOIDS; RADICAL SCAVENGERS; PESTICIDE EXPOSURE; P450 REDUCTASE; TOBACCO-SMOKE AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxin is a chemical inducer of Parkinson's disease (PD) whereas N-methylated beta-carbolines and isoquinolines are naturally occurring analogues of MPTP involved in PD. This research has studied the oxidation of MPTP by human CYP2D6 (CYP2D6*1 and CYP2D6*10 allelic variants) as well as by a mixture of cytochrome P450s-resembling HIM, and the products generated compared with those afforded by human monoamine oxidase (MAO-B). MPTP was efficiently oxidized by CYP2D6 to two main products: MPTP-OH (p-hydroxylation) and PTP (N-demethylation), with turnover numbers of 10.09 min(-1) and K-m of 79.36 +/- 3 mu M (formation of MPTP-OH) and 18.95 min(-1) and K-m 69.6 +/- 2.2 mu M (PTP). Small amounts of dehydrogenated toxins MPDP+ and MPP+ were also detected. CYP2D6 competed with MAO-B for the oxidation of MPTP. MPTP oxidation by MAO-B to MPDP+ and MPP+ toxins (bioactivation) was up to 3-fold higher than CYP2D6 detoxification to PTP and MPTP-OH. Several N-methylated beta-carbolines and isoquinolines were screened for N-demethylation (detoxification) that was not significantly catalyzed by CYP2D6 or. the P450s mixture. In contrast, various beta-carbolines were efficiently hydroxylated to hydroxy-beta-carbolines by CYP2D6. Thus, N(2)-methyl-1,2,3,4-tetrahydro-beta-carboline (a close MPTP analog) was highly hydroxylated to 6-hydroxy-N(2)-methyl-1,2,3,4-tetrahydro-beta-carboline and a corresponding 7-hydroxy-derivative. Thus, CYP2D6 could participate in the bioactivation and/or detoxification of these neuroactive compounds by an active hydroxylation pathway. The CYP2D6*1 enzymatic variant exhibited much higher metabolism of both MPTP and N(2)-methyl-1,2,3,4-tetrahydro-beta-carboline than the CYP2D6*10 variant, highlighting the importance of CYP2D6 polymorphism in the oxidation of these toxins. Altogether, these results suggest that CYP2D6 can play an important role in the metabolic outcome of both MPTP and beta-carbolines. Published by Elsevier Inc. C1 Spanish Council Sci Res, CSIC, Inst Fermentac Ind, Madrid 28006, Spain. Spanish Council Sci Res, CSIC, Inst Quim Med, Madrid 28006, Spain. Charles Univ, Fac Med 1, Inst Pharmacol, Prague 12800, Czech Republic. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Herraiz, T (reprint author), Spanish Council Sci Res, CSIC, Inst Fermentac Ind, Juan Cierva 3, Madrid 28006, Spain. EM therraiz@ifi.csic.es RI Aran, Vicente/K-8245-2014; Herraiz, Tomas/K-9958-2014; OI Aran, Vicente/0000-0002-3390-7157; Herraiz, Tomas/0000-0003-3682-9227; Guillen Fuerte, Hugo/0000-0003-4101-5076 NR 87 TC 24 Z9 25 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2006 VL 216 IS 3 BP 387 EP 398 DI 10.1016/j.taap.2006.06.003 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 101MT UT WOS:000241745600003 PM 16870220 ER PT J AU Liu, J Benbrahim-Tallaa, L Qian, X Yu, LM Xie, YX Boos, J Qu, W WaalkeS, MP AF Liu, Jie Benbrahim-Tallaa, Lamia Qian, Xun Yu, Limei Xie, Yaxiong Boos, Jennifer Qu, Wei Waalkes, Michael P. TI Further studies on aberrant gene expression associated with arsenic-induced malignant transformation in rat liver TRL1215 cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; arsenic transformed TRL1215 cells; gene expression; demethylation ID IN-UTERO; INORGANIC ARSENICALS; DRINKING-WATER; ADULT MICE; CARCINOGENESIS; EXPOSURE; RESISTANCE; METALLOTHIONEIN; OVEREXPRESSION; INDUCTION AB Chronic arsenic exposure of rat liver epithelial TRL1215 cells induced malignant transformation in a concentration-dependent manner. To further define the molecular events of these arsenic-transformed cells (termed CASE cells), gene expressions associated with arsenic carcinogenesis or influenced by methylation were examined. Real-time RT-PCR showed that at carcinogenic concentrations (500 nM, and to a less extent 250 nM of arsenite), the expressions of a-fetoprotein (AFP), Wilm's tumor protein-1 (WT-1), c-jun, c-myc, H-ras, c-met and hepatocyte growth factor, heme oxygenase-1, superoxide dismutase-1, glutathione-S-transferase-pi and metallothionein-1 (MT) were increased between 3 to 12-fold, while expressions of insulin-like growth factor II (IGF-II) and fibroblast growth factor receptor (FGFR1) were essentially abolished. These changes were not significant at the non-carcinogenic concentration (125 nM), except for IGF-II. The positive cell-cycle regulators cyclin D1 and PCNA were overexpressed in CASE cells, while the negative regulators p21 and p16 were suppressed. Western-blot confirmed increases in AFP, WT-1, cyclin D1 and decreases in p16 and p21 protein in CAsE cells. The CASE cells over-expressed MT but the demethylating agent 5-aza-deoxycytidine (5-aza-dC, 2.5 mu M, 72 h) stimulated further MT expression. 5-Aza-deoxycytidine restored the loss of expression of p21 in CASE cells to control levels, but did not restore the expression of p16, IGF-II, or FGFR1, indicating the loss of expression of these genes is due to factors other than DNA methylation changes. Overall, an intricate variety of gene expression changes occur in arsenic-induced malignant transformation of liver cells including oncogene activation and alterations in expression of genes critical to growth regulation. Published by Elsevier Inc. C1 NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Zunyi Med Coll, Zunyi, Peoples R China. RP Liu, J (reprint author), NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect, Mail Drop F-09, Res Triangle Pk, NC 27709 USA. EM Liu6@niehs.nih.gov FU Intramural NIH HHS NR 34 TC 32 Z9 35 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2006 VL 216 IS 3 BP 407 EP 415 DI 10.1016/j.taap.2006.06.006 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 101MT UT WOS:000241745600005 PM 16876216 ER PT J AU Zhang, XJ Chen, DX Xu, HH Zhao, ML Fang, N Du, H Zhou, YS Cheng, ML Yuan, W Jiang, L Xiao, H Wa, QB Liu, LM Liu, J Waalkes, MP AF Zhang, X. J. Chen, D. X. Xu, H. H. Zhao, M. L. Fang, N. Du, H. Zhou, Y. S. Cheng, M. L. Yuan, W. Jiang, L. Xiao, H. Wa, Q. B. Liu, L. M. Liu, J. Waalkes, M. P. TI Increased glycophorin A somatic cell variant frequency in arsenic-exposed patients of Guizhou, China SO TOXICOLOGY LETTERS LA English DT Article DE arsenic; glycophorin A mutation; MN blood type; variant frequency; carcinogenesis; biomarker ID MUTATION ASSAY; WORKERS; LOCUS; MICE; CARCINOGENESIS; INDUCTION; PULMONARY; STYRENE; CANCER; TUMORS AB Exposure to arsenic through domestic burning arsenic-containing coal causes various tumors in a population of Guizhou, China. The glycophorin A (GPA) assay is a human mutation assay detecting somatic variation in erythrocytes expressing the MN blood type, and was used to assess genotoxicity of arsenic-exposed patients. Peripheral blood was collected from 18 adult healthy subjects and 40 arsenic-exposed patients in heparin-treated tubes. Erythrocytes were isolated, fixed in formalin and immuno-labeled with fluorescent antibodies against GPA, followed by flow cytometry analysis. Arsenic exposure increased the variant frequency (expressed as the number of variant red cells per 10(6) erythrocytes): NN, 3.7 in healthy subjects versus 21.2 in arsenic-exposed patients; N phi, 12.6 versus 33.1; MM, 13.1 versus 110; and M phi, 5.2 versus 20.3. The total GPA variant frequency was increased about five-fold (34.7 in healthy subjects versus 185 in arsenosis patients). Furthermore, the variant frequency was significantly higher in skin tumor-bearing patients: NN, 19.4 in arsenic-exposed non-tumor patients versus 31.5 in tumor-bearing patients; N phi, 29.5 versus 54.5; MM, 102 versus 159; M phi, 15.9 versus 45.1. Total GPA variant frequency in arsenic-exposed patients bearing skin tumors was significantly increased compared to patients without skin tumors (167 versus 290). The relationship between arsenic exposure history and GPA variant frequency was less evident. These data demonstrate that arsenic exposure is associated with mutations at the GPA locus, an effect exaggerated in patients bearing arsenic-induced skin tumors. The variant frequency of GPA could be a useful biomarker for arsenic exposure and arsenic carcinogenesis. Published by Elsevier Ireland Ltd. C1 Zunyi Med Coll Hosp, Zunyi 563000, Guizhou, Peoples R China. SW Prefecture CDC, Zunyi, Guizhou, Peoples R China. Guiyang Med Coll, Guiyang, Peoples R China. NIEHS, NCI, LCC, Res Triangle Pk, NC 27709 USA. RP Zhang, XJ (reprint author), Zunyi Med Coll Hosp, Zunyi 563000, Guizhou, Peoples R China. EM xinjiangzhang@sohu.com; liu6@niehs.nih.gov FU Intramural NIH HHS NR 31 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV 1 PY 2006 VL 167 IS 1 BP 47 EP 53 DI 10.1016/j.toxlet.2006.08.008 PG 7 WC Toxicology SC Toxicology GA 104OJ UT WOS:000241967400007 PM 17029826 ER PT J AU Puri, N Roche, PA AF Puri, Niti Roche, Paul A. TI Ternary SNARE complexes are enriched in lipid rafts during mast cell exocytosis SO TRAFFIC LA English DT Article DE exocytosis; lipid rafts; mast cells; RBL cell; SNAP-23; SNARE ID FC-EPSILON-RI; PLASMA-MEMBRANE; PC12 CELLS; EPITHELIAL-CELLS; MODEL MEMBRANES; ALPHA-SNAP; FUSION; PROTEINS; ASSOCIATION; RECEPTOR AB Lipid rafts are membrane microdomains rich in cholesterol and glycosphingolipids that have been implicated in the regulation of intracellular protein trafficking. During exocytosis, a class of proteins termed SNAREs mediate secretory granule-plasma membrane fusion. To investigate the role of lipid rafts in secretory granule exocytosis, we examined the raft association of SNARE proteins and SNARE complexes in rat basophilic leukemia (RBL) mast cells. The SNARE protein SNAP-23 co-localized with a lipid raft marker and was present in detergent-insoluble lipid raft microdomains in RBL cells. By contrast, only small amounts (< 20%) of the plasma membrane SNARE syntaxin 4 or the granule-associated SNARE vesicle-associated membrane protein (VAMP)-2 were present in these microdomains. Despite this, essentially all syntaxin 4 and most of VAMP-2 in these rafts were present in SNARE complexes containing SNAP-23, while essentially none of these complexes were present in nonraft membranes. Whereas SNAP-23 is membrane anchored by palmitoylation, the association of the transmembrane protein syntaxin 4 with lipid rafts was because of its binding to SNAP-23. After stimulating mast cells exocytosis, the amount of syntaxin 4 and VAMP-2 present in rafts increased twofold, and these proteins were now present in raft-associated phospho-SNAP-23/syntaxin 4/VAMP-2 complexes, revealing differential association of SNARE fusion complexes during the process of regulated exocytosis. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU Intramural NIH HHS NR 63 TC 65 Z9 67 U1 2 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD NOV PY 2006 VL 7 IS 11 BP 1482 EP 1494 DI 10.1111/j.1600-0854.2006.00490.x PG 13 WC Cell Biology SC Cell Biology GA 093GO UT WOS:000241156500006 PM 16984405 ER PT J AU Kohn, MH Murphy, WJ Ostrander, EA Wayne, RK AF Kohn, Michael H. Murphy, William J. Ostrander, Elaine A. Wayne, Robert K. TI Genomics and conservation genetics SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Review ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NATURAL-SELECTION; DROSOPHILA-MELANOGASTER; MOLECULAR EVOLUTION; LINKAGE DISEQUILIBRIUM; POPULATION PERSISTENCE; DELETERIOUS MUTATIONS; INBREEDING DEPRESSION; CAPTIVE POPULATIONS; POSITIVE SELECTION AB In large part, the relevance of genetics to conservation rests on the premise that neutral marker variation in populations reflects levels of detrimental and adaptive genetic variation. Despite its prominence, this tenet has been difficult to evaluate, until now. As we discuss here, genome sequence information and new technological and bioinformatics platforms now enable comprehensive surveys of neutral variation and more direct inferences of detrimental and adaptive variation in species with sequenced genomes and in 'genome-enabled' endangered taxa. Moreover, conservation schemes could begin to consider specific pathological genetic variants. A new conservation genetic agenda would utilize data from enhanced surveys of genomic variation in endangered species to better manage functional genetic variation. C1 Rice Univ, Dept Ecol & Evolutionary Biol, Houston, TX 77005 USA. Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX 77843 USA. NHGRI, NIH, Comparat Canc Sect, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Kohn, MH (reprint author), Rice Univ, Dept Ecol & Evolutionary Biol, MS 170,6100 Main St, Houston, TX 77005 USA. EM hmkohn@rice.edu OI Ostrander, Elaine/0000-0001-6075-9738 NR 81 TC 115 Z9 124 U1 4 U2 84 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD NOV PY 2006 VL 21 IS 11 BP 629 EP 637 DI 10.1016/j.tree.2006.08.001 PG 9 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 105DQ UT WOS:000242010000008 PM 16908089 ER PT J AU Zanetti, M Franchini, G AF Zanetti, Maurizio Franchini, Genoveffa TI T cell memory and protective immunity by vaccination: is more better? SO TRENDS IN IMMUNOLOGY LA English DT Review ID RESPIRATORY VIRUS-INFECTIONS; ACTIVE ANTIRETROVIRAL THERAPY; IN-VIVO; IMMUNOLOGICAL MEMORY; LEISHMANIA-MAJOR; DENDRITIC CELLS; CUTTING EDGE; HOMEOSTATIC PROLIFERATION; LYMPHOCYTE-RESPONSES; LINEAGE RELATIONSHIP AB Protection against intracellular pathogens or tumor antigens requires T-cell mediated responses. Recently, it has become apparent that protection against disease correlates with T cells of the central memory type in many instances. Here, we analyze current data to distill a set of rules for the induction and maintenance of central memory T-cell responses. Recent studies show that T-cell help and the lack of overt inflammation at the time of priming are prerequisite for the induction, maintenance and expansion of memory T cells. Central to our hypothesis is that, in addition to these factors, successful vaccination in the immunologically inexperienced individual should be based on low antigen dose, to decelerate replicative senescence in responding cells and favor lineage differentiation of central memory T cells. In the immunologically experienced individual, it will be necessary, in addition, to abate the antigen load in plasma before vaccination. These guiding principles might help to raise improved protective T-cell responses by vaccination in humans. C1 Univ Calif San Diego, Immunol Lab, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. RP Zanetti, M (reprint author), Univ Calif San Diego, Immunol Lab, Dept Med, La Jolla, CA 92093 USA. EM mzanetti@ucsd.edu FU NCI NIH HHS [CA 092119]; NIAID NIH HHS [AI 062894] NR 90 TC 31 Z9 32 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2006 VL 27 IS 11 BP 511 EP 517 DI 10.1016/j.it.2006.09.004 PG 7 WC Immunology SC Immunology GA 104DW UT WOS:000241937400004 PM 16997631 ER PT J AU Mattson, MP Cheng, AW AF Mattson, Mark P. Cheng, Aiwu TI Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses SO TRENDS IN NEUROSCIENCES LA English DT Review ID GARLIC ORGANOSULFUR COMPOUNDS; CULTURED HIPPOCAMPAL-NEURONS; FOCAL CEREBRAL-ISCHEMIA; RED WINE POLYPHENOL; METHYL-D-ASPARTATE; NF-KAPPA-B; OXIDATIVE STRESS; 3-NITROPROPIONIC ACID; CELL-SURVIVAL; NEURODEGENERATIVE DISORDERS AB Diets rich in vegetables and fruits are associated with reduced risk of several major diseases, including neurodegenerative disorders. Although some beneficial phytochernicals might function solely as antioxidants, it is becoming clear that many of the beneficial chemicals in vegetables and fruits evolved as toxins (to dissuade insects and other predators) that, at subtoxic doses, activate adaptive cellular stress-response pathways in a variety of cells including neurons. Examples of such 'preconditioning' or 'neurohormesis' pathways include those involving cell-survival signaling kinases, the transcription factors NRF2 and CREB, and histone deacetylases of the sirtuin family. In these ways, neurolhormetic phytochernicals such as resveratrol, sulforaphanes and curcurnin might protect neurons against injury and disease by stimulating the production of antioxidant enzymes, neurotrophic factors, protein chaperones and other proteins that help cells to withstand stress. Thus, as we discuss in this review, highly conserved longevity and survival pathways in neurons are the targets of many phytochemicals. C1 Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 79 TC 161 Z9 166 U1 3 U2 28 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2006 VL 29 IS 11 BP 632 EP 639 DI 10.1016/j.tins.2006.09.001 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 109FX UT WOS:000242294400006 PM 17000014 ER PT J AU Schlander, M Schwarz, O Hakkaart-van Roijen, L Jensen, PS Persson, U Santosh, PJ Trott, GE AF Schlander, M. Schwarz, O. Hakkaart-van Roijen, L. Jensen, P. S. Persson, U. Santosh, P. J. Trott, G. E. CA MTA Cooperative Grp TI Functional impairment of patients with attention-deficit/hyperactivity disorder (ADHD): An alternative cost-effectiveness analysis of clinically proven treatment strategies based upon the NIMH MTA Study SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, Eschborn, Germany. Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, IHE, Lund, Sweden. Great Ormond St Hosp Children, Inst Child Hlth, London WC1N 3JH, England. Univ Wurzburg, Aschaffenburg, Germany. NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A312 EP A312 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000395 ER PT J AU Schlander, M Schwarz, O Hakkaart-van Roijen, L Jensen, PS Persson, U Santosh, PJ Trott, GE AF Schlander, M. Schwarz, O. Hakkaart-van Roijen, L. Jensen, P. S. Persson, U. Santosh, P. J. Trott, G. E. CA MTA Cooperative Gro O TI Cost-effectiveness of clinically proven treatment strategies for attention-deficit/hyperactivity disorder (ADHD) in five jurisdictions SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, Eschborn, Germany. Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, IHE, Lund, Sweden. Great Ormond St Hosp Children, Inst Child Hlth, London WC1N 3JH, England. Univ Wurzburg, Aschaffenburg, Germany. NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A312 EP A312 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000394 ER PT J AU Schlander, M Schwarz, O Foster, EM Hakkaart-van Roijen, L Jensen, PS Persson, U Santosh, PJ Trott, GE AF Schlander, M. Schwarz, O. Foster, E. M. Hakkaart-van Roijen, L. Jensen, P. S. Persson, U. Santosh, P. J. Trott, G. E. CA MTA Cooperative Grp O TI Cost-effectiveness of clinically proven treatment strategies for attention-deficit/hyperactivity disorder (ADHD): Impact of coexisting conditions SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Inst Innovat & Valuat Hlth Care, Eschborn, Germany. Univ N Carolina, Chapel Hill, NC USA. Inst Med Technol Assessment, Rotterdam, Netherlands. Columbia Univ, New York, NY USA. Swedish Inst Hlth Econ, IHE, Lund, Sweden. Great Ormond St Hosp Children, Inst Child Hlth, London WC1N 3JH, England. Univ Wurzburg, Aschaffenburg, Germany. NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2006 VL 9 IS 6 BP A309 EP A309 DI 10.1016/S1098-3015(10)63533-4 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 090AC UT WOS:000240922000386 ER PT J AU Steele, KE Seth, P Catlin-Lebaron, KMK Schoneboom, BA Husain, MM Grieder, F Maheshwari, RK AF Steele, K. E. Seth, P. Catlin-Lebaron, K. M. K. Schoneboom, B. A. Husain, M. M. Grieder, F. Maheshwari, R. K. TI Tunicamycin enhances neuroinvasion and encephalitis in mice infected with Venezuelan equine encephalitis virus SO VETERINARY PATHOLOGY LA English DT Article DE brain; encephalomyelitis; immunohistochemistry; mice; plaque assay; Venezuelan ID BLOOD-BRAIN-BARRIER; ANNUAL RYEGRASS TOXICITY; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL MENINGITIS; VIRAL NEUROINVASION; BALB/C MICE; GUINEA-PIGS; LIPOPOLYSACCHARIDE; ENCEPHALOMYELITIS; PERMEABILITY AB Venezuelan equine encephalitis (VEE) viruses cause natural outbreaks in humans and horses and represent a significant biothreat agent. The effect of tunicamycin on the course of the disease in mice with VEE was investigated, and the combined effects of these agents was characterized. CD-1 mice given 2.5 mu g of tunicamycin had > 1,000-fold more virus in the brain 48 hours after infection with the virulent VEE strain V3000 and >= 100-fold of the attenuated strain V3034 at all tested times than did untreated mice, indicating enhanced neuroinvasion. Tunicamycin did not alter the viremia profiles of these viruses nor the replication of V3000 in the brain itself. Tunicamycin alone caused ultrastructural blood-brain barrier damage, yet neuroinvasion by V3000 in treated mice appeared to occur via the olfactory system rather than the blood-brain barrier. Tunicamycin-treated, V3000-infected mice also exhibited earlier and more severe weight loss, neurological signs, neuronal infection, neuronal necrosis and apoptosis, and inflammation than untreated, V3000-infected mice. The mean survival time of tunicamycin-treated, V3000-infected mice was 7.3 days versus 9.9 days for untreated, V3000-infected mice. These studies imply that animals that ingest toxins similar to tunicamycin, including the agent of annual ryegrass toxicity in livestock, are conceivably at greater risk from infections by encephalitis viruses and that humans and horses exposed to agents acting similar to tunicamycin may be more susceptible to encephalitis caused by VEE viruses. The exact mechanism of tunicamycin-enhanced neuroinvasion by VEE viruses requires further study. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Ind Toxicol Res Ctr, Lucknow 226001, Uttar Pradesh, India. NIH, Div Comparat Med, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Maheshwari, RK (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM rmaheshwari@usuhs.mil RI khan, raja/B-5726-2012; pasuvalingam, visha/B-5717-2012 NR 32 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 2006 VL 43 IS 6 BP 904 EP 913 DI 10.1354/vp.43-6-904 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 108FN UT WOS:000242225800005 PM 17099147 ER PT J AU Forgacs, E Cartwright, S Kovacs, M Sakamoto, T Sellers, JR Corrie, JET Webb, MR White, HD AF Forgacs, Eva Cartwright, Suzanne Kovacs, Mihaly Sakamoto, Takeshi Sellers, James R. Corrie, John E. T. Webb, Martin R. White, Howard D. TI Kinetic mechanism of myosinV-S1 using a new fluorescent ATP analogue SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; UNCONVENTIONAL MYOSIN; ACTOMYOSIN; ACTIN; MOTOR; ADP; PROCESSIVITY; SKELETAL; BINDING; HYDROLYSIS AB We have used a new fluorescent ATP analogue, 3'-(7-diethylaminocoumarin-3-carbonylamino)3'-deoxyadenosine-5'-triphosphate ( deac-aminoATP), to study the ATP hydrolysis mechanism of the single headed myosinV-S1. Our study demonstrates that deac-aminoATP is an excellent substrate for these studies. Although the deac-amino nucleotides have a low quantum yield in free solution, there is a very large increase in fluorescence emission ( similar to 20-fold) upon binding to the myosinV active site. The fluorescence emission intensity is independent of the hydrolysis state of the nucleotide bound to myosinV-S1. The very good signal-to-noise ratio that is obtained with deac-amino nucleotides makes them excellent substrates for studying expressed proteins that can only be isolated in small quantities. The combination of the fast rate of binding and the favorable signal-to-noise ratio also allows deac- nucleotides to be used in chase experiments to determine the kinetics of ADP and Pi dissociation from actomyosin-ADP-Pi. Although phosphate dissociation from actomyosinV-ADP-Pi does not itself produce a fluorescence signal, it produces a lag in the signal for deac-aminoADP dissociation. The lag provides direct evidence that the principal pathway of product dissociation from actomyosinV-ADP-Pi is an ordered mechanism in which phosphate precedes ADP. Although the mechanism of hydrolysis of deac- aminoATP by ( acto) myosinV-S1 is qualitatively similar to the ATP hydrolysis mechanism, there are significant differences in some of the rate constants. Deac-aminoATP binds 3-fold faster to myosinV-S1, and the rate of deac-aminoADP dissociation from actomyosinV-S1 is 20-fold slower. Deac-aminoATP supports motility by myosinV-HMM on actin at a rate consistent with the slower rate of deac-aminoADP dissociation. C1 Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. Natl Inst Med Res, MRC, London NW7 1AA, England. NHLBI, Lab Mol Physiol, Bethesda, MD 20892 USA. Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. RP White, HD (reprint author), Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. EM whitehd@evms.edu RI Kovacs, Mihaly/A-6841-2011 FU FIC NIH HHS [D43 TW006230, 1 R01 TW0072412S-1]; Medical Research Council [MC_U117512742, MC_U117532185]; NIBIB NIH HHS [EB00209] NR 32 TC 20 Z9 20 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 31 PY 2006 VL 45 IS 43 BP 13035 EP 13045 DI 10.1021/bi060712n PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 100LH UT WOS:000241670100012 PM 17059220 ER PT J AU Amar, MJ Basso, F Demosky, S Stonick, J Remaley, AT AF Amar, Marcelo J. Basso, Federica Demosky, Steve Stonick, John Remaley, Alan T. TI The ApoA-I peptide mimetic 5A protects against atherosclerosis in apoE deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 23 EP 23 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800126 ER PT J AU Pickard, A Buch, MH Gillies, SE Clark, GJ Cartwright, EJ Armesilla, AL Neyses, L AF Pickard, Adam Buch, Mamta H. Gillies, Sheona E. Clark, Geoffrey J. Cartwright, Elizabeth J. Armesilla, Angel L. Neyses, Ludwig TI Ras-association factor 1 - A novel antihypertrophic protein in the myocardium SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Manchester, Manchester, Lancs, England. NCI, Rockville, MD USA. Wolverhampton Univ, Wolverhampton, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 53 EP 53 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800259 ER PT J AU Kathiresan, S Yang, Q Larson, MG Tofler, GH O'Donnell, CJ AF Kathiresan, Sekar Yang, Qiong Larson, Martin G. Tofler, Geoffrey H. O'Donnell, Christopher J. CA Framingham 100K Steering Committee TI A genome-wide association study to identify common sequence variants related to five circulating hemostatic factor proteins: The framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Royal N Shore Hosp, Sydney, NSW, Australia. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 56 EP 56 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800272 ER PT J AU Yang, DM Zhu, WZ Xiao, BL Brochet, DX Chen, SW Xiao, RP Cheng, HP AF Yang, Dongmei Zhu, Wei-Zhong Xiao, Bailong Brochet, Didier X. Chen, S. R. W. Xiao, Rui-Ping Cheng, Heping TI Ca2+/calmodulin kinase II-dependent phosphorylation of ryanodine receptors stabilizes Ca2+ signaling in intact cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. Univ Calgary, Dept Physiol & Biophys, Calgary, AB, Canada. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 57 EP 57 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800278 ER PT J AU Hlaing, T Chopra, N Akin, B Ettensohn, K D Horton, K Weissmann, NJ Pfeifer, K Jones, LR Franzini-Armstrong, C Knollmann, BC AF Hlaing, Thinn Chopra, Nagesh Akin, Brandy Ettensohn, Kristen D Horton, Kenneth Weissmann, Neil J. Pfeifer, Karl Jones, Larry R. Franzini-Armstrong, Clara Knollmann, Bjorn C. TI Sarcoplasmic reticulum volume expansion in response to cardiac calsequestrin deletion maintains sarcoplasmic calcium storage and contractile function in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Washington Hosp Ctr, Washington, DC 20010 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Krannert Cardiovasc Res Inst, Indianapolis, IN USA. NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 58 EP 59 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800284 ER PT J AU Vinogradova, TM Zhu, W Ruknudin, AM Lyashkov, AE Spurgeon, H Lakatta, EG AF Vinogradova, Tatiana M. Zhu, Weizhong Ruknudin, Abdul M. Lyashkov, Alexey E. Spurgeon, Harold Lakatta, Edward G. TI Constitutive phosphodiesterase 3 activity controls cAMP-protein kinase a dependent local subsarcolemmal Ca2+ releases and spontaneous beating rate in rabbit sinoatrial node cells SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 58 EP 58 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800282 ER PT J AU Yoshioka, J Imahashi, K Chutkow, WA Burds, AA Gannon, J MacGillivray, C Schulze, PC Murphy, E Lee, RT AF Yoshioka, Jun Imahashi, Kenichi Chutkow, William A. Burds, Aurora A. Gannon, Joseph MacGillivray, Catherine Schulze, P. C. Murphy, Elizabeth Lee, Richard T. TI Targeted deletion of Thioredoxin-Interacting Protein prevents cardiac dysfunction in response to pressure overload SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Cambridge, MA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 96 EP 96 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800464 ER PT J AU Stoll, P Bassler, N Hagemeyer, CE Schmidt, R Chih, CY Katagiri, Y Bode, C Peter, K AF Stoll, Patrick Bassler, Nicole Hagemeyer, Christoph E. Schmidt, Rene Chih, Chen Y. Katagiri, Yashuhiro Bode, Christoph Peter, Karlheinz TI Ligand-binding induced epitopes on GPIIb/IIIa allow highly efficient clot-targeted anticoagulation without bleeding time prolongation: A biotechnological approach based on the single-chain antibody technology SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Freiburg, Dept Cardiol & Angiol, Freiburg, 20892, Germany. Baker Heart Res Inst, Cntr Thrombosis & Myocardial Infarct, Melbourne, Vic, Australia. Univ Freiburg, Dept Anesthesiol, Freiburg, Germany. NIH, Bethesda, MD USA. RI Hagemeyer, Christoph/E-8958-2011; Peter, Karlheinz/E-8772-2010 OI Hagemeyer, Christoph/0000-0002-7114-4023; Peter, Karlheinz/0000-0002-8040-2258 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 105 EP 105 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800504 ER PT J AU Spiecker, M Zeldin, DC Mugge, A Tenderich, G Korfer, R Liao, JK Milting, H AF Spiecker, Martin Zeldin, Darryl C. Muegge, Andreas Tenderich, Gero Korfer, Reiner Liao, James K. Milting, Hendrik TI Reduced human myocardial mRNA expression of CYP2J2 in individuals with the G-50T promoter polymorphism SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Marien Hosp, D-4630 Marl, Germany. NIEHS, NIH, Res Triangle Pk, NC USA. Ruhr Univ Bochum, Dept Cardiol, Bochum, 02115, Germany. Heart & Diabet Ctr NRW, Bad Oeynhausen, Germany. Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 117 EP 117 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800557 ER PT J AU El-Bizri, N Wang, LL Chang, CP Helms, JA Mishina, Y Rabinovitch, M AF El-Bizri, Nesrine Wang, Lingli Chang, Ching-Pin Helms, Jill A. Mishina, Yuji Rabinovitch, Marlene TI Vascular, cardiac, and craniofacial defects in mice with vascular smooth muscle cell-specific deletion of bone morphogenetic protein type IA receptor (BMPR-IA) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 141 EP 141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792800671 ER PT J AU Olivecrona, GK Gotberg, M Harnek, J Jacobson, KA Jern, S Erlinge, D AF Olivecrona, Goran K. Gotberg, Matthias Harnek, Jan Jacobson, Kenneth A. Jern, Sverker Erlinge, David TI Release of tissue plasminogen activator (t-PA) in response to ischemia and reactive hyperemia is mediated by P2Y(1) receptors SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Dept Cardiol, Lund, Sweden. Univ Lund Hosp, S-22185 Lund, Sweden. Dept Radiol, Lund, Sweden. NIDDK, Kenneth A Jacobson Mol Recognit Sect, LBC, NIH, Bethesda, MD USA. Sahlgrens Univ Hosp, Clin Expt Rsch Lab, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 842 BP 149 EP 149 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801021 ER PT J AU Westermann, D Mersmann, J Petrik, C Melchior, A Lmann-Rauch, R Young, MF Levkau, B Baba, H Tschope, C Fischer, JW AF Westermann, Dirk Mersmann, Jan Petrik, Christian Melchior, Arianne L llmann-Rauch, Renate Young, Marian F. Levkau, Bodo Baba, Hideo Tschope, Carsten Fischer, Jens W. TI Biglycan is required for adaptive remodelling after myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Charite Univ Klinikum Berlin, Abt Kardiol & Pneumol, Dusseldorf, Germany. Univ Dusseldorf, Abt Anasthesie, D-4000 Dusseldorf, Germany. Charite Univ Med Berlin, Inst Pharmacol & Toxikol, Berlin, Germany. Univ Kiel, Inst Anat, D-2300 Kiel, Germany. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Klinikum Essen, Inst Pathophysiol, Essen, Germany. Charite Univ Klinikum Berlin, Abt Kardiol & Pneumol, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 964 BP 175 EP 176 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801142 ER PT J AU Chavakis, E Hain, A Carmona, G Vinci, M Vajkoczy, P Chavakis, T Dimmeler, S AF Chavakis, Emmanoull Hain, Andreas Carmona, Guillaume Vinci, Maria Vajkoczy, Peter Chavakis, Triantafylos Dimmeler, Stefanie TI High mobility group box 1 protein increases integrin-dependent homing of endothelial progenitor cells in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Frankfurt, Dept Internal Med 3, D-6000 Frankfurt, Germany. Univ Heidelberg, Fac Med, Dept Neurosurg, D-6800 Mannheim, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1009 BP 184 EP 185 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801187 ER PT J AU Chavakis, E Chavalkis, T AF Chavakis, Emmanouil Chavalkis, Triantafyllos TI Role of PI3K gamma for integrin-dependent adhesive and migratory functions of endothelial progenitor cells SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Frankfurt, Dept Internal Med 3, D-6000 Frankfurt, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 MA 1014 BP 186 EP 186 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801192 ER PT J AU Howden, R Liu, E Miller-DeGraff, LE Walker, C Clark, JA Myers, PH Rouse, DC Kleeberger, SR AF Howden, Reuben Liu, Eric Miller-DeGraff, Laura E. Walker, Christopher Clark, James A. Myers, Page H. Rouse, D. Clay Kleeberger, Steven R. TI The genetic contribution to heart rate and heart rate variability in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIEHS, Res Triangle Pk, NC 27709 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1052 BP 193 EP 194 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801229 ER PT J AU Phoon, CK Kitabayashi, A Mishina, Y AF Phoon, Colin K. Kitabayashi, Aya Mishina, Yuji TI Outflow tract regurgitation and arrhythmias contribute to in utero demise in early PO-Alk3 knockout mouse embryos as defined in vivo by 40 MHz ultrasound biomicroscopy-doppler SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIEHS, Res Triangle Pk, NC 27709 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1065 BP 196 EP 196 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801242 ER PT J AU Song, L Mishina, Y Baldwin, SH Jiao, K AF Song, Lanying Mishina, Yuji Baldwin, Scott H. Jiao, Kai TI Essential functions of Alk3 during atrioventricular cushion morphogenesis in mouse embryonic hearts SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Alabama, GTM, Dept Genet, Birmingham, AL USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Ctr Med, Dept Pediat, Div Pediat Cardiol, Nashville, TN 37232 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1063 BP 196 EP 196 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801240 ER PT J AU Sethi, AA Stonik, JA Demosky, SJ Remaley, AT AF Sethi, Amar A. Stonik, John A. Demosky, Steve J. Remaley, Alan T. TI Complexation of an ApoA-1 mimetic peptide with phospholipid increases ABCA1-specific cholesterol efflux SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S MA 1203 BP 225 EP 225 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801380 ER PT J AU Chopra, N Yang, T Hlaing, T Ettensohn, K Holinstat, I Zhang, W Pfeifer, K Roden, DM Knollmann, BC AF Chopra, Nagesh Yang, Tao Hlaing, Thinn Ettensohn, Kristen Holinstat, Izabela Zhang, Wei Pfeifer, Karl Roden, Dan M. Knollmann, Bjorn C. TI Cardiac calsequestrin deletion causes premature sarcoplasmic reticulum calcium release and catecholaminergic polymorphic ventricular tachycardia in mice SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Vanderbilt Univ, Sch Med, Nashville, TN USA. Washington Hosp Ctr, Washington, DC 20010 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 267 EP 267 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801574 ER PT J AU Landmesser, U Doerries, C Grote, K Sorrentino, SA Hilfiker-Kleiner, D Luchtefeld, M Schaefer, A Holland, SM Schieffer, B Drexler, H AF Landmesser, Ulf Doerries, Carole Grote, Karsten Sorrentino, Sajoscha A. Hilfiker-Kleiner, Denise Luchtefeld, Maren Schaefer, Amd Holland, Steven M. Schieffer, Bernhard Drexler, Helmut TI Critical role of the NAD(P)H oxidase subunit p47(phox) for LV-Remodeling, dysfunction and survival post-myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Hannover Med Sch, Hannover, Germany. NIH, Lab Clin Infect Dis, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 273 EP 273 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801603 ER PT J AU Jiang, LO Wang, M Zhang, J Spinetti, G Monticone, RE Pintus, G Lakatta, EG AF Jiang, Li-Oun Wang, Mingyi Zhang, Jing Spinetti, Gaia Monticone, Robert E. Pintus, Gianfranco Lakatta, Edward G. TI Aortic calpain-1 increases with aging, activates matrix metalloproteinase II, and promotes vascular smooth muscle cell migration SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. RI Pintus, Gianfranco /C-2975-2009 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 279 EP 279 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792801629 ER PT J AU Shen, JB Cronin, C Sonin, D Joshi, B Nieto, M Harrison, D Jacobson, K Liang, BT AF Shen, Jian-Bing Cronin, Chunxia Sonin, Dmitry Joshi, Bhalchandra Nieto, Maria Harrison, David Jacobson, Kenneth Liang, Bruce T. TI P2X purinergic receptor-mediated ionic current in cardiac myocytes of calsequestrin model of cardiomyopathy. Implications for the treatment of heart failure SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Connecticut, Farmington, CT USA. NIH, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 299 EP 299 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802050 ER PT J AU Xu, X Fassett, J Hu, X Zhu, G Schnermann, J Bache, RJ Chen, Y AF Xu, Xin Fassett, John Hu, Xinli Zhu, Guangshuo Schnermann, Jurgen Bache, Robert J. Chen, Yingjie TI Endogenous adenosine protects the heart from severe systolic overload induced ventricular hypertrophy and congestive heart failure SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Minnesota, Dept Med, Div Cardiovasc, Minneapolis, MN 55455 USA. Univ Minnesota, Vasc Biol Ctr, Minneapolis, MN USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 306 EP 306 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802082 ER PT J AU Ciaccio, EJ Ashikaga, H Kaba, RA Cervantes, D Hopenfeld, B Wit, AL Peters, NS McVeigh, ER Garan, H Coromilas, J AF Ciaccio, Edward J. Ashikaga, Hiroshi Kaba, Riyaz A. Cervantes, Daniel Hopenfeld, Bruce Wit, Andrew L. Peters, Nicholas S. McVeigh, Elliot R. Garan, Hasan Coromilas, James TI Infarct border zone geometry is predictive of the location and characteristics of reentrant circuits causing canine postinfarction ventricular tachycardia SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Columbia Univ, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, London, England. RI Ciaccio, Edward/M-6216-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 331 EP 331 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802199 ER PT J AU Wang, M Zhang, J de Cabo, R Jiang, LO Spinetti, G Pintus, G Monticone, RE Ingram, DK Lakatta, EG AF Wang, Mingyi Zhang, Jing de Cabo, Rafael Jiang, Li-Qun Spinetti, Gala Pintus, Gianfranco Monticone, Robert E. Ingram, Donald K. Lakatta, Edward G. TI Calorie restriction reduces MMP-2 activity and retards age-associated aortic restructuring in rats SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. RI Pintus, Gianfranco /C-2975-2009; de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 MA 1717 BP 335 EP 335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802220 ER PT J AU Aboyans, V McClelland, RL Allison, MA McDermott, MM Goff, DC Manolio, TA AF Aboyans, Victor McClelland, Robyn L. Allison, Matthew A. McDermott, Mary M. Goff, David C., Jr. Manolio, Teri A. TI Intrinsic contribution of gender and ethnicity to normal ankle-brachial index values: The multi-ethnic study of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 CHU Dupuytren, Dept Family & Prevent Med, Limoges, 92103, France. Univ Calif San Diego, Dept Biostat, San Diego, CA 98195 USA. Univ Washington, Feinberg Sch Med, Seattle, WA 60611 USA. Northwestern Univ, Sch Med, Dept Publ Hlth Sci, Chicago, IL 27109 USA. Wake Forest Univ, Div Epidemiol & Clin Applicat, Winston Salem, NC 20892 USA. NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 383 EP 383 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802407 ER PT J AU Cao, JJ Bandettini, WP Pang, J Arai, AE AF Cao, Jie J. Bandettini, W. P. Pang, Johnny Arai, Andrew E. TI Prognostic value of cardiac MRI in patients referred to evaluate known or possible coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 388 EP 388 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802427 ER PT J AU Nicholls, SJ Vonmering, GO Merz, CNB Wolski, K Johnson, BD Pattison, A Sopko, G Sharaff, BL Sizemore, BC Nissen, SE Pepine, CJ AF Nicholls, Stephen J. vonMering, Gregory O. Merz, C. N. Bairey Wolski, Kathy Johnson, B. D. Pattison, Angela Sopko, George Sharaff, Barry L. Sizemore, B. C. Nissen, Steven E. Pepine, Carl J. TI Evolution of the pattern of atherosclerosis assessed by intravascular ultrasound in women: A substudy of the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Cleveland Clin, Cleveland, OH 44106 USA. Univ Florida, Gainesville, FL USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 403 EP 403 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792802494 ER PT J AU Faraday, N Yanek, LR Mathias, R Herrera-Galeano, JE Moy, TF Bray, PF Becker, LC Becker, DM AF Faraday, Nauder Yanek, Lisa R. Mathias, Rasika Herrera-Galeano, J. E. Moy, Taryn F. Bray, Paul F. Becker, Lewis C. Becker, Diane M. TI Heritability of platelet aspirin responsiveness SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NHGRI NIH, Baltimore, MD USA. Baylor Coll Med, Houston, TX 77030 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 489 EP 489 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803222 ER PT J AU Lee, CR North, KE Bray, MS Couper, DJ Heiss, G Zeldin, DC AF Lee, Craig R. North, Kari E. Bray, Molly S. Couper, David J. Heiss, Gerardo Zeldin, Darryl C. TI Genetic variation in CYP2J2 and risk of coronary heart disease: The atherosclerosis risk in communities (ARIC) study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ N Carolina, Chapel Hill, NC 77030 USA. Baylor Coll Med, NIH, Houston, TX 27709 USA. NIEHS, Res Triangle Pk, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 490 EP 490 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803227 ER PT J AU Scuteri, A Tesauro, M Najjar, SS Zonderman, A Brancati, AM Volpe, M AF Scuteri, Angelo Tesauro, Manfredi Najjar, Samer S. Zonderman, Alan Brancati, Anna Maria Volpe, Massimo TI Arterial stiffness as an independent predictor of longitudinal changes in cognitive function in the elderly SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 INRCA, Rome, Italy. Univ Roma Tor Vergata, Dip Med Int, Rome, Italy. NIA, NIH, Baltimore, MD 21224 USA. Univ Roma La Sapienza, Osp Sant Andrea, Rome, Italy. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 491 EP 491 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803233 ER PT J AU Horvath, K Guttman, M Li, M Lederman, R Mazilu, D Kocaturk, O Karmarkar, P Hunt, T Kozlov, S McVeigh, E AF Horvath, Keith Guttman, Michael Li, Ming Lederman, Robert Mazilu, Dumitru Kocaturk, Ozgur Karmarkar, Parag Hunt, Timothy Kozlov, Shawn McVeigh, Elliot TI Transapical aortic valve replacement using real-time magnetic resonance imaging guidance SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 524 EP 524 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803376 ER PT J AU Rogers, JG Tasissa, G Francis, GS DiSalvo, TG Leier, CV Wagoner, LE Pina, IL Stevenson, LW Sopko, G O'Connor, CM AF Rogers, Joseph G. Tasissa, Gudaye Francis, Gary S. DiSalvo, Thomas G. Leier, Carl V. Wagoner, Lynne E. Pina, Ileana L. Stevenson, Lynne W. Sopko, George O'Connor, Christopher M. TI Reduction of filling pressures during hospitalization predicts sustained reduction in heart failure symptoms SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Vanderbilt Univ Sch Med, Nashville, TN USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Univ Hosp, Cincinnati, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 529 EP 529 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803398 ER PT J AU Davis, BR Simpson, LM Black, HR Cushman, WC Einhorn, PT Farber, MA Ford, CE Levy, D Massie, BM Nawaz, S Nawaz, S AF Davis, Barry R. Simpson, Lara M. Black, Henry R. Cushman, Wililam C. Einhorn, Paula T. Farber, Michael A. Ford, Charles E. Levy, Daniel Massie, Barry M. Nawaz, Shah Nawaz, Shah TI Heart failure with preserved and impaired left ventricular systolic function in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Texas, Sch Publ Hlth, Houston, TX USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Memphis VAMC, Memphis, TN USA. NHLBI, DHVD, Bethesda, MD 20892 USA. Pitman Internal Med Associates, Pittman, NJ USA. NHLBI, Framingham Heart Study, Framingham, MA USA. VAMC San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 571 EP 571 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803570 ER PT J AU Alderman, M Calhoun, D Cushman, W Davis, B Eckfeldt, J Einhorn, P Ford, C Franklin, S Furberg, C Ong, S Oparil, S Papademetriou, V Piller, L Probstfield, J AF Alderman, Michael Calhoun, David Cushman, William Davis, Barry Eckfeldt, John Einhorn, Paula Ford, Charles Franklin, Stanley Furberg, Curt Ong, Stephen Oparil, Suzanne Papademetriou, Vasilios Piller, Linda Probstfield, Jeffrey TI Relationship of 1 year hypokalemia incidence to clinical outcomes in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Alabama, Birmingham, AL USA. Memphis VAMC, Memphis, TN USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Univ Minnesota Hosp & Clin, Minneapolis, MN 55455 USA. NHLBI, DHVD, Bethesda, MD 20892 USA. Univ Calif Irvine, Los Angeles, CA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Ong Med Ctr, Oxon Hill, MD USA. VAMC Washington, Washington, DC USA. Univ Washington, Seattle, WA 98195 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 576 EP 576 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792803590 ER PT J AU Doyle, M Pohost, GM Shaw, LJ Sopko, G Kortright, E Vido, D Kelsey, SF Johnson, BD Rogers, WJ Reis, SE Olson, MB Sharaf, BL Pepine, CJ Bairey-Merz, CN Mankad, S Biederman, RW AF Doyle, Mark Pohost, Gerald M. Shaw, Leslee J. Sopko, George Kortright, Eduardo Vido, Diane Kelsey, Sheryl F. Johnson, B. Delia Rogers, William J. Reis, Steven E. Olson, Madan B. Sharaf, Barry L. Pepine, Carl J. Bairey-Merz, C. Noel Mankad, Sunlit Biederman, Robert W. TI CMR-determined regional myocardial perfusion uptake rate predicts events in women without obstructive coronary artery disease: The NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Florida, Gainesville, FL USA. Rhode Isl Hosp, Providence, RI USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Univ New Orleans, New Orleans, LA 70148 USA. NHLBI, NIH, Washington, DC USA. Univ So Calif, Los Angeles, CA USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 595 EP 595 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804021 ER PT J AU Yeon, SB Salton, CJ Gona, P Chuang, ML Larson, MG Levy, D O'Donnell, CJ Manning, WJ AF Yeon, Susan B. Salton, Carol J. Gona, Philimon Chuang, Michael L. Larson, Martin G. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Age-dependent changes in left ventricular parameters with normotensive aging: Application of cardiovascular magnetic resonance to the Framingham Heart Study Offspring Cohort SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, NHLBI, Framingham Heart Study, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 635 EP 635 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804197 ER PT J AU Collard, CD Sherman, SK Fox, AK Vaughn, WK Bernig, T Chanock, SJ Takahashi, K Ezekowitz, AB Jarolim, P Body, SC AF Collard, Charles D. Sherman, Stanton K. Fox, Amanda K. Vaughn, William K. Bernig, Toralf Chanock, Stephen J. Takahashi, Kazue Ezekowitz, Alan B. Jarolim, Petr Body, Simon C. TI The MBL2 "LYQA secretor" haplotype is an independent predictor of postoperative myocardial infarction (MI) in Caucasians undergoing coronary artery bypass graft (CABG) surgery SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Div Biostat & Epidemiol, Houston, TX 77030 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesiol, Houston, TX 77030 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 658 EP 658 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804298 ER PT J AU Koh, KK Quon, MJ Han, SH AF Koh, Kwang K. Quon, Michael J. Han, Seung H. TI Significant differential effects of anti-hypertensive drugs on plasma adiponectin levels in hypertensive patients SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Gil Heart Ctr, Div Cardiol, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 677 EP 678 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804378 ER PT J AU Tesauro, M Schinzari, F Melina, D Mores, N Rovella, V Iantorno, M Lauro, D Quon, MJ Cardillo, C AF Tesauro, Manfredi Schinzari, Francesca Melina, Domenico Mores, Nadia Rovella, Valentina Iantorno, Micaela Lauro, Davide Quon, Michael J. Cardillo, Carmine TI Direct vascular effects of ghrelin to improve enclothelial function by restoring the endothelin/nitric oxide balance in patients with central obesity SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Roma Tor Vergata, I-00161 Rome, Italy. Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. NIH, NCCAM, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 678 EP 679 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804383 ER PT J AU Hasbani, K DiProspero, N Kellman, P Plehn, JF Block, M Vincent, P Arai, AE AF Hasbani, Keren DiProspero, Nicholas Kellman, Peter Plehn, Jonathan F. Block, Marsha Vincent, Pamela Arai, Andrew E. TI High prevalence of myocardial fibrosis and left ventricular hypertrophy in pediatric friedreich's ataxia: a cardiac magnetic resonance imaging study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Natl Inst Hlth, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 680 EP 680 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804390 ER PT J AU Porter, C Bloom, ET Horvath-Arcidiacono, J Horvath, KA Mohiuddin, MM AF Porter, Cynthia Bloom, Eda T. Horvath-Arcidiacono, Judith Horvath, Keith A. Mohiuddin, Muhammad M. TI Baboon CD4(+) CD25(+) T regulatory cells inhibit anti porcine xenogeneic response SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 FDA, Gene Transfer & Immunogenic Branch, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 709 EP 710 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804517 ER PT J AU Sabatine, MS Morrow, DA O'Donoghue, M Jablonski, KA Rice, MM Solomon, SD Rosenberg, YD Domanski, MJ Hsia, J AF Sabatine, Marc S. Morrow, David A. O'Donoghue, Michelle Jablonski, Kathleen A. Rice, Madeline M. Solomon, Scott D. Rosenberg, Yves D. Domanski, Michael J. Hsia, Judith TI Lipoprotein-associated phospholipase A(2) (Lp-PLa2) is an independent predictor of adverse cardiovascular outcomes in patients with stable coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. NHLBI, Bethesda, MD 20892 USA. RI Solomon, Scott/I-5789-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 713 EP 713 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804533 ER PT J AU von Mering, GO Johnson, BD Handberg, E Smith, KM Pauly, DF Wessel, TR Arant, CB Reis, SE Sharaf, B Sopko, G Merz, NB Pepine, CJ AF von Mering, Gregory O. Johnson, B. D. Handberg, Eileen Smith, Karen M. Pauly, Daniel F. Wessel, Timothy R. Arant, Christopher B. Reis, Steven E. Sharaf, Barry Sopko, George Merz, Noel Bairey Pepine, Carl J. TI Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia: Results from the NHLBI women's ischemia syndrome evaluation (WISE) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Florida, Gainesville, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Rhode Isl Hosp, Providence, RI 02902 USA. NHLBI, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 713 EP 713 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804532 ER PT J AU Arant, CB Johnson, BD Wessel, TR von Mering, GO Handberg, E Smith, KM Pauly, DF Reis, SE Sharaf, B Sopko, G Merz, NB Pepine, CJ AF Arant, Christopher B. Johnson, B. Delia Wessel, Timothy R. von Mering, Gregory O. Handberg, Eileen Smith, Karen M. Pauly, Daniel F. Reis, Steven E. Sharaf, Barry Sopko, George Merz, Noel Bairey Pepine, Carl J. TI Multibiomarker approach predicts adverse cardiovascular outcomes in women evaluated for suspected ischemia without obstructive CAD better than traditional risk predictors: Results from the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Florida, Gainesville, FL USA. Univ Pittsburgh, Pittsburgh, PA USA. Rhode Isl Hosp, Providence, RI USA. NHLBI, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 714 EP 714 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792804535 ER PT J AU Plehn, J Liu, C Owens, D Finkel, T Whiteley, G AF Plehn, Jonathan Liu, Chenwei Owens, David Finkel, Toren Whiteley, Gordon TI High-throughput mass spectrometry identifies peptide signature clusters predictive of heart failure outcome: the bucindolol evaluation survival trial (BEST) proteomic substudy SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, Washington, DC USA. NCI Frederick, SAIC Frederick, Gaithersburg, MD USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 771 EP 771 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805092 ER PT J AU Koh, KK Quon, MJ Han, SH Chung, WJ Lee, SJ AF Koh, Kwang K. Quon, Michael J. Han, Seung H. Chung, Wook-Jin Lee, Sang J. TI Ramipril combined with candesartan improves vascular and metabolic responses to a greater extent than monotherapy in the treatment of hypertensive patients SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIH, Diabet Unit, Bethesda, MA USA. Gil Heart Ctr, Div Cardiol, Inchon, South Korea. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 774 EP 774 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805103 ER PT J AU Oyama, N Gona, P Salton, CJ Chuang, ML Blease, SJ Lahiri, M Goddu, EA Levy, D Larson, MG O'Donnell, CJ Manning, WJ AF Oyama, Noriko Gona, Philimon Salton, Carol J. Chuang, Michael L. Blease, Susan J. Lahiri, Marc Goddu, Elizabeth A. Levy, Daniel Larson, Martin G. O'Donnell, Christopher J. Manning, Warren J. TI Subclinical aortic atherosclerosis in men and women in the community free of cardiovascular disease and hypertension SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 775 EP 775 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805110 ER PT J AU Ganesh, SK Skelding, KA Joo, J Zheng, G Yu, A Geller, NL Pan, S Billings, EM Mehta, LS O'Neill, KE Simari, RD Holmes, DR O'Neill, WW Kennedy, GC Nabel, EG AF Ganesh, Santhi K. Skelding, Kimberly A. Joo, Jungnam Zheng, Gang Yu, Adong Geller, Nancy L. Pan, Stephen Billings, Eric M. Mehta, Laxmi S. O'Neill, Kathleen E. Simari, Robert D. Holmes, David R., Jr. O'Neill, William W. Kennedy, Giulia C. Nabel, Elizabeth G. TI Genome wide association study of in-stent restenosis identifies multiple candidate susceptibility loci SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, NHGRI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Affymetrtix Inc, Santa Clara, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 788 EP 788 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805168 ER PT J AU Chuang, ML Gona, P Salton, CJ Yeon, SB Larson, MG Levy, D O'Donnell, CJ Manning, WJ AF Chuang, Michael L. Gona, Philimon Salton, Carol J. Yeon, Susan B. Larson, Martin G. Levy, Daniel O'Donnell, Christopher J. Manning, Warren J. TI Women do more with less: Sex differences in myocardial contraction fraction, a volumetric measure of myocardial function SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 805 EP 805 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805243 ER PT J AU Plehn, JF Owens, DS Asgeirsdottir, L Dis, H Aspelund, T Sigurdsson, S Gudnason, V Launer, L Harris, T AF Plehn, Jonathan F. Owens, David S. Asgeirsdottir, Liljapetra Dis, Harpa Aspelund, Thor Sigurdsson, Sigurdur Gudnason, Vilmundur Launer, Lenore Harris, Tamara TI Echocardiographic associations of prevalent stroke in an elderly cohort: the Age/Gene environmental susceptibility Reykjavik study (AGES-Reykjavik) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. AGES Reykjavik Study, Reykjavik, Iceland. NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 833 EP 833 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805359 ER PT J AU Kathiresan, S Massaro, JM Cury, RC Manders, ES Cupples, LA Hoffmann, U O'Donnell, CJ AF Kathiresan, Sekar Massaro, Joseph M. Cury, Ricardo C. Manders, Emily S. Cupples, L. Adrienne Hoffmann, Udo O'Donnell, Christopher J. TI Long-term exposure to traditional atherosclerotic risk factors and presence of aortic valve calcification SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 840 EP 840 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805386 ER PT J AU Koh, KK Quon, MJ Han, SH Chung, WJ Lee, SJ AF Koh, Kwang K. Quon, Michael J. Han, Seung H. Chung, Wook-Jin Lee, Sang J. TI Comparative effects of ramipril and candesartan on plasma leptin and resistin levels in the treatment of hypertensive patients SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Gil Heart Ctr, Div Cardiol, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 844 EP 844 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805403 ER PT J AU Chen, J Gu, D Jaquish, CE Chen, CS Rao, D Reynolds, K Hixson, JE Hamm, L Whelton, PK He, J AF Chen, Jing Gu, Dongfeng Jaquish, Cashell E. Chen, Chung-Shiuan Rao, D. C. Reynolds, Kristi Hixson, James E. Hamm, Lee Whelton, Paul K. He, Jiang TI Blood pressure response to cold pressor predicts salt-sensitivity in the GenSalt study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Tulane Univ, New Orleans, LA 70118 USA. Univ Texas, Houston, TX USA. Washington Univ, St Louis, MO USA. NHLBI, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 847 EP 848 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805417 ER PT J AU Ding, J Kritchevsky, SB Harris, TB Burke, GL Detrano, R Szklo, M Carr, JJ AF Ding, Jingzhong Kritchevsky, Stephen B. Harris, Tamara B. Burke, Gregory L. Detrano, Robert Szklo, Moyses Carr, John J. TI Pericardial fat is more strongly associated with calcified coronary plaque than body mass index or waist circumference SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. Johns Hopkins Univ, Baltimore, MD USA. RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 854 EP 854 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805446 ER PT J AU Gidding, SS Colangelo, L Lewis, CE Loria, C Liu, K AF Gidding, Samuel S. Colangelo, Laura Lewis, Cora E. Loria, Catherine Liu, Kiang TI Relationship of BMI to change in smoking status: the CARDIA study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Alfred I DuPont Hosp Children, Wilmington, DE 60611 USA. Jefferson Med Coll, Feinberg Sch Med, Wilmington, DE USA. Northwestern Univ, Chicago, IL 20892 USA. Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 855 EP 855 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805452 ER PT J AU Bella, JN Roman, M Umans, J Lee, ET Best, LG Fabsitz, RR Howard, BV Devereux, RB AF Bella, Jonathan N. Roman, Mary Umans, Jason Lee, Elisa T. Best, Lyle G. Fabsitz, Richard R. Howard, Barbara V. Devereux, Richard B. TI Preclinical cardiac disease and outcome in adults with kidney disease: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Medstar Rsch Inst, Washington, DC 10021 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Oklahoma, Sch Publ Hlth Sci, Oklahoma City, OK USA. Missouri Breaks Ind Rsch Inc, Timber Lake, SD 20892 USA. NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 871 EP 871 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805512 ER PT J AU Lippincott, MF Carlow, A Zalos, G Rodrigo, ME Cannon, R AF Lippincott, Margaret F. Carlow, Andrea Zalos, Gloria Rodrigo, Maria E. Cannon, Richard TI Women differ from men in the contribution of vascular progenitor cells to endothelial function and cardiovascular risk SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 874 EP 874 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805525 ER PT J AU Deo, R Fyr, CLW Fried, LF Newman, AB Harris, TB Angleman, S Green, C Kritchevsky, SB Chertow, G Cummings, SR Shlipak, MG AF Deo, Rajat Fyr, Christina L. Wassel Fried, Linda F. Newman, Anne B. Harris, Tamara B. Angleman, Sara Green, Christie Kritchevsky, Stephen B. Chertow, Glenn Cummings, Steven R. Shlipak, Michael G. TI Cystatin C and cardiovascular events in the elderly: The health, aging, and body composition (Health ABC) study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Wake Forest Sch Med, Winston Salem, NC USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 875 EP 875 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805533 ER PT J AU Parikh, NI Hwang, SJ Larson, MG Robins, SJ Sutherland, P Benjamin, EJ Levy, D Fox, CS AF Parikh, Nisha I. Hwang, Shih-Jen Larson, Martin G. Robins, Sander J. Sutherland, Patrice Benjamin, Emelia J. Levy, Dan Fox, Caroline S. TI Association of cystatin-C with cardiovascular disease risk factors: The Framingham Offspring cohort SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 875 EP 876 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805534 ER PT J AU Xu, JS Lee, ET Devereux, RB Knowler, WC Yeh, J Umans, JG Begum, M Fabsitz, RR Howard, BV AF Xu, Jiaqiong (Susan) Lee, Elisa T. Devereux, Richard B. Knowler, William C. Yeh, Jeunliang Umans, Jason G. Begum, Momotaz Fabsitz, Richard R. Howard, Barbara V. TI A longitudinal study of risk factors for the incident abnormal albuminuria in diabetic American Indians: The Strong Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 10021 USA. Cornell Univ, Med Ctr, New York, NY 85016 USA. NIDDKD, NIH, Phoenix, AZ USA. MedStar Res Inst, Washington, DC USA. MedStar Res Inst, Hyattsville, 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 875 EP 875 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805531 ER PT J AU Pou, KM Massaro, JM Hoffman, U Vasan, RS Maurovich-Horvat, P Larson, MG Keaney, JF Meigs, JB Lipinska, I Murabito, JM O'Donnell, CJ Benjamin, EJ Fox, CS AF Pou, Karla M. Massaro, Joseph M. Hoffman, Udo Vasan, Ramachandran S. Maurovich-Horvat, Pal Larson, Martin G. Keaney, John F., Jr. Meigs, James B. Lipinska, Izabella Murabito, Joanne M. O'Donnell, Christopher J. Benjamin, Emelia J. Fox, Caroline S. TI Visceral and subcutaneous adipose tissue volumes are related to markers of inflammation and oxidative stress: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Semmelweis Univ, H-1085 Budapest, Hungary. Boston Univ, Sch Med, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 877 EP 877 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805539 ER PT J AU Majka, DS Chang, RW Vu, THT Palmas, W Geffken, DF Ouyang, P Ni, H Liu, K AF Majka, Darcy S. Chang, Rowland W. Vu, Thanh-Huyen T. Palmas, Walter Geffken, Dominick F. Ouyang, Pamela Ni, Hanyu Liu, Kiang TI Relationship between physical activity and C-reactive protein level in the Multi-Ethnic Study of Atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Columbia Univ, New York, NY USA. NH Darmouth Family Med Residency, Concord, NH USA. Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 878 EP 878 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805546 ER PT J AU Kandula, N Daviglus, M Ni, H Jackson, SA Schreiner, P Diez-Roux, AV AF Kandula, Namratha Daviglus, Martha Ni, Hanyu Jackson, Sharon A. Schreiner, Pamela Diez-Roux, Ana V. TI Acculturation is associated with diabetes prevalence in the multiethnic study of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NHLBI, EBP, DECA, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Minnesota, Minneapolis, MN USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 881 EP 881 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805560 ER PT J AU Sacks, FM Appel, LJ Carey, VJ Conlin, PR Laranjo, N Miller, ER Erlinger, TP AF Sacks, Frank M. Appel, Lawrence J. Carey, Vincent J. Conlin, Paul R. Laranjo, Nancy Miller, Edgar R. Erlinger, Thomas P. TI Enhanced response of lipid risk factors to increasing dietary protein in overweight or obese people: Results of the OmniHeart trial SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIA, NIH, Baltimore, MD 21224 USA. Univ Texas, Med Branch, Austin, TX 78712 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 883 EP 884 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805569 ER PT J AU Fox, CS Massaro, JM Hoffmann, U Pou, KM Maurovich-Horvat, P Vasan, RS Murabito, JM D'Agostino, RB O'Donnell, CJ AF Fox, Caroline S. Massaro, Joseph M. Hoffmann, Udo Pou, Karla M. Maurovich-Horvat, Pal Vasan, Ramachandran S. Murabito, Joanne M. D'Agostino, Ralph B., Sr. O'Donnell, Christopher J. TI The joint impact of visceral adipose tissue and body mass index on metabolic risk factors for cardiovascular disease: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Endocrinol, Framingham, MA USA. Boston Univ, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Dept Gen Med, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 885 EP 885 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805577 ER PT J AU Scuteri, A Orru', M Najjar, SS Albai, G Lai, M Cao, A Uda, M Lakatta, EG Pilia, G AF Scuteri, Angelo Orru', Marco Najjar, Samer S. Albai, Giuseppe Lai, Monica Cao, Antonio Uda, Manuela Lakatta, Edward G. Pilia, Giuseppe TI Age-associated effects of the metabolic syndrome on arterial structure and function. The ProgeNIA study. SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 UO Geriatria INRCA, Rome, Italy. CNR, INN, Cagliari, Italy. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 893 EP 894 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805613 ER PT J AU Scuteri, A Lakatta, EG Mehta, V Najjar, SS Everson-Rose, SA Matthews, KA AF Scuteri, Angelo Lakatta, Eward G. Mehta, Vinay Najjar, Samer S. Everson-Rose, Susan A. Matthews, Karen A. TI Socioeconomic factors predict the development of the metabolic syndrome in different ethnic groups in mid-life women: The study of Women's Health Across the Nation (SWAN) SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Rush Univ, Med Ctr, Rush Inst Healthy Aging, Dept Prevent Med & Behav Sci, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 895 EP 895 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805619 ER PT J AU Shaw, LJ Azziz, R Stanczyk, FZ Sopko, G Braunstein, GD Dehoff, RM Handberg, EM Berga, S Johnson, BD Bittner, V Rogers, W Pepine, CJ Merz, CNB AF Shaw, Leslee J. Azziz, Ricardo Stanczyk, Frank Z. Sopko, George Braunstein, Glenn D. Dehoff, Rhonda M. Handberg, Eileen M. Berga, Sarah Johnson, B. Delia Bittner, Vera Rogers, William Pepine, Carl J. Merz, C. Noel Bairey TI Cardiovascular event-free survival in post-menopausal women with polycystic ovary syndrome: Results from the women's ischemia syndrome evaluation SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, W Hollywood, CA USA. Univ So Calif, Los Angeles, CA 90089 USA. NIH, NHLBI, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32611 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Alabama, Birmingham, AL 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 BP 902 EP 902 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805650 ER PT J AU Rodriguez, BL Abbott, R Wilson, PW Launer, LJ Ross, GW Masaki, KH Strozyk, D Yano, K Popper, JS Petrovitch, H Curb, JD AF Rodriguez, Beatriz L. Abbott, Robert Wilson, Peter W. Launer, Lenore J. Ross, G. W. Masaki, Kamal H. Strozyk, D. Yano, Katsuhiko Popper, Jordan S. Petrovitch, Helen Curb, J. D. TI Endogenous estrogen and risk of stroke in elderly men: The Honolulu Heart Program SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Pacific Hlth Res Inst, Honolulu, HI USA. Univ S Carolina, Columbia, SC 29208 USA. NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 903 EP 903 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805654 ER PT J AU Udell, JA Juurlink, DN Kopp, A Lee, DS Tu, JV Mamdani, MM AF Udell, Jacob A. Juurlink, David N. Kopp, Alexander Lee, Douglas S. Tu, Jack V. Mamdani, Muhammad M. TI Inequitable distribution of implantable cardioverter-defibrillators in Ontario, Canada SO CIRCULATION LA English DT Meeting Abstract CT 79th Annual Scientific Session of the American-Heart-Association CY NOV 12-15, 2006 CL Chicago, IL SP Amer Heart Assoc C1 Univ British Columbia, Vancouver Hosp, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 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 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2006 VL 114 IS 18 SU S BP 1190 EP 1190 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 102EC UT WOS:000241792805684 ER PT J AU Teplyakov, A Lim, K Zhu, PP Kapadia, G Chen, CCH Schwartz, J Howard, A Reddy, PT Peterkofsky, A Herzberg, O AF Teplyakov, Alexey Lim, Kap Zhu, Peng-Peng Kapadia, Geeta Chen, Celia C. H. Schwartz, Jennifer Howard, Andrew Reddy, Prasad T. Peterkofsky, Alan Herzberg, Osnat TI Structure of phosphorylated enzyme I, the phosphoenolpyruvate : sugar phosphotransferase system sugar translocation signal protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sugar transport; phosphorylation; x-ray crystallography ID PYRUVATE PHOSPHATE DIKINASE; N-TERMINAL DOMAIN; ESCHERICHIA-COLI; BACTERIAL PHOSPHOENOLPYRUVATE; CRYSTAL-STRUCTURE; SALMONELLA-TYPHIMURIUM; MONOMER/DIMER TRANSITION; CONFORMATIONAL STABILITY; TRANSPORT; DIMERIZATION AB Bacterial transport of many sugars, coupled to their phosphorylation, is carried out by the phosphoenolpyruvate (PEP):sugar phosphotransferase system and involves five phosphoryl group transfer reactions. Sugar translocation initiates with the Mg(2+-)dependent phosphorylation of enzyme I (El) by PEP. Crystals of Escherichia coli El were obtained by mixing the protein with Mg2+ and PEP, followed by oxalate, an El inhibitor. The crystal structure reveals a dimeric protein where each subunit comprises three domains: a domain that binds the partner PEP:sugar phosphotransferase system protein, HPr; a domain that carries the phosphorylated histidine residue, His-189; and a PEP-binding domain. The PEP-binding site is occupied by Mg2+ and oxalate, and the phosphorylated His-189 is in-line for phosphotransfer to/from the ligand. Thus, the structure represents an enzyme intermediate just after phosphotransfer from PEP and before a conformational transition that brings His-189 similar to P in proximity to the phosphoryl group acceptor, His-15 of HPr. A model of this conformational transition is proposed whereby swiveling around an a-helical linker disengages the His domain from the PEP-binding domain. Assuming that HPr binds to the HPr-binding domain as observed by NMR spectroscopy of an El fragment, a rotation around two linker segments orients the His domain relative to the HPr-binding domain so that His-189 similar to P and His-15 are appropriately stationed for an in-line phosphotransfer reaction. C1 Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. IIT, Chicago, IL 60616 USA. Natl Inst Stand & Technol, Div Biochem Sci, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Herzberg, O (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. EM osnat@carb.nist.gov OI Teplyakov, Alexey/0000-0003-0296-0016 NR 48 TC 41 Z9 42 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 31 PY 2006 VL 103 IS 44 BP 16218 EP 16223 DI 10.1073/pnas.0607587103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500030 PM 17053069 ER PT J AU Mitra, P Oskeritzian, CA Payne, SG Beaven, MA Milstien, S Spiegel, S AF Mitra, Poulami Oskeritzian, Carole A. Payne, Shawn G. Beaven, Michael A. Milstien, Sheldon Spiegel, Sarah TI Role of ABCO in export of sphingosine-1-phosphate from mast cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE secretion; sphingolipids; multidrug resistance; allergic responses; sphingosine kinase ID FC-EPSILON-RI; MULTIDRUG-RESISTANCE PROTEIN-1; SPHINGOSINE 1-PHOSPHATE; P-GLYCOPROTEIN; PLASMA-MEMBRANE; DEPENDENT ACTIVATION; GROWTH-FACTOR; EFFLUX PUMP; KINASE; RECEPTOR AB Mast cells play a pivotal role in inflammatory and immediate-type allergic reactions by secreting a variety of potent inflammatory mediators, including sphingosine-1-phosphate (S1P). However, it is not known how S1P is released from cells. Here, we report that S1P is exported from mast cells independently of their degranulation and demonstrate that it is mediated by ATP binding cassette (ABC) transporters. Constitutive and antigen-stimulated S1P release was inhibited by MK571, an inhibitor of ABCC1 (MRP1), but not by inhibitors of ABCb1 (MDR-1, P-glycoprotein). Moreover, down-regulation of ABCC1 with small interfering RNA, which decreased its cell surface expression, markedly reduced S1P export from both rat RBL-2H3 and human LAD2 mast cells. Transport of S1P byABCC1 influenced migration of mast cells toward antigen but not degranulation. These findings have important implications for S1P functions in mast cell-mediated immune responses. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. NIMH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI 50094, R01 AI050094]; NIAMS NIH HHS [K01 AR053186] NR 45 TC 235 Z9 238 U1 1 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 OCT 31 PY 2006 VL 103 IS 44 BP 16394 EP 16399 DI 10.1073/pnas.0603734103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500060 PM 17050692 ER PT J AU Satpute-Krishnan, P DeGiorgis, JA Conley, MP Jang, M Bearer, EL AF Satpute-Krishnan, Prasanna DeGiorgis, Joseph A. Conley, Michael P. Jang, Marcus Bearer, Elaine L. TI A peptide zipcode sufficient for anterograde transport within amyloid precursor protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fast axonal transport; herpes simplex virus; kinesin anterograde transport; squid giant axon ID HERPES-SIMPLEX-VIRUS; SQUID GIANT-AXON; IMMUNOELECTRON MICROSCOPY; SCAFFOLD PROTEIN; CARGO-BINDING; KINESIN; NEURONS; AXOPLASM; ORGANELLES; MEMBRANE AB Fast anterograde transport of membrane-bound organelles delivers molecules synthesized in the neuronal cell body outward to distant synapses. Identification of the molecular "zipcodes" on organelles that mediate attachment and activation of microtubule-based motors for this directed transport is a major area of inquiry. Here we identify a short peptide sequence (15 aa) from the cytoplasmic C terminus of amyloid precursor protein (APP-C) sufficient to mediate the anterograde transport of peptide-conjugated beads in the squid giant axon. APP-C beads travel at fast axonal transport rates (0.53 mu m/s average velocity, 0.9 mu m/s maximal velocity) whereas beads coupled to other peptides coinjected into the same axon remain stationary at the injection site. This transport appears physiologic, because it mimics behavior of endogenous squid organelles and of beads conjugated to C99, a polypeptide containing the full-length cytoplasmic domain of amyloid precursor protein (APP). Beads conjugated to APP lacking the APP-C domain are not transported. Coinjection of APP-C peptide reduces C99 bead motility by 75% and abolishes APP-C bead motility, suggesting that the soluble peptide competes with protein-conjugated beads for axoplasmic motor(s). The APP-C domain is conserved (13/15 aa) from squid to human, and peptides from either squid or human APP behave similarly. Thus, we have identified a conserved peptide zipcode sufficient to direct anterograde transport of exogenous cargo and suggest that one of APP's roles may be to recruit and activate axonal machinery for endogenous cargo transport. C1 Brown Univ, Sch Med, Dept Pathol & Lab Med, Providence, RI 02912 USA. NINDS, NIH, Bethesda, MD 20892 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. RP Bearer, EL (reprint author), Brown Univ, Sch Med, Dept Pathol & Lab Med, 70 Ship St,G-ES27, Providence, RI 02912 USA. EM elaine_bearer@brown.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM 47562]; NINDS NIH HHS [NS 046810, R01 NS046810] NR 49 TC 42 Z9 43 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 31 PY 2006 VL 103 IS 44 BP 16532 EP 16537 DI 10.1073/pnas.0607527103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103IS UT WOS:000241879500083 PM 17062754 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, Eugene A. Brown, P. Leon TI The role of peripheral and central sodium channels in mediating brain temperature fluctuations induced by intravenous cocaine SO BRAIN RESEARCH LA English DT Article DE brain temperature; behavior; dopamine uptake inhibition; procaine; cocaine methiodide; metabolic brain activation and inhibition; ratsu ID CENTRAL-NERVOUS-SYSTEM; NUCLEUS-ACCUMBENS DOPAMINE; POSITRON-EMISSION-TOMOGRAPHY; UPTAKE INHIBITION; IN-VIVO; LOCAL-ANESTHETICS; UPTAKE BLOCKERS; SAPHENOUS-VEIN; BEHAVING RATS; UNIT-ACTIVITY AB While cocaine's interaction with the dopamine (DA) transporter and subsequent increase in DA transmission are usually considered key factors responsible for its locomotor stimulatory and reinforcing properties, many centrally mediated physiological and psychoemotional effects of cocaine are resistant to DA receptor blockade, suggesting the importance of other non-DA mechanisms. To explore the role of cocaine's interaction with Na+ channels, rats were used to compare locomotor stimulatory and temperature (NAcc, temporal muscle and skin) effects of repeated iv injections of cocaine (1 mg/kg) with those induced by procaine (PRO S mg/kg), a short-acting local anesthetic with negligible effect on the DA transporter, and cocaine methiodide (COC-MET 1.31 mg/kg), a quaternary cocaine derivative that is unable to cross the blood-brain barrier. While PRO, unlike cocaine, did not induce locomotor activation, it mimicked cocaine in its ability to increase brain temperature following the initial injection and to induce biphasic, down-up fluctuations following repeated injections. This similarity suggests that both these effects of cocaine maybe driven by its action on Na+ channels, a common action of both drugs. While COC-MET also did not affect locomotor activity, it shared with cocaine and PRO their ability to increase brain temperature but failed to induce temperature decreases after repeated injections. These findings point toward activation of peripheral Na+ channels as the primary mechanism of rapid excitatory effects of cocaine and inhibition of centrally located Na+ channels as the primary mechanism for transient inhibitory effects of cocaine. DA receptor blockade (SCH23390 + eticlopride) fully eliminated locomotor stimulatory and temperature-increasing effects of cocaine, but its temperature -decreasing effects remained intact. Surprisingly, DA receptor blockade also altered the temperature fluctuations caused by PRO and COC-MET, suggesting that some of the central effects triggered via Na+ channels are in fact DA-dependent. Finally, repeated administration of PRO to animals that had previous cocaine experience led to conditioned locomotion and potentiated temperature-increasing effects of this drug. It appears, therefore, that, in addition to the central effects of cocaine mediated via interaction with the DA transporter and potentiation of DA uptake, interaction with peripheral and central Na+ channels is important for the initial physiological and, perhaps, affective effects of cocaine, likely contributing to the unique abuse potential of this drug. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDA, Intramural Res Program, NIH, Cellular Neurobiol Branch,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Intramural Res Program, NIH, Cellular Neurobiol Branch,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [Z01 DA000445-05] NR 82 TC 6 Z9 6 U1 1 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 OCT 30 PY 2006 VL 1117 BP 38 EP 53 DI 10.1016/j.brainres.2006.08.016 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 107CB UT WOS:000242147200005 PM 16956595 ER PT J AU Wu, XF Sakamoto, T Zhang, F Sellers, JR Hammer, JA AF Wu, Xufeng Sakamoto, Take Zhang, Fang Sellers, James R. Hammer, John A., III TI In vitro reconstitution of a transport complex containing Rab27a, melanophilin and myosin Va SO FEBS LETTERS LA English DT Article DE myosin Va; Rab27a; melanophilin; total internal reflection fluorescence microscopy ID DYNACTIN INCREASES; BINDING DOMAIN; LINKS RAB27A; SLAC2-A/MELANOPHILIN; PROCESSIVITY; ACTIN AB Rab27a and melanophilin (Mlph) are required in vivo to form a melanosome receptor for myosin Va in which Rab27a anchored in the melanosome membrane recruits Mlph, which in turn recruits myosin Va. Here, we show by reconstitution using purified proteins that Rab27a and Mlph are sufficient to form a transport complex with myosin Va in vitro. These results suggest that additional proteins are not required in vivo for assembly of the myosin Va receptor, although other proteins may associate with this tripartite complex to regulate its activity and/or to assist Rab27a in anchoring the complex to the melanosome membrane. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2523,NIH 9000 Rockvill, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov OI Hammer, John/0000-0002-2496-5179 NR 11 TC 34 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 30 PY 2006 VL 580 IS 25 BP 5863 EP 5868 DI 10.1016/j.febslet.2006.09.047 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 100YW UT WOS:000241707100010 PM 17045265 ER PT J AU Opatowsky, Y Sasson, Y Shaked, I Ward, Y Chomsky-Hecht, O Litvak, Y Selinger, Z Kelly, K Hirsch, JA AF Opatowsky, Yarden Sasson, Yehezkel Shaked, Isabella Ward, Yvona Chomsky-Hecht, Orna Litvak, Yael Selinger, Zvi Kelly, Kathleen Hirsch, Joel A. TI Structure-function studies of the G-domain from human gem, a novel small G-protein SO FEBS LETTERS LA English DT Article DE G-protein; crystallography; nucleotide; calcium channel; cytoskeleton ID RGK-FAMILY; RAS FAMILY; GTPASE; EXPRESSION; INSIGHTS; MEMBER; P21 AB Gem, a member of the Rad,Gem/Kir subfamily of small G-proteins, has unique sequence features. We report here the crystallographic structure determination of the Gem G-domain in complex with nucleotide to 2.4 angstrom resolution. Although the basic Ras protein fold is maintained, the Gem switch regions emphatically differ from the Ras paradigm. Our ensuing biochemical characterization indicates that Gem G-domain markedly prefers GDP over GTP. Two known functions of Gem are distinctly affected by spatially separated clusters of mutations. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Tel Aviv Univ, Daniella Rich Inst Struct Biol, Fac Life Sci, Dept Biochem, IL-69978 Ramat Aviv, Israel. NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. RP Hirsch, JA (reprint author), Tel Aviv Univ, Daniella Rich Inst Struct Biol, Fac Life Sci, Dept Biochem, IL-69978 Ramat Aviv, Israel. EM jhirsch@post.tau.ac.il OI Litvak, Yael/0000-0002-0183-2816 FU NEI NIH HHS [R01 EY003529, EY03529, R01 EY003529-26] NR 15 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 30 PY 2006 VL 580 IS 25 BP 5959 EP 5964 DI 10.1016/j.febslet.2006.09.067 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 100YW UT WOS:000241707100025 PM 17052716 ER PT J AU Ray, R Zhang, ZJ Lee, YC Gao, JL Mukherjee, AB AF Ray, Rabindranath Zhang, Zhongjian Lee, Yi-Ching Gao, Ji-Liang Mukherjee, Anil B. TI Uteroglobin suppresses allergen-induced T(H)2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes SO FEBS LETTERS LA English DT Article DE uteroglobin; airway inflammation; allergy ID N-FORMYLPEPTIDE RECEPTOR; T-CELLS; CHEMOTAXIS; DISEASE; FPR2 AB Allergen-induced airway inflammation may lead to allergic asthma, a chronic inflammatory disease of the respiratory system. Despite its high incidence, the majority of the world's population is unaffected by allergic airway inflammation most likely due to innate protective mechanism(s) in the respiratory system. The mammalian airway epithelia constitutively express uteroglobin (UG), a protein with potent anti-inflammatory and anti-chemotactic properties. We report here that UG binds to FPR2, a G-protein coupled receptor, inhibits chemotaxis, down-regulates SOCS-3 gene expression and STAT-1 activation, which are critical for the differentiation of T-helper 2 (T(H)2) cells that secrete pro-inflammatory T(H)2 cytokines. We propose that UG suppresses allergen-mediated activation of T(H)2 response by down-regulating the expression of genes that are critical for T(H)2 differentiation. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bldg 10,Rm 9D42,10,Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD000910-26] NR 16 TC 13 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 30 PY 2006 VL 580 IS 25 BP 6022 EP 6026 DI 10.1016/j.febslet.2006.09.059 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 100YW UT WOS:000241707100034 PM 17046755 ER PT J AU Yurchenko, E Tritt, M Hay, V Shevach, EM Belkaid, Y Piccirillo, CA AF Yurchenko, Ekaterina Tritt, Michael Hay, Valerie Shevach, Ethan M. Belkaid, Yasmine Piccirillo, Ciriaco A. TI CCR5-dependent homing of naturally occurring CD4(+) regulatory T cells to sites of Leishmania major infection favors pathogen persistence SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; CHEMOKINE RECEPTORS; PERIPHERAL TOLERANCE; IMMUNITY; EXPRESSION; DISEASE; MICE; INFLAMMATION; RESPONSES; EFFECTOR AB Pathogen persistence after clinical cure is a hallmark of many chronic infections. Previously, we showed that naturally occurring CD4(+)CD25(+) regulatory T (nTreg) cells rapidly accumulate within chronic dermal sites of Leishmania major infection where they suppress antipathogen CD4(+) T cell responses, favor parasite persistence and dermal pathology, and consequently control concomitant immunity. Here, we postulated that chemokines might direct nTreg cell homing in sites of infection and show that CD4(+)CD25(+) nTreg cells, compared with normal CD4(+) T cells, preferentially express the CCR5 chemokine receptor, which enables them to migrate in response to CCR5 ligands in vitro. We show that in contrast to their wild-type (WT) counterparts, CCR5(-/-) CD4(+)CD25(+) nTreg cells resulted in an increased magnitude of parasite-specific, interferon gamma-producing CD4(+) T cells within infection sites, dramatically reduced parasite numbers, and potent resistance to infection, a finding consistent with the clinical outcome of infected CCR5(-/-) mice. Interestingly, this resistance was related to an inefficient migration of CCR5(-/-) nTreg cells to infected dermal sites compared with WT nTreg cells. Thus, this study shows that CCR5 directs the homing of CD4(+) CD25(+) nTreg cells to L. major-infected dermal sites where they promote the establishment of infection and long-term survival of the parasite in the immune host. C1 McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. McGill Univ, Strateg Training Ctr Infect Dis & Autoimmun, Montreal, PQ H3A 2B4, Canada. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Piccirillo, CA (reprint author), McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. EM ciro.piccirillo@mcgill.ca NR 48 TC 137 Z9 140 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 30 PY 2006 VL 203 IS 11 BP 2451 EP 2460 DI 10.1084/jem.20060956 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 100LO UT WOS:000241670800010 PM 17015634 ER PT J AU Kullberg, MC Jankovic, D Feng, CG Hue, S Gorelick, PL McKenzie, BS Cua, DJ Powrie, F Cheever, AW Maloy, KJ Sher, A AF Kullberg, Marika C. Jankovic, Dragana Feng, Carl G. Hue, Sophie Gorelick, Peter L. McKenzie, Brent S. Cua, Daniel J. Powrie, Fiona Cheever, Allen W. Maloy, Kevin J. Sher, Alan TI IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; COLLAGEN-INDUCED ARTHRITIS; ACTIVE CROHNS-DISEASE; IFN-GAMMA; AUTOIMMUNE INFLAMMATION; ADAPTIVE IMMUNITY; DENDRITIC CELLS; MICE; IL-12; INTERLEUKIN-12 AB Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is caused in part by a dysregulated immune response to the intestinal flora. The common interleukin(IL)-12/IL-23p40 subunit is thought to be critical for the pathogenesis of IBD. We have analyzed the role of IL-12 versus IL-23 in two models of Helicobacter hepaticus-triggered T cell-dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of infected T cell-sufficient hosts, and the other involving CD4(+) T cell transfer into infected Rag(-/-) recipients. Our data demonstrate that IL-23 and not IL-12 is essential for the development of maximal intestinal disease. Although IL-23 has been implicated in the differentiation of IL-17-producing CD4(+) T cells that alone are sufficient to induce autoimmune tissue reactivity, our results instead support a model in which IL-23 drives both interferon gamma and IL-17 responses that together synergize to trigger severe intestinal inflammation. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ York, Dept Biol, Immunol & Infect Unit, York YO10 5YW, N Yorkshire, England. Hull York Med Sch, York YO10 5YW, N Yorkshire, England. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. Sci Applicat Int Corp, FCRDC, NCI,Lab Anim Sci Program, Anim Hlth Diagnost Lab, Frederick, MD 21702 USA. Schering Plough Biopharma, Dept Discovery Res, Palo Alto, CA 94304 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Kullberg, MC (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mk512@york.ac.uk FU Wellcome Trust [, 070361] NR 51 TC 341 Z9 352 U1 1 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 30 PY 2006 VL 203 IS 11 BP 2485 EP 2494 DI 10.1084/jem.20061082 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 100LO UT WOS:000241670800013 PM 17030948 ER PT J AU Mentis, GZ Gravell, M Hamilton, R Shneider, NA O'Donovan, MJ Schubert, M AF Mentis, George Z. Gravell, Maneth Hamilton, Rebecca Shneider, Neil A. O'Donovan, Michael J. Schubert, Manfred TI Transduction of motor neurons and muscle fibers by intramuscular injection of HIV-1-based vectors pseudotyped with select rabies virus glycoproteins SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE HIV-1; rabies virus glycoprotein; motor neuron; gene therapy ID CENTRAL-NERVOUS-SYSTEM; LENTIVIRAL VECTOR; GENE DELIVERY; SPINAL-CORD; IN-VIVO; NEUROTROPHIC FACTOR; MOTONEURONS; MICE; CELLS; RAT AB For studies of motor neuron function or for therapeutic purposes, novel pseudotype HIV-1-based vectors were developed that are capable of expressing transgenes in motor neurons following injection into mouse hind limb muscles. To specifically target motor neurons, glycoproteins from two rabies virus (RV) isolates, the mouse-brain adapted challenge virus 24 (CVS-24) variants, CVS-N2c and CVS-B2c were evaluated for pseudotype formation with an HIV-1-based vector. Both RV glycoproteins incorporated into vector envelopes, and both pseudotypes yielded high titers with Hek293T and cortical plate neuron cultures. Increased neuronotropism by the CVS-N2c pseudotype was not observed, suggesting that vector tropism is not solely determined by the fusogenic viral glycoprotein. Vector injection into hind limb muscles resulted in EYFP reporter gene expression in the injected muscle fibers and in spinal cord motor neurons innervating the same muscle, indicating retrograde vector transport. Intramuscular vector injections into the soleus and tibialis anterior muscles transduced 26% and 16% of all motor neurons in each motor nucleus, respectively. These transduction efficiencies may allow novel approaches to functional studies of the motor system and the treatment of neuromuscular disease. Published by Elsevier B.V. C1 NINDS, Mol Virol & Neurogenet Sect, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NINDS, Dev Neurobiol Sect, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Schubert, M (reprint author), NINDS, Mol Virol & Neurogenet Sect, Basic Neurosci Program, NIH, 5625 Fishers Lane,Rm 4S-18,MSC 9403, Bethesda, MD 20892 USA. EM mentisg@mail.nih.gov; shneider@mail.nih.gov; odonovm@ninds.nih.gov; schuberm@ninds.nih.gov RI o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Shneider, Neil/0000-0002-3223-7366 FU Intramural NIH HHS NR 46 TC 32 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 30 PY 2006 VL 157 IS 2 BP 208 EP 217 DI 10.1016/j.jneumeth.2006.04.011 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 101PU UT WOS:000241753600003 PM 16725205 ER PT J AU Bertolino, A Caforio, G Petruzzella, V Latorre, V Rubino, V Dimalta, S Torraco, A Blasi, G Quartesan, R Mattay, VS Callicott, JH Weinberger, DR Scarabino, T AF Bertolino, Alessandro Caforio, Grazia Petruzzella, Vittoria Latorre, Valeria Rubino, Valeria Dimalta, Savino Torraco, Alessandra Blasi, Giuseppe Quartesan, Roberto Mattay, Venkata S. Callicott, Joseph H. Weinberger, Daniel R. Scarabino, Tommaso TI Prefrontal dysfunction in schizophrenia controlling for COMT Val(158)Met genotype and working memory performance SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE working memory; catechol-O-methyltransferase; prefrontal cortex; functional magnetic resonance imaging ID VAL(108/158) MET GENOTYPE; CORTEX DYSFUNCTION; OLANZAPINE; FMRI AB Earlier studies with functional imaging in schizophrenia have demonstrated dysfunction of the dorsolateral prefrontal cortex during working memory. Controlling for behavioral performance and for catechol-O-methyltransferase (COMT) Val(158)Met genotype, we here demonstrate in a functional magnetic resonance imaging paradigm that patients recruit greater neuronal resources in prefrontal cortex during working memory, suggesting that this phenotype is a core functional trait of the disease. We also replicated earlier findings that the Val allele of the COMT polymorphism is associated with greater engagement of the prefrontal cortex. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Bari, Dipartimento Sci Neurol & Psichiatr, Sect Mental Disorders, Psychiat Neurosci Grp, I-70124 Bari, Italy. Univ Bari, Dept Med Biochem & Mol Biol, I-70124 Bari, Italy. Univ Perugia, Dept Clin & Expt Med, I-06100 Perugia, Italy. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. IRCCS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, FG, Italy. RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiatr, Sect Mental Disorders, Psychiat Neurosci Grp, Piazz Giulio Cesare 9, I-70124 Bari, Italy. EM bertolia@psichiat.uniba.it RI Picchioni, Marco/E-3300-2010; Callicott, Joseph/C-9102-2009; Torraco, Alessandra/J-9127-2016; Bertolino, Alessandro/O-6352-2016; OI Picchioni, Marco/0000-0001-6681-147X; Callicott, Joseph/0000-0003-1298-3334; Torraco, Alessandra/0000-0002-2489-8535; Bertolino, Alessandro/0000-0002-1251-1380; Petruzzella, Vittoria/0000-0001-8771-6033 NR 13 TC 44 Z9 46 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD OCT 30 PY 2006 VL 147 IS 2-3 BP 221 EP 226 DI 10.1016/j.pscychresns.2006.04.001 PG 6 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 095RX UT WOS:000241326800013 PM 16952445 ER PT J AU Rizzo, C Viboud, C Montomoli, E Simonsen, L Miller, MA AF Rizzo, Caterina Viboud, Cecile Montomoli, Emanuele Simonsen, Lone Miller, Mark A. TI Influenza-related mortality in the Italian elderly: No decline associated with increasing vaccination coverage SO VACCINE LA English DT Article DE influenza; vaccination; mortality ID UNITED-STATES; IMPACT; COMMUNITY; VACCINES; SENIORS; DISEASE; AGE AB We investigated trends in influenza-related mortality among the elderly population in Italy associated with increased vaccination coverage. Using Italian vital statistics data, we studied monthly death rates for pneumonia and influenza and all-cause for persons >= 65 years of age by 5-year age groups for 1970-2001. Using a classic seasonal regression modelling approach, we estimated the age-specific seasonal excess mortality rates among Italian elderly as a measure of influenza-related deaths. We studied trends in excess mortality after adjusting for population aging and analyzing separately seasons dominated by the severe A/H3N2 subtype and those dominated by other circulating influenza subtypes. After the late 1980s, no decline in age-adjusted excess mortality was associated with increasing influenza vaccination distribution primarily targeted for the elderly. These findings suggest that either the vaccine failed to protect the elderly against mortality (possibly due to immune senescence), and/or the vaccination efforts did not adequately target the frailest elderly. As in the US, our study challenges current strategies to best protect the elderly against mortality, warranting the need for better controlled trials with alternative vaccination strategies. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Bari, Dept Pharmacobiol, I-70121 Bari, Italy. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Siena, Dept Physiopathol Expt Med & Publ Hlth, I-53100 Siena, Italy. NIAID, NIH, Bethesda, MD 20892 USA. RP Rizzo, C (reprint author), Univ Bari, Dept Pharmacobiol, I-70121 Bari, Italy. EM caterina.rizzo@iss.it RI Rizzo, Caterina/H-4092-2012; MONTOMOLI, EMANUELE/Q-2122-2015; OI Rizzo, Caterina/0000-0002-5583-7508; MONTOMOLI, EMANUELE/0000-0001-7595-4974; Simonsen, Lone/0000-0003-1535-8526 NR 39 TC 34 Z9 36 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 30 PY 2006 VL 24 IS 42-43 BP 6468 EP 6475 DI 10.1016/j.vaccine.2006.06.052 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 102XL UT WOS:000241846700003 PM 16876293 ER PT J AU Greene, MW Ruhoff, MS Roth, RA Kim, JA Quon, MJ Krause, JA AF Greene, Michael W. Ruhoff, Mary S. Roth, Richard A. Kim, Jeong-a Quon, Michael J. Krause, Jean A. TI PKC delta-mediated IRS-1 Ser24 phosphorylation negatively regulates IRS-1 function SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE insulin receptor substrate; PKC; insulin resistance; serine phosphorylation; shRNA ID INSULIN-RECEPTOR SUBSTRATE-1; PROTEIN-KINASE-C; PLECKSTRIN HOMOLOGY DOMAIN; BINDING DOMAINS; PTB DOMAIN; RESISTANCE; ACTIVATION; CELLS; PHOSPHOINOSITIDES; EXPRESSION AB The IRS-1 PH and PTB domains are essential for insulin-stimulated IRS-1 Tyr phosphorylation and insulin signaling, while Ser/Thr phosphorylation of IRS-1 disrupts these signaling events. To investigate consensus PKC phosphorylation sites in the PH-PTB domains of human IRS-1, we changed Ser24, Ser58, and Thr191 to Ala (3A) or Glu (3E), to block or mimic phosphorylation, respectively. The 3A mutant abrogated the inhibitory effect of PKC delta on insulin-stimulated IRS-1 Tyr phosphorylation, while reductions in insulin-stimulated IRS-1 Tyr phosphorylation, cellular proliferation, and Akt activation were observed with the 3E mutant. When single Glu mutants were tested, the Ser24 to Glu mutant had the greatest inhibitory effect on insulin-stimulated IRS-1 Tyr phosphorylation. PKC delta-mediated IRS-1 Ser24 phosphorylation was confirmed in cells with PKC delta catalytic domain mutants and by an RNAi method. Mechanistic studies revealed that IRS-1 with Ala and Glu point mutations at Ser24 impaired phosphatidylinositol-4,5-bisphosphate binding. In summary, our data are consistent with the hypothesis that Ser24 is a negative regulatory phosphorylation site in IRS-1. (c) 2006 Elsevier Inc. All rights reserved. C1 Mary Imogene Bassett Hosp, Bassett Res Inst, Cooperstown, NY 13326 USA. Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. Natl Ctr Complementary & Alternat Med, Diabet Unit, NIH, Bethesda, MD 20892 USA. RP Greene, MW (reprint author), Mary Imogene Bassett Hosp, Bassett Res Inst, Cooperstown, NY 13326 USA. EM michael.greene@bassett.org RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Greene, Michael/0000-0002-6443-8269 FU NIDDK NIH HHS [DK34976] NR 44 TC 32 Z9 32 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 27 PY 2006 VL 349 IS 3 BP 976 EP 986 DI 10.1016/j.bbrc.2006.08.158 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 089UW UT WOS:000240907800015 PM 16970908 ER PT J AU Martin, DN Boersma, BJ Howe, TM Goodman, JE Mechanic, LE Chanock, SJ Ambs, S AF Martin, Damali N. Boersma, Brenda J. Howe, Tiffany M. Goodman, Julie E. Mechanic, Leah E. Chanock, Stephen J. Ambs, Stefan TI Association of MTHFR gene polymorphisms with breast cancer survival SO BMC CANCER LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; SINGLE NUCLEOTIDE POLYMORPHISMS; DIETARY-FOLATE INTAKE; ONE-CARBON METABOLISM; RHEUMATOID-ARTHRITIS; ESTROGEN-RECEPTOR; C677T POLYMORPHISM; DNA METHYLATION; RISK; METHOTREXATE AB Background: Two functional single nucleotide polymorphisms ( SNPs) in the 5,10-methylenetetrahydrofolate reductase ( MTHFR) gene, C677T and A1298C, lead to decreased enzyme activity and affect chemosensitivity of tumor cells. We investigated whether these MTHFR SNPs were associated with breast cancer survival in African- American and Caucasian women. Methods: African- American ( n = 143) and Caucasian ( n = 105) women, who had incident breast cancer with surgery, were recruited between 1993 and 2003 from the greater Baltimore area, Maryland, USA. Kaplan- Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between MTHFR SNPs and disease- specific survival. Results: We observed opposite effects of the MTHFR polymorphisms A1298C and C677T on breast cancer survival. Carriers of the variant allele at codon 1298 ( A/ C or C/ C) had reduced survival when compared to homozygous carriers of the common A allele [ Hazard ratio ( HR) = 2.05; 95% confidence interval ( CI), 1.05 - 4.00]. In contrast, breast cancer patients with the variant allele at codon 677 ( C/ T or T/ T) had improved survival, albeit not statistically significant, when compared to individuals with the common C/ C genotype ( HR = 0.65; 95% CI, 0.31 - 1.35). The effects were stronger in patients with estrogen receptor- negative tumors ( HR = 2.70; 95% CI, 1.17 - 6.23 for A/ C or C/ C versus A/ A at codon 1298; HR = 0.36; 95% CI, 0.12 - 1.04 for C/ T or T/ T versus C/ C at codon 677). Interactions between the two MTHFR genotypes and race/ ethnicity on breast cancer survival were also observed ( A1298C, p(interaction) = 0.088; C677T, p(interaction) = 0.026). Conclusion: We found that the MTHFR SNPs, C677T and A1298C, were associated with breast cancer survival. The variant alleles had opposite effects on disease outcome in the study population. Race/ ethnicity modified the association between the two SNPs and breast cancer survival. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Gradient Corp, Cambridge, MA USA. NCI, Sect Genom Variat, Pediat Oncol Branch,CCR, NIH, Bethesda, MD 20892 USA. RP Ambs, S (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM martinda@mail.nih.gov; boersmab@mail.nih.gov; howet@mail.nih.gov; jgoodman@gradientcorp.com; mechanil@mail.nih.gov; chanocks@mail.nih.gov; ambss@mail.nih.gov RI Boersma, Brenda/A-9270-2009 OI Boersma, Brenda/0000-0002-8992-2735 FU Intramural NIH HHS NR 44 TC 26 Z9 26 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD OCT 27 PY 2006 VL 6 AR 257 DI 10.1186/1471-2407-6-257 PG 10 WC Oncology SC Oncology GA 104VN UT WOS:000241988800001 PM 17069650 ER PT J AU Bogdanov, KY Maltsev, VA Vinogradova, TM Lyashkov, AE Spurgeon, HA Stern, MD Lakatta, EG AF Bogdanov, Konstantin Y. Maltsev, Victor A. Vinogradova, Tatiana M. Lyashkov, Alexey E. Spurgeon, Harold A. Stern, Michael D. Lakatta, Edward G. TI Membrane potential fluctuations resulting from submembrane Ca2(+) releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state SO CIRCULATION RESEARCH LA English DT Article DE membrane potential; Na+/Ca2+ exchange; ryanodine receptor; sarcoplasmic reticulum; sinoatrial node ID CURRENT I-F; L-TYPE CA2+; PACEMAKER ACTIVITY; RYANODINE RECEPTOR; ELECTRICAL-ACTIVITY; CARDIAC PACEMAKING; BEATING RATE; AUTOMATICITY; CURRENTS; MODULATION AB Stochastic but roughly periodic LCRs ((L) under bar ocal subsarcolemmal ryanodine receptor-mediated (C) under bara(2+) Releases) during the late phase of diastolic depolarization ( DD) in rabbit sinoatrial nodal pacemaker cells (SANCs) generate an inward current (I-NCX) via the Na+/Ca2+ exchanger. Although LCR characteristics have been correlated with spontaneous beating, the specific link between LCR characteristics and SANC spontaneous beating rate, ie, impact of LCRs on the fine structure of the DD, have not been explicitly defined. Here we determined how LCRs and resultant INCX impact on the DD fine structure to control the spontaneous SANC firing rate. Membrane potential (V-m) recordings combined with confocal Ca2+ measurements showed that LCRs impart a nonlinear, exponentially rising phase to the DD later part, which exhibited beat-to-beat Vm fluctuations with an amplitude of approximately 2 mV. Maneuvers that altered LCR timing or amplitude of the nonlinear DD (ryanodine, BAPTA, nifedipine or isoproterenol) produced corresponding changes in Vm fluctuations during the nonlinear DD component, and the V-m fluctuation response evoked by these maneuvers was tightly correlated with the concurrent changes in spontaneous beating rate induced by these perturbations. Numerical modeling, using measured LCR characteristics under these perturbations, predicted a family of local I-NCX that reproduced Vm fluctuations measured experimentally and determined the onset and amplitude of the nonlinear DD component and the beating rate. Thus, beat-to-beat Vm fluctuations during late DD phase reflect the underlying LCR/I-NCX events, and the ensemble of these events forms the nonlinear DD component that ultimately controls the SANC chronotropic state in tight cooperation with surface membrane ion channels. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS NR 28 TC 62 Z9 67 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 27 PY 2006 VL 99 IS 9 BP 979 EP 987 DI 10.1161/01.RES.000247933.66532.0b PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 099EZ UT WOS:000241577400011 PM 17008599 ER PT J AU Gerken, TA Raman, J Fritz, TA Jamison, O AF Gerken, Thomas A. Raman, Jayalakshmi Fritz, Timothy A. Jamison, Oliver TI Identification of common and unique peptide substrate preferences for the UDP-GalNAc: Polypeptide alpha-N-acetylgalactosaminyltransferases T1 and T2 derived from oriented random peptide substrates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEIGHBORING RESIDUE GLYCOSYLATION; FAMILIAL TUMORAL CALCINOSIS; O-LINKED GLYCOSYLATION; MUCIN TANDEM REPEAT; D-GALACTOSAMINE; LECTIN DOMAIN; CDNA CLONING; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; MOLECULAR-CLONING AB A large family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAc Ts) catalyzes the first step of mucin-type protein O-glycosylation by transferring GalNAc to serine and threonine residues of acceptor polypeptides. The acceptor peptide substrate specificity and specific protein targets of the individual ppGalNAc T family members remain poorly characterized and poorly understood, despite the fact that mutations in two individual isoforms are deleterious to man and the fly. In this work a series of oriented random peptide substrate libraries, based on the GAGAXXX-TXXXAGAGK sequence motif (where X = randomized positions), have been used to obtain the first comprehensive determination of the peptide substrate specificities of the mammalian ppGalNAc T1 and T2 isoforms. ppGalNAc T-glycosylated random peptides were isolated by lectin affinity chromatography, and transferase amino acid preferences were determined by Edman amino acid sequencing. The results reveal common and unique position-sensitive features for both transferases, consistent with previous reports of the preferences of ppGalNAc T1 and T2. The random peptide substrates also reveal additional specific features that have never been described before that are consistent with the x-ray crystal structures of the two transferases and furthermore are reflected in a data base analysis of in vivo O-glycosylation sites. By using the transferase-specific preferences, optimum and selective acceptor peptide substrates have been generated for each transferase. This approach represents a relatively complete, facile, and reproducible method for obtaining ppGalNAc T peptide substrate specificity. Such information will be invaluable for identifying isoform-specific peptide acceptors, creating isoform-specific substrates, and predicting O-glycosylation sites. C1 Case Western Reserve Univ, Dept Pediat, Sch Med, WA Bernbaum Ctr Cyst Fibrosis Res, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biochem, Sch Med, WA Bernbaum Ctr Cyst Fibrosis Res, Cleveland, OH 44106 USA. NIDDK, Sect Biol Chem, NIH, Bethesda, MD 20892 USA. RP Gerken, TA (reprint author), Case Western Reserve Univ, Dept Pediat, Sch Med, WA Bernbaum Ctr Cyst Fibrosis Res, BRB,2109 Adelbert Rd, Cleveland, OH 44106 USA. EM txg2@cwru.edu FU NCI NIH HHS [R01 CA 78834, R01 CA078834] NR 52 TC 44 Z9 44 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 27 PY 2006 VL 281 IS 43 BP 32403 EP 32416 DI 10.1074/jbc.M605149200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500038 PM 16912039 ER PT J AU Johnson, AA Sayer, JM Yagi, H Patil, SS Debart, F Maier, MA Corey, DR Vasseur, JJ Burke, TR Marquez, VE Jerina, DM Pommier, Y AF Johnson, Allison A. Sayer, Jane M. Yagi, Haruhiko Patil, Sachindra S. Debart, Francoise Maier, Martin A. Corey, David R. Vasseur, Jean-Jacques Burke, Terrence R., Jr. Marquez, Victor E. Jerina, Donald M. Pommier, Yves TI Effect of DNA modifications on DNA processing by HIV-1 integrase and inhibitor binding - Role of DNA backbone flexibility and an open catalytic site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 INTEGRASE; DIOL EPOXIDE ADDUCTS; VIRAL-DNA; MINOR-GROOVE; TOPOISOMERASE-I; VACCINIA TOPOISOMERASE; STRAND TRANSFER; CLEAVAGE SITE; DEOXYADENOSINE; POLYMERASE AB Integration of the viral cDNA into host chromosomes is required for viral replication. Human immunodeficiency virus integrase catalyzes two sequential reactions, 3'-processing (3'-P) and strand transfer (ST). The first integrase inhibitors are undergoing clinical trial, but interactions of inhibitors with integrase and DNA are not well understood in the absence of a co-crystal structure. To increase our understanding of integrase interactions with DNA, we examined integrase catalysis with oligonucleotides containing DNA backbone, base, and groove modifications placed at unique positions surrounding the 3'-processing site. 3'-Processing was blocked with substrates containing constrained sugars and alpha-anomeric residues, suggesting that integrase requires flexibility of the phosphodiester backbone at the 3'-P site. Of several benzo[a]pyrene 7,8-diol 9,10-epoxide (BaPDE) adducts tested, only the adduct in the minor groove at the 3'-P site inhibited 3'-P, suggesting the importance of the minor groove contacts for 3'-P. ST occurred in the presence of bulky BaP DE DNA adducts attached to the end of the viral DNA suggesting opening of the active site for ST. Position-specific effects of these BaP DE DNA adducts were found for inhibition of integrase by diketo acids. Together, these results demonstrate the importance of DNA structure and specific contacts with the viral DNA processing site for inhibition by integrase inhibitors. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Med Chem Lab, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. Univ Montpellier 2, CNRS, LCOBS, UMR 5625, F-34095 Montpellier, France. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Dept Hlth & Human Serv,NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Burke, Terrence/N-2601-2014; OI Vasseur, Jean-Jacques/0000-0002-4379-6139 FU Intramural NIH HHS; NIGMS NIH HHS [GM 60642] NR 55 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 27 PY 2006 VL 281 IS 43 BP 32428 EP 32438 DI 10.1074/jbc.M605101200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500040 PM 16943199 ER PT J AU Yan, ZH Liang, ZD Obsil, T Stojilkovic, SS AF Yan, Zonghe Liang, Zhaodong Obsil, Tomas Stojilkovic, Stanko S. TI Participation of the Lys(313)-Ile(333) sequence of the purinergic P2X4 receptor in agonist binding and transduction of signals to the channel gate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN P2X(1) RECEPTORS; ATP-BINDING; ION CHANNELS; TRANSMEMBRANE SEGMENTS; DEPENDENT CHANGES; SWISS-MODEL; AMINO-ACIDS; SITE; PORE; IDENTIFICATION AB To study the roles of the Lys(313)-Ile(333) ectodomain sequence of the rat P2X(4) receptor in ATP binding and transduction of signals to the channel gate, the conserved Lys(313), Tyr(315), Gly(316), Ike(317), Arg(318), Asp(320), Val(323), Lys(329), Phe(330), and Ile(333) residues were mutated. Current recordings were done on lifted cells and ATP was applied using an ultrafast solution-switching system. The rates of wild type channel opening and closing in the presence of ATP, but not the rate of washout-induced closing, were dependent on agonist concentration. All mutants other than I317A were expressed in the plasma membrane at comparable levels. The majority of mutants showed significant changes in the peak amplitude of responses and the EC50 values for ATP. When stimulated with the supramaximal (1.4mM) ATP concentration, mutants also differed in the kinetics of their activation, deactivation, and/or desensitization. The results suggest a critical role of the Lys(313) residue in receptor function other than coordination of the phosphate group of ATP and possible contribution of the Tyr(315) residue to the agonist binding module. The pattern of changes of receptor function by mutation of other residues was consistent with the operation of the Gly(316) Ile(333) sequence as a signal transduction module between the ligand binding domain and the channel gate in the second transmembrane domain. C1 NICHD, ERRB, Sect Cellular Signaling, NIH, Bethesda, MD 20892 USA. Charles Univ, Fac Sci, Dept Phys & Macromol Chem, Prague 12843, Czech Republic. RP Stojilkovic, SS (reprint author), NICHD, ERRB, Sect Cellular Signaling, NIH, Bldg 49,Rm 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Obsil, Tomas/B-7142-2012 OI Obsil, Tomas/0000-0003-4602-1272 FU Intramural NIH HHS NR 49 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 27 PY 2006 VL 281 IS 43 BP 32649 EP 32659 DI 10.1074/jbc.M512791200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500063 PM 16954225 ER PT J AU Dang, YJ Kedersha, N Low, WK Romo, D Gorospe, M Kaufman, R Anderson, P Liu, JO AF Dang, Yongjun Kedersha, Nancy Low, Woon-Kai Romo, Daniel Gorospe, Myriam Kaufman, Randal Anderson, Paul Liu, Jun O. TI Eukaryotic initiation factor 2 alpha-independent pathway of stress granule induction by the natural product pateamine A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING PROTEIN TIAR; MESSENGER-RNA; TRANSLATION; RECRUITMENT; PHOSPHORYLATION; ARSENITE; INHIBITION; COMPLEXES AB Stress granules are aggregates of small ribosomal subunits, mRNA, and numerous associated RNA-binding proteins that include several translation initiation factors. Stress granule assembly occurs in the cytoplasm of higher eukaryotic cells under a wide variety of stress conditions, including heat shock, UV irradiation, hypoxia, and exposure to arsenite. Thus far, a unifying principle of eukaryotic initiation factor 2 alpha phosphorylation prior to stress granule formation has been observed from the majority of experimental evidence. Pateamine A, a natural product isolated from marine sponge, was recently reported to inhibit eukaryotic translation initiation and induce the formation of stress granules. In this report, the protein composition and fundamental progression of stress granule formation and disassembly induced by pateamine A was found to be similar to that for arsenite. However, pateamine A-induced stress granules were more stable and less prone to disassembly than those formed in the presence of arsenite. Most significantly, pateamine A induced stress granules independent of eukaryotic initiation factor 2 alpha phosphorylation, suggesting an alternative mechanism of formation from that previously described for other cellular stresses. Taking into account the known inhibitory effect of pateamine A on eukaryotic translation initiation, a model is proposed to account for the induction of stress granules by pateamine A as well as other stress conditions through perturbation of any steps prior to the rejoining of the 60S ribosomal subunit during the entire translation initiation process. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol & Immunol, Boston, MA 02115 USA. Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA. NIA, RNA Regulat Sect, NIH, Baltimore, MD 21224 USA. Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Biol Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Liu, JO (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Hunterian 516,725 N Wolfe St, Baltimore, MD 21205 USA. EM joliu@jhu.edu RI dang, yongjun/A-8095-2011; dang, yongjun/M-6531-2016 OI dang, yongjun/0000-0001-7237-1132 FU NIAID NIH HHS [AI 033600]; NIDDK NIH HHS [DK 42394] NR 34 TC 130 Z9 131 U1 2 U2 9 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 OCT 27 PY 2006 VL 281 IS 43 BP 32870 EP 32878 DI 10.1074/jbc.M606149200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500085 PM 16951406 ER PT J AU Hozumi, K Suzuki, N Nielsen, PK Nomizu, M Yamada, Y AF Hozumi, Kentaro Suzuki, Nobuharu Nielsen, Peter K. Nomizu, Motoyoshi Yamada, Yoshihiko TI Laminin alpha 1 chain LG4 module promotes cell attachment through syndecans and cell spreading through integrin alpha 2 beta 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; SITE-DIRECTED MUTAGENESIS; G-DOMAIN; BINDING-SITES; DYSTROGLYCAN-BINDING; SYNTHETIC PEPTIDES; GLOBULAR DOMAIN; BASEMENT-MEMBRANES; CARCINOMA CELLS; SWISS-MODEL AB The laminin alpha 1 chain is a subunit of laminin-1, a heterotrimeric basement membrane protein. The LG4-5 module at the C terminus of laminin alpha 1 contains major binding sites for heparin, sulfatide, and alpha-dystroglycan and plays a critical role in early embryonic development. We previously identified active synthetic peptides AG73 and EF-1 from the sequence of laminin alpha 1 LG4 for binding to syndecan and integrin alpha 2 beta 1, respectively. However, their activity and functional relationship within the laminin-1 and LG4 as well as the functional relation between these sites and alpha-dystroglycan binding sites in LG4 are not clear. To address these questions, we created mutant recombinant LG4 proteins containing alanine substitutions within the AG73 (M1), EF-1 (M2, M3), and alpha-dystroglycan binding sites (M4, M5) and analyzed their activities. We found that recombinant proteins rec-M1 and rec-M5, containing mutations within M1 and M5, respectively, did not bind heparin or lymphoid cell lines expressing syndecans. These results suggest that LG4 binds to heparin and syndecans through M1 and M5. Rec-M1 and rec-M5 reduced fibroblast attachment, whereas mutant rec-M2 and rec-M3 retained cell attachment activity but did not promote cell spreading. Fibroblast attachment to rec- LG4 was inhibited by heparin but not by integrin antibodies. Spreading of fibroblasts on rec-LG4 was inhibited by anti-integrin alpha 2 and beta 1 but not by anti-integrin alpha 1 and alpha 6. These results suggest that the M1 and M5 sites are necessary for cell attachment on LG4 through syndecans and that the EF-1 site is for cell spreading activity through integrin alpha 2 beta 1. In contrast, laminin-1-mediated fibroblast attachment and spreading were not inhibited by heparin or anti-integrin alpha 2. Our findings indicate that LG4 has a unique function distinct from laminin-1 and suggest that laminin alpha 1 LG4-5 may also be produced by a proteolytic cleavage in certain tissues where it exerts its activity. C1 NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo 1920392, Japan. RP Yamada, Y (reprint author), NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Rm 407,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM yoshi.yamada@nih.gov FU Intramural NIH HHS NR 55 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 27 PY 2006 VL 281 IS 43 BP 32929 EP 32940 DI 10.1074/jbc.M605708200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 096ZB UT WOS:000241414500091 PM 16945929 ER PT J AU Xu, Q Appella, DH AF Xu, Qun Appella, Daniel H. TI Practical synthesis of trans-tert-butyl-2-aminocyclopentylcarbamate and resolution of enantiomers SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ASYMMETRIC-SYNTHESIS; BINDING-AFFINITY; AZIRIDINES; TRANS-CYCLOPENTANE-1,2-DIAMINE; COMPLEXES; CATALYSIS; CLEAVAGE; AMINES; ACIDS; SULFONAMIDES AB Optically active trans-tert-butyl-2-aminocyclopentylcarbamate (1) has potential utility as a scaffold for chiral ligands and as a modified backbone unit for peptide nucleic acids (PNAs). We have developed a short and practical synthesis of 1 via aziridine opening of tosyl-activated cyclopentene aziridine 2 and optical resolution of racemic 1 with 10-camphorsulfonic acid (CSA). The route provides ready access to multigram quantities of both enantiomers without the need for chromatography. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Appella, DH (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov RI Xu, Qun /C-6996-2011 FU Intramural NIH HHS NR 35 TC 12 Z9 12 U1 1 U2 10 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 OCT 27 PY 2006 VL 71 IS 22 BP 8655 EP 8657 DI 10.1021/jo061409v PG 3 WC Chemistry, Organic SC Chemistry GA 097GQ UT WOS:000241435600050 PM 17064052 ER PT J AU Tserentsoodol, N Sztein, J Campos, M Gordiyenko, N Fariss, R Lee, J Fliesler, S Rodriguez, I AF Tserentsoodol, Nomingerel Sztein, Jorge Campos, Mercedes Gordiyenko, Natalya V. Fariss, Robert N. Lee, Jung Wha Fliesler, Steven J. Rodriguez, Ignacio R. TI Uptake of cholesterol by the retina occurs primarily via a low density lipoprotein receptor-mediated process SO MOLECULAR VISION LA English DT Article ID AGE-RELATED MACULOPATHY; PIGMENT EPITHELIUM; APOLIPOPROTEIN-B; DELIVERED BENZOPORPHYRIN; LIPID-METABOLISM; RPE CELLS; IN-VIVO; LDL; BIOSYNTHESIS; FLUORESCENT AB PURPOSE: In this study we examined the uptake of circulating lipoproteins into the retina, using a naturally fluorescent cholesterol analog for imaging and deuterated cholesterol for quantification by mass spectroscopy. The purpose of this study was to better understand cholesterol uptake, transport and homeostasis in the retina. METHODS: Human low density lipoprotein (LDL) and high density lipoprotein (HDL) were labeled with the fluorescent cholesterol analog cholesta-5,7,9(11)-trien-3 beta ol (CTL) and deuterated cholesterol (25,26,26,26,27,27,27-[H-2]cholesterol, D7Ch). Rats were injected intravenously with CTL-LDL, CTL-HDL and D7Ch-LDL. Fluorescent confocal microscopy was used to image the uptake of CTL and mass spectroscopy was used to quantify D7Ch. Immunohistochemistry and fluorescent confocal microscopy were used to localize apoB (an LDL marker protein) and LDL receptor (LDLR) protein in rat and monkey retinas. RESULTS: CTL-specific fluorescence was imaged by confocal microscopy in the retinal pigment epithelium (RPE), choriocapillaris and parts of the neural retina within 2 h post-injection and was visualized in the photoreceptor outer segments by 4 h. Replacing LDL with HDL as the CTL carrier gave a less robust and more delayed labeling of retinal layers. Human apolipoprotein B (apoB) was also localized in the rat choriocapillaris and RPE by 4 h post-injection. Human apoB was detected by immunoblot analysis in the rat retina primarily as a about 70 kDa protein, suggesting proteolytic degradation. LDL-mediated uptake of cholesterol was quantified by mass spectroscopy using deuterated cholesterol in place of CTL. In addition, apoB and LDLR were localized in monkey retina by immunohistochemistry. CONCLUSIONS: The retina is capable of rapid uptake of circulating LDL via an LDLR-mediated process primarily occurring in the RPE and also possibly MUller cells. Despite the dominance of HDL over LDL in rat serum, LDL appears to be the preferred carrier for cholesterol transport to and uptake by the retina. The results also suggest that blood-borne LDL represents a significant contributor to the steady-state levels of cholesterol and possibly other lipids in the retina. C1 NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, Bethesda, MD 20892 USA. NEI, Vet Res & Resources Sect, NIH, Bethesda, MD 20892 USA. NEI, Biol Imaging Core, NIH, Bethesda, MD 20892 USA. St Louis Univ, Inst Eye, St Louis, MO 63103 USA. St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63103 USA. RP Rodriguez, I (reprint author), NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, 7 Mem Dr,MSC0706,Bldg 7 Rm 302, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov RI Sztein, Jorge/B-7165-2012; OI Sztein, Jorge Mario/0000-0001-7047-2634 FU Intramural NIH HHS; NEI NIH HHS [EY07361] NR 37 TC 70 Z9 71 U1 1 U2 6 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 OCT 27 PY 2006 VL 12 IS 148-49 BP 1306 EP 1318 PG 13 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 105NI UT WOS:000242036600001 PM 17110914 ER PT J AU Tserentsoodol, N Gordiyenko, N Pascual, I Lee, J Fliesler, S Rodriguez, I AF Tserentsoodol, Nomingerel Gordiyenko, Natalyia V. Pascual, Iranzu Lee, Jung Wha Fliesler, Steven J. Rodriguez, Ignacio R. TI Intraretinal lipid transport is dependent on high density lipoprotein-like particles and class B scavenger receptors SO MOLECULAR VISION LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; CHOLESTERYL ESTER UPTAKE; CENTRAL-NERVOUS-SYSTEM; APOLIPOPROTEIN-A-II; SR-BI; OXIDIZED LDL; OUTER SEGMENTS; GLIAL-CELLS; IN-VIVO; CD36 AB PURPOSE: In our companion paper we demonstrated that circulating lipoproteins enter the retina via the retinal pigment epithelium (RPE) and possibly MUller cells. In order to understand how these lipids are transported within the retina, expression and localization of the main proteins known to be involved in systemic lipid transport was determined. METHODS: Expression of ABCA1, apoA1 (the major HDL protein), SR-BI, SR-BII, CD36, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP) was determined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblots. Localization was determined by immunohistochemistry using fresh monkey vibrotome sections and imaged by confocal microscopy. RESULTS: ABCA1 and apoA1 were localized to the ganglion cell layer, retinal pigment epithelium (RPE), and rod photoreceptor inner segments. ApoA1 was also observed associated with rod photoreceptor outer segments, presumably localized to the interphotoreceptor matrix (IPM). The scavenger receptors SR-BI and SR-BII localized mainly to the ganglion cell layer and photoreceptor outer segments; in the latter they appear to be associated with microtubules. LCAT and CETP localized mainly to the IPM. CONCLUSIONS: The presence and specific localization of these well-known lipid transport proteins suggest that the retina employs an internal lipid transport mechanism that involves processing and maturation of HDL-like particles. C1 NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, Bethesda, MD 20892 USA. St Louis Univ, Inst Eye, St Louis, MO 63103 USA. St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63103 USA. RP Rodriguez, I (reprint author), NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, 7 Mem Dr,MSC0706,Bldg 7 Rm 302, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [EY007361] NR 58 TC 88 Z9 89 U1 0 U2 3 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 OCT 27 PY 2006 VL 12 IS 148-49 BP 1319 EP 1333 PG 15 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 105NI UT WOS:000242036600002 PM 17110915 ER PT J AU Bohringer, D Spierings, E Enczmann, J Bohringer, S Sundmacher, R Goulmy, E Reinhard, T AF Boehringer, Daniel Spierings, Eric Enczmann, Juergen Boehringer, Stefan Sundmacher, Rainer Goulmy, Els Reinhard, Thomas TI Matching of the minor histocompatibility antigen HLA-Al/H-Y may improve prognosis in corneal transplantation SO TRANSPLANTATION LA English DT Article DE minor H antigens; HLA; HA-3; H-Y; graft rejection; penetrating keratoplasty ID SYSTEMIC CYCLOSPORINE-A; ALLOGRAFT-REJECTION; RISK-FACTOR; CLASS-I; GRAFT; KERATOPLASTY; COMPATIBILITY; PRIVILEGE; PREGNANCY; SURVIVAL AB Background. Minor histocompatibility (H) antigens are peptides of allelic intracellular proteins that play an important role in human leukocyte antigen (HLA) matched transplantations. In an animal model of keratoplasty, minor H antigens have even been reported to exceed the immunogenicity of major H antigens (MHC). This investigation is to assess any benefit of matching the broadly expressed gender (H-Y) and HA-3 antigens in HLA-A1 donor positive human keratoplasty. Methods. A total of 229 HLA-A1 donor positive keratoplasties were analyzed. A Cox proportional hazards model and Kaplan-Meier analysis were applied to estimate the effect of H-Y or HA-3 mismatches on rejection-free graft survival. Results. Eighty-one cases were mismatched for H-Y (male donor to female recipient). A mean follow up of two years showed graft survival as high as 88% in the H-Y compatible group compared to only 77% in the H-Y mismatched group (P=0.02). Eight out of 62 cases were mismatched for HA-3. No statistically significant influence of HA-3 matching on rejection-free graft survival was observed (85% vs. 73%, P=0.52). Conclusion. HLA-Al/H-Y matching and matching for other broadly expressed minor H antigens may further improve prognosis in keratoplasty. C1 Univ Hosp Freiburg, Hosp Eye, Freiburg, Germany. Univ Hosp Freiburg, LIONS Cornea Bank Reg Baden Wurttemberg, Freiburg, Germany. Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, NL-2300 RA Leiden, Netherlands. Univ Hosp, Inst Transplantat Immunol, Dusseldorf, Germany. Univ Klinikum Duisburg Essen, Inst Humangenet, Essen, Germany. Natl Canc Inst, Biostat Branch, Bethesda, MD USA. Univ Hosp, Hosp Eye, Dusseldorf, Germany. Univ Hosp, LIONS Cornea Bank N Rhine Westphalia, Dusseldorf, Germany. RP Bohringer, D (reprint author), Univ Klinikum, Augenklin, Killianstr 5, D-79106 Freiburg, Germany. EM daniel.boehringer@uniklinik-freiburg.de RI Reinhard, Thomas/E-4012-2010 NR 31 TC 27 Z9 27 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2006 VL 82 IS 8 BP 1037 EP 1041 DI 10.1097/01.tp.0000235908.54766.44 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 101WY UT WOS:000241773100006 PM 17060851 ER PT J AU Wolf, YI Viboud, C Holmes, EC Koonin, EV Lipman, DJ AF Wolf, Yuri I. Viboud, Cecile Holmes, Edward C. Koonin, Eugene V. Lipman, David J. TI Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus SO BIOLOGY DIRECT LA English DT Article ID PHYLOGENETIC ANALYSIS; H3N2 VIRUSES; DARWINIAN EVOLUTION; HEMAGGLUTININ GENE; ANTIGENIC DRIFT; NEUTRALITY; SEQUENCES; GENOME; REASSORTMENT; LIKELIHOOD AB Background: The interpandemic evolution of the influenza A virus hemagglutinin (HA) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance. Results: We performed phylogenetic analyses of the recently obtained large and relatively unbiased samples of the HA sequences from 1995-2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus. Unexpectedly, it was found that the evolution of H3N2 HA includes long intervals of generally neutral sequence evolution without apparent substantial antigenic change ("stasis" periods) that are characterized by an excess of synonymous over nonsynonymous substitutions per site, lack of association of amino acid replacements with epitope regions, and slow extinction of coexisting virus lineages. These long periods of stasis are punctuated by shorter intervals of rapid evolution under positive selection during which new dominant lineages quickly displace previously coexisting ones. The preponderance of positive selection during intervals of rapid evolution is supported by the dramatic excess of amino acid replacements in the epitope regions of HA compared to replacements in the rest of the HA molecule. In contrast, the stasis intervals showed a much more uniform distribution of replacements over the HA molecule, with a statistically significant difference in the rate of synonymous over nonsynonymous substitution in the epitope regions between the two modes of evolution. A number of parallel amino acid replacements-the same amino acid substitution occurring independently in different lineages-were also detected in H3N2 HA. These parallel mutations were, largely, associated with periods of rapid fitness change, indicating that there are major limitations on evolutionary pathways during antigenic change. The finding that stasis is the prevailing modality of H3N2 evolution suggests that antigenic changes that lead to an increase in fitness typically result from epistatic interactions between several amino acid substitutions in the HA and, perhaps, other viral proteins. The strains that become dominant due to increased fitness emerge from low frequency strains thanks to the last amino acid replacement that completes the set of replacements required to produce a significant antigenic change; no subset of substitutions results in a biologically significant antigenic change and corresponding fitness increase. In contrast to H3N2, no clear intervals of evolution under positive selection were detected for the H1N1 HA during the same time span. Thus, the ascendancy of H1N1 in some seasons is, most likely, caused by the drop in the relative fitness of the previously prevailing H3N2 lineages as the fraction of susceptible hosts decreases during the stasis intervals. Conclusion: We show that the common view of the evolution of influenza virus as a rapid, positive selection-driven process is, at best, incomplete. Rather, the interpandemic evolution of influenza appears to consist of extended intervals of stasis, which are characterized by neutral sequence evolution, punctuated by shorter intervals of rapid fitness increase when evolutionary change is driven by positive selection. These observations have implications for influenza surveillance and vaccine formulation; in particular, the possibility exists that parallel amino acid replacements could serve as a predictor of new dominant strains. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. Fogarty Int Ctr, NIH, Bethesda, MD USA. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. RP Lipman, DJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. EM wolf@ncbi.nlm.nih.gov; viboudc@mail.nih.gov; ech15@psu.edu; koonin@ncbi.nlm.nih.gov; lipman@ncbi.nlm.nih.gov OI Holmes, Edward/0000-0001-9596-3552 NR 47 TC 96 Z9 103 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD OCT 26 PY 2006 VL 1 AR 34 DI 10.1186/1745-6150-1-34 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TR UT WOS:000244036900001 PM 17067369 ER PT J AU Aleman, C Zanuy, D Casanovas, J Cativiela, C Nussinov, R AF Aleman, Carlos Zanuy, David Casanovas, Jordi Cativiela, Carlos Nussinov, Ruth TI Backbone conformational preferences and pseudorotational ring puckering of 1-aminocyclopentane-1-carboxylic acid SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID X-RAY-DIFFRACTION; C-ALPHA,ALPHA-DIALKYLATED GLYCINES; STRUCTURAL VERSATILITY; LINEAR OLIGOPEPTIDES; AMINO-ACIDS; CRYSTALLOGRAPHIC CHARACTERIZATION; SYSTEMATIC EVALUATION; MOLECULAR-DYNAMICS; SIMPLE DERIVATIVES; DIPEPTIDE ANALOGS AB We have used quantum mechanical calculations at the B3LYP/6-311G(d, p) level to determine the conformational preferences of the N-acetyl-N'-methylamide derivative of 1-aminocyclopentane-1-carboxylic acid in the gas phase, chloroform solution, and water solution. The backbone conformation of this dipeptide has been described through the dihedral angles and,, while the pseudorotational phase angle was used to define the conformation of the cyclopentane ring. Results indicate that the backbone flexibility of this amino acid is restricted by the cyclic nature of the side chain, the relative stability of the different conformations depending on the polarity of the environment. The potential energy of the pseudorotation was also studied as a function of the backbone conformation. Interestingly, the conformation of the cyclic side chain depends on the backbone arrangement. Furthermore, the number of pseudorotational states accessible at room temperature is high in all the investigated environments, especially in aqueous solution. Finally, a set of force-field parameters for classical molecular mechanics calculations was developed for the investigated amino acid. Molecular dynamics simulations in both chloroform and aqueous solutions were performed to demonstrate the reliability of such parameters. C1 Univ Politecn Catalunya, ETS Engn Ind Barcelona, Dept Engn Quim, E-08028 Barcelona, Spain. Univ Lleida, Escola Politecn Super, Dept Quim, E-25001 Lleida, Spain. Univ Zaragoza, CSIC, Inst Ciencia Mat Aragon, Dept Quim Organ, E-50009 Zaragoza, Spain. SAIC Frederick Inc, NCI, Basic Res Program, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. RP Aleman, C (reprint author), Univ Politecn Catalunya, ETS Engn Ind Barcelona, Dept Engn Quim, Diagonal 647, E-08028 Barcelona, Spain. EM carlos.aleman@upc.edu; david.zanuy@upc.edu RI Casanovas, Jordi/B-5435-2013; Zanuy, David/G-3930-2014 OI Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 55 TC 22 Z9 22 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 26 PY 2006 VL 110 IS 42 BP 21264 EP 21271 DI 10.1021/jp062804s PG 8 WC Chemistry, Physical SC Chemistry GA 096MQ UT WOS:000241381600082 PM 17048955 ER PT J AU Riazuddin, SA Zulfiqar, F Zhang, QJ Yao, WL Li, SL Jiao, XD Shahzadi, A Amer, M Iqbal, M Hussnain, T Sieving, P Riazuddin, S Hejtmancik, JF AF Riazuddin, S. Amer Zulfiqar, Fareeha Zhang, Qingjiong Yao, Wenliang Li, Shouling Jiao, Xiaodong Shahzadi, Amber Amer, Muhammad Iqbal, Muhammad Hussnain, Tayyab Sieving, Paul Riazuddin, Sheikh Hejtmancik, J. Fielding TI Mutations in the gene encoding the alpha-subunit of rod phosphodiesterase in consanguineous Pakistani families SO MOLECULAR VISION LA English DT Article ID RETINITIS-PIGMENTOSA; LINKAGE ANALYSIS; DYSTROPHIES; CATARACT AB Purpose: To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa (RP) in consanguineous Pakistani families. Methods: Families were ascertained and patients underwent complete ophthalmological examinations. Blood samples were collected and DNA was extracted. A genome-wide scan was performed using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. Results: A genome-wide scan of 50 families gave a lod score of 7.4172 with D5S2015 using HOMOG1. RP in all 4 linked families mapped to a 13.85 cM (14.87 Mb) region on chromosome 5q31-33 flanked by D5S2090 and D5S422. This region harbors the PDE6A gene, which is known to cause autosomal recessive RP. Sequencing of PDE6A showed a homozygous single base pair change; c.889C-> T, single base pair insertion; c.2218-2219insT, and single base pair substitution in the splice acceptor site; IVS10-2A-> G in each of three families. In the fourth family linked to this region, no disease-causing mutation was identified in the PDE6A gene. Conclusions: These results provide strong evidence that mutations in PDE6A result in recessive RP in three consanguineous Pakistani families. Although a fourth family was linked to markers in the 5q31-33 interval, no mutation was identified in PDE6A. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, Bldg 10,Room 10B10,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI Husnain, Tayyab/G-3805-2015 FU Intramural NIH HHS NR 16 TC 10 Z9 10 U1 0 U2 1 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 OCT 26 PY 2006 VL 12 IS 139-47 BP 1283 EP 1291 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 105NG UT WOS:000242036400007 PM 17110911 ER PT J AU Weinstock, GM Robinson, GE Gibbs, RA Worley, KC Evans, JD Maleszka, R Robertson, HM Weaver, DB Beye, M Bork, P Elsik, CG Hartfelder, K Hunt, GJ Zdobnov, EM Amdam, GV Bitondi, MMG Collins, AM Cristino, AS Lattorff, HMG Lobo, CH Moritz, RFA Nunes, FMF Page, RE Simoes, ZLP Wheeler, D Carninci, P Fukuda, S Hayashizaki, Y Kai, C Kawai, J Sakazume, N Sasaki, D Tagami, M Albert, S Baggerman, G Beggs, KT Bloch, G Cazzamali, G Cohen, M Drapeau, MD Eisenhardt, D Emore, C Ewing, MA Fahrbach, SE Foret, S Grimmelikhuijzen, CJP Hauser, F Hummon, AB Huybrechts, J Jones, AK Kadowaki, T Kaplan, N Kucharski, R Leboulle, G Linial, M Littleton, JT Mercer, AR Richmond, TA Rodriguez-Zas, SL Rubin, EB Sattelle, DB Schlipalius, D Schoofs, L Shemesh, Y Sweedler, JV Velarde, R Verleyen, P Vierstraete, E Williamson, MR Ament, SA Brown, SJ Corona, M Dearden, PK Dunn, WA Elekonich, MM Fujiyuki, T Gattermeier, I Gempe, T Hasselmann, M Kadowaki, T Kage, E Kamikouchi, A Kubo, T Kucharski, R Kunieda, T Lorenzen, MD Milshina, NV Morioka, M Ohashi, K Overbeek, R Ross, CA Schioett, M Shippy, T Takeuchi, H Toth, AL Willis, JH Wilson, MJ Gordon, KHJ Letunic, I Hackett, K Peterson, J Felsenfeld, A Guyer, M Solignac, M Agarwala, R Cornuet, JM Monnerot, M Mougel, F Reese, JT Vautrin, D Gillespie, JJ Cannone, JJ Gutell, RR Johnston, JS Eisen, MB Iyer, VN Iyer, V Kosarev, P Mackey, AJ Solovyev, V Souvorov, A Aronstein, KA Bilikova, K Chen, YP Clark, AG Decanini, LI Gelbart, WM Hetru, C Hultmark, D Imler, JL Jiang, HB Kanost, M Kimura, K Lazzaro, BP Lopez, DL Simuth, J Thompson, GJ Zou, Z De Jong, P Sodergren, E Csuros, M Milosavljevic, A Osoegawa, K Richards, S Shu, CL Duret, L Elhaik, E Graur, D Anzola, JM Campbell, KS Childs, KL Collinge, D Crosby, MA Dickens, CM Grametes, LS Grozinger, CM Jones, PL Jorda, M Ling, X Matthews, BB Miller, J Mizzen, C Peinado, MA Reid, JG Russo, SM Schroeder, AJ St Pierre, SE Wang, Y Zhou, PL Jiang, HY Kitts, P Ruef, B Venkatraman, A Zhang, L Aquino-Perez, G Whitfield, CW Behura, SK Berlocher, SH Sheppard, WS Smith, DR Suarez, AV Tsutsui, ND Wei, XH Wheeler, D Havlak, P Li, BS Liu, Y Sodergren, E Jolivet, A Lee, S Nazareth, LV Pu, LL Thorn, R Stolc, V Newman, T Samanta, M Tongprasit, WA Claudianos, C Berenbaum, MR Biswas, S de Graaf, DC Feyereisen, R Johnson, RM Oakeshott, JG Ranson, H Schuler, MA Muzny, D Chacko, J Davis, C Dinh, H Gill, R Hernandez, J Hines, S Hume, J Jackson, L Kovar, C Lewis, L Miner, G Morgan, M Nguyen, N Okwuonu, G Paul, H Santibanez, J Savery, G Svatek, A Villasana, D Wright, R AF Weinstock, George M. Robinson, Gene E. Gibbs, Richard A. Worley, Kim C. Evans, Jay D. Maleszka, Ryszard Robertson, Hugh M. Weaver, Daniel B. Beye, Martin Bork, Peer Elsik, Christine G. Hartfelder, Klaus Hunt, Greg J. Zdobnov, Evgeny M. Amdam, Gro V. Bitondi, Marcia M. G. Collins, Anita M. Cristino, Alexandre S. Lattorff, H. Michael G. Lobo, Carlos H. Moritz, Robin F. A. Nunes, Francis M. F. Page, Robert E., Jr. Simoes, Zila L. P. Wheeler, Diana Carninci, Piero Fukuda, Shiro Hayashizaki, Yoshihide Kai, Chikatoshi Kawai, Jun Sakazume, Naoko Sasaki, Daisuke Tagami, Michihira Albert, Stefan Baggerman, Geert Beggs, Kyle T. Bloch, Guy Cazzamali, Giuseppe Cohen, Mira Drapeau, Mark David Eisenhardt, Dorothea Emore, Christine Ewing, Michael A. Fahrbach, Susan E. Foret, Sylvain Grimmelikhuijzen, Cornelis J. P. Hauser, Frank Hummon, Amanda B. Huybrechts, Jurgen Jones, Andrew K. Kadowaki, Tatsuhiko Kaplan, Noam Kucharski, Robert Leboulle, Gerard Linial, Michal Littleton, J. Troy Mercer, Alison R. Richmond, Timothy A. Rodriguez-Zas, Sandra L. Rubin, Elad B. Sattelle, David B. Schlipalius, David Schoofs, Liliane Shemesh, Yair Sweedler, Jonathan V. Velarde, Rodrigo Verleyen, Peter Vierstraete, Evy Williamson, Michael R. Ament, Seth A. Brown, Susan J. Corona, Miguel Dearden, Peter K. Dunn, W. Augustine Elekonich, Michelle M. Fujiyuki, Tomoko Gattermeier, Irene Gempe, Tanja Hasselmann, Martin Kadowaki, Tatsuhiko Kage, Eriko Kamikouchi, Azusa Kubo, Takeo Kucharski, Robert Kunieda, Takekazu Lorenzen, Marce D. Milshina, Natalia V. Morioka, Mizue Ohashi, Kazuaki Overbeek, Ross Ross, Christian A. Schioett, Morten Shippy, Teresa Takeuchi, Hideaki Toth, Amy L. Willis, Judith H. Wilson, Megan J. Gordon, Karl H. J. Letunic, Ivica Hackett, Kevin Peterson, Jane Felsenfeld, Adam Guyer, Mark Solignac, Michel Agarwala, Richa Cornuet, Jean Marie Monnerot, Monique Mougel, Florence Reese, Justin T. Vautrin, Dominique Gillespie, Joseph J. Cannone, Jamie J. Gutell, Robin R. Johnston, J. Spencer Eisen, Michael B. Iyer, Venky N. Iyer, Vivek Kosarev, Peter Mackey, Aaron J. Solovyev, Victor Souvorov, Alexandre Aronstein, Katherine A. Bilikova, Katarina Chen, Yan Ping Clark, Andrew G. Decanini, Laura I. Gelbart, William M. Hetru, Charles Hultmark, Dan Imler, Jean-Luc Jiang, Haobo Kanost, Michael Kimura, Kiyoshi Lazzaro, Brian P. Lopez, Dawn L. Simuth, Jozef Thompson, Graham J. Zou, Zhen De Jong, Pieter Sodergren, Erica Csuroes, Miklos Milosavljevic, Aleksandar Osoegawa, Kazutoyo Richards, Stephen Shu, Chung-Li Duret, Laurent Elhaik, Eran Graur, Dan Anzola, Juan M. Campbell, Kathryn S. Childs, Kevin L. Collinge, Derek Crosby, Madeline A. Dickens, C. Michael Grametes, L. Sian Grozinger, Christina M. Jones, Peter L. Jorda, Mireia Ling, Xu Matthews, Beverly B. Miller, Jonathan Mizzen, Craig Peinado, Miguel A. Reid, Jeffrey G. Russo, Susan M. Schroeder, Andrew J. St Pierre, Susan E. Wang, Ying Zhou, Pinglei Jiang, Huaiyang Kitts, Paul Ruef, Barbara Venkatraman, Anand Zhang, Lan Aquino-Perez, Gildardo Whitfield, Charles W. Behura, Susanta K. Berlocher, Stewart H. Sheppard, Walter S. Smith, Deborah R. Suarez, Andrew V. Tsutsui, Neil D. Wei, Xuehong Wheeler, David Havlak, Paul Li, Bingshan Liu, Yue Sodergren, Erica Jolivet, Angela Lee, Sandra Nazareth, Lynne V. Pu, Ling-Ling Thorn, Rachel Stolc, Viktor Newman, Thomas Samanta, Manoj Tongprasit, Waraporn A. Claudianos, Charles Berenbaum, May R. Biswas, Sunita de Graaf, Dirk C. Feyereisen, Rene Johnson, Reed M. Oakeshott, John G. Ranson, Hilary Schuler, Mary A. Muzny, Donna Chacko, Joseph Davis, Clay Dinh, Huyen Gill, Rachel Hernandez, Judith Hines, Sandra Hume, Jennifer Jackson, LaRonda Kovar, Christie Lewis, Lora Miner, George Morgan, Margaret Nguyen, Ngoc Okwuonu, Geoffrey Paul, Heidi Santibanez, Jireh Savery, Glenford Svatek, Amanda Villasana, Donna Wright, Rita CA Honeybee Genome Sequencing Consort TI Insights into social insects from the genome of the honeybee Apis mellifera SO NATURE LA English DT Review ID DROSOPHILA-NINAG OXIDOREDUCTASE; BEETLE TRIBOLIUM-CASTANEUM; ANOPHELES-GAMBIAE; TRANSPOSABLE ELEMENTS; MITOCHONDRIAL-DNA; NUCLEAR RECEPTOR; GENE-EXPRESSION; BOMBYX-MORI; FRUIT-FLY; STATISTICAL-ANALYSIS AB Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement. 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Michael/0000-0002-8603-6332; Cristino, Alexandre/0000-0002-3468-0919; Sweedler, Jonathan/0000-0003-3107-9922; Bitondi, Marcia/0000-0002-5619-6378; Peinado, Miguel A./0000-0002-4090-793X; Schiott, Morten/0000-0002-4309-8090; Moritz, Robin/0000-0003-0791-887X; Bork, Peer/0000-0002-2627-833X; Marion-Poll, Frederic/0000-0001-6824-0180; Maleszka, Ryszard/0000-0003-1855-555X; Feyereisen, Rene/0000-0002-9560-571X; Wilson, Megan/0000-0003-3425-5071; Bloch, Guy/0000-0003-1624-4926; Letunic, Ivica/0000-0003-3560-4288; /0000-0001-5576-2887; Solovyev, Victor/0000-0001-8885-493X; Gillespie, Joseph/0000-0002-5447-7264; Ranson, Hilary/0000-0003-2332-8247 NR 180 TC 930 Z9 995 U1 43 U2 365 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 26 PY 2006 VL 443 IS 7114 BP 931 EP 949 DI 10.1038/nature05260 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098LZ UT WOS:000241523400044 ER PT J AU Puck, JM Candotti, F AF Puck, Jennifer M. Candotti, Fabio TI Lessons from the Wiskott-Aldrich syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NR 0 TC 16 Z9 16 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 26 PY 2006 VL 355 IS 17 BP 1759 EP 1761 DI 10.1056/NEJMp068209 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 098HV UT WOS:000241512500003 PM 17065636 ER PT J AU Ahmed, A Fleg, JL Gheorghiade, M AF Ahmed, Ali Fleg, Jerome L. Gheorghiade, Mihai TI Heart failure with preserved ejection fraction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Univ Alabama, Birmingham, AL 35294 USA. NHLBI, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Ahmed, A (reprint author), Univ Alabama, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 26 PY 2006 VL 355 IS 17 BP 1829 EP 1830 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 098HV UT WOS:000241512500020 PM 17072998 ER PT J AU Liu, F Stephen, AG Adamson, CS Gousset, K Aman, MJ Freed, EO Fisher, RJ Burke, TR AF Liu, Fa Stephen, Andrew G. Adamson, Catherine S. Gousset, Karine Aman, M. Javad Freed, Eric O. Fisher, Robert J. Burke, Terrence R., Jr. TI Hydrazone- and hydrazide-containing N-substituted glycines as peptoid surrogates for expedited library synthesis: Application to the preparation of Tsg101-directed HIV-1 budding antagonists SO ORGANIC LETTERS LA English DT Article ID SOLID-PHASE SYNTHESIS; FLUORESCENCE ANISOTROPY; PROTEIN; PEPTIDOMIMETICS; INHIBITORS; DISCOVERY; OLIGOMERS; PEPTIDES; SEQUENCE; RECEPTOR AB Replacing the Pro6 in the p6(Gag)-derived 9-mer "P-E-P-T-A-(P) under bar -P-E-E" with N-substituted glycine (NSG) residues is problematic. However, incorporation of hydrazone amides ("peptoid hydrazones") can be readily achieved in library fashion. Furthermore, reduction of these hydrazones to N-substituted "peptoid hydrazides" affords a facile route to library diversification. This approach is demonstrated by application to Tsg101-binding compounds designed as potential HIV budding antagonists. C1 NCI Frederick, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, Prot Chem Lab, Frederick, MD 21702 USA. NCI Frederick, Hiv Drug Resistance Program, CCR, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI Frederick, Med Chem Lab, CCR, NIH, Bldg 376,Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014; OI Gousset, Karine/0000-0002-0988-2332 FU Intramural NIH HHS [Z01 BC007363-13]; NCI NIH HHS [N01 CO 12400, N01CO12400] NR 22 TC 29 Z9 32 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD OCT 26 PY 2006 VL 8 IS 22 BP 5165 EP 5168 DI 10.1021/ol0622211 PG 4 WC Chemistry, Organic SC Chemistry GA 096MS UT WOS:000241381800046 PM 17048869 ER PT J AU Zuna, RE Wang, SS Schiffman, M Solomon, D AF Zuna, Rosemary E. Wang, Sophia S. Schiffman, Mark Solomon, Diane CA Atypical Squamous Cells TI Comparison of human papillomavirus distribution in cytologic subgroups of low-grade squamous intraepithelial lesion SO CANCER CYTOPATHOLOGY LA English DT Article DE low-grade squamous intraepithelial lesion; koilocytotic atypia; cervical intraepithelial neoplasia Grade 1; human papillomavirus; Papanicolaou test; cervical cancer screening ID ASCUS-LSIL TRIAGE; KOILOCYTOTIC ATYPIA; CERVICAL-CANCER; BETHESDA SYSTEM; CONDYLOMATOUS LESIONS; PAPANICOLAOU SMEARS; UTERINE CERVIX; REPRODUCIBILITY; INFECTION; WOMEN AB BACKGROUND. Low-grade squamous intraepithelial lesion (LSIL) subsumes the formerly delineated cytologic categories of human papillornavirus (HPV)-associated cell changes (koilocytotic atypia) and low-grade dysplasia/cervical intraepithelial neoplasia (CIN) Grade 1 (CIN1). In this study, the objective was to determine whether these 2 morphologic subcategories are characterized by differences in risk for CIN3 and/or HPV type distribution. METHODS. Within the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study, all cytologic interpretations of HPV cellular changes and CIN1 rendered by any of the pathology reviewers (community laboratory, clinical center, or Pathology Quality-Control Group) on referral Papanicolaou (Pap) tests or enrollment ThinPrep (R) Pap tests were included for analysis. HPV testing was performed by Hybrid Capture (TM) 2 (HC2) and by polymerase chain reaction based reverse-line blot analysis for 27 HPV types. The absolute risks of cumulative detection of CIN3 or cancer (CIN3 +) and CIN2 or worse (CIN2 +) over 2 years of follow-up were calculated for the various cytologic interpretations. RESULTS. For each review group and cytology preparation, most LSIL interpretations (from approximately 2 of 3 interpretations to 3 of 4 interpretations) were subcategorized as CIN1 rather than HPV cellular changes. HPV type 16 (HPV-16) was the most common HPV type and was identified in 21% to 24% of CIN1 and in 14% to 18% of HPV cellular changes. Nononcogenic types were identified alone in from 9% to 11% of CIN1 compared with 17% to 20% of HPV cellular change. The absolute risks of CIN1 and HPV cellular changes for cumulatively detected CIN3 + ranged from 12% to 16% for CIN1 and from 6% to 9% for HPV cellular changes. CONCLUSIONS. Both cytologic subcategories of LSIL were associated predominantly with oncogenic HPV types; however, the proportion of nononcogenic HPV types was lower and the absolute risks for CIN3 + were higher for CIN1 compared with HPV cellular changes. The concordance in subcategorizing LSIL was low, and the authors concluded that the diagnostic distinction is of limited clinical utility for individual patient management. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Zuna, RE (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, BMSB 451, Oklahoma City, OK 73104 USA. EM rosemary-zuna@ouhsc.edu FU NCI NIH HHS [CN-55158, CN-55155, CN-55105, CN-55157, CN-55159, CN-55153, CN-55154, CN-55156] NR 36 TC 10 Z9 10 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 BP 288 EP 297 DI 10.1002/cncr.22168 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 098EL UT WOS:000241503700004 PM 16952155 ER PT J AU Sherman, ME Castle, PE Solomon, D AF Sherman, Mark E. Castle, Philip E. Solomon, Diane CA ASCUS LSIL Triage Grp TI Cervical cytology of atypical squamous cells-cannot exclude high-grade squarnous intraepithelial lesion (ASC-H) SO CANCER CYTOPATHOLOGY LA English DT Article DE cervix; cytology; human papillonnavirus; screening; Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS) ID HUMAN-PAPILLOMAVIRUS-DNA; UNDETERMINED SIGNIFICANCE; BETHESDA SYSTEM; WOMEN; PARTICIPANTS; CATEGORY; FEATURES; TRIAGE; RULE; HSIL AB BACKGROUND. The 2001 Bethesda System category of atypical squamous cells (ASC) denotes changes suggestive, but inconclusive for, a squamous intraepithelial lesion (SIL). ASC is subcategorized as: 1) "undetermined significance (ASC-US)," when changes suggest low-grade or indeterminate-grade SIL and 2) "cannot exclude high-grade squamous intraepithelial lesion (ASC-H)," when a cancer precursor is suspected. METHODS. To better define the characteristics of ASC-H, the authors analyzed and compared human papillornavirus (HPV) testing data and outcomes after 2 years for participants in the Atypical Squamous Cells of Undetermined Significance Low-Grade SIL Triage Study (ALTS), a randomized trial of 5060 women. RESULTS. Among women with thin-layer cytology findings of ASC-H, 84% tested positive for HPV, 50% (95% confidence interval [95% CI], 41%-60%) were diagnosed with cervical intraepithelial neoplasia (CIN) type 2+, and 30% (95% CI, 22-39%) were diagnosed with CIN3+. Positive HPV tests and diagnoses of CIN2+ and CIN3+ were found to be more common among women with ASCH compared with those with ASC-US, but the highest frequencies were found to be associated with high-grade SIL. For women age < 35 years with ASC-H, HPV detection exceeded 85%, whereas only 4 of 10 women (40%) age < 35 years tested positive for HPV (P = 0.009). CONCLUSIONS. A finding of ASC-H seems to confer a substantially higher risk for CIN2+ and CIN3+ than ASC-US. Immediate colposcopy may be the appropriate management for young women with ASC-H, but the utility of HPV testing for managing older women with ASC-H requires additional study. C1 NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov NR 22 TC 48 Z9 52 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2006 VL 108 IS 5 BP 298 EP 305 DI 10.1002/cncr.21844 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 098EL UT WOS:000241503700005 PM 16544318 ER PT J AU Huang, Z Shimazu, K Woo, NH Zang, KL Muller, U Lu, B Reichardt, LF AF Huang, Zhen Shimazu, Kazuhiro Woo, Newton H. Zang, Keling Mueller, Ulrich Lu, Bai Reichardt, Louis F. TI Distinct roles of the beta 1-class integrins at the developing and the mature hippocampal excitatory synapse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE beta 1 integrin; cell adhesion molecule; hippocampus; synaptic maturation; synaptic vesicle pool; long-term potentiation ID LONG-TERM POTENTIATION; MOTOR-NERVE TERMINALS; HIGH-FREQUENCY TRANSMISSION; READILY RELEASABLE POOL; TRANSMITTER RELEASE; NEURONAL MIGRATION; NMDA RECEPTOR; ALPHA-3-BETA-1 INTEGRIN; NEURITE OUTGROWTH; VESICLE DOCKING AB Integrins are a large family of cell adhesion receptors involved in a variety of cellular functions. To study their roles at central synapses, we used two cre recombinase lines to delete the Itgb1 beta 1 integrin gene in forebrain excitatory neurons at different developmental stages. Removal of the beta 1 integrins at an embryonic stage resulted in severe cortical lamination defects without affecting the cellular organization of pyramidal neurons in the CA3 and CA1 regions of the hippocampus. Whereas the hippocampal neurons underwent normal dendritic and synaptic differentiation, the adult synapses exhibited deficits in responses to high-frequency stimulation (HFS), as well as in long-term potentiation (LTP). Deletion of beta 1 integrin at a later postnatal stage also impaired LTP but not synaptic responses to HFS. Thus, the beta 1-class integrins appear to play distinct roles at different stages of synaptic development, critical for the proper maturation of readily releasable pool of vesicles during early development but essential for LTP throughout adult life. C1 Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA. NICHHD, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Cell Biol, La Jolla, CA 92037 USA. RP Reichardt, LF (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, 1550 4th St, San Francisco, CA 94143 USA. EM lfr@cgl.ucsf.edu RI Lu, Bai/A-4018-2012 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS019090, R01 NS019090-26, R01NS19090] NR 83 TC 80 Z9 81 U1 1 U2 7 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 OCT 25 PY 2006 VL 26 IS 43 BP 11208 EP 11219 DI 10.1523/JNEUROSCI.3526-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 098WO UT WOS:000241553900027 PM 17065460 ER PT J AU Fuxe, K Canals, M Torvinen, M Terasmaa, A Marcellino, D Scheel-Kruger, J Lluis, C Woods, A Tanganelli, S Ferro, S Franco, R Agnati, LF AF Fuxe, K. Canals, M. Torvinen, M. Terasmaa, A. Marcellino, D. Scheel-Kruger, J. Lluis, C. Woods, A. Tanganelli, S. Ferro, S. Franco, R. Agnati, L. F. TI The A2A/D2 heteromeric receptor complexes of the striatopallidal gaba neurons. From molecular mechanisms to relevance for Parkinson's disease and schizophrenia SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT International Symposium on Dementia in Parkinson's Disease CY OCT 24-27, 2004 CL Salzburg, AUSTRIA C1 Karolinska Inst, Dept Neurosci, I-44100 Stockholm, Sweden. Catedretico Biochem Biol, Dept Biochem, I-41100 Catalunya, Spain. NeuroSearch AS, Ballerup, Denmark. NIH, Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD USA. Univ Ferrara, Dept Clin & Expt Med, Pharmacol Sect, Ferrara, Italy. Univ Modena, Dept Biomed Sci, Modena, Italy. RI Franco, Rafael/C-3694-2015; Terasmaa, Anton/I-3312-2015; Tanganelli, Sergio/I-7704-2015 OI Franco, Rafael/0000-0003-2549-4919; Terasmaa, Anton/0000-0002-5139-1764; Tanganelli, Sergio/0000-0001-7576-3510 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 25 PY 2006 VL 248 IS 1-2 MA 182 BP 318 EP 319 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 109JX UT WOS:000242305200227 ER PT J AU D Maguire, J Lederman, ER Barcus, MJ O'Meara, WAP Jordon, RG Duong, S Muth, S Sismadi, P Bangs, MJ Prescott, WR Baird, JK Wongsrichanalai, C AF D Maguire, Jason Lederman, Edith R. Barcus, Mazie J. O'Meara, Wendy A. Prudhomme Jordon, Robert G. Duong, Socheat Muth, Sinuon Sismadi, Priyanto Bangs, Michael J. Prescott, W. Roy Baird, J. Kevin Wongsrichanalai, Chansuda TI Production and validation of durable, high quality standardized malaria microscopy slides for teaching, testing and quality assurance during an era of declining diagnostic proficiency SO MALARIA JOURNAL LA English DT Article ID LABORATORY DIAGNOSIS; ACCURACY AB Background: Sets of Giemsa-stained, blood smear slides with systematically verified composite diagnoses would contribute substantially to development of externally validated quality assurance systems for the microscopic diagnosis of malaria. Methods: whole blood from Plasmodium-positive donors in Cambodia and Indonesia and individuals with no history of risk for malaria was collected. Using standard operating procedures, technicians prepared Giemsa-stained thick and thin smears from each donor. One slide from each of the first 35 donations was distributed to each of 28 individuals acknowledged by reputation as having expertise in the microscopic diagnosis of malaria. These reference readers recorded presence or absence of Plasmodium species and parasite density. A composite diagnosis for each donation was determined based on microscopic findings and species-specific small subunit ribosomal RNA (ssrRNA) DNA polymerase chain reaction (PCR) amplification. Results: More than 12, 000 slides were generated from 124 donations. Reference readers correctly identified presence of parasites on 85% of slides with densities < 100 parasites/mu l, which improved to 100% for densities > 350 parasites/mu l. Percentages of agreement with composite diagnoses were highest for Plasmodium falciparum (99%), followed by Plasmodium vivax (86%). Conclusion: Herein, a standardized method for producing large numbers of consistently high quality, durable Giemsa-stained blood smears and validating composite diagnoses for the purpose of creating a malaria slide repository in support of initiatives to improve training and competency assessment amidst a background of variability in diagnosis is described. C1 USN, Med Res Unit 2, Jakarta, Indonesia. Hydas Inc, Hershey, PA USA. NIH, Bethesda, MD 20892 USA. Natl Ctr Parasitol Entomol & Malaria Control CNM, Phnom Penh, Cambodia. Minist Hlth, Natl Inst Hlth Res & Dev, Jakarta, Indonesia. USN, Med Ctr Portsmouth, Portsmouth, VA 23708 USA. RP D Maguire, J (reprint author), USN, Med Res Unit 2, NAMRU 2, Jakarta, Indonesia. EM jdmaguire@mar.med.navy.mil; dvk9@cdc.gov; mazie_barcus@yahoo.com; prudhomw@mail.nih.gov; Robert.Jordon@hydasworldhealth.org; socheatd@cnm.gov.kh; sinuonm@cnm.gov.kh; sismadi@litbang.depkes.go.id; bangs_michael@yahoo.com; Roy@Hydas.com; JKB@VHAsia.com.sg; dr.chansuda@gmail.com NR 24 TC 0 Z9 0 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD OCT 25 PY 2006 VL 5 AR 92 DI 10.1186/1475-2875-5-92 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 103HW UT WOS:000241877300001 ER PT J AU Thomas, JA Shulenin, S Coren, LV Bosche, WJ Gagliardi, TD Gorelick, RJ Oroszlan, S AF Thomas, James A. Shulenin, Sergey Coren, Lori V. Bosche, William J. Gagliardi, Tracy D. Gorelick, Robert J. Oroszlan, Stephen TI Characterization of human immunodeficiency virus type 1 (HIV-1) containing mutations in the nucleocapsid protein at a putative HIV-1 protease cleavage site SO VIROLOGY LA English DT Article DE HIV-1; nucleocapsid; protease; viral DNA; provirus; mutant; replication; early infection ID ACID-CHAPERONE ACTIVITY; MURINE LEUKEMIA-VIRUS; IN-VITRO; ZINC FINGERS; REVERSE TRANSCRIPTION; GENOMIC RNA; VIRAL-DNA; N-ETHYLMALEIMIDE; CAPSID PROTEIN; ZN2+ FINGERS AB The HIV-1 nucleocapsid protein (NC) has been hypothesized to be cleaved by the viral protease (PR) during early infection. Characterization of viruses, with amino-acid substitutions that modulate PR cleavage of NC in vitro, was performed in cell culture. Two of the NC mutants, NCN17F and NCN17G, had decreased infectivity and exhibited severe H9 replication defects. Examination of viral DNA after infections revealed defects in reverse transcription and integration, although integration defects were cell-type dependent. However, while the defects in reverse transcription and integration correlate with lowered infectivity in a single-round of infection, they did not approach the magnitude of the replication defect measured in H9 cells over multiple rounds. Importantly, we fail to see evidence that H9 cells are re-infected with the NCN17G and NCN17F Viruses 24 h after the initial infection, which suggests that the principal defect caused by these NC mutations occurs during late events of viral replication. Published by Elsevier Inc. C1 NCI, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, Frederick, MD 21702 USA. RP Gorelick, RJ (reprint author), NCI, SAIC Frederick Inc, AIDS Vaccine Program, Bldg 535,Room 410,POB B, Frederick, MD 21702 USA. EM jathomas@ncifcrf.gov; sshulenin@agrx.net; coren@ncifcrf.gov; bosche@ncifcrf.gov; gagliardi@ncifcrf.gov; gorelick@ncifcrf.gov; oroszlans@ncifcrf.gov OI Thomas, James/0000-0002-2509-490X FU NCI NIH HHS [N01-CO-12400] NR 63 TC 9 Z9 11 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2006 VL 354 IS 2 BP 261 EP 270 DI 10.1016/j.virol.2006.07.011 PG 10 WC Virology SC Virology GA 098GU UT WOS:000241509800004 PM 16904152 ER PT J AU Voelkel, NF Quaife, RA Leinwand, LA Barst, RJ McGoon, MD Meldrum, DR Dupuis, J Long, CS Rubin, LJ Smart, FW Suzuki, YJ Gladwin, M Denholm, EM Gail, DB AF Voelkel, Norbert F. Quaife, Robert A. Leinwand, Leslie A. Barst, Robyn J. McGoon, Michael D. Meldrum, Daniel R. Dupuis, Jocelyn Long, Carlin S. Rubin, Lewis J. Smart, Frank W. Suzuki, Yuichiro J. Gladwin, Mark Denholm, Elizabeth M. Gail, Dorothy B. TI Right ventricular function and failure - Report of a National Heart, lung, and Blood Institute working group on cellular and molecular mechanisms of right heart failure SO CIRCULATION LA English DT Article ID PRIMARY PULMONARY-HYPERTENSION; IDIOPATHIC-DILATED CARDIOMYOPATHY; BRAIN NATRIURETIC PEPTIDE; MYOSIN HEAVY-CHAIN; LONG-TERM SURVIVAL; EJECTION FRACTION; TRICUSPID REGURGITATION; ARTERIAL-HYPERTENSION; EISENMENGER-SYNDROME; PROGNOSTIC IMPLICATIONS C1 Univ Colorado, Pulm Hypertens Ctr, Denver, CO 80262 USA. Univ Colorado Hosp, Dept Nucl Med & Radiol, Denver, CO USA. Univ Colorado, Dept Cardiol, CVI Inst, Boulder, CO 80309 USA. Columbia Presbyterian Med Ctr, Babies Hosp, New York, NY 10032 USA. Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. Indiana Univ, Dept Surg, Sch Med, Bloomington, IN 47405 USA. Univ Colorado, Dept Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Diego, Pulm Hypertens Ctr, San Diego, CA 92103 USA. St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Houston, TX USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NHLBI, Bethesda, MD 20892 USA. RP Voelkel, NF (reprint author), Univ Colorado, Pulm Hypertens Ctr, 4200 E 9th Ave,MC C272, Denver, CO 80262 USA. EM norbert.voelkel@uchsc.edu RI Dupuis, Jocelyn/B-3898-2009; Dupuis, Jocelyn/C-6613-2013; OI Dupuis, Jocelyn/0000-0002-3193-1014; LEINWAND, LESLIE/0000-0003-1470-4810 NR 93 TC 512 Z9 539 U1 1 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 24 PY 2006 VL 114 IS 17 BP 1883 EP 1891 DI 10.1161/CIRCULATIONAHA.106.632208 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 098AB UT WOS:000241490900016 PM 17060398 ER PT J AU Gamaldo, A Moghekar, A Kilada, S Resnick, SM Zonderman, AB O'Brien, R AF Gamaldo, A. Moghekar, A. Kilada, S. Resnick, S. M. Zonderman, A. B. O'Brien, R. TI Effect of a clinical stroke on the risk of dementia in a prospective cohort SO NEUROLOGY LA English DT Article ID BASE-LINE FREQUENCY; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR HEALTH; POSTSTROKE DEMENTIA; COGNITIVE DECLINE; CASE-FATALITY; WHITE-MATTER; DETERMINANTS AB Objective: To examine the risk and determinants of dementia following a clinically overt stroke in a prospectively followed cohort of elderly subjects. Methods: We examined the effect of a clinically detectable stroke on the risk of dementia using prospective data from 335 subjects in the Baltimore Longitudinal Study of Aging, all of whom were cognitively and neurologically normal at entry into the study (mean age at entry 75.1 +/- 4.2 years). Results: Clinically overt strokes are common in our cohort (cumulative risk by age 90, 15.4%; 95% CI: 10 to 22%) and confer an increased risk of dementia compared to subjects without stroke (odds ratio [OR] 5.55; 95% CI: 2.76 to 11.4). The majority of patients who became demented after a stroke had evidence of mild cognitive impairment preceding the stroke (14 of 19). Moreover, a clinically symptomatic stroke was a major risk factor for the conversion of mild cognitive impairment to dementia (OR 12.4; 95% CI: 1.5 to 99). When cognitive impairment did not precede the stroke, there was no increase in the risk of subsequent dementia. Pathologic data indicate that both vascular and Alzheimer pathology leads to the prestroke impairment. Conclusion: Dementia after stroke may be determined by cognitive impairments that exist prior to the stroke. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD USA. NIA, Intramural Res Program, Lab Personal & Cognit, NIH, Bethesda, MD 20892 USA. RP O'Brien, R (reprint author), Johns Hopkins Bayview Med Ctr, Mason F Lord Ctr Tower,Suite 5100,5200 Eastern Av, Baltimore, MD 21224 USA. EM robrien@jhmi.edu OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS; NIA NIH HHS [P50 AG05146] NR 36 TC 45 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 24 PY 2006 VL 67 IS 8 BP 1363 EP 1369 DI 10.1212/01.wnl.0000240285.89067.3f PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 098BI UT WOS:000241494800011 PM 17060561 ER PT J AU Roh, TY Cuddapah, S Cui, KR Zhao, KJ AF Roh, Tae-Young Cuddapah, Suresh Cui, Kairong Zhao, Keji TI The genomic landscape of histone modifications in human T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin landscape; epigenome; gene expression; genome-wide mapping ID EMBRYONIC STEM-CELLS; H3 METHYLATION; TRANSCRIPTIONAL REGULATION; MODIFICATION PATTERN; CHROMATIN-STRUCTURE; ACETYLATION; GENES; HETEROCHROMATIN; REGULATORS; PROMOTERS AB To understand the molecular basis that supports the dynamic gene expression programs unique to T cells, we investigated the genomic landscape of activating histone modifications, including histone H3 K9/K14 diacetylation (H3K9acK14ac), H3 K4 trimethylation (H3K4me3), and the repressive histone modification H3 K27 trimethylation (H3K27me3) in primary human T cells. We show that H3K9acK14ac and H3K4me3 are associated with active genes required for T cell function and development, whereas H3K27me3 is associated with silent genes that are involved in development in other cell types. Unexpectedly, we find that 3,330 gene promoters are associated with all of these histone modifications. The gene expression levels are correlated with both the absolute and relative levels of the activating H3K4me3 and the repressive H3K27me3 modifications. Our data reveal that rapidly inducible genes are associated with the H3 acetylation and H3K4me3 modifications, suggesting they assume a chromatin structure poised for activation. In addition, we identified a subpopulation of chromatin regions that are associated with high levels of H3K4me3 and H3K27me3 but low levels of H3K9acK14ac. Therefore, these regions have a distinctive chromatin modification pattern and thus may represent a distinct class of chromatin domains. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N311,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov NR 34 TC 302 Z9 308 U1 0 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 OCT 24 PY 2006 VL 103 IS 43 BP 15782 EP 15787 DI 10.1073/pnas.0607617103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500012 PM 17043231 ER PT J AU Lindhurst, MJ Fiermonte, G Song, SW Struys, E De Leonardis, F Schwartzberg, PL Chen, A Castegna, A Verhoeven, N Mathews, CK Palmieri, F Biesecker, LG AF Lindhurst, Marjorie J. Fiermonte, Giuseppe Song, Shiwei Struys, Eduard De Leonardis, Francesco Schwartzberg, Pamela L. Chen, Amy Castegna, Alessandra Verhoeven, Nanda Mathews, Christopher K. Palmieri, Ferclinando Biesecker, Leslie G. TI Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE development; mitochondrial transporter; mouse model; thiamine pyrophosphate deficiency; neural tube defect ID DEOXYNUCLEOTIDE CARRIER; DNA; DEFICIENCY; RECONSTITUTION; EMBRYOGENESIS; TRANSPORTER; BIOGENESIS; EXPRESSION; STRESS; GENE AB SLC25A19 mutations cause Amish lethal microcephaly (MCPHA), which markedly retards brain development and leads to a-ketoglutaric aciduria. Previous data suggested that SLC25A19, also called DNC, is a mitochondrial deoxyribonucleoticle transporter. We generated a knockout mouse model of Slc25a19. These animals had 100% prenatal lethality by embryonic day 12. Affected embryos at embryonic day 10.5 have a neural-tube closure defect with ruffling of the neural fold ridges, a yolk sac erythropoietic failure, and elevated a-ketoglutarate in the amniotic fluid. We found that these animals have normal mitochondrial ribo- and deoxyribonucleoside triphosphate levels, suggesting that transport of these molecules is not the primary role of SLC25A19. We identified thiamine pyrophosphate (ThPP) transport as a candidate function of SLC25A19 through homology searching and confirmed it by using transport assays of the recombinant reconstituted protein. The mitochondria of Slc25a19(-/-) and MCPHA cells have undetectable and markedly reduced ThPP content, respectively. The reduction of ThPP levels causes dysfunction of the a-ketoglutarate dehydrogenase complex, which explains the high levels of this organic acid in MCPHA and suggests that mitochondrial ThPP transport is important for CNS development. C1 Univ Bari, Dipartimento Farm Biol, Lab Biochem & Mol Biol, I-70125 Bari, Italy. NHGRI, NIH, Bethesda, MD 20892 USA. Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. VU Univ, Med Ctr, Dept Clin Chem, NL-1081 HV Amsterdam, Netherlands. RP Lindhurst, MJ (reprint author), Univ Bari, Dipartimento Farm Biol, Lab Biochem & Mol Biol, Via E Orabona 4, I-70125 Bari, Italy. EM marjr@mail.nih.gov; fpalm@farmbiol.uniba.it RI Fiermonte, Giuseppe/F-3159-2010; castegna, alessandra/M-5106-2013 FU Intramural NIH HHS; LSPPPO CDC HHS [LS-45039] NR 22 TC 69 Z9 73 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2006 VL 103 IS 43 BP 15927 EP 15932 DI 10.1073/pnas.0607661103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500037 PM 17035501 ER PT J AU Kong, WP Hood, C Yang, ZY Wei, CJ Xu, L Garcia-Sastre, A Tumpey, TM Nabel, GJ AF Kong, Wing-pui Hood, Chantelle Yang, Zhi-yong Wei, Chih-Jen Xu, Ling Garcia-Sastre, Adolfo Tumpey, Terrence M. Nabel, Gary J. TI Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE influenza vaccines; neutralizing antibody; vaccines ID TYPE-1 DNA VACCINES; IMMUNOGENICITY; HEMAGGLUTININ; GENE; NUCLEOPROTEIN; MICE AB The remarkable infectivity and virulence of the 1918 influenza virus resulted in an unprecedented pandemic, raising the question of whether it is possible to develop protective immunity to this virus and whether immune evasion may have contributed to its spread. Here, we report that the highly lethal 1918 virus is susceptible to immune protection by a preventive vaccine, and we define its mechanism of action. Immunization with plasmid expression vectors encoding hemagglutinin (HA) elicited potent CD4 and CD8 cellular responses as well as neutralizing antibodies. Antibody specificity and titer were defined by a microneutralization and a pseuclotype assay that could assess antibody specificity without the need for high-level biocontainment. This pseuclotype inhibition assay can define evolving serotypes of influenza viruses and facilitate the development of immune sera and neutralizing monoclonal antibodies that may help contain pandemic influenza. Notably, mice vaccinated with 1918 HA plasmid IDNAs showed complete protection to lethal challenge. T cell depletion had no effect on immunity, but passive transfer of purified IgG from antiHl(1918) immunized mice provided protective immunity for nallive mice challenged with infectious 1918 virus. Thus, humoral immunity directed at the viral HA can protect against the 1918 pandemic virus. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Ctr Dis Control & Prevent, Influenza Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Room 4502,Bldg 40,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov OI Garcia-Sastre, Adolfo/0000-0002-6551-1827 FU Intramural NIH HHS NR 19 TC 59 Z9 65 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 OCT 24 PY 2006 VL 103 IS 43 BP 15987 EP 15991 DI 10.1073/pnas.0607564103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500047 PM 17043214 ER PT J AU Petridou, N Plenz, D Silva, AC Loew, M Bodurka, J Bandettini, PA AF Petridou, Natalia Plenz, Dietmar Silva, Afonso C. Loew, Murray Bodurka, Jerzy Bandettini, Peter A. TI Direct magnetic resonance detection of neuronal electrical activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell culture; functional MRI; neuronal current imaging; brain ID HUMAN BRAIN; MRI DETECTION; WATER DIFFUSION; SNAIL GANGLIA; CURRENTS; FIELDS; CORTEX; MAGNETOENCEPHALOGRAPHY; STIMULATION; CULTURES AB Present noninvasive neuroimaging methods measure neuronal activity indirectly, via either cerebrovascular changes or extracranial measurements of electrical/magnetic signals. Recent studies have shown evidence that MRI may be used to directly and noninvasively map electrical activity associated with human brain activation, but results are inconclusive. Here, we show that MRI can detect cortical electrical activity directly. We use organotypic rat-brain cultures in vitro that are spontaneously active in the absence of a cerebrovascular system. Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly correlated with multi-site extracellular local field potential recordings of the same cultures before and after blockade of neuronal activity with tetrodotoxin. Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels containing the culture, thus allowing the spatial localization of the active neuronal tissue. C1 Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Lab Syst Neurosci, Neural Network Physiol Unit, NIH, Bethesda, MD 20892 USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Elect & Comp Engn, Inst Med Imaging & Image Anal, Washington, DC 20052 USA. RP Bandettini, PA (reprint author), Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM bandettini@nih.gov RI Silva, Afonso/A-7129-2009 NR 32 TC 58 Z9 60 U1 1 U2 8 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 OCT 24 PY 2006 VL 103 IS 43 BP 16015 EP 16020 DI 10.1073/pnas.0603219103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 099BW UT WOS:000241568500052 PM 17038505 ER PT J AU Kondrashov, FA Koonin, EV Morgunov, IG Finogenova, TV Kondrashova, MN AF Kondrashov, Fyodor A. Koonin, Eugene V. Morgunov, Igor G. Finogenova, Tatiana V. Kondrashova, Marie N. TI Evolution of glyoxylate cycle enzymes in Metazoa: evidence of multiple horizontal transfer events and pseudogene formation SO BIOLOGY DIRECT LA English DT Article ID RAT-LIVER; SEQUENCE ALIGNMENT; INTRON POSITIONS; ISOCITRATE LYASE; MALATE SYNTHASE; GENE-TRANSFER; CHICK LIVER; ACID CYCLE; PSI-BLAST; PROTEIN AB Background: The glyoxylate cycle is thought to be present in bacteria, protists, plants, fungi, and nematodes, but not in other Metazoa. However, activity of the glyoxylate cycle enzymes, malate synthase (MS) and isocitrate lyase (ICL), in animal tissues has been reported. In order to clarify the status of the MS and ICL genes in animals and get an insight into their evolution, we undertook a comparative-genomic study. Results: Using sequence similarity searches, we identified MS genes in arthropods, echinoderms, and vertebrates, including platypus and opossum, but not in the numerous sequenced genomes of placental mammals. The regions of the placental mammals' genomes expected to code for malate synthase, as determined by comparison of the gene orders in vertebrate genomes, show clear similarity to the opossum MS sequence but contain stop codons, indicating that the MS gene became a pseudogene in placental mammals. By contrast, the ICL gene is undetectable in animals other than the nematodes that possess a bifunctional, fused ICL-MS gene. Examination of phylogenetic trees of MS and ICL suggests multiple horizontal gene transfer events that probably went in both directions between several bacterial and eukaryotic lineages. The strongest evidence was obtained for the acquisition of the bifunctional ICL-MS gene from an as yet unknown bacterial source with the corresponding operonic organization by the common ancestor of the nematodes. Conclusion: The distribution of the MS and ICL genes in animals suggests that either they encode alternative enzymes of the glyoxylate cycle that are not orthologous to the known MS and ICL or the animal MS acquired a new function that remains to be characterized. Regardless of the ultimate solution to this conundrum, the genes for the glyoxylate cycle enzymes present a remarkable variety of evolutionary events including unusual horizontal gene transfer from bacteria to animals. C1 Univ Calif San Diego, Div Biol Sci, Sect Ecol Behav & Evolut, La Jolla, CA 92093 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Russian Acad Sci, Skryabin Inst Biochem & Physiol Microorganisms, Pushchino 142292, Russia. Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Russia. RP Kondrashov, FA (reprint author), Univ Calif San Diego, Div Biol Sci, Sect Ecol Behav & Evolut, 2218 Muir Biol Bldg, La Jolla, CA 92093 USA. EM fkondrashov@ucsd.edu; koonin@ncbi.nlm.nih.gov; morgunovs@rambler.ru; finog@ibpm.puschino.ru; kondrashova@iteb.ru RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 59 TC 62 Z9 65 U1 4 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD OCT 23 PY 2006 VL 1 AR 31 DI 10.1186/1745-6150-1-31 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TO UT WOS:000244036600001 PM 17059607 ER PT J AU Chernomordik, LV Zimmerberg, J Kozlov, MM AF Chernomordik, Leonid V. Zimmerberg, Joshua Kozlov, Michael M. TI Membranes of the world unite! SO JOURNAL OF CELL BIOLOGY LA English DT Review ID PHOSPHOLIPID-BILAYER MEMBRANES; HEMAGGLUTININ-MEDIATED FUSION; INFLUENZA HEMAGGLUTININ; BIOLOGICAL-MEMBRANES; PLANAR MEMBRANE; PORE FORMATION; CELL-MEMBRANE; HEMIFUSION; PROTEIN; MODEL AB Despite diverse origins, cellular fusion mechanisms converge at a pathway of phospholipid bilayer fusion. In this mini-review, we discuss how proteins can mediate each of the three major stages in the fusion pathway: contact, hemifusion, and the opening of an expanding fusion pore. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Chernomordik, LV (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov; joshz@helix.nih.gov; michk@post.tau.ac.il FU Intramural NIH HHS NR 63 TC 121 Z9 126 U1 1 U2 20 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 OCT 23 PY 2006 VL 175 IS 2 BP 201 EP 207 DI 10.1083/jcb.200607083 PG 7 WC Cell Biology SC Cell Biology GA 099EO UT WOS:000241575500002 PM 17043140 ER PT J AU Filbey, FM Slack, KJ Sunderland, TP Cohen, RM AF Filbey, Francesca M. Slack, Kelly J. Sunderland, Trey P. Cohen, Robert M. TI Functional magnetic resonance imaging and magnetoencephalography differences associated with APOE epsilon 4 in young healthy adults SO NEUROREPORT LA English DT Article DE Alzheimer's disease; apolipoprotein E; encoding; functional magnetic resonance imaging; magnetoencephalography; memory; young adults ID APOLIPOPROTEIN-E GENOTYPE; ALZHEIMER-DISEASE; WORKING-MEMORY; GAMMA-OSCILLATIONS; FMRI EVIDENCE; GENETIC RISK; THETA; ACTIVATION; MEG; AGE AB Functional neural alterations are present in middle-aged to late-aged healthy individuals carrying the epsilon 4 allele of the apolipoprotein E (APOE epsilon 4) gene, a known risk factor for Alzheimer's disease. Neural activity was measured in young adults with and without the epsilon 4 allele (APOE epsilon 4+ and APOE epsilon 4-) by functional magnetic resonance imaging and magnetoencephalography while performing a visual working memory task on two separate days. Greater activity was observed in frontal areas and cingulate gyri in APOE epsilon 4+ participants by both functional magnetic resonance imaging and magnetoencephalography with regional blood oxygenation level-dependent responses correlating with increased theta band power. The findings suggest that the presence of the APOE epsilon 4 allele has physiological consequences before aging that may contribute to risk for Alzheimer's disease. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Filbey, FM (reprint author), Univ Colorado, Dept Psychol, Muenzinger Bldg,D-326-B, Boulder, CO 80309 USA. EM Francesca.Filbey@colorado.edu FU NIMH NIH HHS [Z01 MH00330-14] NR 16 TC 28 Z9 30 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 23 PY 2006 VL 17 IS 15 BP 1585 EP 1590 DI 10.1097/01.wnr.0000234745.27571.d1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 129UY UT WOS:000243756800005 PM 17001273 ER PT J AU Matarin, MM Singleton, AB Houlden, H AF Matarin, M. M. Singleton, A. B. Houlden, H. TI PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease SO NEUROSCIENCE LETTERS LA English DT Article DE PANK2; neurodegeneration; PKAN; NBIA; mutation ID HALLERVORDEN-SPATZ-SYNDROME; KINASE-ASSOCIATED NEURODEGENERATION; THE-TIGER SIGN; PATIENT AB Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G -> A transition at base 1238 (G411R) and a C -> A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Houlden, H (reprint author), Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM h.houlden@ion.ucl.ac.uk RI Houlden, Henry/C-1532-2008; Singleton, Andrew/C-3010-2009; Matarin, Mar/F-1771-2016 OI Houlden, Henry/0000-0002-2866-7777; Matarin, Mar/0000-0002-4717-5735 FU Medical Research Council [G108/638] NR 21 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 23 PY 2006 VL 407 IS 2 BP 162 EP 165 DI 10.1016/j.neulet.2006.08.030 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 094PC UT WOS:000241250400015 PM 16962235 ER PT J AU Howat, TJ Barreca, C O'Hare, P Gog, JR Grenfell, BT AF Howat, Tom J. Barreca, Cristina O'Hare, Peter Gog, Julia R. Grenfell, Bryan T. TI Modelling dynamics of the type I interferon response to in vitro viral infection SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE innate immunity; viral infection; cytokines; interferon; stochastic model; dose dependence ID HERPES-SIMPLEX-VIRUS; DOUBLE-STRANDED-RNA; HUMAN MXA PROTEIN; INNATE IMMUNITY; HIV-1 INFECTION; DIFFUSION-MODEL; GENE-EXPRESSION; INFLUENZA-VIRUS; CELLS; RESISTANCE AB Innate immunity is crucial in the early stages of resistance to novel viral infection. The family of cytokines known as the interferons (IFNs) forms an essential component of this system: they are responsible for signalling that an infection is underway and for promoting an antiviral response in susceptible cells. We construct a spatial stochastic model, parameterized by experimental data and informed by analytic approximation, to capture the dynamics of virus-IFN interaction during in vitro infection of Madin-Darby bovine kidney cell monolayers by Herpes simplex virus 1. The dose dependence of infection progression, subsequent monolayer destruction and IFN-beta production are investigated. Implications for in vivo infections, in particular the priming of susceptible cells by IFN-beta during infection, are considered. C1 Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. Marie Curie Res Inst, Oxted RH8 0TL, Surrey, England. Penn State Univ, Dept Biol, State Coll, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Howat, TJ (reprint author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England. EM tjh44@cam.ac.uk NR 43 TC 22 Z9 22 U1 0 U2 1 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD OCT 22 PY 2006 VL 3 IS 10 BP 699 EP 709 DI 10.1098/rsif.2006.0136 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108GH UT WOS:000242227800011 PM 16971338 ER PT J AU Jiang, S Li, P Peach, ML Bindu, L Worthy, KW Fisher, RJ Burke, TR Nicklaus, M Roller, PP AF Jiang, Sheng Li, Peng Peach, Megan L. Bindu, Lakshman Worthy, Karen W. Fisher, Robert J. Burke, Terrence R., Jr. Nicklaus, Marc Roller, Peter P. TI Structure-based design of potent Grb2-SH2 domain antagonists not relying on phosphotyrosine mimics SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Grb2-SH2 domain; cyclic peptides; G1TE analogs; D-alanine; non-phosphotyrosine; Grb2-SH2 antagonist; tyrosine kinase ID BREAST-CANCER CELLS; SH2 DOMAIN; HIGH-AFFINITY; NONPHOSPHORYLATED INHIBITOR; ABSOLUTE-CONFIGURATION; SIGNAL-TRANSDUCTION; CONTAINING PEPTIDE; BIOSENSOR ANALYSIS; BINDING; PROTEIN AB Development of Grb2-SH2 domain antagonists is considered to be an effective and non-cytotoxic strategy to develop new antipro-liferative agents because of their potential to shut down the Ras signaling pathway. We developed a concise route for the efficient synthesis of G1TE analogs on solid phase. Using this route, a series of cyclic peptides that do not rely on phosphotyrosine or its mimics were designed and synthesized based upon the phage library-derived cyclopeptide, ME Considering that Gly(7) plays prominent roles for G1TE binding to the Grb2-SH2 domain, we introduced different amino acids in the 7th position. The D-Ala(7)-containing peptide 3 demonstrates improved binding affinity by adopting favorable conformation for protein binding. This can be rationalized by molecular modeling. The optimization at the Leu(2) position was also studied, and the resulting cyclopeptides exhibited remarkably improved binding affinity. Based upon these global modifications, a highly potent peptide ligand 9 was discovered with a K-d = 17 nM, evaluated by Biacore binding assay. This new analog is one of the most potent non-phosphorus-containing Grb2-SH2 antagonists reported to date. This potent peptidomimetic provides a new template for the development of non-pTyr containing Grb2-SH2 domain antagonists and acts as a chemotherapeutic lead for the treatment of erbB2-related cancer. Published by Elsevier Inc. C1 NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. RP Roller, PP (reprint author), NCI, Med Chem Lab, NIH, Ft Detrick, MD 21702 USA. EM proll@helix.nih.gov RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 40 TC 9 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 20 PY 2006 VL 349 IS 2 BP 497 EP 503 DI 10.1016/j.bbrc.2006.08.059 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 088DN UT WOS:000240791800007 PM 16945340 ER PT J AU Niimi, T Kurotani, R Kimura, S Kitagawa, Y AF Niimi, Tomoaki Kurotani, Reiko Kimura, Shioko Kitagawa, Yasuo TI Identification and expression of alternative splice variants of the mouse Ppp1r3b gene in lung epithelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE TITF-1; Nkx2.1; glycogen-targeting subunit; protein phosphatase-1; lung development ID THYROID TRANSCRIPTION FACTOR-1; GLYCOGEN-TARGETING SUBUNIT; ENHANCER-BINDING PROTEIN; RAT LUNG; FACTOR-I; FETAL; PHOSPHATASE-1; MORPHOGENESIS; HOMEODOMAIN; METABOLISM AB Hepatic glycogen-targeting subunit G(L) of protein phosphatase-1 (PP1), which is encoded by the gene Ppp1r3b, is one of a family of proteins that target PP1 to glycogen and regulate its activity on enzymes of glycogen metabolism. G(L) is primarily expressed in the liver where it promotes hepatic glycogen synthesis in response to insulin. Here, we show that G(L) is highly expressed in embryonic mouse lungs. G(L) utilizes two alternative promoters and 5' non-coding exons, which produce at least three alternatively spliced transcripts that encode identical proteins. Expression of G(L) in the lung is detectable as early as embryonic day (E) 12.5 and increases by E16.5, however, it declines before birth. In situ hybridization of mouse embryonic lung revealed that G(L) is expressed in bronchial epithelial cells. Thus, the temporal and spatial expression of G(L) in the lung suggests that it has a potential role in glycogen metabolism during lung development. (c) 2006 Elsevier Inc. All rights reserved. C1 Nagoya Univ, Grad Sch Bioagr Sci, Dept Bioengn Sci, Nagoya, Aichi 4648601, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Niimi, T (reprint author), Nagoya Univ, Grad Sch Bioagr Sci, Dept Bioengn Sci, Nagoya, Aichi 4648601, Japan. EM tniimi@agr.nagoya-u.ac.jp NR 39 TC 3 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 20 PY 2006 VL 349 IS 2 BP 588 EP 596 DI 10.1016/j.bbrc.2006.08.091 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 088DN UT WOS:000240791800019 PM 16949035 ER PT J AU Jelinkova, I Yan, ZH Liang, ZD Moonat, S Teisinger, J Stojilkovic, SS Zemkova, H AF Jelinkova, Irena Yan, Zonghe Liang, Zhaodong Moonat, Sachin Teisinger, Jan Stojilkovic, Stanko S. Zemkova, Hana TI Identification of P2X(4) receptor-specific residues contributing to the ivermectin effects on channel deactivation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE purinergic receptor-channels; P2X(4); ATP; ivermectin; gating; activation; deactivation; desensitization; chimeras ID FUNCTIONAL-CHARACTERIZATION; ION CHANNELS; FACILITATION; DEPENDENCE; MECHANISM; DOMAIN AB Ivermectin (IVM) applied extracellularly increases the sensitivity of P2X(4) receptor (P2X(4)R) to ATP, enhances the maximum current amplitudes, and greatly prolongs the deactivation kinetics. In this manuscript, we focused on identification of receptor-specific residues responsible for IVM effects on channel gating using the wild-type rat homomeric P2X(4)R, several chimeric P2X(2)/P2X(4) receptors, and single-point P2X(4)R-specific mutants in the ectodomain and two transmembrane domains. Experiments with chimeric receptors revealed that the Val(49)-Val(61) but not the Val(64)-Tyr(315) ectodomain sequence is important for the effects of IVM on channel deactivation. Receptor-specific mutations placed in the Gly(29)-Val(61) and Asp(338)-Leu(358) regions showed the importance of Trp(50), Val(60), and Val(357) residues in IVM regulation of the rate of channel deactivation, but not on the maximum current amplitude. These results suggest that the transmembrane domains and the nearby ectodomain region contribute to the effects of IVM on channel deactivation. (c) 2006 Elsevier Inc. All rights reserved. C1 Acad Sci Czech Republ, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, CR-14220 Prague 4, Czech Republic. NICHD, ERRB, NIH, Bethesda, MD 20892 USA. RP Zemkova, H (reprint author), Acad Sci Czech Republ, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Videnska 1083, CR-14220 Prague 4, Czech Republic. EM zemkova@biomed.cas.cz RI Zemkova, Hana/C-1844-2012; Teisinger, Jan /B-7122-2012 FU Intramural NIH HHS NR 20 TC 35 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 20 PY 2006 VL 349 IS 2 BP 619 EP 625 DI 10.1016/j.bbrc.2006.08.084 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 088DN UT WOS:000240791800023 PM 16949036 ER PT J AU Sternberg, EM Wilson, MA AF Sternberg, Esther M. Wilson, Matthew A. TI Neuroscience and architecture: Seeking common ground SO CELL LA English DT Editorial Material ID MEMORY; HIPPOCAMPUS; CELLS AB As these paired Commentaries discuss, neuroscientists and architects are just beginning to collaborate, each bringing what they know about their respective fields to the task of improving the environment of research buildings and laboratories. C1 NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. MIT, Picower Inst Learning & Mem, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov; mwilson@mit.edu NR 9 TC 9 Z9 10 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 20 PY 2006 VL 127 IS 2 BP 239 EP 242 DI 10.1016/j.cell.2006.10.012 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102QH UT WOS:000241827100006 PM 17055420 ER PT J AU Li, QX Ali, MA Cohen, JI AF Li, Qingxue Ali, Mir A. Cohen, Jeffrey I. TI Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread SO CELL LA English DT Article ID AMYLOID BETA-PROTEIN; GLYCOPROTEIN-I; MONOCLONAL-ANTIBODIES; POLIOVIRUS RECEPTOR; MANNOSE 6-PHOSPHATE; HEPARAN-SULFATE; ENTRY; DEGRADATION; GE; FUSION AB Varicella-zoster virus (VZV) causes chickenpox and shingles. While varicella is likely spread as cell-free virus to susceptible hosts, the virus is transmitted by cell-to-cell spread in the body and in vitro. Since VZV glycoprotein E (gE) is essential for virus infection, we postulated that gE binds to a cellular receptor. We found that insulin-degrading enzyme (IDE) interacts with gE through its extracellular domain. Downregulation of IDE by siRNA, or blocking of IDE with antibody, with soluble IDE protein extracted from liver, or with bacitracin inhibited VZV infection. Cell-to-cell spread of virus was also impaired by blocking IDE. Transfection of cell lines impaired for VZV infection with a plasmid expressing human IDE resulted in increased entry and enhanced infection with cell-free and cell-associated virus. These studies indicate that IDE is a cellular receptor for both cell-free and cell-associated VZV. C1 NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU Intramural NIH HHS NR 50 TC 80 Z9 84 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 20 PY 2006 VL 127 IS 2 BP 305 EP 316 DI 10.1016/j.cell.2006.08.046 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 102QH UT WOS:000241827100018 PM 17055432 ER PT J AU He, HJ Zhu, TN Xie, Y Fan, JS Kole, S Saxena, S Bernier, M AF He, Hua-Jun Zhu, Tie-Nian Xie, Yi Fan, Jinshui Kole, Sutapa Saxena, Satya Bernier, Michel TI Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; HUMAN ENDOTHELIAL-CELLS; C/EBP-BETA; INSULIN-RESISTANCE; OXIDATIVE STRESS; GENE-EXPRESSION; DNA-BINDING; ALPHA(2)-MACROGLOBULIN GENE; TYROSINE PHOSPHORYLATION; HAPTOGLOBIN GENE AB Interleukin (IL)-6 is a proinflammatory cytokine that has been implicated in the expression of acute phase plasma proteins and hepatic insulin resistance through activation of the JAK/STAT3 pathway. Although previous studies have demonstrated that pyrrolidine dithiocarbamate (PDTC) exerts protection against inflammatory responses, its role in the regulation of IL-6 receptor signaling remains unclear. Here we show that treatment of cultured HepG2 hepatoma cells with PDTC inhibits IL-6-stimulated tyrosine phosphorylation and subsequent nuclear translocation of STAT3 in a dose- and time-dependent fashion. No inhibition of JAK-1 activity was observed. To provide insight into PDTC signaling, we constructed a conditionally active STAT3 by fusing it with the ligand binding domain of the estrogen receptor (STAT3-ER). In the presence of 4-hydroxytamoxifen STAT3-ER was translocated in the nucleus of HepG2 cells in a phosphorylation-independent manner, and treatment with PDTC mitigated the response. Although STAT3 coprecipitated with heat-shock protein 90 (Hsp90) in control cells, coprecipitation of the two proteins was greatly reduced after PDTC treatment or after exposure to geldanamycin, an Hsp90 inhibitor. As a result there was a decrease in IL-6-induced association of STAT3 with the transcriptional coactivators FOXO1a and C/EBP beta together with significant reduction in the expression of SOCS-3 protein and that of two major acute phase plasma proteins. Importantly, treatment of HepG2 cells and a primary culture of rat hepatocytes with PDTC restored insulin responsiveness that was abrogated by IL-6. These studies are consistent with the ability of PDTC to down-regulate IL-6-induced STAT3 activation by altering the stability of STAT3-Hsp90 complex. C1 NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. NIA, Proteom & Mass Spectrometry Unit, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Diabet Sect, Clin Invest Lab, NIH, Box 23,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Bernierm@mail.nih.gov OI Bernier, Michel/0000-0002-5948-368X FU Intramural NIH HHS NR 67 TC 28 Z9 30 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 20 PY 2006 VL 281 IS 42 BP 31369 EP 31379 DI 10.1074/jbc.M603762200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094JI UT WOS:000241235300021 PM 16926159 ER PT J AU Mueller, S Kleinau, G Jaeschke, H Neumann, S Krause, G Paschke, R AF Mueller, Sandra Kleinau, Gunnar Jaeschke, Holger Neumann, Susanne Krause, Gerd Paschke, Ralf TI Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROTROPIN TSH RECEPTOR; EXTRACELLULAR DOMAIN; CONSTITUTIVE ACTIVITY; TRANSMEMBRANE DOMAIN; INVERSE AGONIST; MUTATIONS; BINDING; PATHOPHYSIOLOGY; AUTOANTIBODIES; IDENTIFICATION AB Recently, we identified constitutively activating mutations at positions Asp-403, Glu-404, and Asn-406 in the third extracellular cysteine box (C-b3) of the thyroid-stimulating hormone receptor. We hypothesized that this region could act as a molecular interface between the extracellular and serpentine domain. In this study we present a model for properties of potential interaction partners for this region. Moreover, we show that Pro-400 and Pro-407 adjacent to this epitope are also important for stabilizing the partially active, basal conformation of the wild-type (WT) thyroid-stimulating hormone receptor. Furthermore, the mutation K291A in the second extracellular cysteine box (C-b2) was identified as a new constitutively activating mutation that releases the basal conformation of the WT receptor like the known tryptic cleavage in its close vicinity. Taken together, we provide an activation scenario at the C-b2/C-b3 unit. Three anchor fragments (anchors I-III) most likely constrain the basal conformation. The three anchor fragments are tightly packed. A disulfide bridge holds the C-b2/C-b3 portions in close positions. Independent of the type of conformational interference such as side chain modifications, tryptic cleavage, or hormone stimulation that act on the constrained C-b2/C-b3 WT conformation, it will always release one of the anchor fragments. Subsequently, this results in a conformational displacement of the C-b2/C-b3 portions relative to each other, inducing receptor activation. C1 Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. Leibniz Inst Mol Pharmakol, D-13125 Berlin, Germany. NIDDK, NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Paschke, R (reprint author), Univ Leipzig, Dept Med 3, Str 27, D-04103 Leipzig, Germany. EM pasr@medizin.uni-leipzig.de FU Intramural NIH HHS NR 35 TC 25 Z9 25 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 OCT 20 PY 2006 VL 281 IS 42 BP 31638 EP 31646 DI 10.1074/jbc.M604770200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094JI UT WOS:000241235300049 PM 16899458 ER PT J AU Zhang, J Diamond, JS AF Zhang, Jun Diamond, Jeffrey S. TI Distinct perisynaptic and synaptic localization of NMDA and AMPA receptors on ganglion cells in rat retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE NMDA; AMPA; synaptic and perisynaptic distribution; postembedding immunogold; retinal ganglion cell ID IONOTROPIC GLUTAMATE RECEPTORS; TIGER SALAMANDER RETINA; LONG-TERM POTENTIATION; INNER PLEXIFORM LAYER; MAMMALIAN RETINA; CAT RETINA; PRIMATE RETINA; IMMUNOGOLD LOCALIZATION; HIPPOCAMPAL SYNAPSES; BIPOLAR CELLS AB At most excitatory synapses, AMPA and NMDA receptors (AMPARs and NMDARs) occupy the postsynaptic density (PSD) and contribute to miniature excitatory postsynaptic currents (mEPSCs) elicited by single transmitter quanta. Juxtaposition of AMPARs and NMDARs may be crucial for certain types of synaptic plasticity, although extrasynaptic NMDARs may also contribute. AMPARs and NMDARs also contribute to evoked EPSCs in retinal ganglion cells (RGCs), but mEPSCs are mediated solely by AMPARs. Previous work indicates that an NMDAR component emerges in mEPSCs when glutamate uptake is reduced, suggesting that NMDARs are located near the release site but perhaps not directly beneath in the PSD. Consistent with this idea, NMDARs on RGCs encounter a lower glutamate concentration during synaptic transmission than do AMPARs. To understand better the roles of NMDARs in RGC function, we used immunohistochemical and electron microscopic techniques to determine the precise subsynaptic localization of NMDARs in RGC dendrites. RGC dendrites were labeled retrogradely with cholera toxin B subunit (CTB) injected into the superior colliculus (SC) and identified using postembedding immunogold methods. Colabeling with antibodies directed toward AMPARs and/or NMDARs, we found that nearly all AMPARs are located within the PSD, while most NMDARs are located perisynaptically, 100-300 nm from the PSD. This morphological evidence for exclusively perisynaptic NMDARs localizations suggests a distinct role for NMDARs in RGC function. C1 NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Unit, NIH, 35 Convent Dr,Bldg 35,Room 3C-1000, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Zhang, Jun/K-2424-2012; Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU Intramural NIH HHS [Z01 NS003039-01] NR 91 TC 52 Z9 52 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 20 PY 2006 VL 498 IS 6 BP 810 EP 820 DI 10.1002/cne.21089 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 081ZP UT WOS:000240356400006 PM 16927255 ER PT J AU Barinka, C Parry, G Callahan, J Shaw, DE Kuo, A Bdeir, K Cines, DB Mazar, A Lubkowski, J AF Barinka, Cyril Parry, Graham Callahan, Jennifer Shaw, David E. Kuo, Alice Bdeir, Khalil Cines, Douglas B. Mazar, Andrew Lubkowski, Jacek TI Structural basis of interaction between urokinase-type plasminogen activator and its receptor SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE urokinase receptor; X-ray crystallography; protein/protein interactions; kringle domain; plasminogen ID LIGAND-BINDING; VITRONECTIN BINDING; MONOCYTIC CELLS; DOMAIN-II; PROTEIN; GLYCOSYLATION; CLEAVAGE; PEPTIDE; IDENTIFICATION; INTEGRINS AB Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 angstrom. We report the 1.9 angstrom crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Canc Res Ctr, Frederick, MD 21702 USA. Attenuon, LLC, San Diego, CA 92121 USA. DE Shaw Res & Dev, New York, NY 10036 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Lubkowski, J (reprint author), NCI, Canc Res Ctr, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Barinka, Cyril/G-9803-2014 FU Intramural NIH HHS [Z01 BC010761-02]; NCI NIH HHS [CA83121, R01 CA083121]; NHLBI NIH HHS [HL076206, HL60169, HL76406, P01 HL076406, R01 HL060169, R01 HL076206] NR 57 TC 72 Z9 84 U1 0 U2 5 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 OCT 20 PY 2006 VL 363 IS 2 BP 482 EP 495 DI 10.1016/j.jmb.2006.08.063 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095RC UT WOS:000241324500015 PM 16979660 ER PT J AU Li, Q Shivachandra, SB Leppla, SH Rao, VB AF Li, Qin Shivachandra, Sathish B. Leppla, Stephen H. Rao, Venigalla B. TI Bacteriophage T4 capsid: A unique platform for efficient surface assembly of macromolecular complexes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phage T4; macromolecular assembly; Hoc; Soc; phage display ID ANTHRAX PROTECTIVE ANTIGEN; LETHAL FACTOR; BACILLUS-ANTHRACIS; CRYSTAL-STRUCTURE; MAMMALIAN-CELLS; DISPLAY; TOXIN; BINDING; PROTEINS; PHAGE AB We report the first description of a macromolecular complex display system using bacteriophage T4. Decorated with two dispensable outer capsid proteins, Hoc (155 copies) and Soc (810 copies), the 120 mn x 86 nm T4 capsid particle offers a unique binding site-rich platform for surface assembly of hetero-oligomeric complexes. To display the 710 kDa anthrax toxin complex, two bipartite functional fusion proteins, LF-Hoc and LFn-Soc, were constructed. Using a defined in vitro binding system, sequential assembly was performed by first attaching LF-Hoc and/or LFn-Soc to hoc(-)soc(-) phage, saturating the Hoc and Soc binding sites. Trypsin-nicked PA63 was then assembled into heptamers through specific interaction with the capsid-exposed LFn domain. EF was then attached to the unoccupied sites of PA63 heptamers, completing the assembly of the tripartite anthrax toxin. Negative electron microscopy showed decoration of each capsid with a layer of heptameric PA63 rings. Up to 229 anthrax toxin complexes, equivalent to a total of 2400 protein molecules and a mass of about 133 MDa (2.7 times the mass of capsid shell), were anchored on a single particle, making it the highest density display reported on any virus. The phage T4 capsid lattice provides a stable biological platform allowing maximum display of large hetero-oligomeric complexes in vitro and offers insights for developing novel vaccines, analysis of protein-protein interactions, and structure determination of complexes. (c) 2006 Elsevier Ltd. All rights reserved. C1 Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Rao, VB (reprint author), Catholic Univ Amer, Dept Biol, 620 Michigan Ave,NE, Washington, DC 20064 USA. EM rao@cua.edu FU Intramural NIH HHS; NIAID NIH HHS [AI056443, R01 AI102725] NR 41 TC 29 Z9 31 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 OCT 20 PY 2006 VL 363 IS 2 BP 577 EP 588 DI 10.1016/j.jmb.2006.08.049 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095RC UT WOS:000241324500022 PM 16982068 ER PT J AU Dorrello, NV Peschiaroli, A Guardavaccaro, D Colburn, NH Sherman, NE Pagano, M AF Dorrello, N. Valerio Peschiaroli, Angelo Guardavaccaro, Daniele Colburn, Nancy H. Sherman, Nicholas E. Pagano, Michele TI S6K1- and beta TRCP-mediated degradation of PDCD4 promotes protein translation and cell growth SO SCIENCE LA English DT Article ID INITIATION-FACTOR 4A; SUPPRESSOR PDCD4; TRANSFORMATION; NUTRIENT; BINDING; KINASE; TARGET AB The tumor suppressor programmed cell death protein 4 (PDCD4) inhibits the translation initiation factor eIF4A, an RNA helicase that catalyzes the unwinding of secondary structure at the 5' untranslated region (5'UTR) of messenger RNAs (mRNAs). In response to mitogens, PDCD4 was rapidly phosphorylated on Ser(67) by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase SCF beta TRCP. Expression in cultured cells of a stable PDCD4 mutant that is unable to bind beta TRCP inhibited translation of an mRNA with a structured 5' UTR, resulted in smaller cell size, and slowed down cell cycle progression. We propose that regulated degradation of PDCD4 in response to mitogens allows efficient protein synthesis and consequently cell growth. C1 NYU, Sch Med, Inst Canc, Dept Pathol, New York, NY 10016 USA. NCI, Lab Canc Prevent, Frederick, MD 21702 USA. Univ Virginia, WM Keck Biomed Mass Spectrometry Lab, Charlottesville, VA 22908 USA. RP Pagano, M (reprint author), NYU, Sch Med, Inst Canc, Dept Pathol, 550 1st Ave,MSB 599, New York, NY 10016 USA. EM michele.pagano@med.nyu.edu OI PESCHIAROLI, ANGELO/0000-0001-6311-2382; pagano, michele/0000-0003-3210-2442 FU NCI NIH HHS [R01-CA76584]; NIGMS NIH HHS [R01-GM57587] NR 16 TC 354 Z9 369 U1 0 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 20 PY 2006 VL 314 IS 5798 BP 467 EP 471 DI 10.1126/science.1130276 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 096MW UT WOS:000241382500043 PM 17053147 ER PT J AU Wang, GP Nikolovska-Coleska, Z Yang, CY Wang, RX Tang, GZ Guo, J Shangary, S Qiu, S Gao, W Yang, DJ Meagher, J Stuckey, J Krajewski, K Jiang, S Roller, PP Abaan, HO Tomita, Y Wang, SM AF Wang, Guoping Nikolovska-Coleska, Zaneta Yang, Chao-Yie Wang, Renxiao Tang, Guozhi Guo, Jie Shangary, Sanjeev Qiu, Su Gao, Wei Yang, Dajun Meagher, Jennifer Stuckey, Jeanne Krajewski, Krzysztof Jiang, Sheng Roller, Peter P. Abaan, Hatice Ozel Tomita, York Wang, Shaomeng TI Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID FAMILY PROTEINS; CELL-DEATH; DISCOVERY; REGULATORS; BCL-X(L) AB A structure-based approach was employed to design a new class of small-molecule inhibitors of Bcl-2. The most potent compound 5 (TW-37) binds to Bcl-2 with a K-i value of 290 nM and also to BclxL and Mcl-1 with high affinities. Compound 5 potently inhibits cell growth in PC-3 prostate cancer cells with an IC50 value of 200 nM and effectively induces apoptosis in a dose-dependent manner. C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pharmacol & Med Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. NCI, Lab Med Chem, NIH, Frederick, MD 21702 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Med Ctr, Washington, DC 20057 USA. RP Wang, SM (reprint author), Univ Michigan, Ctr Comprehens Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM shaomeng@umich.edu RI Wang, Shaomeng/E-9686-2010; OI Tang, Guozhi/0000-0002-7131-4678 FU NCI NIH HHS [U19CA113317] NR 16 TC 182 Z9 190 U1 3 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2006 VL 49 IS 21 BP 6139 EP 6142 DI 10.1021/jm060460o PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 093TL UT WOS:000241192400001 PM 17034116 ER PT J AU Nagarajan, M Morrell, A Ioanoviciu, A Antony, S Kohlhagen, G Agama, K Hollingshead, M Pommier, Y Cushman, M AF Nagarajan, Muthukaman Morrell, Andrew Ioanoviciu, Alexandra Antony, Smitha Kohlhagen, Glenda Agama, Keli Hollingshead, Melinda Pommier, Yves Cushman, Mark TI Synthesis and evaluation of indenoisoquinoline topoisomerase I inhibitors substituted with nitrogen heterocycles SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA COVALENT COMPLEX; BIOLOGICAL EVALUATION; DESIGN; TOPOTECAN; MECHANISM; POISON AB In connection with an ongoing investigation of indenoisoquinoline topoisomerase I (Top1) inhibitors as potential therapeutic agents, the pharmacophore possessing di(methoxy) and methylenedioxy substituents was held constant, and new derivatives were synthesized with nitrogen heterocycles appended to the lactam side chain. Compounds were evaluated for Top1 inhibition and for cytotoxicity in the National Cancer Institute's human cancer cell screen. Some of the more potent derivatives were also screened for in vivo activity in a hollow fiber assay. The results of these studies indicate that lactam substituents possessing nitrogen heterocycles can provide highly cytotoxic compounds with potent Top1 inhibition. Molecular modeling of these compounds in complex with DNA and Top1 suggests that some of the lactam substituents are capable of interacting with the DNA base pairs above and below the site of intercalation and/or with Top1 amino acid residues, resulting in increased biological activity. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Sch Pharm & Pharmaceut Sci, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diagnos,NIH,Fairview Ctr, Frederick, MD 21701 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [U01 CA089566-05, N01 CO56000, ST32 CA09634-12, T32 CA009634, U01 CA089566, U01 CA089566-01A1, U01 CA089566-02, U01 CA089566-03, U01 CA089566-04, U01 CA89566] NR 22 TC 67 Z9 67 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2006 VL 49 IS 21 BP 6283 EP 6289 DI 10.1021/jm060564z PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 093TL UT WOS:000241192400019 PM 17034134 ER PT J AU Furrer, J Luy, B Basrur, V Roberts, DD Barchi, JJ AF Furrer, Julien Luy, Burkhard Basrur, Venkatesha Roberts, David D. Barchi, Joseph J., Jr. TI Conformational analysis of an alpha 3 beta 1 integrin-binding peptide from thrombospondin-1: Implications for antiangiogenic drug design SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID LAMININ G-LIKE; CRYSTAL-STRUCTURE; CELL-ADHESION; SENSITIVITY IMPROVEMENT; NMR-SPECTROSCOPY; RECOGNITION; ANTAGONISTS; SEQUENCES; MODULES; PROTEIN AB The integrin alpha 3 beta 1 plays important roles in development, angiogenesis, and the pathogenesis of cancer, suggesting potential therapeutic uses for antagonists of this receptor. Recently, an alpha 3 beta 1 integrin-binding site was mapped to residues 190-201 (FQGVLQNVRFVF) of the N-terminal domain of the secreted protein thrombospondin-1 (TSP1). This sequence displays diverse biological activities in vitro and inhibits angiogenesis in vivo. Herein we describe the NMR solution conformation of this segment in both water and dodecylphosphocholine micelles. While essentially unstructured in water, a more well-defined conformation is populated in micelles, particularly in the C-terminal half of the peptide and correlated with increased biological activity of the micellar peptide. The data suggested that the residues that are critical for biological activity are contained in a structurally well-defined segment of the peptide. These data support the role of the NVR motif as a required element of full-length TSP1 for specific molecular recognition by the alpha 3 beta 1 integrin. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Inst Organ Chem & Biochem 2, Garching, Germany. Natl Canc Inst, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Roberts, DD (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov; barchi@helix.nih.gov RI Roberts, David/A-9699-2008; Perez , Claudio Alejandro/F-8310-2010; Luy, Burkhard/I-1918-2013; Furrer, Julien/A-9482-2015 OI Roberts, David/0000-0002-2481-2981; Perez , Claudio Alejandro/0000-0001-9688-184X; Luy, Burkhard/0000-0001-9580-6397; Furrer, Julien/0000-0003-2096-0618 FU Intramural NIH HHS NR 55 TC 3 Z9 4 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2006 VL 49 IS 21 BP 6324 EP 6333 DI 10.1021/jm0608331 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 093TL UT WOS:000241192400023 PM 17034138 ER PT J AU Zou, MF Cao, JJ Kopajtic, T Desai, RI Katz, JL Newman, AH AF Zou, Mu-Fa Cao, Jianjing Kopajtic, Theresa Desai, Rajeev I. Katz, Jonathan L. Newman, Amy Hauck TI Structure-activity relationship studies on a novel series of (S)-2 beta-substituted 3 alpha-[bis(4-fluoro- or 4-chlorophenyl)methoxy]tropane analogues for in vivo investigation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DOPAMINE UPTAKE INHIBITORS; BENZTROPINE ANALOGS; NOREPINEPHRINE TRANSPORTERS; MONOAMINE TRANSPORTERS; COCAINE RECEPTOR; HIGH-AFFINITY; BINDING; RECOGNITION; DERIVATIVES; SEROTONIN AB In general, 3 alpha-(diphenylmethoxy)tropane (benztropine)-based dopamine uptake inhibitors do not demonstrate cocaine-like pharmacological activity in models of psychostimulant abuse and have been proposed as potential medications for the treatment of cocaine addiction. However, several (S)-2-carboalkoxy-substituted-3 alpha[bis(4-fluorophenyl)methoxy]tropane analogues were discovered to stimulate locomotor activity and substitute in subjects trained to discriminate cocaine, suggesting a role of the 2-position substituent in mediating these cocaine-like actions. Herein, we describe the synthesis of a series of novel N- and 2-substituted-3 alpha-[bis(4-fluoro-or 4-chlorophenyl)methoxy]tropane analogues. Most of these analogues demonstrated high affinity binding to the dopamine transporter (DAT; K-i = 1.8-40 nM), and selectivity over the other monoamine transporters and muscarinic M-1 receptors. When the (S)-2-carboalkoxy substituent was replaced with (S)-2-ethenyl, the resulting analogue 11 demonstrated the highest DAT binding affinity in the series (K-i = 1.81 nM) with DAT selectivity over serotonin transporters (SERT; 989-fold), norepinephrine transporters (NET; 261-fold) and muscarinic receptors (90-fold). When the 4'-F groups of compounds 5 (K-i = 2.94 nM) and 8 (K-i = 6.87 nM) were replaced with 4'-Cl in the (S)-2-carboalkoxy series, DAT binding affinities were slightly reduced (K-i = 12.6 and 14.6 nM for 6 and 7, respectively), yet inhibition of dopamine uptake potency remained comparably high (IC50 range = 1.5-2.5 nM). Interestingly, the 4'-Cl analogue (+/-)-6 substituted less in rats trained to discriminate cocaine than the 4'-F analogue (+/-)-5. These studies demonstrate that manipulation of the 2-, N-, and 3-position substituents in the 3 alpha-(diphenylmethoxy) tropane class of dopamine uptake inhibitors can result in ligands with high affinity and selectivity for the DAT, and distinctive in vivo pharmacological profiles that cannot be predicted by their effects in vitro. C1 NIAID, Med Chem Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. NIAID, Psychobiol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIAID, Med Chem Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov FU Intramural NIH HHS NR 33 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2006 VL 49 IS 21 BP 6391 EP 6399 DI 10.1021/jm060762q PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 093TL UT WOS:000241192400029 PM 17034144 ER PT J AU Romagnoli, R Baraldi, PG Remusat, V Carrion, MD Cara, CL Preti, D Fruttarolo, F Pavani, MG Tabrizi, MA Tolomeo, M Grimaudo, S Balzarini, J Jordan, MA Hamel, E AF Romagnoli, Romeo Baraldi, Pier Giovanni Remusat, Vincent Carrion, Maria Dora Cara, Carlota Lopez Preti, Delia Fruttarolo, Francesca Pavani, Maria Giovanna Tabrizi, Mojgan Aghazadeh Tolomeo, Manlio Grimaudo, Stefania Balzarini, Jan Jordan, Mary Ann Hamel, Ernest TI Synthesis and biological evaluation of 2-(3 ',4 ',5 '-trimethoxybenzoyl)-3-amino 5-aryl thiophenes as a new class of tubulin inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC NATURAL-PRODUCTS; ANTINEOPLASTIC AGENTS; CANCER; COMBRETASTATIN-A-4; POLYMERIZATION; COLCHICINE; ANALOGS; GROWTH AB 2-(3', 4', 5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at the para- position of the 5-phenyl group showed antiproliferative activity in the order of F=CH3 > OCH3=Br=NO2 > CF3=I > OEt. Several of these compounds led to arrest of HL-60 cells in the G2/M phase of the cell cycle and induction of apoptosis. C1 Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. Univ Palermo, Dipartimento Oncol, Policlin P Giaccone, Div Ematol, Palermo, Italy. Univ Palermo, Dipartimento Oncol, Policlin P Giaccone, Serv AIDS, Palermo, Italy. Rega Inst, Lab Virol & Chemotherapy, B-3000 Louvain, Belgium. Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. Natl Canc Inst, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Romagnoli, R (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. EM rmr@unife.it; baraldi@unife.it RI Aghazadeh Tabrizi, Mojgan/I-9169-2014; LOPEZ-CARA, LUISA CARLOTA/F-9686-2014; Carrion, M. Dora/G-8638-2015; preti, delia/G-9916-2015; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017; OI LOPEZ-CARA, LUISA CARLOTA/0000-0003-1142-6448; Carrion, M. Dora/0000-0002-6794-3949; preti, delia/0000-0002-1075-3781; Grimaudo, Stefania/0000-0003-3225-4112 NR 17 TC 40 Z9 41 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 19 PY 2006 VL 49 IS 21 BP 6425 EP 6428 DI 10.1021/jm060804a PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 093TL UT WOS:000241192400035 PM 17034150 ER PT J AU Saenz, P Cachau, RE Seoane, G Kieninger, M Ventura, ON AF Saenz, Patricia Cachau, Raul E. Seoane, Gustavo Kieninger, Martina Ventura, Oscar N. TI A new perspective in the Lewis acid catalyzed ring opening of epoxides. Theoretical study of some complexes of methanol, acetic acid, dimethyl ether, diethyl ether, and ethylene oxide with boron trifluoride SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; DENSITY-FUNCTIONAL THEORY; HYDROGEN-BONDED DIMERS; AB-INITIO; ADDITION COMPOUNDS; INFRARED-SPECTRUM; BF3 COMPLEXES; BF3-CATALYZED REARRANGEMENT; CONFORMATIONAL RESTRICTION; INDUCED INTERCONVERSIONS AB Several 1: 1, 1: 2, and 2: 2 complexes between BF3 and CH3OH ( Met), CH3COOH (AcA), (CH3)(2)O (DME), (CH3CH2)(2)O ( DEE), and (CH2)(2)O (EOX) have been studied using ab initio (MP2) and density functional theory (DFT) (PBE, B3LYP) methods and the 6-311++ G(3df, 2pd) basis set. Geometrical structures and vibrational frequencies are reported, in most cases, for the first time. A detailed comparison of the vibrational frequencies for the O center dot center dot center dot BF3 vibrational modes, as well as for the v( OH) band in the methanol and acetic acid complexes with BF3, is performed, and the theoretical frequency shifts are compared with the available experimental information. Thermochemical properties are calculated by employing counterpoise correction to alleviate the basis set superposition error. The DFT enthalpy of complexation of the 1: 1 complexes results in the order of stability ( AcA)(2) > AcA: BF3 > DEE: BF3 > DME: BF3 > Met: BF3 > EOX: BF3 > ( Met)(2); in contrast, MP2 shows the noticeable difference that the AcA: BF3 complex is much less stable ( similar to Met: BF3). The order of stability shows that, even though acetic acid prefers dimerization to complexation with BF3, the case is exactly the opposite for methanol. In both cases, the interaction of BF3 with the dimer gives rise to very stable trimers. However, in contrast to the interaction of BF3 with the methanol dimer being stronger than that with the monomer, the interaction of BF3 with the acetic acid dimer is weaker than that with the monomer. The relative strength of the complexes, discussed in the context of BF3-catalyzed ring opening of epoxides, suggests that the effect of the catalyst in a nonprotogenic solvent should be more properly ascribed to activation of the nucleophile instead of activation of the epoxide. C1 Univ Republica, Computat Chem Phys Grp, Detema, Montevideo 11800, Uruguay. Univ Republica, Fac Chem, Dept Organ Chem, Montevideo 11800, Uruguay. NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Ventura, ON (reprint author), Univ Republica, Computat Chem Phys Grp, Detema, CC1157,Avda Gral Flores 2124, Montevideo 11800, Uruguay. EM onv@fq.edu.uy RI Saenz-Mendez, Patricia/G-3678-2011 OI Saenz-Mendez, Patricia/0000-0002-6711-4972 NR 100 TC 5 Z9 5 U1 2 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD OCT 19 PY 2006 VL 110 IS 41 BP 11734 EP 11751 DI 10.1021/jp061359y PG 18 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 093TJ UT WOS:000241192100018 PM 17034168 ER PT J AU Min, W Gopich, IV English, BP Kou, SC Xie, XS Szabo, A AF Min, Wei Gopich, Irina V. English, Brian P. Kou, S. C. Xie, X. Sunney Szabo, Attila TI When does the Michaelis-Menten equation hold for fluctuating enzymes? SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SINGLE-MOLECULE; STEADY-STATE; DYNAMICS; KINETICS; DIFFUSION AB Enzymes are dynamic entities: both their conformation and catalytic activity fluctuate over time. When such fluctuations are relatively fast, it is not surprising that the classical Michaelis-Menten (MM) relationship between the steady-state enzymatic velocity and the substrate concentration still holds. However, recent single-molecule experiments have shown that this is the case even for an enzyme whose catalytic activity fluctuates on the 10(-4)-10 s range. The purpose of this paper is to examine various scenarios in which slowly fluctuating enzymes would still obey the MM relationship. Specifically, we consider (1) the quasi-static condition (e. g., the conformational fluctuation of the enzyme-substrate complex is much slower than binding, catalysis, and the conformational fluctuations of the free enzyme), (2) the quasi-equilibrium condition (when the substrate dissociation is much faster than catalysis, irrespective of the time scales or amplitudes of conformational fluctuations), and (3) the conformational-equilibrium condition (when the dissociation and catalytic rates depend on the conformational coordinate in the same way). For each of these scenarios, the physical meaning of the apparent Michaelis constant and catalytic rate constant is provided. Finally, as an example, the theoretical analysis of a recent single-molecule enzyme assay is considered in light of the perspectives presented in this paper. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Szabo, A (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM attilas@nih.gov RI Szabo, Attila/H-3867-2012; English, Brian/O-8156-2016 OI English, Brian/0000-0002-4037-6294 FU Intramural NIH HHS NR 28 TC 83 Z9 84 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 19 PY 2006 VL 110 IS 41 BP 20093 EP 20097 DI 10.1021/jp065187g PG 5 WC Chemistry, Physical SC Chemistry GA 093TK UT WOS:000241192200007 PM 17034179 ER PT J AU Yang, SY Shin, K Kim, SH Jeon, H Kang, JH Yang, HC Park, CE AF Yang, Sang Yoon Shin, Kwonwoo Kim, Se Hyun Jeon, Hayoung Kang, Jin Ho Yang, Hoichang Park, Chan Eon TI Enhanced electrical percolation due to interconnection of three-dimensional pentacene islands in thin films on low surface energy polyimide gate dielectrics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID ATOMIC-FORCE MICROSCOPY; TRANSISTORS; TRANSPORT; MORPHOLOGY; MOBILITY; GROWTH; MONOLAYER; OXIDE AB The role of lateral interconnections between three-dimensional pentacene islands on low surface energy polyimide gate dielectrics was investigated by the measurement of the surface coverage dependence of the charge mobility and the use of conducting-probe atomic force microscopy (CP-AFM). From the correlation between the electrical characteristics and the morphological evolution of the three-dimensionally grown pentacene films-based field-effect transistors, we found that during film growth, the formation of interconnections between the three-dimensional pentacene islands that are isolated at the early stage contributes significantly to the enhancement process of charge mobility. The CP-AFM current mapping images of the pentacene films also indicate that the lateral interconnections play an important role in the formation of good electrical percolation pathways between the three-dimensional pentacene islands. C1 Rensselaer Polytech Inst, Rensselaer Nanotechnol Ctr, Troy, NY 12180 USA. Pohang Univ Sci & Technol, Dept Chem Engn, Polymer Res Inst, Pohang 790784, South Korea. NIA, NASA LaRC, Hampton, VA 23681 USA. RP Yang, HC (reprint author), Rensselaer Polytech Inst, Rensselaer Nanotechnol Ctr, Troy, NY 12180 USA. EM yangh3@rpi.edu; cep@postech.ac.kr NR 27 TC 20 Z9 21 U1 3 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD OCT 19 PY 2006 VL 110 IS 41 BP 20302 EP 20307 DI 10.1021/jp0646527 PG 6 WC Chemistry, Physical SC Chemistry GA 093TK UT WOS:000241192200039 PM 17034211 ER PT J AU Caughey, B Baron, GS AF Caughey, Byron Baron, Gerald S. TI Prions and their partners in crime SO NATURE LA English DT Review ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; KDA LAMININ RECEPTOR; PROTEASE-RESISTANT STATE; INFECTED NEURONAL CELLS; SCRAPIE-ASSOCIATED FORM; CELLULAR PRION; IN-VITRO; HEPARAN-SULFATE; NEURITE OUTGROWTH; PRPSC PROPAGATION AB Prions, the infectious agents of transmissible spongiform encephalopathies ( TSEs), have defied full characterization for decades. The dogma has been that prions lack nucleic acids and are composed of a pathological, self-inducing form of the host's prion protein (PrP). Recent progress in propagating TSE infectivity in cell-free systems has effectively ruled out the involvement of foreign nucleic acids. However, host-derived nucleic acids or other non-PrP molecules seem to be crucial. Interactions between TSE-associated PrP and its normal counterpart are also pathalogically important, so the physiological functions of normal PrP and how they might be corrupted by TSE infections have been the subject of recent research. C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM bcaughey@nih.gov; gbaron@nih.gov FU Intramural NIH HHS NR 96 TC 208 Z9 214 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 19 PY 2006 VL 443 IS 7113 BP 803 EP 810 DI 10.1038/nature05294 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 096FJ UT WOS:000241362700040 PM 17051207 ER PT J AU Wintermantel, TM Campbell, RE Porteous, R Bock, D Grone, HJ Todman, MG Korach, KS Greiner, E Perez, CA Schutz, G Herbison, AE AF Wintermantel, Tim M. Campbell, Rebecca E. Porteous, Robert Bock, Dagmar Groene, Hermann-Josef Todman, Martin G. Korach, Kenneth S. Greiner, Erich Perez, Cristian A. Schuetz, Guenther Herbison, Allan E. TI Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility SO NEURON LA English DT Article ID DEPENDENT PROTEIN-KINASE; LUTEINIZING-HORMONE; PREOPTIC AREA; RAT-BRAIN; PSEUDORABIES VIRUS; NERVOUS-SYSTEM; LHRH NEURONS; FEMALE RAT; SURGE; ALPHA AB The mechanisms through which estrogen regulates gonadotropin-releasing hormone (GnRH) neurons to control mammalian ovulation are unknown. We found that estrogen positive feedback to generate the preovulatory gonadotropin surge was normal in estrogen receptor beta knockout (ER beta) mutant mice, but absent in ER alpha mutant mice. An ER alpha-selective compound was sufficient to generate positive feedback in wild-type mice. As GnRH neurons do not express ER alpha, estrogen positive feedback upon GnRH neurons must be indirect in nature. To establish the cell type responsible, we generated a neuron-specific ERa mutant mouse line. These mice failed to exhibit estrogen positive feedback, demonstrating that neurons expressing ER alpha are critical. We then used a GnRH neuron-specific Pseudorabies virus (PRV) tracing approach to show that the ER alpha-expressing neurons innervating GnRH neurons are located within rostral periventricular regions of the hypothalamus. These studies demonstrate that ovulation is driven by estrogen actions upon ER alpha-expressing neuronal afferents to GnRH neurons. C1 German Canc Res Ctr, D-69120 Heidelberg, Germany. Univ Otago, Sch Med Sci, Ctr Neuroendocrinol, Dunedin 9001, New Zealand. Univ Otago, Sch Med Sci, Dept Physiol, Dunedin 9001, New Zealand. NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA. RP Schutz, G (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM g.schuetz@dkfz.de; allan.herbison@stonebow.otago.ac.nz RI Campbell, Rebecca/F-6430-2010; Perez, Cristian/A-2341-2008; OI Campbell, Rebecca/0000-0002-0309-532X; Korach, Kenneth/0000-0002-7765-418X; Herbison, Allan/0000-0002-9615-3022 FU Wellcome Trust NR 50 TC 321 Z9 324 U1 4 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 19 PY 2006 VL 52 IS 2 BP 271 EP 280 DI 10.1016/j.neuron.2006.07.023 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 102GV UT WOS:000241799900008 PM 17046690 ER PT J AU Costa, RM Lin, SC Sotnikova, TD Cyr, M Gainetdinov, RR Caron, MG Nicolelis, MAL AF Costa, Rui M. Lin, Shih-Chieh Sotnikova, Tatyana D. Cyr, Michel Gainetdinov, Raul R. Caron, Marc G. Nicolelis, Miguel A. L. TI Rapid alterations in corticostriatal ensemble coordination during acute dopamine-dependent motor dysfunction SO NEURON LA English DT Article ID LOCAL-FIELD POTENTIALS; PARKINSONS-DISEASE; GLOBUS-PALLIDUS; SUBTHALAMIC NUCLEUS; BASAL GANGLIA; IN-VIVO; CORTEX STIMULATION; PROJECTION NEURONS; GABA INTERNEURONS; SUBSTANTIA-NIGRA AB Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia (similar to 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (< 0.2%) with akinesia in the same animal. Surprisingly, although most cortical and striatal neurons (similar to 70%) changed firing rate during the transition between dopamine-related hyperkinesia and akinesia, the overall cortical firing rate remained unchanged. Conversely, neuronal oscillations and ensemble activity coordination within and between cortex and striatum did change rapidly between these periods. During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits. C1 Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychol & Brain Sci, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Neuroengn, Durham, NC 27710 USA. NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Costa, RM (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. EM costarui@mail.nih.gov RI Gainetdinov, Raul/G-5875-2011; OI Lin, Shih-Chieh/0000-0003-3693-5476; Costa, Rui/0000-0003-0495-8374; Gainetdinov, Raul/0000-0003-2951-6038 NR 60 TC 147 Z9 151 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD OCT 19 PY 2006 VL 52 IS 2 BP 359 EP 369 DI 10.1016/j.neuron.2006.07.030 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 102GV UT WOS:000241799900015 PM 17046697 ER PT J AU Eichacker, PQ Natanson, C Danner, RL AF Eichacker, Peter Q. Natanson, Charles Danner, Robert L. TI Surviving sepsis - Practice guidelines, marketing campaign, and Eli Lilly SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 116 Z9 122 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 19 PY 2006 VL 355 IS 16 BP 1640 EP 1642 DI 10.1056/NEJMp068197 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 096DN UT WOS:000241357300004 PM 17050887 ER PT J AU Gorelick, DA AF Gorelick, David A. TI Counseling plus buprenorphine-naloxone for opioid dependence SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID COCAINE C1 NIDA, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 19 PY 2006 VL 355 IS 16 BP 1736 EP 1736 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 096DN UT WOS:000241357300018 PM 17050900 ER PT J AU Davies, GC Ryan, PE Rahman, L Zajac-Kaye, M Lipkowitz, S AF Davies, G. C. Ryan, P. E. Rahman, L. Zajac-Kaye, M. Lipkowitz, S. TI EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins SO ONCOGENE LA English DT Article DE EGFRvIII; Cbl proteins; ubiquitin; cancer ID EPIDERMAL-GROWTH-FACTOR; MUTANT EGF-RECEPTOR; CONFERS ENHANCED TUMORIGENICITY; HUMAN GLIOBLASTOMA CELLS; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; KINASE INHIBITORS; RING FINGER; CANCER; EXPRESSION AB The overexpression or mutation of tyrosine kinases (TKs), such as the epidermal growth factor receptor (EGFR), can lead to the development of cancer. The most common mutation of the EGFR in glioblastomas is the deletion of exons 2-7 known as the EGFRvIII. This mutant receptor cannot bind EGF but, instead, is constitutively active. The Cbl family of ubiquitin ligases (Cbl, Cbl-b, and Cbl-c) targets the activated EGFR for degradation. As the EGFRvIII is transforming, we investigated whether it could be downregulated by the Cbl proteins. The overexpression of all three Cbl proteins resulted in the ubiquitination and degradation of the EGFRvIII. As with the wild-type EGFR, the TK-binding domain and the RING finger of Cbl-b are sufficient for the downregulation of the EGFRvIII. Also, we found that Cbl-b is recruited to the EGFRvIII and inhibits the transformation of NIH 3T3 cells by the EGFRvIII. Mutation of the Cbl-binding site (Y1045F) in the EGFRvIII inhibits its ubiquitination and downregulation by Cbl-b and enhances its ability to transform. Furthermore, the EGFR TK inhibitor, AG 1478, prevents the downregulation of the EGFRvIII by the Cbl proteins and antagonizes the ability of an immunotoxin directed against the EGFRvIII to kill cells expressing this receptor. In conclusion, the EGFRvIII does not transform by escaping regulation by Cbl proteins and this activation-induced downregulation of the EGFRvIII has an important role in mediating the toxicity of anti-EGFRvIII immunotoxins. C1 NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Washington, DC USA. NCI, Mol Therapeut Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lipkowitz, S (reprint author), NCI, LCMB, CCR, NIH, Bldg 37,Rm 2066,37 Convent Dr, Bethesda, MD 20892 USA. EM LipkowiS@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 49 TC 18 Z9 21 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 19 PY 2006 VL 25 IS 49 BP 6497 EP 6509 DI 10.1038/sj.onc.1209662 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 096RS UT WOS:000241395100006 PM 16702950 ER PT J AU To, KKW Sedelnikova, OA Samons, M Bonner, WM Huang, LE AF To, Kenneth K. -W Sedelnikova, Olga A. Samons, Melissa Bonner, William M. Huang, L. Eric TI The phosphorylation status of PAS-B distinguishes HIF-1 alpha from HIF-2 alpha in NBS1 repression SO EMBO JOURNAL LA English DT Article DE double-strand break; hypoxia; NBS1; PAS-B; PKD1 ID HYPOXIA-INDUCIBLE FACTOR; NIJMEGEN BREAKAGE SYNDROME; RENAL-CELL CARCINOMA; DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; PROTEIN-KINASE-D; GENETIC INSTABILITY; HOMOLOGOUS RECOMBINATION; EMBRYONIC-DEVELOPMENT; TRANSCRIPTION FACTOR AB Hypoxia promotes genetic instability for tumor progression. Recent evidence indicates that the transcription factor HIF-1 alpha impairs DNA mismatch repair, yet the role of HIF-1 alpha isoform, HIF-2 alpha, in tumor progression remains obscure. In pursuit of the involvement of HIF-alpha in chromosomal instability, we report here that HIF-1 alpha, specifically its PAS-B, induces DNA double-strand breaks at least in part by repressing the expression of NBS1, a crucial DNA repair gene constituting the MRE11A-RAD50-NBS1 complex. Despite strong similarities between the two isoforms, HIF-2 alpha fails to do so. We demonstrate that this functional distinction stems from phosphorylation of HIF-2 alpha Thr-324 by protein kinase D1, which discriminates between subtle differences of the two PAS-B in amino-acid sequence, thereby precluding NBS1 repression. Hence, our findings delineate a molecular pathway that functionally distinguishes HIF-1 alpha from HIF-2 alpha, and arguing a unique role for HIF-1 alpha in tumor progression by promoting genomic instability. C1 Univ Utah, Sch Med, Dept Neurosurg, Salt Lake City, UT 84112 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Huang, LE (reprint author), Univ Utah, Sch Med, Dept Neurosurg, 30 N 1900 E,Suite 3B409, Salt Lake City, UT 84112 USA. EM eric.huang@hsc.utah.edu RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS NR 63 TC 57 Z9 57 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 18 PY 2006 VL 25 IS 20 BP 4784 EP 4794 DI 10.1038/sj.emboj.7601369 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104VY UT WOS:000241989900009 PM 17024177 ER PT J AU Kalia, LV Pitcher, GM Pelkey, KA Salter, MW AF Kalia, Lorraine V. Pitcher, Graham M. Pelkey, Kenneth A. Salter, Michael W. TI PSD-95 is a negative regulator of the tyrosine kinase Src in the NMDA receptor complex SO EMBO JOURNAL LA English DT Article DE LTP; NMDA receptor; PSD-95; SH2 domain; Src ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; POSTSYNAPTIC DENSITY FRACTION; SH2 DOMAIN; CRYSTAL-STRUCTURES; FAMILY KINASES; PROTEIN; SUBUNIT; PHOSPHORYLATION; PEPTIDE AB The tyrosine kinase Src upregulates the activity of the N-methyl-D-aspartate subtype of glutamate receptor ( NMDAR) and tyrosine phosphorylation of this receptor is critical for induction of NMDAR-dependent plasticity of synaptic transmission. A binding partner for Src within the NMDAR complex is the protein PSD-95. Here we demonstrate an interaction of PSD-95 with Src that does not require the well-characterized domains of PSD-95. Rather, we show binding to Src through a 12-amino-acid sequence in the N-terminal region of PSD-95, a region not previously known to participate in protein-protein interactions. This region interacts directly with the Src SH2 domain. Contrary to typical SH2 domain binding, the PSD-95-Src SH2 domain interaction is phosphotyrosine-independent. Binding of the Src-interacting region of PSD-95 inhibits Src kinase activity and reduces NMDAR phosphorylation. Intracellularly administering a peptide matching the Src SH2 domain-interacting region of PSD-95 depresses NMDAR currents in cultured neurons and inhibits induction of long-term potentiation in hippocampus. Thus, the PSD-95-Src SH2 domain interaction suppresses Src-mediated NMDAR upregulation, a finding that may be of broad importance for synaptic transmission and plasticity. C1 Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. Univ Toronto, Dept Physiol, Toronto, ON, Canada. NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Salter, MW (reprint author), Hosp Sick Children, Program Neurosci & Mental Hlth, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM mike.salter@utoronto.ca NR 43 TC 39 Z9 41 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 18 PY 2006 VL 25 IS 20 BP 4971 EP 4982 DI 10.1038/sj.emboj.7601342 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104VY UT WOS:000241989900026 PM 16990796 ER PT J AU Quiroz, C Gomes, C Pak, AC Ribeiro, JA Goldberg, SR Hope, BT Ferre, S AF Quiroz, Cesar Gomes, Catarina Pak, Arlene C. Ribeiro, Joaquim A. Goldberg, Steven R. Hope, Bruce T. Ferre, Sergi TI Blockade of adenosine A(2A) receptors prevents protein phosphorylation in the striatum induced by cortical stimulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE caffeine; adenosine A(2A) receptor; striatum; phosphorylation; ERK1/2; AMPA receptor ID DOPAMINE-D-2 RECEPTORS; SYNAPTIC PLASTICITY; AMPA RECEPTOR; MGLU5 RECEPTORS; NMDA RECEPTOR; RAT STRIATUM; KINASE; NEURONS; CASCADE; HETEROMERS AB Previous studies have shown that cortical stimulation selectively activates extracellular signal- regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A(2A) receptors with caffeine or a selective A2A receptor antagonist counteracts the striatal activation of cAMP protein kinase A cascade (phosphorylation of the Ser(845) residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogenactivated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A(2A) receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Lisbon, Inst Mol Med, Fac Med, Inst Pharmacol & Neurosci, P-1649028 Lisbon, Portugal. RP Ferre, S (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sferre@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; Ferre, Sergi/K-6115-2014; Gomes, Catarina/K-6218-2015; OI Hope, Bruce/0000-0001-5804-7061; Ferre, Sergi/0000-0002-1747-1779; Gomes, Catarina/0000-0001-9415-2109; Ribeiro, Joaquim/0000-0002-9330-3507 FU Intramural NIH HHS NR 29 TC 19 Z9 19 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 18 PY 2006 VL 26 IS 42 BP 10808 EP 10812 DI 10.1523/JNEUROSCI.1661-06.2006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 101GE UT WOS:000241727300023 PM 17050719 ER PT J AU Kamangar, F Dawsey, SM Blaser, MJ Perez-Perez, GI Pietinen, P Newschaffer, CJ Abnet, CC Albanes, D Virtamo, J Taylor, PR AF Kamangar, Farin Dawsey, Sanford M. Blaser, Martin J. Perez-Perez, Guillermo I. Pietinen, Pirjo Newschaffer, Craig J. Abnet, Christian C. Albanes, Demetrius Virtamo, Jarmo Taylor, Philip R. TI Opposing risks of gastric cardia and noncardia gastric adenocarcinomas associated with Helicobacter pylori seropositivity SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SERUM PEPSINOGEN-I; GASTROESOPHAGEAL JUNCTION; HISTOLOGIC SUBTYPES; CAGA SEROPOSITIVITY; INTESTINAL-TYPE; INFECTION; CANCER; CARCINOMA; ESOPHAGUS; POPULATION AB Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions. Methods: Case and control subjects were selected from the 29133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided. Results: H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR=7.9, 95% CI=3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR=0.31, 95% CI=0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100 000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100000 person-years, respectively. Conclusion: H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NYU, Sch Med, Dept Med, New York, NY USA. NYU, Sch Med, Dept Microbiol, New York, NY USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 3034, Bethesda, MD 20892 USA. EM Kamangaf@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; OI Abnet, Christian/0000-0002-3008-7843; Perez Perez, Guillermo /0000-0002-0131-5798 FU Intramural NIH HHS NR 54 TC 157 Z9 169 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 18 PY 2006 VL 98 IS 20 BP 1445 EP 1452 DI 10.1093/jnci/djj393 PG 8 WC Oncology SC Oncology GA 101EJ UT WOS:000241721400008 PM 17047193 ER PT J AU Narayanan, N Gorelick, RJ DeStefano, JJ AF Narayanan, Nirupama Gorelick, Robert J. DeStefano, Jeffrey J. TI Structure/function mapping of amino acids in the N-terminal zinc finger of the human immunodeficiency virus type 1 nucleocapsid protein: Residues responsible for nucleic acid helix destabilizing activity SO BIOCHEMISTRY LA English DT Article ID STRAND TRANSFER-REACTIONS; MURINE LEUKEMIA-VIRUS; RNA PACKAGING SIGNAL; PRIMER BINDING-SITE; STRONG-STOP DNA; STEM-LOOP SL2; REVERSE TRANSCRIPTION; IN-VITRO; CHAPERONE ACTIVITY; GENOMIC RNA AB The nucleocapsid protein (NC) of HIV-1 is 55 amino acids in length and possesses two CCHC-type zinc fingers. Finger one (N-terminal) contributes significantly more to helix destabilizing activity than finger two (C-terminal). Five amino acids differ between the two zinc fingers. To determine at the amino acid level the reason for the apparent distinction between the fingers, each different residue in finger one was incrementally replaced by the one at the corresponding location in finger two. Mutants were analyzed in annealing assays with unstructured and structured substrates. Three groupings emerged: (1) those similar to wild-type levels (N17K, A25M), (2) those with diminished activity (I24Q, N27D), and (3) mutant F16W, which had substantially greater helix destabilizing activity than that of the wild type. Unlike I24Q and the other mutants, N27D was defective in DNA binding. Only I24Q and N27D showed reduced strand transfer in in Vitro assays. Double and triple mutants F16W/I24Q, F16W/N27D, and F16W/I24Q/N27D all showed defects in DNA binding, strand transfer, and helix destabilization, suggesting that the I24Q and N27D mutations have a dominant negative effect and abolish the positive influence of F16W. Results show that amino acid differences at positions 24 and 27 contribute significantly to finger one's helix destabilizing activity. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD USA. RP DeStefano, JJ (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM jdestefa@umd.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO 12400, N01CO12400]; NIGMS NIH HHS [GM051140, R29 GM051140, R01 GM051140] NR 56 TC 18 Z9 18 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 17 PY 2006 VL 45 IS 41 BP 12617 EP 12628 DI 10.1021/bi060925c PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092OK UT WOS:000241107000022 PM 17029416 ER PT J AU Menon, V Sarnak, MJ Pereira, AA Levey, AS Greene, T Wang, XL Beck, GJ Kusek, JW Selhub, J Collins, AJ Shlipak, MG AF Menon, Vandana Sarnak, Mark J. Pereira, Arema A. Levey, Andrew S. Greene, Tom Wang, Xuelei Beck, Gerald J. Kusek, John W. Selhub, Jacob Collins, Allan J. Shlipak, Michael G. TI Response to letter regarding article, "Relationship between homocysteine and mortality in chronic kidney disease" SO CIRCULATION LA English DT Letter ID CORONARY-HEART-DISEASE; PLASMA; WOMEN; LEVEL C1 Tufts New England Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Menon, V (reprint author), Tufts New England Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 17 PY 2006 VL 114 IS 16 BP E548 EP E548 DI 10.1161/CIRCULATIONAHA.106.644674 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 095RD UT WOS:000241324600024 ER PT J AU Hart, JR Glebov, O Ernst, RJ Kirsch, IR Barton, JK AF Hart, Jonathan R. Glebov, Oleg Ernst, Russell J. Kirsch, Ilan R. Barton, Jacqueline K. TI DNA mismatch-specific targeting and hypersensitivity of mismatch-repair-deficient cells to bulky rhodium(III) intercalators SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MICROSATELLITE INSTABILITY; DIIMINE COMPLEXES; BASE MISMATCHES; COLON-CANCER; RECOGNITION; REPLICATION; MUTATIONS; SYSTEM; AGENT; LINES AB Mismatch repair (MMR) is critical to maintaining the integrity of the genome, and deficiencies in MMR are correlated with cancerous transformations. Bulky rhodium intercalators target DNA base mismatches with high specificity. Here we describe the application of bulky rhodium intercalators to inhibit cellular proliferation differentially in MMR-deficient cells compared with cells that are MMR-proficient. Preferential inhibition by the rhodium complexes associated with MMR deficiency is seen both in a human colon cancer cell line and in normal mouse fibroblast cells; the inhibition of cellular proliferation depends strictly on the MMR deficiency of the cell. Furthermore, our assay of cellular proliferation is found to correlate with DNA mismatch targeting by the bulky metallointercalators. It is the Delta-isomer that is active both in targeting base mismatches and in inhibiting DNA synthesis. Additionally, the rhodium intercalators promote strand cleavage at the mismatch site with photoactivation, and we observe that the cellular response is enhanced with photoactivation. Targeting DNA mismatches may therefore provide a cell-selective strategy for chemotherapeutic design. C1 CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. NCI, Natl Naval Med Ctr, Canc Res Ctr, Genet Branch, Bethesda, MD 20889 USA. RP Barton, JK (reprint author), CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. EM jkbarton@caltech.edu OI Hart, Jonathan/0000-0002-3905-225X FU NIGMS NIH HHS [R01 GM033309, GM33309, R37 GM033309] NR 25 TC 47 Z9 48 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 OCT 17 PY 2006 VL 103 IS 42 BP 15359 EP 15363 DI 10.1073/pnas.0607576103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200017 PM 17030786 ER PT J AU Baba, M Hong, SB Sharma, N Warren, MB Nickerson, ML Iwamatsu, A Esposito, D Gillette, WK Hopkins, RF Hartley, JL Furihata, M Oishi, S Zhen, W Burke, TR Linehan, WM Schmidt, LS Zbar, B AF Baba, Masaya Hong, Seung-Beom Sharma, Nirmala Warren, Michelle B. Nickerson, Michael L. Iwamatsu, Akihiro Esposito, Dominic Gillette, William K. Hopkins, Ralph F., III Hartley, James L. Furihata, Mutsuo Oishi, Shinya Zhen, Wei Burke, Terrence R., Jr. Linehan, W. Marston Schmidt, Laura S. Zbar, Berton TI Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hamartoma syndrome; renal cancer; Birt-Hogg-Dube; tumor suppressor ID HOGG-DUBE-SYNDROME; PEUTZ-JEGHERS-SYNDROME; SPONTANEOUS PNEUMOTHORAX; TUBEROUS SCLEROSIS; KIDNEY NEOPLASIA; KINASE CASCADE; RENAL TUMORS; CELL-GROWTH; PATHWAY; TSC2 AB Birt-Hogg-Dube syndrome, a hamartoma disorder characterized by benign tumors of the hair follicle, lung cysts, and renal neoplasia, is caused by germ-line mutations in the BHD(FLCN) gene, which encodes a tumor-suppressor protein, folliculin (FLCN), with unknown function. The tumor-suppressor proteins encoded by genes responsible for several other hamartoma syndromes, LKB1, TSC1/2, and PTEN, have been shown to be involved in the mammalian target of rapamycin (mTOR) signaling pathway. Here, we report the identification of the FLCN-interacting protein, FNIP1, and demonstrate its interaction with 5' AMP-activated protein kinase (AMPK), a key molecule for energy sensing that negatively regulates mTOR activity. FNIP1 was phosphorylated by AMPK, and its phosphorylation was reduced by AMPK inhibitors, which resulted in reduced FNIP1 expression. AMPK inhibitors also reduced FLCN phosphorylation. Moreover, FLCN phosphorylation was diminished by rapamycin and amino acid starvation and facilitated by FNIP1 overexpression, suggesting that FLCN may be regulated by mTOR and AMPK signaling. Our data suggest that FLCN, mutated in Birt-Hogg-Dube syndrome, and its interacting partner FNIP1 may be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. C1 NCI, Immunobiol Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. NCI, Med Chem Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. Prot Express Lab, Res Technol Program, Frederick, MD USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, Frederick, MD 21702 USA. Kochi Univ, Kochi Med Sch, Dept Pathol, Kochi 7838505, Japan. Prot Res Network, Yokohama, Kanagawa 2360004, Japan. NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20894 USA. RP Schmidt, LS (reprint author), NCI, Immunobiol Lab, Ctr Canc Res, Bldg 560,Room 12-69, Ft Detrick, MD 21702 USA. EM schmidtl@ncifcrf.gov RI Baba, Masaya/L-7490-2013; Burke, Terrence/N-2601-2014; Oishi, Shinya/C-1350-2011 OI Baba, Masaya/0000-0002-5308-6683; Oishi, Shinya/0000-0002-2833-2539 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 41 TC 211 Z9 223 U1 5 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 17 PY 2006 VL 103 IS 42 BP 15552 EP 15557 DI 10.1073/pnas.0603781103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200051 PM 17028174 ER PT J AU Jewett, TJ Fischer, ER Mead, DJ Hackstadt, T AF Jewett, Travis J. Fischer, Elizabeth R. Mead, David J. Hackstadt, Ted TI Chlamydial TARP is a bacterial nucleator of actin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chlamydia; type III secretion; cytoskeleton; endocytosis ID BURKHOLDERIA-PSEUDOMALLEI; DEPOLYMERIZING PROTEIN; LISTERIA-MONOCYTOGENES; BINDING PROTEINS; ARP2/3 COMPLEX; HOST-CELLS; HELA-CELLS; N-WASP; TRACHOMATIS; POLYMERIZATION AB Chlamydia trachomatis entry into host cells results from a parasite-directed remodeling of the actin cytoskeleton. A type III secreted effector, TARP (translocated actin recruiting phosphoprotein), has been implicated in the recruitment of actin to the site of internalization. To elucidate the role of TARP in actin recruitment, we identified host cell proteins that associated with recombinant GST-TARP fusions. TARP directly associated with actin, and this interaction promoted actin nucleation as determined by in vitro polymerization assays. Domain analysis of TARP identified an actin-binding domain that bears structural and primary amino acid sequence similarity to WH2 domain family proteins. In addition, a proline-rich domain was found to promote TARP oligomerization and was required for TARP-dependent nucleation of new actin filaments. Our findings reveal a mechanism by which chlamydiae induce localized cytoskeletal changes by the translocated effector TARP during entry into host cells. C1 NIAID, Rocky Mt Lab, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Lab, RTS Microscopy Unit, NIH, Hamilton, MT 59840 USA. RP Jewett, TJ (reprint author), NIAID, Rocky Mt Lab, Host Parasite Interact Sect, Intracellular Parasites Lab,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU Intramural NIH HHS NR 41 TC 102 Z9 107 U1 0 U2 8 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 OCT 17 PY 2006 VL 103 IS 42 BP 15599 EP 15604 DI 10.1073/pnas.0603044103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200059 PM 17028176 ER PT J AU Makarova, K Slesarev, A Wolf, Y Sorokin, A Mirkin, B Koonin, E Pavlov, A Pavlova, N Karamychev, V Polouchine, N Shakhova, V Grigoriev, I Lou, Y Rohksar, D Lucas, S Huang, K Goodstein, DM Hawkins, T Plengvidhya, V Welker, D Hughes, J Goh, Y Benson, A Baldwin, K Lee, JH Diaz-Muniz, I Dosti, B Smeianov, V Wechter, W Barabote, R Lorca, G Altermann, E Barrangou, R Ganesan, B Xie, Y Rawsthorne, H Tamir, D Parker, C Breidt, F Broadbent, J Hutkins, R O'Sullivan, D Steele, J Unlu, G Saier, M Klaenhammer, T Richardson, P Kozyavkin, S Weimer, B Mills, D AF Makarova, K. Slesarev, A. Wolf, Y. Sorokin, A. Mirkin, B. Koonin, E. Pavlov, A. Pavlova, N. Karamychev, V. Polouchine, N. Shakhova, V. Grigoriev, I. Lou, Y. Rohksar, D. Lucas, S. Huang, K. Goodstein, D. M. Hawkins, T. Plengvidhya, V. Welker, D. Hughes, J. Goh, Y. Benson, A. Baldwin, K. Lee, J. -H. Diaz-Muniz, I. Dosti, B. Smeianov, V. Wechter, W. Barabote, R. Lorca, G. Altermann, E. Barrangou, R. Ganesan, B. Xie, Y. Rawsthorne, H. Tamir, D. Parker, C. Breidt, F. Broadbent, J. Hutkins, R. O'Sullivan, D. Steele, J. Unlu, G. Saier, M. Klaenhammer, T. Richardson, P. Kozyavkin, S. Weimer, B. Mills, D. TI Comparative genomics of the lactic acid bacteria SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE evolutionary genomics; fermentation ID HORIZONTAL GENE-TRANSFER; LACTOCOCCUS-LACTIS; LACTOBACILLUS-PLANTARUM; RADIATION-RESISTANCE; MOLECULAR CLOCK; COG DATABASE; TRANSFER-RNA; SEQUENCE; EVOLUTION; ARCHAEAL AB Lactic acid-producing bacteria are associated with various plant and animal niches and play a key role in the production of fermented foods and beverages. We report nine genome sequences representing the phylogenetic and functional diversity of these bacteria. The small genomes of lactic acid bacteria encode a broad repertoire of transporters for efficient carbon and nitrogen acquisition from the nutritionally rich environments they inhabit and reflect a limited range of biosynthetic capabilities that indicate both prototrophic and auxotrophic strains. Phylogenetic analyses, comparison of gene content across the group, and reconstruction of ancestral gene sets indicate a combination of extensive gene loss and key gene acquisitions via horizontal gene transfer during the coevolution of lactic acid bacteria with their habitats. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Fidel Syst Inc, Gaithersburg, MD 20879 USA. Univ London, Birkbeck Coll, Sch Informat Syst & Comp Sci, London WC1E 7HX, England. Joint Gen Inst, US Dept Energy, Walnut Creek, CA 94598 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. USDA ARS, Raleigh, NC 27695 USA. Utah State Univ, Dept Biol, Logan, UT 84322 USA. Utah State Univ, Dept Nutr & Food Sci, Logan, UT 84322 USA. Utah State Univ, Ctr Integrated Biosyst, Logan, UT 84322 USA. Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55108 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Wisconsin, Dept Food Sci, Madison, WI 53706 USA. Univ Idaho, Dept Food Sci & Toxicol, Moscow, ID 83844 USA. Univ Calif Davis, Dept Viticulture & Enol, Davis, CA 95616 USA. RP Koonin, E (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov; trk@unity.ncsu.edu; bcweimer@cc.usu.edu; damills@ucdavis.edu RI Barabote, Ravi/B-8727-2011; Broadbent, Jeff/A-9626-2010; Mills, David/G-2282-2011; Barrangou, Rodolphe/I-2878-2014; Barabote, Ravi/C-1299-2017; OI Broadbent, Jeff/0000-0002-0751-0877; Mills, David/0000-0003-1913-9865; Mirkin, Boris/0000-0001-5470-8635; Barrangou, Rodolphe/0000-0002-0648-3504; Barabote, Ravi/0000-0002-0403-246X; Altermann, Eric/0000-0003-1376-1549 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM055434, R01 GM55434] NR 56 TC 678 Z9 3042 U1 31 U2 224 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 OCT 17 PY 2006 VL 103 IS 42 BP 15611 EP 15616 DI 10.1073/pnas.0607117103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200061 PM 17030793 ER PT J AU Moll, J Krueger, F Zahn, R Pardini, M de Oliveira-Souzat, R Grafman, J AF Moll, Jorge Krueger, Frank Zahn, Roland Pardini, Matteo de Oliveira-Souzat, Ricardo Grafman, Jordan TI Human fronto-mesolimbic networks guide decisions about charitable donation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE altruism; brain; moral; reward; social ID NEURAL BASIS; PREFRONTAL CORTEX; ALTRUISTIC PUNISHMENT; ORBITOFRONTAL CORTEX; INDIRECT RECIPROCITY; REWARD PREFERENCE; ROMANTIC LOVE; EVOLUTION; RESPONSES; TRUST AB Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal-subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are distinctively recruited when altruistic choices prevail over selfish material interests. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Hosp Network, Cognit & Behav Neurosci Unit, LABS, Rio De Janeiro, Brazil. Univ Genoa, Sch Med, I-16132 Genoa, Italy. Gaffree & Guinle Univ Hos, BR-20270004 Rio De Janeiro, Brazil. Philippe Pinel Inst, BR-20270004 Rio De Janeiro, Brazil. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Pardini, Matteo/F-8414-2010; Moll, Jorge/B-2654-2013 OI Grafman, Jordan H./0000-0001-8645-4457; Zahn, Roland/0000-0002-8447-1453; Pardini, Matteo/0000-0002-4740-1982; FU Intramural NIH HHS NR 36 TC 331 Z9 350 U1 8 U2 53 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 OCT 17 PY 2006 VL 103 IS 42 BP 15623 EP 15628 DI 10.1073/pnas.0604475103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200063 PM 17030808 ER PT J AU Wang, GJ Yang, J Volkow, ND Telang, F Ma, YM Zhu, W Wong, CT Tomasi, D Thanos, PK Fowler, JS AF Wang, Gene-Jack Yang, Julia Volkow, Nora D. Telang, Frank Ma, Yeming Zhu, Wei Wong, Christopher T. Tomasi, Dardo Thanos, Panayotis K. Fowler, Joanna S. TI Gastric stimulation in obese subjects activates the hippocampus and other regions involved in brain reward circuitry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain activation; obesity ID VAGUS NERVE-STIMULATION; ORBITOFRONTAL CORTEX; FOOD-INTAKE; PREFRONTAL CORTEX; MEMORY; DOPAMINE; RATS; INDIVIDUALS; MECHANISMS; MOTIVATION AB The neurobiological mechanisms underlying overeating in obesity are not understood. Here, we assessed the neurobiological responses to an Implantable Gastric Stimulator (IGS), which induces stomach expansion via electrical stimulation of the vagus nerve to identify the brain circuits responsible for its effects in decreasing food intake. Brain metabolism was measured with positron emission tomography and 2-deoxy-2[F-18]fluoro-D-glucose in seven obese subjects who had the IGS implanted for 1-2 years. Brain metabolism was evaluated twice during activation (on) and during deactivation (off) of the IGS. The Three-Factor Eating Questionnaire was obtained to measure the behavioral components of eating (cognitive restraint, uncontrolled eating, and emotional eating). The largest difference was in the right hippocampus, where metabolism was 18% higher (P < 0.01) during the "on" than "off" condition, and these changes were associated with scores on "emotional eating," which was lower during the on than off condition and with "uncontrolled eating," which did not differ between conditions. Metabolism also was significantly higher in right anterior cerebellum, orbitofrontal cortex, and striatum during the on condition. These findings corroborate the role of the vagus nerve in regulating hippocampal activity and the importance of the hippocampus in modulating eating behaviors linked to emotional eating and lack of control. IGS-induced activation of regions previously shown to be involved in drug craving in addicted subjects (orbitofrontal cortex, hippocampus, cerebellum, and striatum) suggests that similar brain circuits underlie the enhanced motivational drive for food and drugs seen in obese and drug-addicted subjects, respectively. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NIAAA, Natl Inst Drug Abuse, Rockville, MD 20857 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. RP Wang, GJ (reprint author), Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. EM gjwang@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [M01 RR010710, M01RR 10710]; NIAAA NIH HHS [AA9481, R01 AA009481, Y1AA3009]; NIDA NIH HHS [DA6278, DA6891, R01 DA006278, R01 DA006891] NR 43 TC 81 Z9 84 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 17 PY 2006 VL 103 IS 42 BP 15641 EP 15645 DI 10.1073/pnas.0601977103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200066 PM 17023542 ER PT J AU Lee, HJ Palkovits, M Young, WS AF Lee, Heon-Jin Palkovits, Miklos Young, W. Scott, III TI MiR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AP-1; hyperosmolality; microarray; paraventricular nucleus; suprachiasmatic ID MAMMALIAN NERVOUS-SYSTEM; RAT SUPRAOPTIC NUCLEUS; C-FOS; MESSENGER-RNA; GENE-EXPRESSION; HOST GENES; TRANSCRIPTION; BRAIN; VASOPRESSIN; REPRESSION AB The transcription factor activator protein 1 (AP-1) is formed through the dimerization of immediate-early genes Fos and Jun family members. Activator protein 1 is known as a pivotal regulator of major biological events such as cell proliferation, differentiation, organogenesis, memory formation, and apoptosis. During a search for microRNAs (miRNAs; small, endogenous, noncoding RNAs that repress gene expression of target mRNAs in animals posttranscriptionally) that are differentially expressed in the mouse paraventricular and supraoptic nuclei after 10 days of drinking 2% saline, one candidate microRNA that is relatively highly expressed, mmu-miR-7b (miR-7b), was studied further because sequence analysis suggested a likely interaction with the 3' untranslated region of Fos mRNA. We show that miR-7b expression inhibits Fos translation in vitro and that it and its host gene are prominently expressed in the PVN and other brain areas, including the suprachiasmatic nucleus. No effect on Fos mRNA levels was observed. Normally, Fos is expressed at low to undetectable levels in cells, but it shows rapid induction and decay after acute stimuli. Various pathways have been identified through which Fos family proteins are degraded; our results indicate a significant additional mechanism by which Fos protein and activity may be regulated. C1 Dept Hlth & Human Serv, Sect Neural Gene Express, NIMH, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Anat Histol & Embryol, H-1094 Budapest, Hungary. Hungarian Acad Sci, Neuromorphol Lab, H-1245 Budapest, Hungary. RP Young, WS (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A56, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; Palkovits, Miklos/F-2707-2013; OI Young, W Scott/0000-0001-6614-5112; Palkovits, Miklos/0000-0003-0578-0387; , Heon-Jin/0000-0002-1911-5014 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002498] NR 50 TC 56 Z9 56 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 17 PY 2006 VL 103 IS 42 BP 15669 EP 15674 DI 10.1073/pnas.0605781103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097VC UT WOS:000241476200071 PM 17028171 ER PT J AU Yitzhaki, S Shainberg, A Cheporko, Y Vidne, BA Sagie, A Jacobson, KA Hochhauser, E AF Yitzhaki, Smadar Shainberg, Asher Cheporko, Yelena Vidne, Bernardo A. Sagie, Alex Jacobson, Kenneth A. Hochhauser, Edith TI Uridine-5 '-triphosphate (UTP) reduces infarct size and improves rat heart function after myocardial infarct SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE heart protection; ischemia; P2Y receptors ID CARDIAC MYOCYTES; ADENOSINE A(1); RECEPTORS; NUCLEOTIDES; ISCHEMIA; INJURY; CARDIOPROTECTION; PURINOCEPTORS; MITOCHONDRIA; ACTIVATION AB We have previously found that uridine 5'-triphosphate (UTP) significantly reduced cardiomyocyte death induced by hypoxia via activating P2Y(2) receptors. To explore the effect of UTP following myocardial infarction (MI) in vivo we studied four groups: sham with or without LAD ligation, injected with UTP (0.44 mu g/kg i.v.) 30 min before MI, and UTP injection (4.4 mu g/kg i.v.) 24 h prior to MI. Left ventricular end diastolic area (LVEDA), end systolic area (LVESA) fractional shortening (FS), and changes in posterior wall (PW) thickness were performed by echocardiography before and 24 h after MI. In addition, we measured different biochemical markers of damage and infarct size using Evans blue and TTC staining. The increase in LVEDA and LVESA of the treated animals was significantly smaller when compared to the MI rats (p < 0.01). Concomitantly, FS was higher in groups pretreated with UTP 30 min or 24 h (56 +/- 14.3 and 36.7 +/- 8.2%, p < 0.01, respectively). Ratio of infarct size to area at risk was smaller in the UTP pretreated hearts than MI rats (22.9 +/- 6.6, 23.1 +/- 9.1%, versus 45.4 +/- 7.6%, respectively, p < 0.001). Troponin T and ATP measurements, demonstrated reduced myocardial damage. Using Rhod-2-AM loaded cardiomyocytes, we found that UTP reduced mitochondrial calcium levels following hypoxia. In conclusion, early or late UTP preconditioning is effective, demonstrating reduced infarct size and superior myocardial function. The resulting cardioprotection following UTP treatment post ischemia demonstrates a reduction in mitochondrial calcium overload, which can explain the beneficial effect of UTP. (c) 2006 Elsevier Inc. All rights reserved. C1 Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. Tel Aviv Univ, Cardiac Res Lab, Dept Cardiothorac Surg, Felsenstein Med Res Ctr,Rabin Med Ctr, Petah Tiqwa, Israel. Rabin Med Ctr, Dept Cardiol, Petah Tiqwa, Israel. NIDDK, Lab Bioorgan Chem, NIH, Bethesda, MD USA. RP Shainberg, A (reprint author), Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel. EM shaina@mail.biu.ac.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20] NR 27 TC 41 Z9 44 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 16 PY 2006 VL 72 IS 8 BP 949 EP 955 DI 10.1016/j.bcp.2006.07.019 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 091ZR UT WOS:000241067300004 PM 16939682 ER PT J AU Mamedova, LK Gao, ZG Jacobson, KA AF Mamedova, Liaman K. Gao, Zhan-Guo Jacobson, Kenneth A. TI Regulation of death and survival in astrocytes by ADP activating P2Y(1) and P2Y(12) receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE apoptosis; nucleotides; G protein-coupled receptors; tumor necrosis factor; phospholipase C; protein kinase C ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; ANTITHROMBOTIC DRUGS; NUCLEOTIDE RECEPTORS; PURINERGIC RECEPTOR; SIGNAL-TRANSDUCTION; PROTEIN-KINASES; PC12 CELLS; APOPTOSIS AB ADP is the endogenous agonist for both P2Y(1), and P2Y(12) receptors, which are important therapeutic targets. It was previously demonstrated that ADP and a synthetic agonist, 2-methylthioadenosine 5'-diphosphate (2MeSADP), can induce apoptosis by activating the human P2Y(1), receptor heterologously expressed in astrocytoma cells. However, it was not known whether the P2Y(12) receptor behaved similarly. We demonstrated here that, unlike with the G(q)-coupled P2Y(1) receptor, activation of the G(i)-coupled P2Y(12) receptor does not induce apoptosis. Furthermore, activation of the P2Y(12) receptor by either ADP or 2MeSADP significantly attenuates the tumor necrosis factor alpha (TNF alpha)-induced apoptosis in 1321N1 human astrocytoma cells. This protective effect was blocked by the P2Y(12) receptor antagonist 2-methylthioAMP and by inhibitors of phospholipase C (U73122) and protein kinase C (chelerythrin), but not by the P2Y(1), receptor antagonist MRS2179. Toward a greater mechanistic understanding, we showed that hP2y(12) receptor activation by 10 nM 2MeSADP, activates Erk1/2, Akt, and INK by phosphorylation. However, at a lower protective concentration of 100 pM 2MeSADP, activation of the hP2Y(12) receptor involves only phosphorylated Erk1/2, but not Akt or INK. This activation is hypothesized as the major mechanism for the protective effect induced by P2y(12) receptor activation. Apyrase did not affect the ability of TNFa to induce apoptosis in hP2Y(12)-1321N1 cells, suggesting that the endogenous nucleotides are not involved. These results may have important implications for understanding the signaling cascades that follow activation of P2Y(1), and P2y(12) receptors and their opposing effects on cell death pathways. Published by Elsevier Inc. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20] NR 44 TC 29 Z9 30 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 16 PY 2006 VL 72 IS 8 BP 1031 EP 1041 DI 10.1016/j.bcp.2006.07.017 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 091ZR UT WOS:000241067300013 PM 16934758 ER PT J AU Ishai, A Bikle, PC Ungerleider, LG AF Ishai, Alumit Bikle, Philip C. Ungerleider, Leslie G. TI Temporal dynamics of face repetition suppression SO BRAIN RESEARCH BULLETIN LA English DT Article DE MEG; face perception; emotion; valence enhancement; context effects ID EVENT-RELATED FMRI; RECOGNITION MEMORY; TIME-COURSE; BRAIN; CORTEX; PERCEPTION; ATTENTION; EXPLICIT; IMPLICIT; HUMANS AB Single-unit recordings and functional brain imaging studies have shown reduced neural responses to repeated stimuli in the visual cortex. Using MEG, we compared responses evoked by repetitions of neutral faces to those evoked by fearful faces, which were either task relevant (targets) or irrelevant (distracters). Faces evoked a bi-phasic response in extrastriate cortex, peaking at 160-185 ms and at 220-250 ms, with stronger responses to neutral faces at the earlier interval and stronger responses to fearful faces at the later interval. At both latencies, repetitions of neutral and fearful targets resulted in reduced amplitude of the MEG signal. Additionally, we found that the context in which targets were presented affected their processing: fearful distracters increased the responses evoked by both neutral and fearful targets. Our data indicate that valence enhancement and context effects can be detected in extrastriate visual cortex within 250 ms and that these processes likely reflect feedback from other regions. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Zurich, Inst Neuroradiol, CH-8057 Zurich, Switzerland. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Ishai, A (reprint author), Univ Zurich, Inst Neuroradiol, Winterhurerstr 190, CH-8057 Zurich, Switzerland. EM ishai@hifo.unizh.ch FU Intramural NIH HHS NR 39 TC 25 Z9 25 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD OCT 16 PY 2006 VL 70 IS 4-6 BP 289 EP 295 DI 10.1016/j.brainresbull.2006.06.002 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 098TU UT WOS:000241546500004 PM 17027764 ER PT J AU Chen, LJ DeRose, EF Burka, LT AF Chen, Ling-Jen DeRose, Eugene F. Burka, Leo T. TI Metabolism of furans in vitro: Ipomeanine and 4-ipomeanol SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; POTATOES IPOMOEA-BATATAS; GLUTATHIONE; BIOACTIVATION; LUNG; DIMETHYLDIOXIRANE; IDENTIFICATION; SPECTROSCOPY; ACTIVATION; TOXICITY AB Ipomeanine (IPN), 4-ipomeanol (4-IPO), 1-ipomeanol (1-IPO), and 1,4-ipomeadiol ( DIOL) are toxic 3-substituted furans found in mold-damaged sweet potatoes. IPN and 4-IPO are the most toxic, but all produce pulmonary toxicity in cattle and rodents, and 4-IPO induces hepatotoxicity in humans. These furans require metabolic activation to elicit toxicity, but the limited information obtained from previous metabolism studies prompted us to initiate the investigation reported here. Our initial studies of 4-IPO metabolism by rat liver microsomes demonstrated that the oxidation of 4-IPO to IPN and reduction to DIOL occurred and that more IPN was metabolized to a reactive species than 4-IPO or DIOL. Incubation of IPN and Gly produced a 2 '-pyrrolin-5 '-one adduct establishing that IPN was metabolized to an enedial. N-Acetylcysteine reacted with the 5 '-aldehyde of the enedial to give two 2 ',5 '-dihydro-2 '-hydroxyfurans stabilized by H bonding between the 2 '-OH and 3 '-keto group. Reaction of the enedial metabolite of IPN with one GSH gave several adducts including a pyrrole derived from the 1,2-addition of GSH to the 5 '-aldehyde as well as two tricyclic 2 '-pyrrolines derived from the 1,4-addition of GSH at the 4 '-position. The identities of the pyrrole and 2 '-pyrroline GSH adducts were confirmed by observation of structurally similar adducts from Cys conjugation with the enedial metabolite of IPN. Several minor adducts from the conjugation of the enedial metabolite of IPN with two GSH were also detected. Mono-GSH and bis-GSH adducts were derived from both the 1,2- and 1,4-addition of GSH to the enedial metabolite of 4-IPO in rat liver microsomal incubations of 4-IPO and GSH. Sequential oxidation of 4-IPO to IPN and then to the enedial metabolite followed by GSH conjugation also occurred in the 4-IPO incubations. The complex structures of the reaction products of the enedial with biological nucleophiles may explain why the many attempts to identify 4-IPO adducts to protein have not been successful. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Chen, LJ (reprint author), NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. EM ferguso2@niehs.nih.gov FU Intramural NIH HHS NR 27 TC 10 Z9 10 U1 5 U2 13 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 OCT 16 PY 2006 VL 19 IS 10 BP 1320 EP 1329 DI 10.1021/tx060128f PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 094IK UT WOS:000241232900008 PM 17040101 ER PT J AU Bhatti, P Church, DM Rutter, JL Struewing, JP Sigurdson, AJ AF Bhatti, Parveen Church, Deanna M. Rutter, Joni L. Struewing, Jeffery P. Sigurdson, Alice J. TI Candidate single nucleotide polymorphism selection using publicly available tools: A guide for epidemiologists SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE amino acid sequence; base sequence; epidemiologic methods; genetic predisposition to disease; polymorphism, single nucleotide ID STRAND BREAK REPAIR; EXONIC SPLICING ENHANCERS; EUKARYOTIC MESSENGER-RNAS; 3' UNTRANSLATED REGIONS; MOLECULAR EPIDEMIOLOGY; CANCER-SUSCEPTIBILITY; GENETIC POLYMORPHISMS; FUNCTIONAL-ANALYSIS; DNA-SEQUENCES; SKIN-CANCER AB Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation, with millions present in the human genome. Because only 1% might be expected to confer more than modest individual effects in association studies, the selection of predictive candidate variants for complex disease analyses is formidable. Technologic advances in SNP discovery and the ever-changing annotation of the genome have led to massive informational resources that can be difficult to master across disciplines. A simplified guide is needed. Although methods for evaluating nonsynonymous coding SNPs are known, several other publicly available computational tools can be utilized to assess polymorphic variants in noncoding regions. As an example, the authors applied multiple methods to select SNPs in DNA double-strand break repair genes. They chose to evaluate SNPs that occurred among a preexisting set of 57 validated assays and to justify new assay development for 83 potential SNPs in the DNA-dependent protein kinase catalytic subunit. Of the 140 SNPs, the authors eliminated 119 variants with low or neutral predictions. The existing computational methods they used and the semiquantitative relative ranking strategy they developed can be adapted to a priori SNP selection or post hoc evaluation of variants identified in whole genome scans or within haplotype blocks associated with disease. The authors show a "real world" application of some existing bioinformatics tools for use in large epidemiologic studies and genetic analyses. They also reviewed alternative approaches that provide related information. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. Natl Inst Drug Abuse, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NCI, Lab Populat Genet, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7060,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov RI Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Rutter, Joni/0000-0002-6502-2361 FU Intramural NIH HHS NR 58 TC 21 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2006 VL 164 IS 8 BP 794 EP 804 DI 10.1093/aje/kwj269 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 092IR UT WOS:000241090700012 PM 16923772 ER PT J AU McInerney-Leo, A Hadley, D Kase, RG Giambarresi, TR Struewing, JP Biesecker, BB AF McInerney-Leo, Aideen Hadley, Donald Kase, Ronald G. Giambarresi, Therese R. Struewing, Jeffery P. Biesecker, Barbara Bowles TI BRCA1/2 testing in hereditary breast and ovarian cancer families III: Risk perception and screening SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE BRCA1; BRCA2; risk perception; cancer screening; genetic testing ID FIRST-DEGREE RELATIVES; PSYCHOLOGICAL DISTRESS; PROPHYLACTIC SURGERY; SELF-EXAMINATION; PERCEIVED RISK; RANDOMIZED-TRIAL; WOMEN; HISTORY; IMPACT; MUTATION AB This study aimed to ascertain whether cancer risk perception changed following the offer and subsequent receipt of BRCA1/2 results and to evaluate breast and ovarian screening practices in testers and non-testers. Members of thirteen HBOC families were offered BRCA1/2 testing for a known family mutation. Perceived risk for developing breast cancer, ovarian cancer or for carrying the familial BRCA-1/2 mutation, was assessed at baseline and again at 6-9 months following the receipt of test results. Breast and ovarian cancer screening data were obtained at both time-points. A total of 138 women participated and 120 (87%) chose to be tested for a known familial mutation. Twenty-eight women (24%) were identified as carriers and their perceived ovarian cancer risk and their perception of being a mutation carrier increased (P = 0.01 for both). Those testing negatives had a significant decrease in all dimensions of risk perception (P < 0.01). Regression analysis showed test results to be strong predictors of follow-up risk perception (P = 0.001), however, they were not predictors of screening practices at follow-tip. Testers were more likely to have completed a clinical breast exam following testing than decliners. Mammography was positively associated with baseline adherence, age, and intrusive thoughts. Ovarian cancer worries only predicted pelvic ultrasound screening post-testing. Baseline practices and psychological factors appear to be stronger predictors of health behavior than test results. Published 2006 Wiley-Liss, Inc.dagger C1 NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Westat Res, Rockville, MD USA. NCI, Clin Genet Branch, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, Bldg 2,Room 4W17,2 Ctr Dr,MSC 0249, Bethesda, MD 20892 USA. EM barbarab@mail.nih.gov RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU Intramural NIH HHS NR 61 TC 16 Z9 16 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT 15 PY 2006 VL 140A IS 20 BP 2198 EP 2206 DI 10.1002/ajmg.a.31432 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 091TJ UT WOS:000241050900006 PM 16969872 ER PT J AU Feigenbaum, A Bai, RK Doherty, ES Kwon, H Tan, D Sloane, A Cutz, E Robinson, BH Wong, LJC AF Feigenbaum, Annette Bai, Ren-Kui Doherty, Emily S. Kwon, Haeyoung Tan, Duanjun Sloane, Avril Cutz, Ernest Robinson, Brian H. Wong, Lee-Jun C. TI Novel mitochondrial DNA mutations associated with myopathy, cardiomyopathy, renal failure, and deafness SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE mtDNA mutation; mitochondrial myopathy; cardiomyopathy; 5783G > A; 15458T > C; 15519T > C ID DISEASE; QUANTIFICATION; ENCEPHALOPATHY; AMPLIFICATION; SEQUENCE; COMPLEX; GENOME AB Patients with mitochondrial disease usually manifest multisystemic dysfunction with a broad clinical spectrum. When the tests for common mitochondrial DNA (mtDNA) point mutations are negative and the mtDNA defects are still hypothesized, it is necessary to screen the entire mitochondrial genome for unknown mutations in order to confirm the diagnosis. We report an 8-year-old girl who had a long history of ragged-red fiber myopathy, short statute, and deafness, who ultimately developed renal failure and fatal cardiac dysfunction. Respiratory chain enzyme analysis on muscle biopsy revealed deficiency in complexes I, II/III, and IV. Whole mitochondrial genome sequencing analysis was performed. Three novel changes: homoplasmic 15458T > C and 15519T > C in cytochrome b, and a near homoplasmic 5783G > A in tRNA(cys), were found in the proband in various tissues. Her mother and asymptomatic sibling also carry the two homoplasmic mutations and the heteroplasmic 5783G > A mutation in blood, hair follicles, and buccal cells, at lower percentage. The 5783G > A mutation occurs at the T arm of tRNA(cys), resulting in the disruption of the stem structure, which may reduce the stability of the tRNA. 15458T > C changes an amino acid serine to proline at a conserved alpha-helix, which may force the helix to bend. These two mutations may have pathogenic significance. This case emphasizes the importance of pursuing more extensive mutational analysis of mtDNA in the absence of common mtDNA point mutations or large deletions, when there is a high suspicion of a mitochondrial disorder. (c) 2006 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. NHGRI, NIH, Bethesda, MD 20892 USA. Dongduk Womens Univ, Dept Appl Chem, Seoul, South Korea. Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. Hosp Sick Children, Div Pathol, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. RP Wong, LJC (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Pl,NAB 2015, Houston, TX 77030 USA. EM ljwong@bcm.tmc.edu NR 24 TC 13 Z9 15 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT 15 PY 2006 VL 140A IS 20 BP 2216 EP 2222 DI 10.1002/ajmg.a.31436 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 091TJ UT WOS:000241050900009 PM 16955414 ER PT J AU Parker, EA Hovanes, K Germak, J Porter, F Merke, DP AF Parker, Elizabeth A. Hovanes, Karine Germak, John Porter, Forbes Merke, Deborah P. TI Maternal 21-hydroxylase deficiency and uniparental isodisomy of chromosome 6 and X results in a child with 21-hydroxylase deficiency and Klinefelter syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID CONGENITAL ADRENAL-HYPERPLASIA; DISOMY; PATIENT; ORIGIN C1 NCI, Ctr Clin, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Dev Endocrinol Branch, Bethesda, MD USA. Esoterix Inc, Dept Mol Genet, Calabasas Hills, CA USA. Novo Nordisk AS, Princeton, NJ USA. NICHD, NIH, Heritable Disorders Branch, Bethesda, MD USA. NICHD, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. RP Merke, DP (reprint author), NCI, Ctr Clin, NIH, Bldg 10,Room 1-2740,MSC 1932,10 Ctr Dr, Bethesda, MD 20892 USA. EM dmerke@nih.gov NR 14 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT 15 PY 2006 VL 140A IS 20 BP 2236 EP 2240 DI 10.1002/ajmg.a.31408 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 091TJ UT WOS:000241050900013 PM 16906568 ER PT J AU Kim, HS Wainer, IW AF Kim, Hee Seung Wainer, Irving W. TI On-line drug metabolism in capillary electrophoresis. 1. Glucuronidation using rat liver microsomes SO ANALYTICAL CHEMISTRY LA English DT Article ID UDP-GLUCURONYL TRANSFERASE; URIDINE-DIPHOSPHATE GLUCURONOSYLTRANSFERASE; IMMOBILIZED ENZYME REACTOR; ELECTRIC-FIELD; 7-HYDROXYCOUMARIN; VARIABILITY; INHIBITORS; DISEASE AB A rat liver microsome pseudostationary phase has been used for the on-line capillary electrophoresis monitoring of glucuronidation. Uridine diphosphate glucuronosyltransferase (EC 2.4.1.17) containing microsomes was isolated from rat liver and directly injected onto neutrally coated capillary containing polymeric replaceable gels followed by injection of the substrate mixture. On-line glucuronidation was observed within 15 min without any sample preparation. The factors affecting the separation of glucuronides and parent compounds were investigated by varying the applied electric fields and the size ( length and internal diameter) of capillary. The Michaelis-Menten parameters (K-m and V-max) for the glucuronidation of 4-methyl-7-hydroxy coumarin and 4-nitrophenol were determined using the CE method and by off-line microsomal incubation. No significant differences were observed for K-m and V-max values for 4-methyl-7-hydroxycoumarin and 4-nitrophenol between on-line and off-line glucuronidation of these two compounds. This method was also used to determine the inhibition constant (IC50 value) for the competitive inhibition of morphine glucuronidation by codeine, IC50 (on-line)) 170 vs 580 mu M (off-line). The results demonstrate that this method can be used to screen for the glucuronidation of test compounds and should reduce the time required for this screening process. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov FU Intramural NIH HHS NR 30 TC 21 Z9 21 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 15 PY 2006 VL 78 IS 20 BP 7071 EP 7077 DI 10.1021/ac060970q PG 7 WC Chemistry, Analytical SC Chemistry GA 094DO UT WOS:000241219800001 PM 17037905 ER PT J AU Miller, AH Manji, HK AF Miller, Andrew H. Manji, Husseini K. TI On redefining the role of the immune system in psychiatric disease SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID STRESS; DEPRESSION; RESPONSES C1 Emory Univ, Sch Med, Winship Canc Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Miller, AH (reprint author), Emory Univ, Sch Med, Winship Canc Ctr, Dept Psychiat & Behav Sci, 1365-C Clifton Rd, Atlanta, GA 30322 USA. EM amill02@emory.edu NR 17 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2006 VL 60 IS 8 BP 796 EP 798 DI 10.1016/j.biopsych.2006.09.013 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 094UH UT WOS:000241264100003 PM 17045861 ER PT J AU Rydrnark, I Wahlberg, K Ghatan, PH Modell, S Nygren, A Ingvar, M Asberg, M Heilig, M AF Rydrnark, Ingrid Wahlberg, Kristina Ghatan, Per Harnid Modell, Sieglinde Nygren, Ake Ingvar, Martin Asberg, Marie Heilig, Markus TI Neuroendocrine, cognitive and structural imaging characteristics of women on longterm sickleave with job stress-induced depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; cortisol; CRH; hippocampus; stress; workplace ID MEDIAL PREFRONTAL CORTEX; DEXAMETHASONE/CORTICOTROPIN-RELEASING HORMONE; ALTERS DENDRITIC MORPHOLOGY; HIPPOCAMPAL VOLUME LOSS; DEX-CRH TEST; MAJOR DEPRESSION; CORTISOL-LEVELS; CUSHINGS-DISEASE; MOOD DISORDERS; MEMORY AB Background: A recent increase in long-term sick leave (LTSL) in Sweden affects mostly women in the public sector. Depression-related diagnoses account for most of the increase, and work-related stress has been implicated. Methods. We examined dexametbasone/corticotropin-releasing hormone (dex/CRH) test responses, magnetic resonance imaging measures of prefrontocortical and hippocampal volumes, and cognitive performance in 29 female subjects fulfilling three core criteria: 1) LTSL > 90 days; 2) unipolar depression or maladaptive stress reaction with depressed mood; 3) Job-related stress given as a reason for disability. This group was compared with 28 healthy matched controls. Results: The cortisol response to CRH differed markedly between the two groups (p = .002), with a dampened response in patients. This difference remained after removing subjects on antidepressant drugs (p = .006) or smokers (p = .003). Neither hippocampal nor prefrontocortical volumes differed. Performance on on hippocampus-dependent declarative memory tests did not differ between groups, but the LTSL group bad impaired working memory. Conclusions: Our most salient finding is an attenuated dex-CRH response inpatients on LTSL due to job-stress related depression. This is opposite to what has been described in major depression. It remains to be established whether this impairment is the end result Of prolonged stress exposure, or a pre-existing susceptibility factor. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Bristol Myers Squibb, Munich, Germany. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10-1E-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482; Ingvar, Martin/0000-0002-9041-5714 NR 48 TC 1 Z9 1 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2006 VL 60 IS 8 BP 867 EP 873 DI 10.1016/j.biopsych.2006.04.029 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 094UH UT WOS:000241264100015 ER PT J AU Choi, WJ Shi, ZD Worthy, KM Bindu, L Karki, RG Nicklaus, MC Fisher, RJ Burke, TR AF Choi, Won Jun Shi, Zhen-Dan Worthy, Karen M. Bindu, Lakshman Karki, Raieshri G. Nicklaus, Marc C. Fisher, Robert J. Burke, Terrence R., Jr. TI Application of azide-alkyne cycloaddition 'click chemistry' for the synthesis of Grb2 SH2 domain-binding macrocycles SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE macrocycle; click chemistry; Grb2 SH2 domain; cycloaddition; peptide mimetic ID RING-CLOSING METATHESIS; AMINO-ACIDS; TERMINAL ALKYNES; PEPTIDE MIMETICS; DESIGN; AFFINITY; PHOSPHOTYROSINE; ANTAGONISTS; INHIBITOR; RESIDUES AB Copper (I) promoted [3+2] Huisgen cycloaddition of azides with terminal alkynes was used to prepare triazole-containing macrocycles based on the Grb2 SH2 domain-binding motif, 'Pmp-Ac(6)c-Asn', where Pmp and Ac(6)c stand for 4-phosphonomethyl-phenylalanine and I-aminocyclohexanecarboxylic acid, respectively. When cycloaddition reactions were conducted at 1 mM substrate concentrations, cyclization of monomeric units occurred. At 2 mM substrate concentrations the predominant products were macrocyclic dimers. In Grb2 SH2 domain-binding assays the monomeric (S)-Pmp-containing macrocycle exhibited a K-d value of 0.23 mu M, while the corresponding dimeric macrocycle was found to have greater than 50-fold higher affinity. The open-chain dimer was also found to have affinity equal to the dimeric macrocycle. This work represents the first application of 'click chemistry' to the synthesis of SH2 domain-binding inhibitors and indicates its potential utility. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Lab Med Chem, CCR, NIH, Frederick, MD 21702 USA. NCI, Lab Med Chem, CCR, NIH, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Lab Med Chem, CCR, NIH, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014; OI Nicklaus, Marc/0000-0002-4775-7030 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 30 TC 27 Z9 27 U1 0 U2 6 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 OCT 15 PY 2006 VL 16 IS 20 BP 5265 EP 5269 DI 10.1016/j.bmcl.2006.08.004 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 095YO UT WOS:000241344400002 PM 16908148 ER PT J AU Wiestner, A AF Wiestner, Adrian TI Gene expression relates WM to CLL SO BLOOD LA English DT Editorial Material ID DIAGNOSIS AB Waldenstrom macroglobulinemia (WM) shares traits with both chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). Chng and colleagues now demonstrate that by gene expression WM appears more closely related to CLL than MM. C1 NHLBI, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 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 OCT 15 PY 2006 VL 108 IS 8 BP 2499 EP 2500 DI 10.1182/blood-2006-08-037374 PG 2 WC Hematology SC Hematology GA 092XT UT WOS:000241131700005 ER PT J AU Kato, GJ Gladwin, MT AF Kato, Gregory J. Gladwin, Mark T. TI A novel defense against hemolytic-oxidative stress SO BLOOD LA English DT Editorial Material ID HEMOGLOBIN; DISEASE AB The findings of Nielsen and colleagues that haptoglobin-related protein (Hpr) binds to free hemoglobin as avidly as haptoglobin emphasize the critical redundancy in hemoglobin clearance mechanisms and suggest the existence of intravascular cross talk between pathways often considered distinct: vasomotor, hemostatic, immunologic, metabolic, and oxidative. C1 NHLBI, Bethesda, MD 20892 USA. RP Kato, GJ (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 5 TC 1 Z9 1 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 OCT 15 PY 2006 VL 108 IS 8 BP 2504 EP 2505 DI 10.1182/blood-2006-07-037424 PG 2 WC Hematology SC Hematology GA 092XT UT WOS:000241131700011 ER PT J AU Young, NS Calado, RT Scheinberg, P AF Young, Neal S. Calado, Rodrigo T. Scheinberg, Phillip TI Current concepts in the pathophysiology and treatment of aplastic anemia SO BLOOD LA English DT Review ID BONE-MARROW-TRANSPLANTATION; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; STEM-CELL TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; HIGH-DOSE CYCLOPHOSPHAMIDE; COLONY-STIMULATING FACTOR; TERM-FOLLOW-UP; TELOMERASE COMPLEX MUTATIONS; TOTAL-BODY IRRADIATION; VERSUS-HOST-DISEASE AB Aplastic anemia, an unusual hematologic disease, is the paradigm of the human bone marrow failure syndromes. Almost universally fatal just a few decades ago, aplastic anemia can now be cured or ameliorated by stem-cell transplantation or immunosuppressive drug therapy. The pathophysiology is immune mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Immunosuppression with antithymocyte globulins and cyclosporine is effective at restoring blood-cell production in the majority of patients, but relapse and especially evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenges are extending the benefits of transplantation to patients who are older or who lack family donors. Recent results with alternative sources of stem cells and a variety of conditioning regimens to achieve their engraftment have been promising, with survival in small pediatric case series rivaling conventional transplantation results. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD USA. RP Young, NS (reprint author), 10 Ctr Dr,Bldg 10-CRC,Rm 3E-5140, Bethesda, MD 20892 USA. EM youngns@mail.nih.gov RI Calado, Rodrigo/G-2619-2011; OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS NR 127 TC 340 Z9 420 U1 3 U2 27 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 OCT 15 PY 2006 VL 108 IS 8 BP 2509 EP 2519 DI 10.1182/blood-2006-03-010777 PG 11 WC Hematology SC Hematology GA 092XT UT WOS:000241131700014 PM 16778145 ER PT J AU Liu, CL Saito, F Liu, ZJ Lei, Y Uehara, S Love, P Lipp, M Kondo, S Manley, N Takahama, Y AF Liu, Cunlan Saito, Fumi Liu, Zhijie Lei, Yu Uehara, Shoji Love, Paul Lipp, Martin Kondo, Shunzo Manley, Nancy Takahama, Yousuke TI Coordination between CCR7-and CCR9-mediated chemokine signals in prevascular fetal thymus colonization SO BLOOD LA English DT Article ID EPIDERMAL T-CELLS; HEMATOPOIETIC STEM-CELLS; MOUSE EMBRYO; SKIN; MICE; MICROENVIRONMENTS; RECRUITMENT; PRECURSORS; PROGENITORS; EXPRESSION AB Thymus seeding by T-lymphoid progenitor cells is a prerequisite for T-cell development. However, molecules guiding thymus colonization and their roles before and after thymus vascularization are unclear. Here we show that mice doubly deficient for chemokine receptors CCR7 and CCR9 were defective specifically in fetal thymus colonization before, but not after, thymus vascularization. The defective prevascular fetal thymus colonization was followed by selective loss of the first wave of T-cell development generating epidermal Vy3(+) gamma delta T cells. Unexpectedly, CCL21, a CCR7 ligand, was expressed not by Foxn1-dependent thymic primordium but by Gcm2-dependent parathyroid primordium, whereas CCL25, a CCR9 ligand, was predominantly expressed by Foxn1-dependent thymic primordium, revealing the role of the adjacent parathyroid in guiding fetal thymus colonization. These results indicate coordination between Gcm2-dependent parathyroid and Foxn1-dependent thymic primordia in establishing CCL21/CCR7- and CCL25/CCR9-mediated chemokine guidance essential for prevascular fetal thymus colonization. C1 Univ Tokushima, Inst Genome Res, Div Expt Immunol, Tokushima 7708503, Japan. Univ Georgia, Dept Genet, Athens, GA USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. Max Delbruck Ctr Mol Med, Dept Mol Tumorgenet & Immunogenet, Berlin, Germany. JEOL, Akishima, Tokyo, Japan. RP Takahama, Y (reprint author), Univ Tokushima, Inst Genome Res, Div Expt Immunol, Tokushima 7708503, Japan. EM takahama@genome.tokushima-u.ac.jp RI Takahama, Yousuke/A-5863-2010; Lipp, Martin/G-2235-2010 NR 36 TC 113 Z9 116 U1 2 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2006 VL 108 IS 8 BP 2531 EP 2539 DI 10.1182/blood-2006-05-024190 PG 9 WC Hematology SC Hematology GA 092XT UT WOS:000241131700016 PM 16809609 ER PT J AU Lucas, PJ Kim, SJ Mackall, CL Telford, WG Chu, YW T Hakim, F Gress, RE AF Lucas, Philip J. Kim, Seong-Jin Mackall, Crystal L. Telford, William G. Chu, Yu-Waye T Hakim, Frances Gress, Ronald E. TI Dysregulation of IL-15-mediated T-cell homeostasis in TGF-beta dominant-negative receptor transgenic mice SO BLOOD LA English DT Article ID GROWTH-FACTOR; IN-VIVO; NATURAL-KILLER; INTERLEUKIN-2 RECEPTOR; INHIBITORY RECEPTORS; POSITIVE SELECTION; EFFECTOR FUNCTION; CUTTING EDGE; MEMORY; NAIVE AB T-cell subpopulations, defined by their expression of CD4, CD8, naive, and memory cell-surface markers, occupy distinct homeostatic compartments that are regulated primarily by cytokines. CD8(+) memory T cells, as defined by CD44(hl) surface expression, are dependent on IL-15 as a positive regulator of their homeostatic maintenance. Manipulation of IL-15 signaling through gene aberration, overexpression, or receptor alterations has been shown to dramatically affect T-cell homeostasis, with overexpression leading to fatal leukemia. Here we show that TGF-beta is the critical negative regulator of murine CD8(+) memory T-cell homeostasis with direct opposition to the positive effects of IL-15. This negative regulation is mediated, at least in part, by the ability of TGF-beta to modulate expression of the beta-chain of the IL-15 receptor, thus establishing a central axis between these 2 cytokines for homeostatic control of CD8(+) memory T-cell populations. These data establish TGF-beta as a critical and dominant tumor-suppressor pathway opposing IL-15-mediated CD8(+) T-cell expansion and potential malignant transformation. C1 NCI, Expt Transplantat & Immunol Branch, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Lucas, PJ (reprint author), NCI, Expt Transplantat & Immunol Branch, Lab Cell Regulat & Carcinogenesis, NIH, CRC 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA. EM pjlucas@nih.gov NR 59 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2006 VL 108 IS 8 BP 2789 EP 2795 DI 10.1182/blood-2006-05-025676 PG 7 WC Hematology SC Hematology GA 092XT UT WOS:000241131700048 PM 16788095 ER PT J AU Howe, HL Wu, XC Ries, LAG Cokkinides, V Ahmed, F Jemal, A Miller, B Williams, M Ward, E Wingo, PA Ramirez, A Edwards, BK AF Howe, Holly L. Wu, Xiaocheng Ries, Lynn A. G. Cokkinides, Vilma Ahmed, Faruque Jemal, Ahmedin Miller, Barry Williams, Melanie Ward, Elizabeth Wingo, Phyllis A. Ramirez, Amelie Edwards, Brenda K. TI Annual report to the nation on the status of cancer, 1975-2003, featuring cancer among US Hispanic/Latino populations SO CANCER LA English DT Review DE cancer; incidence; mortality; Hispanic; Latino; NAACCR; SEER; NPCR; vital statistics; United States; health disparity; cancer inequality ID DISPARITIES GEOCODING PROJECT; RENAL-CELL CANCER; NEW-YORK-CITY; UNITED-STATES; BREAST-CANCER; THYROID-CANCER; CERVICAL-CANCER; SOUTH FLORIDA; SOCIOECONOMIC-STATUS; INCIDENCE RATES AB BACKGROUND. The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries collaborate annually to provide U.S. cancer information, this year featuring the first comprehensive compilation of cancer information for U.S. Latinos. METHODS. Cancer incidence was obtained from 90% of the Hispanic/Latino and 82% of the U.S. populations. Cancer deaths were obtained for the entire U.S. population. Cancer screening, risk factor, incidence, and mortality data were compiled for Latino and non-Latino adults and children (incidence only). Long-term (19752003) and fixed-interval (1995-2003) trends and comparative analyses by disease stage, urbanicity, and area poverty were evaluated. RESULTS. The long-term trend in overall cancer death rates, declining since the early 1990s, continued through 2003 for all races and both sexes combined. However, female lung cancer incidence rates increased from 1975 to 2003, decelerating since 1991 and breast cancer incidence rates stabilized from 2001 to 2003. Latinos had lower incidence rates in 1999-2003 for most cancers, but higher rates for stomach, liver, cervix, and myeloma (females) than did non-Latino white populations. Latino children have higher incidence of leukemia, retinoblastoma, osteosarcoma, and germ-cell tumors than do non-Latino white children. For several common cancers, Latinos were less likely than non-Latinos to be diagnosed at localized stages. CONCLUSIONS. The lower cancer rates observed in Latino immigrants could be sustained by maintenance of healthy behaviors. Some infection-related cancers in Latinos could be controlled by evidence-based interventions. Affordable, culturally sensitive, linguistically appropriate, and timely access to cancer information, prevention, screening, and treatment are important in Latino outreach and community networks. Published 2006 by the American Cancer Society. C1 N Amer Assoc, Cent Canc Reg, Springfield, IL 62704 USA. Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, New Orleans, LA 70112 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Texas Dept State Hlth Serv, Austin, TX USA. Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. RP Howe, HL (reprint author), N Amer Assoc, Cent Canc Reg, 2121 W White Oaks Dr, Springfield, IL 62704 USA. EM hhowe@naaccr.org FU NCI NIH HHS [N02-PC-44401]; PHS HHS [HHSN261200444001C, U75/CCU523346] NR 157 TC 265 Z9 275 U1 3 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 BP 1711 EP 1742 DI 10.1002/cncr.22193 PG 32 WC Oncology SC Oncology GA 093MB UT WOS:000241171300001 PM 16958083 ER PT J AU Abrahamson, PE Gammon, MD Lund, MJ Britton, JA Marshall, SW Flagg, EW Porter, PL Brinton, LA Eley, JW Coates, RJ AF Abrahamson, Page E. Gammon, Marilie D. Lund, Mary Jo Britton, Julie A. Marshall, Stephen W. Flagg, Elaine W. Porter, Peggy L. Brinton, Louise A. Eley, J. William Coates, Ralph J. TI Recreational physical activity and survival among young women with breast cancer SO CANCER LA English DT Article DE breast cancer; survival; mortality; physical activity; exercise ID AGE 45 YEARS; PROGNOSTIC-FACTORS; UNITED-STATES; BODY-SIZE; RISK; EXERCISE; HEALTH; LIFE; INDICATORS; DIAGNOSIS AB BACKGROUND. Most epidemiologic studies report a reduced risk of developing breast cancer associated with higher levels of recreational physical activity, but little is known regarding its effect on prognosis. METHODS. in this study, the authors investigated whether activity undertaken prior to diagnosis influenced breast cancer survival in a population-based cohort. A follow-up study was conducted among 1264 women ages 20 to 54 years who were diagnosed with invasive breast cancer between 1990 and 1992. Women in the study were interviewed within several months of diagnosis and were asked about their average frequency of moderate and vigorous activity at age 13 years, age 20 years, and during the year before diagnosis. With 8 to 10 years of follow-up, all-cause mortality status was determined by using the National Death Index (n = 290 deaths). RESULTS. A modest reduction in the hazards ratio (HR) was observed for the highest quartile of activity in the year before diagnosis compared with the lowest quartile (stage-adjusted and income-adjusted HR, 0.78; 95% confidence interval [95% CI], 0.56-1.08). High activity was associated with a reduced HR among women who were overweight or obese at the time of diagnosis (HR, 0.70; 95% CI, 0.49-0.99) but not among ideal weight or underweight women (HR, 1.08; 95% CI, 0.77-1.52). A reduced HR was not evident for activity at age 13 years or 20 years or for average activity across the 3 periods studied. CONCLUSIONS. The results of this study provided some suggestive evidence for a beneficial effect on survival of recreational physical activity undertaken in the year before diagnosis, particularly among women who are over-weight or obese near the time of diagnosis. Published 2006 by the American Cancer Society. C1 Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Human Biol, Seattle, WA 98109 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. Emory Univ, Winship Canc Inst, Atlanta, GA USA. CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Surveillance & Epidemiol Branch, Atlanta, GA USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. US Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. RP Abrahamson, PE (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Human Biol, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM pabraham@fhcrc.org RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Marshall, Stephen/0000-0002-2664-9233 FU Intramural NIH HHS; NCI NIH HHS [R25 CA57726, R25 CA94880]; NIEHS NIH HHS [P30ES10126] NR 41 TC 59 Z9 62 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 BP 1777 EP 1785 DI 10.1002/cncr.22201 PG 9 WC Oncology SC Oncology GA 093MB UT WOS:000241171300006 PM 16967443 ER PT J AU Clanton, M AF Clanton, Mark TI The National Cancer Institute's special populations networks for cancer awareness, research, and training SO CANCER LA English DT Editorial Material C1 NCI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Clanton, M (reprint author), NCI, NIH, US Dept Hlth & Human Serv, 31 Ctr Dr,Room 11A03, Bethesda, MD 20892 USA. EM clantoma@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 SU S BP 1931 EP 1932 DI 10.1002/cncr.22161 PG 2 WC Oncology SC Oncology GA 095DX UT WOS:000241289500001 PM 16958025 ER PT J AU Freeman, HP Vydelingum, NA AF Freeman, Harold P. Vydelingum, Nadarajen A. TI The role of the Special Populations Networks Program in eliminating cancer health disparities SO CANCER LA English DT Editorial Material C1 Ralph Lauren Ctr Canc Care & Prevent, New York, NY 10035 USA. NCI, Off Director, Bethesda, MD 20892 USA. NCI, Ctr Reduce Canc Hlth Disparities, Bethesda, MD 20892 USA. RP Freeman, HP (reprint author), Ralph Lauren Ctr Canc Care & Prevent, 1919 Madison Ave, New York, NY 10035 USA. EM hfreeman@mail.nih.gov NR 5 TC 11 Z9 11 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 SU S BP 1933 EP 1935 DI 10.1002/cncr.22162 PG 3 WC Oncology SC Oncology GA 095DX UT WOS:000241289500002 PM 16929523 ER PT J AU Haynes, MA AF Haynes, M. Alfred TI Reflections on programs designed to reduce cancer disparities SO CANCER LA English DT Editorial Material C1 Natl Acad Sci, Inst Med, Comm Canc Res Minor & Medically Underserved, Washington, DC 20418 USA. RP Haynes, MA (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, 6116 Execut Blvd,Suite 602,MSC 8341, Rockville, MD 20852 USA. EM vydelinn@mail.nih.gov NR 11 TC 2 Z9 2 U1 1 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 OCT 15 PY 2006 VL 107 IS 8 SU S BP 1936 EP 1938 DI 10.1002/cncr.22163 PG 3 WC Oncology SC Oncology GA 095DX UT WOS:000241289500003 PM 16929484 ER PT J AU Jackson, FE Chu, KC Garcia, R AF Jackson, Frank E. Chu, Kenneth C. Garcia, Roland TI Special Populations Networks - How this innovative community-based initiative affected minority and underserved research programs SO CANCER LA English DT Article DE community health networks; minority groups; cancer disparities research; policy; education; programs; community participation; cancer AB The Special Populations Networks (SPN) Program was created to address both community needs for cancer information and NCI's desire to obtain community-based answers to research questions and promote training opportunities for racial/ethnic minority and underserved researchers in populations with an unequal burden of cancer. The SPN program included 3 components: 1) infrastructure and capacity building combined with cancer awareness, 2) community-based research, and 3) community-centered training. The 18 SPN grantees conducted more than 1000 cancer awareness activities. More than 2000 community lay health workers were trained. Communities formalized more than 300 partnerships with Memoranda of Understanding (MOU). More than 255 pilot research project applications were submitted by junior researchers and over 135 were funded. Approximately 90% of the applications were submitted by minority junior researchers; of which more than 100 were funded. More than 290 scientific publications thus far have resulted from the work of the SPNs. In the first 3 years of the program, the SPNs also secured an additional $20 million in outside funding. The SPN program effected a paradigm shift for minority research programs by combining community-based cancer awareness, research, and training into a single program. By engaging research leaders of minority and underserved populations to aid their own, train their own, and develop research to help their own, the SPN program activated the power of their commitment to their own. That commitment was reflected in the trust and participation offered by their communities. C1 NCI, Ctr Reduce Canc Hlth Dispar, Bethesda, MD 20852 USA. RP Chu, KC (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, 6116 Execut Blvd,Suite 602, Bethesda, MD 20852 USA. EM chuk@mail.nih.gov NR 3 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 SU S BP 1939 EP 1944 DI 10.1002/cncr.22164 PG 6 WC Oncology SC Oncology GA 095DX UT WOS:000241289500004 PM 16944469 ER PT J AU Van Duyn, MAS Reuben, SH Macario, E AF Van Duyn, Mary Ann S. Reuben, Suzanne H. Macario, Everly TI Special Populations Networks: Themes and lessons learned SO CANCER LA English DT Article DE community health networks; minority groups; cancer disparities research; policy; education; programs; community participation; cancer ID CANCER; HEALTH AB The Special Populations Networks (SPN) Program was a 5-year, nationwide project funded by the National Cancer Institute to reduce cancer-related health disparities in minority and other underserved communities by building community health infrastructure, improving cancer awareness and use of cancer screening services, and increasing the cadre of minority junior scientists studying disparities issues. Through collaborations with a wide range of community and academic partners, the 18 grantee organizations: 1) developed culturally sensitive cancer communications approaches and materials; 2) conducted outreach and educational activities appropriate to their communities' needs and diverse cultures; and 3) trained and mentored young minority investigators who succeeded in winning support for pilot projects addressing local cancer health disparities issues, trained and deployed lay health workers, and worked with community and health provider organizations to improve understanding of cancer risk in these populations and encourage participation in appropriate clinical trials. SPN activities were grounded in community-based participatory research principles and practice. This overview highlights major project themes, provides examples of differing individual grantee approaches to similar issues, and describes key lessons learned, as reported by the SPN projects, that may guide future programmatic and research efforts to eliminate cancer health disparities in the United States. C1 NCI, Ctr Reduce Canc Hlth Dispar, Rockville, MD 20852 USA. Progress Hlth Syst, Potomac, MD USA. Independent Publ Hlth Consultant, Chicago, IL USA. RP Van Duyn, MAS (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, Suite 602,6116 Execut Blvd, Rockville, MD 20852 USA. EM vanduynm@mail.nih.gov NR 24 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2006 VL 107 IS 8 SU S BP 1945 EP 1954 DI 10.1002/cncr.22165 PG 10 WC Oncology SC Oncology GA 095DX UT WOS:000241289500005 PM 16983655 ER PT J AU Myers, RE Berry, A AF Myers, Ronald E. Berry, Audrey TI Increasing access to clinical and educational studies SO CANCER LA English DT Article DE community health networks; African Americans; cancer; prevention and control; behavior; clinical trial; training; educational activities; community outreach; interventions AB In 2001, the National Cancer Institute (NCI) provided funds to support the Increasing Access to Clinical and Educational Studies (ACES) Project of the Thomas Jefferson University, Kimmel Cancer Center in Philadelphia. The ACES Project enabled the Center to engage in the systematic development of approaches for reducing cancer health disparities among African Americans in Philadelphia. This project brought together community partners, clinical partners, cancer prevention and control experts, and staff from an NCI-designated cancer center to develop and implement a community-based outreach education program, a special populations investigator (SPI) training program, and SPI pilot studies in cancer screening and clinical trials participation. At the end of 5 years, the ACES Project had 1) organized a steering committee, expert panel, and a network of community collaborators and clinical partners; 2) implemented a clinical trials education program for community-based nurses, lay health advocates active in community organizations, and health ministries in community churches; 3) mentored 4 SPIs in cancer prevention and control research; 4) completed SPI pilot studies; and 5) leveraged these activities to gain support for cancer health disparities related research. The Project established a successful dialogue between an NCI-designated cancer center and the African American population related to cancer research, and enabled SPIs from the community to adapt evidence-informed interventions for application in cancer prevention and control research. Lessons learned from the Project can guide the implementation of such projects in the future. C1 Thomas Jefferson Univ, Div Genet & Prevent Med, Philadelphia, PA 19104 USA. Villanova Univ, Coll Nursing, Villanova, PA 19085 USA. Thomas Jefferson Univ, Div Biostat, Glenside, PA USA. Hlth Educators Cultural Divers Inc, Philadelphia, PA USA. NCI, Canc Informat Serv Patnership Program Atlantic Re, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Family Med, Philadelphia, PA 19107 USA. RP Myers, RE (reprint author), Thomas Jefferson Univ, Div Genet & Prevent Med, Suite 400,1100 Walnut St, Philadelphia, PA 19104 USA. EM ron.myers@mail.tju.edu OI Myers, Ronald E./0000-0002-8059-7390 FU NCI NIH HHS [U01-CA86084, U10 CA101178] NR 9 TC 1 Z9 1 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 OCT 15 PY 2006 VL 107 IS 8 SU S BP 1962 EP 1970 DI 10.1002/cncr.22149 PG 9 WC Oncology SC Oncology GA 095DX UT WOS:000241289500007 PM 16986164 ER PT J AU Goldstein, AM Chan, M Harland, M Gillanders, EM Hayward, NK Avril, MF Azizi, E Bianchi-Scarra, G Bishop, DT Bressac-de Paillerets, B Bruno, W Calista, D Albright, LAC Demenais, F Elder, DE Ghiorzo, P Gruis, NA Hansson, J Hogg, D Holland, EA Kanetsky, PA Kefford, RF Landi, MT Lang, J Leachman, SA MacKie, RM Magnusson, V Mann, GJ Niendorf, K Bishop, JN Palmer, JM Puig, S Puig-Butille, JA de Snoo, FA Stark, M Tsao, H Tucker, MA Whitaker, L Yakobson, E AF Goldstein, Alisa M. Chan, May Harland, Mark Gillanders, Elizabeth M. Hayward, Nicholas K. Avril, Marie-Francoise Azizi, Esther Bianchi-Scarra, Giovanna Bishop, D. Timothy Bressac-de Paillerets, Brigitte Bruno, William Calista, Donato Cannon Albright, Lisa A. Demenais, Florence Elder, David E. Ghiorzo, Paola Gruis, Nelleke A. Hansson, Johan Hogg, David Holland, Elizabeth A. Kanetsky, Peter A. Kefford, Richard F. Landi, Maria Teresa Lang, Julie Leachman, Sancy A. MacKie, Rona M. Magnusson, Veronica Mann, Graham J. Niendorf, Kristin Newton Bishop, Julia Palmer, Jane M. Puig, Susana Puig-Butille, Joan A. de Snoo, Femke A. Stark, Mitchell Tsao, Hensin Tucker, Margaret A. Whitaker, Linda Yakobson, Emanuel CA Lund Melanoma Stdy Grp Melanoma Genetics Consortium GenoM TI High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL SO CANCER RESEARCH LA English DT Article ID MULTIPLE PRIMARY MELANOMAS; POPULATION-BASED SAMPLE; FAMILIAL MELANOMA; GERMLINE MUTATIONS; CDKN2A MUTATIONS; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; PRONE FAMILIES; CDK4 MUTATION; P16 AB GenoMEL, comprising major familial melanoma research groups from North America, Europe, Asia, and Australia has created the largest familial melanoma sample yet available to characterize mutations in the high-risk melanoma susceptibility genes CDKN2A/alternate reading frames (ARF), which encodes p16 and p14ARF, and CDK4 and to evaluate their relationship with pancreatic cancer (PC), neural system tumors (NST), and uveal melanoma (UM). This study included 466 families (2,137 patients) with at least three melanoma patients from 17 GenoMEL centers. Overall, 41% (n = 190) of families had mutations; most involved p16 (n = 178). Mutations in CDK4 (n = 5) and ARF (n = 7) occurred at similar frequencies (2-3%). There were striking differences in mutations across geographic locales. The proportion of families with the most frequent founder mutation(s) of each locale differed significantly across the seven regions (P = 0.0009). Single founder CDKN2A mutations were predominant in Sweden (p.R112_L113insR, 92% of family's mutations) and the Netherlands (c.225_243del19, 90% of family's mutations). France, Spain, and Italy had the same most frequent mutation (p.G101W). Similarly, Australia and United Kingdom had the same most common mutations (p.M53I, cdVS2-105A > G, p.R24P, and p.L32P). As reported previously, there was a strong association between PC and CDKN2A mutations (P < 0.0001). This relationship differed by mutation. In contrast, there was little evidence for an association between CDKN2A mutations and NST (P = 0.52) or UM (P = 0.25). There was a marginally significant association between NST and ARF (P = 0.05). However, this particular evaluation had low power and requires confirmation. This GenoMEL study provides the most extensive characterization of mutations in high-risk melanoma susceptibility genes in families with three or more melanoma patients yet available. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Inherited Dis Res Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Canc Res UK Clin Ctr, Genet Epidemiol Div, Leeds, W Yorkshire, England. Univ Glasgow, Dept Med Genet, Glasgow, Lanark, Scotland. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW 2006, Australia. Inst Gustave Roussy, Serv Dermatol, F-94805 Villejuif, France. Inst Gustave Roussy, Serv Genet, F-94805 Villejuif, France. Univ Evry, INSERM, U794, Evry, France. Tel Aviv Univ, Sackler Fac Med, Chaim Sheba Med Ctr, Dept Internal Med C,Mol Cell Biol Lab, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Dermatol, IL-69978 Tel Aviv, Israel. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy. Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands. Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden. Karolinska Univ Hosp Solna, Stockholm, Sweden. Univ Hosp, Lund Canc Ctr, Dept Oncol, Lund, Sweden. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Barcelona, Dept Dermatol, Barcelona, Spain. Univ Barcelona, Genet Serv, Melanoma Unit,Hosp Clin, Inst Invest Biomed August Pi Surie, Barcelona, Spain. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Execut Plaza S,Room 7004,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. EM goldstea@exchange.nih.gov RI Stark, Mitchell/E-3542-2010; Hoiom, Veronica/F-4153-2012; Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013; Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015; Whiteman, David/P-2728-2014; Bruno, William/N-7477-2013; OI Stark, Mitchell/0000-0002-4510-2161; Mann, Graham/0000-0003-1301-405X; Gruis, Nelleke/0000-0002-5210-9150; Bianchi Scarra, Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936; hayward, nicholas/0000-0003-4760-1033; Whiteman, David/0000-0003-2563-9559; Bruno, William/0000-0002-0337-0168; Bishop, Tim/0000-0002-8752-8785; albright, lisa/0000-0003-2602-3668; Puig, Susana/0000-0003-1337-9745; Martin, Nicholas/0000-0003-4069-8020 FU Intramural NIH HHS; NCI NIH HHS [N01-PC-35141, 1 R01 CA83115-01A2, R01 CA 88363, R01 CA102422] NR 60 TC 200 Z9 200 U1 1 U2 14 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 OCT 15 PY 2006 VL 66 IS 20 BP 9818 EP 9828 DI 10.1158/0008-5472.CAN-06-0494 PG 11 WC Oncology SC Oncology GA 096QU UT WOS:000241392700007 PM 17047042 ER PT J AU Hyodo, F Matsumoto, K Matsumoto, A Mitchell, JB Krishna, MC AF Hyodo, Fuminori Matsumoto, Ken-ichiro Matsumoto, Atsuko Mitchell, James B. Krishna, Murali C. TI Probing the intracellular redox status of tumors with magnetic resonance imaging and redox-sensitive contrast agents SO CANCER RESEARCH LA English DT Article ID NITROXIDE SPIN LABELS; BREAST-CANCER; PROSTATE-CANCER; SOD MIMICS; REDUCTION; RADICALS; CELL; MRI; QUANTIFICATION; IDENTIFICATION AB Nitroxide radicals are paramagnetic contrast agents, used in magnetic resonance imaging (MRI), that also exert antioxidant effects. Participating in cellular redox reactions, they lose their ability to provide contrast as a function of time after administration. In this study, the rate of contrast loss was correlated to the reducing power of the tissue or the "redox status." The preferential reduction of nitroxides in tumors compared with normal tissue was observed by MRI. The influence of the structure of the nitroxide on the reduction rate was investigated by Mill using two cell-permeable nitroxides, 4-hydroxy-2,2,6,6,-tetramethyl-1-piperidynyloxyl (Tempol) and 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP), and one cell-impermeable nitroxide, 3-carboxy-2, 2,5,5,5-tetramethylpyrrolidine-1-oxyl (3CxP). Pharmacokinetic images of these nitroxides in normal tissue, tumor, kidney, and artery regions in mice were simultaneously obtained using MRI. The decay of Tempol and 3CP in tumor tissue was significantly faster than in normal tissue. No significant change in the total nitroxide (oxidized + reduced forms) was noted from tissue extracts, suggesting that the loss in contrast as a function of time is a result of intracellular bioreduction. However, in the case of 3CxP (membrane impermeable), there was no difference in the reduction rates between normal and tumor tissue. The time course of T, enhancement by 3CxP and the total amount of 3CxP (oxidized + reduced) in the femoral region showed similar pharmacokinetics. These results show that the differential bioreduction of cell-permeable nitroxides in tumor and normal tissue is supported by intracellular processes and the reduction rates are a means by which the intracellular redox status can be assessed noninvasively. C1 NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 45 TC 89 Z9 91 U1 3 U2 19 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 OCT 15 PY 2006 VL 66 IS 20 BP 9921 EP 9928 DI 10.1158/0008-5472.CAN-06-0879 PG 8 WC Oncology SC Oncology GA 096QU UT WOS:000241392700019 PM 17047054 ER PT J AU Lee, TK Man, K Poon, RTP Lo, CM Yuen, AP Ng, IO Ng, KT Leonard, W Fan, ST AF Lee, Terence K. Man, Kwan Poon, Ronnie T. P. Lo, Chung Mau Yuen, Anthony P. Ng, Irene O. Ng, Kevin T. Leonard, Warren Fan, Sheung Tat TI Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial-mesenchymal transition SO CANCER RESEARCH LA English DT Article ID CELLS; EXPRESSION; CANCER; CARCINOGENESIS; HEPATITIS; STAT5B; RISK; SRC; DIFFERENTIATION; MORPHOGENESIS AB Poor prognosis of hepatocellular carcinoma (HCC) is associated with a high potential of vascular invasion and metastasis. Epithelial-mesenchymal transition (EMT) is a key event in the tumor invasion process. Recently, signal transducers and activators of transcription 5 (STAT5) has been linked to tumor progression by EMT induction. However, the precise roles of STAT5 genes (STAT5a and STAT5b) in human epithelial cancers have not been elucidated clearly. The aim of this study is to analyze the roles of STAT5 isoforms in HCC progression using HCC clinical samples. We showed that activation of STAT5b, but not STAT5a, was found in HCC clinical samples and its expression was significantly associated with younger age (P = 0.037), advanced tumor stages (P = 0.003), venous infiltration (P = 0.016), microsatellite formation (P = 0.024), multiple tumor nodules (P = 0.02), and poor patient survival. To specifically investigate the mechanism underlying constitutive activation of STAT5b in HCC, EGFP-HBX was introduced into Huh-7 cells. STAT5b activation in HCC is at least partially mediated by HBX activation. Ectopic STAT5b transfection conferred increased HCC cell motility and invasiveness by induction of EMT changes. In conclusion, STAT5b activation enhanced HCC aggressiveness by induction of EMT, which was possibly mediated by HBX activation. STAT5b could serve as a novel molecular target for HCC treatment. C1 Univ Hong Kong, Ctr Canc Res, Pokfulam, Hong Kong, Peoples R China. Univ Hong Kong, Dept Surg, Pokfulam, Hong Kong, Peoples R China. Univ Hong Kong, Dept Pathol, Pokfulam, Hong Kong, Peoples R China. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Man, K (reprint author), Univ Hong Kong, Dept Surg, L9-55,Fac Med Bldg,21 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. EM kwanman@hkucc.hku.hk; poontp@hkucc.hku.hk RI Man, Kwan/C-4365-2009; Poon, Ronnie/C-4383-2009; Lo, Chung Mau/C-4352-2009; Fan, Sheung Tat/C-4138-2009; Ng, Tak Pan/C-4698-2009 NR 35 TC 66 Z9 77 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2006 VL 66 IS 20 BP 9948 EP 9956 DI 10.1158/0008-5472.CAN-06-1092 PG 9 WC Oncology SC Oncology GA 096QU UT WOS:000241392700022 PM 17047057 ER PT J AU Kovacic, MB Castle, PE Herrero, R Schiffman, M Sherman, ME Wacholder, S Rodriguez, AC Hutchinson, ML Bratti, MC Hildesheim, A Morales, J Alfaro, M Burk, RD AF Kovacic, Melinda Butsch Castle, Philip E. Herrero, Rolando Schiffman, Mark Sherman, Mark E. Wacholder, Sholom Rodriguez, Ana C. Hutchinson, Martha L. Bratti, M. Concepcion Hildesheim, Allan Morales, Jorge Alfaro, Mario Burk, Robert D. TI Relationships of human papillomavirus type, qualitative viral load, and age with cytologic abnormality SO CANCER RESEARCH LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ATYPICAL SQUAMOUS CELLS; CARCINOMA IN-SITU; HYBRID CAPTURE; HIGH-RISK; COSTA-RICA; UNDETERMINED SIGNIFICANCE; CANCER WORLDWIDE; DNA DETECTION; WOMEN AB Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for similar to 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% Cl), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha 3/alpha 15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha 9/alpha 11/alpha 7/alpha 5/alpha 6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (> 54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha 9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha 7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha 7-related lesions. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. Caja Costarricense Seguro Social, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Caja Costarricense Seguro Social, Lab Nacl Citol, San Jose, Costa Rica. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Kovacic, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Suite 550,EPS MSC 7234, Bethesda, MD 20892 USA. EM kovacicm@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA78527, N01-CP-33061, N01-CP-21081, N01-CP-40542, N01-CP-50535, N01-CP-81023] NR 47 TC 85 Z9 88 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 OCT 15 PY 2006 VL 66 IS 20 BP 10112 EP 10119 DI 10.1158/0008-5472.CAN-06-1812 PG 8 WC Oncology SC Oncology GA 096QU UT WOS:000241392700040 PM 17047075 ER PT J AU Okamoto, H Li, J Vortmeyer, AO Jaffe, H Lee, YS Glasker, S Sohn, TS Zeng, WF Ikejiri, B Proescholdt, MA Mayer, C Weil, RJ Oldfield, EH Zhuang, ZP AF Okamoto, Hiroaki Li, Jie Vortmeyer, Alexander O. Jaffe, Howard Lee, Youn-Soo Glasker, Sven Sohn, Tae-Sung Zeng, Weifen Ikejiri, Barbara Proescholdt, Martin A. Mayer, Christina Weil, Robert J. Oldfield, Edward H. Zhuang, Zhengping TI Comparative proteomic profiles of meningioma subtypes SO CANCER RESEARCH LA English DT Article ID MACROPHAGE ACTIVATING FACTOR; D-BINDING PROTEIN; TUMOR-SUPPRESSOR; ANAPLASTIC MENINGIOMAS; HUMAN GLIOMAS; MALIGNANT MENINGIOMAS; SPORADIC MENINGIOMAS; GENETIC MODEL; CELL-DEATH; NF2 GENE AB Meningiomas are classified into three groups (benign, atypical, and anaplastic) based on morphologic characteristics. Atypical meningiomas, which are WHO grade 2 tumors, and anaplastic meningiomas, which are WHO grade 3 tumors, exhibit an increased risk of recurrence and premature death compared with benign WHO grade I tumors. Although atypical and anaplastic meningiomas account for < 10% of all of meningiomas, it can be difficult to distinguish them from benign meningiomas by morphologic criteria alone. We used selective tissue microdissection to examine 24 human meningiomas and did two-dimensional gel electrophoresis to determine protein expression patterns. Proteins expressed differentially by meningiomas of each WHO grade were identified and sequenced. Proteomic analysis revealed protein expression patterns unique to WHO grade 1, 2, and 3 meningiomas and identified 24 proteins that distinguish each subtype. Fifteen proteins showed significant changes in expression level between benign and atypical meningiomas, whereas nine distinguished atypical from anaplastic meningiomas. Differential protein expression was confirmed by Western blotting and immunohistochemistry. We established differential proteomic profiles that characterize and distinguish meningiomas of increasing grades. The proteins and proteomic profiles enhance understanding of the pathogenesis of meningiomas and have implications for diagnosis, prognosis, and treatment. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. Saga Univ, Fac Med, Dept Neurosurg, Saga 840, Japan. Catholic Univ Korea, Coll Med, Dept Clin Pathol, Seoul, South Korea. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. Univ Regensburg, Med Ctr, Dept Neurosurg, D-8400 Regensburg, Germany. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D 37,10 Ctr Dr, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov FU Intramural NIH HHS NR 45 TC 23 Z9 23 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 OCT 15 PY 2006 VL 66 IS 20 BP 10199 EP 10204 DI 10.1158/0008-5472.CAN-06-0955 PG 6 WC Oncology SC Oncology GA 096QU UT WOS:000241392700050 PM 17047085 ER PT J AU Stolzenberg-Solomon, RZ Vieth, R Azad, A Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, Rachael Z. Vieth, Reinhold Azad, Azar Pietinen, Pirjo Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers SO CANCER RESEARCH LA English DT Article ID INSULIN-RECEPTOR GENE; D DEFICIENCY; D ANALOGS; 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE; 1,25-DIHYDROXYVITAMIN D-3; D METABOLITES; HEIGHT; SECRETION; GLUCOSE; CELLS AB Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies. Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [25(OH)D]. Pancreatic islet and duct cells express 25(OH)D-3-1 alpha-hydroxylase that generates the biologically active 1,25(OH)2 vitamin D form. Thus, 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology. We conducted a prospective nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort of male Finnish smokers, ages 50 to 69 years at baseline, to test whether more adequate vitamin D status, as determined by prediagnostic serum 25(OH)D concentrations, was associated with lower pancreatic cancer risk. Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 (up to 16.7 years of follow-up) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, > 65.5 versus < 32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, P-trend = 0.001) that remained after excluding cases diagnosed early during follow-up. Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer. C1 NCI, Nutr Epidemiol Brnach, US Dept HHS, Rockville, MD USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS, Rockville, MD USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Stolzenberg-Solomon, RZ (reprint author), 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM rs221z@nih.gov RI zhao, yanrong/D-1885-2013; Albanes, Demetrius/B-9749-2015 OI zhao, yanrong/0000-0002-0627-6003; FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 41 TC 118 Z9 123 U1 1 U2 5 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 OCT 15 PY 2006 VL 66 IS 20 BP 10213 EP 10219 DI 10.1158/0008-5472.CAN-06-1876 PG 7 WC Oncology SC Oncology GA 096QU UT WOS:000241392700052 PM 17047087 ER PT J AU Stein, WD Litman, T AF Stein, Wilfred D. Litman, Thomas TI Data on the recurrence of breast tumors fit a model in which dormant cells are subject to slow attrition but can randomly awaken to become malignant SO CELL CYCLE LA English DT Article DE breast cancer; tumor recurrence; metastasis; multi-hit models; dormancy; attrition; pancreas ID CANCER METASTASIS; GENES; EXPRESSION; SIGNATURE; SURVIVAL AB We successfully modeled the recurrence of tumors in breast cancer patients, assuming that: (i) A breast cancer patient is likely to have some circulating metastatic cells, even after initial surgery. (ii) These metastatic cells are dormant. (iii) The dormant cells are subject to attrition by the body's immune system, or by random apoptosis or senescence. (iv) Recurrence suppressor mechanisms exist. (v) When such genes are disabled by random mutations, the dormant metastatic cell is activated, and will develop to a cancer recurrence. The model was also fitted to data on the survival of pancreatic cancer patients. The time course of cancer recurrence in a group of poor prognosis breast cancer patients could not be linked to the over- (or under-) expression of any gene in the primary tumors from which the recurrent tumors derived. Thus, the recurrence of the tumor in breast cancer patients appears to be a random event. Inasmuch as the kinetics of cancer recurrence in published data sets closely follows the model found for the appearance of sporadic retinoblastoma, tumor recurrence could be triggered by mutations in awakening- suppressor mechanisms. The retinoblastoma tumor suppressor gene was identified by tracing its occurrence in familial retinoblastoma pedigrees. Will it be possible to track the postulated cancer recurrence, awakening suppressor gene(s) in early recurrence breast cancer patients? C1 Hebrew Univ Jerusalem, IL-96263 Jerusalem, Israel. NCI, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, DK-1168 Copenhagen, Denmark. RP Stein, WD (reprint author), Hebrew Univ Jerusalem, 18 Shachar, IL-96263 Jerusalem, Israel. EM wdstein@huji.ac.il NR 17 TC 1 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 15 PY 2006 VL 5 IS 20 BP 2348 EP 2353 DI 10.4161/cc.5.20.3349 PG 6 WC Cell Biology SC Cell Biology GA 098KR UT WOS:000241519900012 PM 17102622 ER PT J AU Babu, MM Balaji, S Iyer, LM Aravind, L AF Babu, M. Madan Balaji, S. Iyer, Lakshminarayan. M. Aravind, L. TI Estimating the prevalence and regulatory potential of the telomere looping effect in yeast transcription regulation SO CELL CYCLE LA English DT Article DE telomere looping effect (TLE); long range regulation; telomere; transciptional network; chromatin looping ID SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; RIBOSOMAL-PROTEIN; FUNCTIONAL-ORGANIZATION; CHROMOSOME DYNAMICS; GLOBIN GENE; IN-VIVO; CHROMATIN; EVOLUTION; POSITION AB Telomeres have long been implicated in the regulation of gene expression. Some studies have reported that telomere looping effect (TLE) can juxtapose genes and regulatory sequences that are far apart and facilitate long-distance control of gene expression. In this work, we report a detailed investigation on the prevalence and regulatory potential of TLE on a genomic scale by assembling data on protein-DNA interactions from several large-scale ChIp-chip experiments in Saccharomyces cerevisiae. Analysis of the assembled data revealed that a statistically significant number of DNA segments that were inferred to be bound by ten or more transcription factors in these experiments physically mapped to the ends of several chromosomes (19 of 32 chromosome ends). For the 83 transcription factors that were inferred to interact with these DNA segments, we found a statistically significant skew in the distribution of their internal binding sites over the length of the entire chromosome, such that more than expected binding events occurred proximal to chromosomal ends than elsewhere. Taken together these observations suggest that the telomere looping effect is their most likely explanation and imply that a notable fraction of the internally bound yeast transcription factors potentially interact with looped back telomeres. Further, we also identified several components of the basal transcriptional machinery that are also frequently linked to these chromosome end segments, strengthening the proposal for a direct interaction between the chromo some ends and internally located transcriptional complexes. We observed that certain chromatin factors might participate in the TLE and potentially modulate gene expression by chromatin modifications such as histone deacetylation. Our findings provide the first computational evidence for a significant role of long-range regulatory interactions due to telomere looping. Based on these observations, we also propose that genome-wide chromatin immunoprecipitation data might be useful to systematically uncover long-range chromatin looping effects in gene expression. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM madanm@mrc-lmb.cam.ac.uk; aravind@ncbi.nlm.nih.gov FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 90 TC 5 Z9 5 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 15 PY 2006 VL 5 IS 20 BP 2354 EP 2363 DI 10.4161/cc.5.20.3386 PG 10 WC Cell Biology SC Cell Biology GA 098KR UT WOS:000241519900013 PM 17102608 ER PT J AU Darcy, V Abdullaev, ZK Pore, N Docquier, F Torrano, V Chernukhin, I Smart, M Farrar, D Metodiev, M Fernandez, N Richard, C Delgado, MD Lobanenkov, V Klenova, E AF Darcy, Vivien Abdullaev, Ziedulla K. Pore, Naresh Docquier, France Torrano, Veronica Chernukhin, Igor Smart, Melissa Farrar, Dawn Metodiev, Metodi Fernandez, Nelson Richard, Carlos Delgado, M. Dolores Lobanenkov, Victor Klenova, Elena TI The potential of BORIS detected in the leukocytes of breast cancer patients as an early marker of tumorigenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER/TESTIS ANTIGENS; PROSTATE-CANCER; TUMOR-MARKERS; CTCF; EXPRESSION; CELLS; NEUTROPHILS; BIOMARKER; BINDING; PROTEIN AB Purpose: Brother of the regulator of imprinted sites (BORIS) is a novel member of the cancer testis antigen gene family. These genes are normally expressed only in spermatocytes but abnormally activated in different malignancies, including breast cancer. The aim of this study was to investigate the expression of BORIS in the leukocytes of breast cancer patients and the correlation between BORIS levels and clinical /pathologic variables. Experimental Design: Leukocytes were obtained from whole blood of 87 breast cancer patients and 52 donors not diagnosed with cancer. BORIS protein was detected in leukocytes by immunohistochemical staining; the immunoreactivity score (IRS) of each sample was determined. Additionally, BORIS expression was assessed by Western blot analysis and real-time reverse transcription-PCR. Results: We describe significantly high levels of BORIS (IRS = 4.25 +/- 0.034) in a subpopulation of leukocytes, the neutrophil polymorphonuclear granulocytes, in 88.5% of breast cancer patients. Increased IRS for BORIS in these patients correlated with increased tumor size. In comparison, 19.2% samples from the control group were BORIS positive with only very low levels of BORIS (IRS = 0.25 +/- 0.009). Conclusion: We report here the novel finding of BORIS expression in polymorphonuclear granulocytes of breast cancer patients. This tumor-related occurrence is a phenomenon not observed in donors with injuries and immune and inflammatory diseases. Detection of BORIS in a high proportion of patients with various types of breast tumors indicates that BORIS can be a valuable early blood marker of breast cancer. We conclude that BORIS represents a new class of cancer biomarkers different from those currently used in medical practice. C1 Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD USA. Univ Cantabria, CSIC, Unidad Biomed, Dept Biol Mol,Grp Biol Mol Canc, Santander, Spain. Hosp Univ Marques Valdecilla, Inst Formac & Invest Marques Valdecilla, Serv Hematol, Santander, Spain. Anglia Ruskin Univ, Helen Rollason Canc Care Lab, Chelmsford, Essex, England. RP Klenova, E (reprint author), Univ Essex, Dept Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM klenovae@essex.ac.uk RI Torrano Moya, Veronica/D-3285-2014; OI Lobanenkov, Victor/0000-0001-6665-3635; Metodiev, Metodi V/0000-0001-6810-0719; Smart, Melissa/0000-0002-2655-3880 FU Medical Research Council [G0401088]; Wellcome Trust; Worldwide Cancer Research [99-0514] NR 45 TC 28 Z9 28 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 OCT 15 PY 2006 VL 12 IS 20 BP 5978 EP 5986 DI 10.1158/1078-0432.CCR-05-2731 PN 1 PG 9 WC Oncology SC Oncology GA 097SH UT WOS:000241468300011 PM 17062669 ER PT J AU Kershaw, MH Westwood, JA Parker, LL Wang, G Eshhar, Z Mavroukakis, SA White, DE Wunderlich, JR Canevari, S Rogers-Freezer, L Chen, CC Yang, JC Rosenberg, SA Hwu, P AF Kershaw, Michael H. Westwood, Jennifer A. Parker, Linda L. Wang, Gang Eshhar, Zelig Mavroukakis, Sharon A. White, Donald E. Wunderlich, John R. Canevari, Silvana Rogers-Freezer, Linda Chen, Clara C. Yang, James C. Rosenberg, Steven A. Hwu, Patrick TI A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; FOLATE-BINDING-PROTEIN; MONOCLONAL-ANTIBODY; PROSTATE-CANCER; METASTATIC MELANOMA; CARCINOMA PATIENTS; ANTITUMOR-ACTIVITY; THERAPY; ANTIGEN; RECEPTOR AB Purpose: A phase I study was conducted to assess the safety of adoptive immunotherapy using gene-modified autologous T cells for the treatment of metastatic ovarian cancer. Experimental Design: T cells with reactivity against the ovarian cancer-associated antigen a-folate receptor (FR) were generated by genetic modification of autologous T cells with a chimeric gene incorporating an anti-FR single-chain antibody linked to the signaling domain of the Fc receptor gamma chain. Patients were assigned to one of two cohorts in the study. Eight patients in cohort 1 received a dose escalation of T cells in combination with high-dose interleukin-2, and six patients in cohort 2 received dual-specific T cells (reactive with both FR and allogeneic cells) followed by immunization with allogeneic peripheral blood mononuclear cells. Results: Five patients in cohort 1 experienced some grade 3 to 4 treatment-related toxicity that was probably due to interleukin-2 administration, which could be managed using standard measures. Patients in cohort 2 experienced relatively mild side effects with grade 1 to 2 symptoms. No reduction in tumor burden was seen in any patient. Tracking In-111-labeled adoptively transferred T cells in cohort 1 revealed a lack of specific localization of T cells to tumor except in one patient where some signal was detected in a peritoneal deposit. PCR analysis showed that gene-modified T cells were present in the circulation in large numbers for the first 2 days after transfer, but these quickly declined to be barely detectable 1 month later in most patients. An inhibitory factor developed in the serum of three of six patients tested over the period of treatment, which significantly reduced the ability of gene-modified T cells to respond against FR+ tumor cells. Conclusions: Large numbers of gene-modified tumor-reactive T cells can be safely given to patients, but these cells do not persist in large numbers long term. Future studies need to employ strategies to extend T cell persistence. This report is the first to document the use of genetically redirected T cells for the treatment of ovarian cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Peter MacCallum Canc Ctr, Canc Immunol Res Program, Melbourne, Vic, Australia. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Ist Nazl Tumori, I-20133 Milan, Italy. RP Hwu, P (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1515 Holcombe Blvd,Unit 430, Houston, TX 77030 USA. EM phwu@mdanderson.org OI Kershaw, Michael/0000-0002-2697-487X FU Intramural NIH HHS [Z01 SC003811-32] NR 34 TC 414 Z9 429 U1 6 U2 45 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 OCT 15 PY 2006 VL 12 IS 20 BP 6106 EP 6115 DI 10.1158/1078-0432.CCR-06-1183 PN 1 PG 10 WC Oncology SC Oncology GA 097SH UT WOS:000241468300030 PM 17062687 ER PT J AU Anaissie, EJ Segal, BH Graybill, JR Arndt, C Perfect, JR Kleinberg, M Pappas, P Benjamin, D Rubin, R Aberg, JA Adderson, EE Adler-Shohet, FC Akan, H Akova, M Almyroudis, NG Alexander, BD Andes, D Arrieta, A Baddley, JW Barron, MA Belzberg, H Boucher, HW Boyce, TG Casadevall, A Chandrasekar, PH Cleary, JD Cordonnier, C Cornely, OA Cuenca-Estrella, M Daly, JS Daoura, N Denning, DW dePauw, B de Repentigny, L Dignani, MC Dismukes, WE Donnelly, JP Donowitz, GR Dupont, B Drusano, G Ellis, M Espinel-Ingroff, A Fishman, JA Fleming, R Forrest, G Ghannoum, M Goldman, M Grazziutti, M Greene, JN Greenberg, RN Gubbins, PO Hadley, S Herbrecht, R Hiemenz, JW Hope, W Hospenthal, DR Husain, S Ito, JI Jacobson, RM Johnson, M Keating, MR Kett, DH Knapp, K Kontoyiannis, DP Krcmery, VC Larsen, R Laverdiere, M Ljungman, P Lortholary, O Maertens, J Marriott, D Mattiuzzi, G McGinnis, MR Morris, M Nucci, M Odds, FC Pankey, GA Patterson, T Pfaller, M Razonable, RR Reboli, AC Rinaldi, MG Roberts, GD Tudela, JL Rotstein, C Ruhnke, M Schuster, M Shoham, S Sia, IG Siebel, N Silviera, F Singh, N Sobel, J Solomkin, JS Sorrell, TC Steinbach, WJ Temesgen, Z Tortorano, A Vartivarian, S VerWeij, P Viscoli, C Viviani, MA Walker, RC Wheat, JL Wiley, J Williamson, P Wingard, JR Yu, VL Zaoutis, T AF Anaissie, Elias J. Segal, Brahm H. Graybill, John R. Arndt, Carola Perfect, John R. Kleinberg, Michael Pappas, Peter Benjamin, Danny Rubin, Robert Aberg, Judith A. Adderson, Elisabeth E. Adler-Shohet, Felice C. Akan, Hamdi Akova, Murat Almyroudis, Nikolaos G. Alexander, Barbara D. Andes, David Arrieta, Antonio Baddley, John W. Barron, Michelle A. Belzberg, Howard Boucher, Helen W. Boyce, Thomas G. Casadevall, Arturo Chandrasekar, P. H. Cleary, John D. Cordonnier, Catherine Cornely, Oliver A. Cuenca-Estrella, Manuel Daly, Jennifer S. Daoura, Nicholas Denning, David W. dePauw, Ben de Repentigny, Louis Dignani, Maria Cecilia Dismukes, William E. Donnelly, J. Peter Donowitz, Gerald R. Dupont, Bertrand Drusano, George Ellis, Michael Espinel-Ingroff, Ana Fishman, Jay A. Fleming, Rhonda Forrest, Graeme Ghannoum, Mahmoud Goldman, Mitchell Grazziutti, Monica Greene, John N. Greenberg, Richard N. Gubbins, Paul O. Hadley, Susan Herbrecht, Raoul Hiemenz, John W. Hope, William Hospenthal, Durane R. Husain, Shahid Ito, James I. Jacobson, Robert M. Johnson, Melissa Keating, Michael R. Kett, Daniel H. Knapp, Katherine Kontoyiannis, Dimitrios P. Krcmery, Vladimir C. Larsen, Robert Laverdiere, Michel Ljungman, Per Lortholary, O. Maertens, Johan Marriott, Debbie Mattiuzzi, Gloria McGinnis, Michael R. Morris, Michele Nucci, Marcio Odds, Frank C. Pankey, George A. Patterson, Thomas Pfaller, Mike Razonable, Raymond R. Reboli, Annette C. Rinaldi, Michael G. Roberts, Glenn D. Rodriguez Tudela, Juan Luis Rotstein, Coleman Ruhnke, Markus Schuster, Mindy Shoham, Shmuel Sia, Irene G. Siebel, Nita Silviera, Fernanda Singh, Nina Sobel, Jack Solomkin, Joseph S. Sorrell, Tania C. Steinbach, William J. Temesgen, Zelalem Tortorano, AnnaMaria Vartivarian, Shahe VerWeij, Paul Viscoli, Claudio Viviani, Maria Anna Walker, Randall C. Wheat, Joseph L. Wiley, Joseph Williamson, Peter Wingard, John R. Yu, Victor L. Zaoutis, Theoklis TI Clinical research in the lay press: Irresponsible journalism raises a huge dose of doubt SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LIPOSOMAL AMPHOTERICIN-B; EMPIRICAL ANTIFUNGAL THERAPY; ACUTE-RENAL-FAILURE; INVASIVE ASPERGILLOSIS; NEUTROPENIC PATIENTS; PERSISTENT FEVER; DOUBLE-BLIND; CASPOFUNGIN; CANCER; SAFETY C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharm Practice, Little Rock, AR 72205 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA. Metropolitan Infect Dis, Houston, TX USA. Texas Tech Univ, Hlth Sci Ctr, Div Infect Dis, El Paso, TX USA. Univ Texas, Dept Pathol, Galveston, TX 77555 USA. Univ Texas, Dept Dermatol, Galveston, TX 77555 USA. Univ Texas, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Brooke Army Med Ctr, Infect Dis Serv, Ft Sam Houston, TX 78234 USA. Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Childrens Hosp Sinai, Div Pediat Hematol Oncol, Dept Pediat, Baltimore, MD USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. Univ Pittsburgh, Div Infect Dis, Dept Med, Pittsburgh, PA USA. Childrens Hosp Philadelphia, Dept Pediat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. Ochsner Clin Fdn, New Orleans, LA USA. Louisiana State Univ, Feist Weiller Canc Ctr, Hlth Sci Ctr, Shreveport, LA 71105 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med Genet, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Microbiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Infect Dis, Durham, NC 27710 USA. Duke Univ, Med Ctr, Clin Mycol Lab, Durham, NC 27710 USA. Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Tufts Univ, Sch Med, Div Geog Med, Tufts New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Div Infect Dis, Tufts New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Crit Care Serv, Los Angeles, CA USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Childrens Hosp Orange Cty, Los Angeles, CA USA. Miller Childrens Hosp, Long Beach, CA USA. City Hope Natl Med Ctr, Dept Infect Dis, Duarte, CA 91010 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA USA. Univ Florida, Coll Med, Dept Infect Dis, H Lee Moffitt Canc Ctr, Tampa, FL USA. Jackson Mem Hosp, Med Intens Care Unite, Miami, FL 33136 USA. Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33152 USA. Mayo Clin, Coll Med, Div Infect Dis, Dept Med, Jacksonville, FL 32224 USA. Univ Florida, Coll Med, Dept Med, Div Hematol Oncol, Gainesville, FL USA. Indiana Univ, Sch Med, Dept Med, Immunocompromised Infect Dis Serv, Indianapolis, IN 46204 USA. MiraVista Diagnost MiraBella Technol, Indianapolis, IN USA. Univ Colorado, Dept Med, Div Infect Dis, Denver, CO 80202 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Microbiol, Madison, WI USA. Univ Virginia, Hlth Syst, Dept Med, Charlottesville, VA USA. Virginia Commonwealth Univ, Med Ctr, Dept Med, Richmond, VA USA. Mayo Clin, Div Clin Microbiol, Rochester, NY USA. Mayo Clin, Dept Pediat, Rochester, NY USA. Mayo Clin, Dept Med, Div Infect Dis, Rochester, NY USA. Mayo Clin, Coll Med, Dept Med, Div Infect Dis, Buffalo, NY USA. Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. NYU, Sch Med, New York, NY USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, New York, NY USA. Roswell Pk Canc Ctr, Div Infect Dis, Buffalo, NY USA. Albany Med Coll, Div Clin Pharmacol, Albany, NY USA. Univ Mississippi, Med Ctr, Sch Pharm, Dept Pharm Practice, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Sch Med, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Mycot Res Ctr, Dept Med,Div Infect Dis, Jackson, MS 39216 USA. Univ Kentucky, Sch Med, Div Infect Dis, Dept Internal Med, Lexington, KY 40536 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. George Washington Univ, Sch Med & Publ Hlth, Dept Pediat, Washington, DC USA. Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. Case Western Reserve Univ, Sch Med, Dept Dermatol, Cleveland, OH 44106 USA. Univ Cincinnati, Div Trauma & Crit Care, Dept Surg, Cincinnati, OH USA. Wayne State Univ, Div Infect Dis, Detroit, MI USA. Cooper Univ Hosp, Robert Wood Johnson Med Sch, Dept Med, Div Infect Dis, Camden, NJ USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Aberdeen, Dept Mycol, Aberdeen AB9 1FX, Scotland. Wythenshawe Hosp, Dept Med, Educ Res Ctr, Manchester M23 9LT, Lancs, England. Wythenshawe Hosp, Dept Med Mycol, Educ Res Ctr, Manchester M23 9LT, Lancs, England. Catholic Univ Louvain, Dept Clin Haematol, B-3000 Louvain, Belgium. Univ Nijmegen Hosp, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Hematol, NL-6500 HB Nijmegen, Netherlands. Radboud Univ Nijmegen Med Ctr, Dept Haematol, Nijmegen, Netherlands. Univ Nijmegen, Ctr Infect Dis, Nijmegen, Netherlands. Karolinska Inst, Dept Med, Stockholm, Sweden. Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden. Hosp Maisonneuve Rosemont, Dept Microbiol Infect Dis, Montreal, PQ, Canada. Univ Montreal, Hop St Justine, Dept Microbiol & Immunol, Montreal, PQ H3T 1C5, Canada. McMaster Univ, Div Infect Dis, Hamilton, ON, Canada. Hamilton Hlth Serv, Infect Dis Serv, Hamilton, ON, Canada. Hop Necker Enfants Malad, Serv Malad Infect & Trop, Paris, France. CHU Henri Mondor, Dept Hematol, F-94010 Creteil, France. Hop Hautepierre, Dept Hematol & Oncol, Strasbourg, France. Univ Fed Rio de Janeiro, Univ Hosp, Rio De Janeiro, Brazil. Univ Cologne, Dept Internal Med, Cologne, Germany. Charite Univ Med, Med Klin & Poliklin 2, Berlin, Germany. Fdn Fight Against Leukemia, Dept Infect Dis, Buenos Aires, DF, Argentina. Univ Milan, Dept Publ Hlth Microbiol & Virol, Milan, Italy. Univ Genoa, Div Infect Dis, San Martino Univ Hosp, Genoa, Italy. Ankara Univ, Dept Hematol, TR-06100 Ankara, Turkey. Ankara Univ, Bone Marrow Transplant Unit, TR-06100 Ankara, Turkey. Hacettepe Univ, Sch Med, Dept Med, Ankara, Turkey. Univ Sydney, Westmead Hosp, Ctr Infect Dis & Microbiol, Dept Infect Dis, Westmead, NSW 2145, Australia. St Vincents Hosp, Dept Clin Microbiol & Infect Dis, Darlinghurst, NSW 2010, Australia. Inst Salud Carlos III, Dept Mycol, Spanish Natl Ctr Microbiol, Madrid, Spain. United Arab Emirates Med Sch, Dept Med, Al Ain, U Arab Emirates. RP Anaissie, EJ (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham,Slot 816, Little Rock, AR 72205 USA. EM anaissieeliasj@uams.edu RI Nucci, Marcio/G-4515-2012; Herbrecht, Raoul/D-3471-2013; Verweij, P.E./H-8108-2014; OI Nucci, Marcio/0000-0003-4867-0014; Dignani, Maria Cecilia/0000-0002-7446-6183; Johnson, Melissa/0000-0002-6606-9460; Tortorano, Anna Maria/0000-0003-2093-8250; Herbrecht, Raoul/0000-0002-9381-4876; Denning, David/0000-0001-5626-2251; Jacobson, Robert/0000-0002-6355-8752; Hope, William/0000-0001-6187-878X NR 18 TC 2 Z9 2 U1 0 U2 2 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 OCT 15 PY 2006 VL 43 IS 8 BP 1031 EP 1039 DI 10.1086/509116 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 086IE UT WOS:000240666200013 PM 16983616 ER PT J AU Karaczyn, AA Golebiowski, F Kasprzak, KS AF Karaczyn, Aldona A. Golebiowski, Filip Kasprzak, Kazimierz S. TI Ni(II) affects ubiquitination of core histones H2B and H2A SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE nickel(II); histones; ubiquitination; histone H2B; histone H2A; lung cells; Rad6; UbcH6 ID DAMAGE-INDUCED RESPONSE; REPAIR PROTEIN XPA; DNA-REPAIR; CARCINOGENIC NICKEL(II); MOLECULAR MECHANISMS; EPITHELIAL-CELLS; GENE-EXPRESSION; H3 METHYLATION; H4 ACETYLATION; OXIDATIVE DNA AB The molecular mechanisms of nickel-induced malignant cell transformation include effects altering the structure and covalent modifications of core histories. Previously, we found that exposure of cells to Ni(II) resulted in truncation of histories H2A and H2B and thus elimination of some modification sites. Here, we investigated the effect of Ni(II) on one such modification, ubiquitination, of histories H2B and H2A in nuclei of cultured 1HAEo- and HPL1D human lung cells. After 1-5 days of exposure, Ni(II) up to 0.25 mM stimulated monoubiquitination of both histones, while at higher concentrations a suppression was found. Di-ubiquitination of H2A was not affected except for a drop after 5 days at 0.5 mM Ni(II). The decrease in mono-ubiquitination coincided with the appearance of truncated H2B that lacks the K120 ubiquitination site. However, prevention of truncation did not avert the decrease of H2B ubiquitination, indicating mechanistic independence of these effects. The changes in H2B ubiquitination did not fully coincide with concurrent changes in the nuclear levels of the ubiquitin-conjugating enzymes Rad6 and UbcH6. Overall, our results suggest that dysregulation of H2B ubiquitination is a part of Ni(II) adverse effects on gene expression and DNA repair which may assist in cell transformation. Published by Elsevier Inc. C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. RP Kasprzak, KS (reprint author), NCI, Lab Comparat Carcinogenesis, Bldg 538,Room 205E, Frederick, MD 21702 USA. EM kasprkaz@mail.ncifcrf.gov FU Intramural NIH HHS NR 58 TC 28 Z9 30 U1 0 U2 9 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 15 PY 2006 VL 312 IS 17 BP 3252 EP 3259 DI 10.1016/j.yexcr.2006.06.025 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 089UX UT WOS:000240907900005 PM 16870173 ER PT J AU Moon, HS Even-Ram, S Kleinman, HK Cha, HJ AF Moon, Hye-Sung Even-Ram, Sharona Kleinman, Hynda K. Cha, Hee-Jae TI Zyxin is upregulated in the nucleus by thymosin beta 4 in SiHa cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE actin; thymosin beta 4; migration; zyxin; focal adhesions; nucleus ID ACTIN CYTOSKELETAL ORGANIZATION; LIM DOMAIN; IN-VIVO; SEQUESTERING PROTEIN; CANCER CELLS; F-ACTIN; ADHESION; BINDING; BETA(4); EXPRESSION AB Thymosin beta 4 is a 43-amino acid actin-binding protein that promotes cell migration and is important in angiogenesis, wound healing, and tumor metastasis. We searched for genes upregulated by thymosin beta 4 and identified zyxin as increased in SiHa cells in the presence of exogenously added thymosin beta 4 and when thymosin beta 4 is overexpressed using adenoviral vectors. Both zyxin and thymosin beta 4 show increased localization in the nucleus. We conclude that thymosin beta 4 may exert some of its migration promoting activity via increased zyxin expression. Published by Elsevier Inc. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov OI Even-Ram, Sharona/0000-0002-5540-3822 NR 49 TC 19 Z9 22 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 15 PY 2006 VL 312 IS 17 BP 3425 EP 3431 DI 10.1016/j.yexcr.2005.07.021 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 089UX UT WOS:000240907900020 PM 16956606 ER PT J AU Bilodeau, S Vallette-Kasic, S Gauthier, Y Figarella-Branger, D Brue, T Berthelet, F Lacroix, A Batista, D Stratakis, C Hanson, J Meij, B Drouin, J AF Bilodeau, Steve Vallette-Kasic, Sophie Gauthier, Yves Figarella-Branger, Dominique Brue, Thierry Berthelet, France Lacroix, Andre Batista, Dalia Stratakis, Constantine Hanson, Jeanette Meij, Bjorn Drouin, Jacques TI Role of Brg1 and HDAC2 in GR trans-repression of the pituitary POMC gene and misexpression in Cushing disease SO GENES & DEVELOPMENT LA English DT Article DE repression; nuclear receptor; Swi/Snf; pituitary tumors; POMC; Cushing ID PROTEIN-PROTEIN-INTERACTION; ORPHAN NUCLEAR RECEPTORS; T-BOX FACTOR; NF-KAPPA-B; GLUCOCORTICOID-RECEPTOR; TRANSCRIPTIONAL REPRESSION; PROOPIOMELANOCORTIN GENE; TERMINAL DOMAIN; DNA-BINDING; FACTOR TPIT AB Negative feedback regulation of the proopiomelanocortin ( POMC) gene by the glucocorticoid (Gc) receptor (GR) is a critical feature of the hypothalamo-pituitary-adrenal axis, and it is in part exerted by trans-repression between GR and the orphan nuclear receptors related to NGFI-B. We now show that Brg1, the ATPase subunit of the Swi/Snf complex, is essential for this trans-repression and that Brg1 is required in vivo to stabilize interactions between GR and NGFI-B as well as between GR and HDAC2. Whereas Brg1 is constitutively present at the POMC promoter, recruitment of GR and HDAC2 is ligand-dependent and results in histone H4 deacetylation of the POMC locus. In addition, GR-dependent repression inhibits promoter clearance by RNA polymerase II. Thus, corecruitment of repressor and activator at the promoter and chromatin modification jointly contribute to trans-repression initiated by direct interactions between GR and NGFI-B. Loss of Brg1 or HDAC2 should therefore produce Gc resistance, and we show that similar to 50% of Gc-resistant human and dog corticotroph adenomas, which are the hallmark of Cushing disease, are deficient in nuclear expression of either protein. In addition to providing a molecular basis for Gc resistance, these deficiencies may also contribute to the tumorigenic process. C1 Clin Res Inst Montreal, Genet Mol Lab, Montreal, PQ H2W 1R7, Canada. Univ Mediterranee, Lab Interact Cellulaires Neuroendocriniennes, Inst Jean Roche, CNRS,UMR 6544, F-13385 Marseille, France. CHUM, Hotel Dieu, Dept Med, Res Ctr, Montreal, PQ H2W 1T8, Canada. NICHHD, Dev Endocrinol Branch, SEGEN, Bethesda, MD 20892 USA. Univ Utrecht, Fac Vet Med, Dept Clin Sci & Compan Anim, NL-3508 TD Utrecht, Netherlands. RP Drouin, J (reprint author), Clin Res Inst Montreal, Genet Mol Lab, 110 Pine Ave W, Montreal, PQ H2W 1R7, Canada. EM jacques.drouin@ircm.qc.ca NR 51 TC 120 Z9 121 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 2006 VL 20 IS 20 BP 2871 EP 2886 DI 10.1101/dag.1444606 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 095RB UT WOS:000241324400011 PM 17043312 ER PT J AU Hashimoto, R Numakawa, T Ohnishi, T Kumamaru, E Yagasaki, Y Ishimoto, T Mori, T Nemoto, K Adachi, N Izumi, A Chiba, S Noguchi, H Suzuki, T Iwata, N Ozaki, N Taguchi, T Kamiya, A Kosuga, A Tatsumi, M Kamijima, K Weinberger, DR Sawa, A Kunugi, H AF Hashimoto, Ryota Numakawa, Tadahiro Ohnishi, Takashi Kumamaru, Emi Yagasaki, Yuki Ishimoto, Tetsuya Mori, Takeyuki Nemoto, Kiyotaka Adachi, Naoki Izumi, Aiko Chiba, Sachie Noguchi, Hiroko Suzuki, Tatsuyo Iwata, Nakao Ozaki, Norio Taguchi, Takahisa Kamiya, Atsushi Kosuga, Asako Tatsumi, Masahiko Kamijima, Kunitoshi Weinberger, Daniel R. Sawa, Akira Kunugi, Hiroshi TI Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling SO HUMAN MOLECULAR GENETICS LA English DT Article ID LATE-LIFE DEPRESSION; SUBGENUAL PREFRONTAL CORTEX; FRONTAL WHITE-MATTER; BIPOLAR-DISORDER; SCHIZOAFFECTIVE DISORDER; ORBITOFRONTAL CORTEX; ANTERIOR CINGULATE; NEURITE OUTGROWTH; GLUTAMATE RELEASE; CORTICAL-NEURONS AB Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD. C1 Osaka Univ, Osaka Hamamtsu Joint Res Ctr Child Mental Dev, Grad Sch Med, Osaka 5650871, Japan. Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka 5650871, Japan. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Kodaira, Tokyo 187, Japan. Natl Ctr Neurol & Psychiat, Natl Ctr Hosp Mental Nervous & Muscular Disorders, Dept Radiol, Kodaira, Tokyo 187, Japan. Natl Inst Adv Ind Sci & Technol, Neuron RG Special Div Human Life Technol, Ikeda, Osaka, Japan. Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, Koganei, Tokyo, Japan. Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 47011, Japan. Nagoya Univ, Dept Psychiat, Grad Sch Med, Nagoya, Aichi, Japan. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21205 USA. Showa Univ, Sch Med, Dept Psychiat, Tokyo 142, Japan. NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Program Cellular Mol Med, Dept Neurosci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Program Cellular Mol Med, Dept Psychiat, Baltimore, MD USA. RP Hashimoto, R (reprint author), Osaka Univ, Osaka Hamamtsu Joint Res Ctr Child Mental Dev, Grad Sch Med, 2-2 Yamadaoka,D3,4-1-1 Suita, Osaka 5650871, Japan. EM hashimor@psy.med.osaka-u.ac.jp RI Hashimoto, Ryota/P-8572-2014; Ozaki, Norio/M-8908-2014; kamiya, atsushi/L-8550-2016; OI Hashimoto, Ryota/0000-0002-5941-4238; Ozaki, Norio/0000-0002-7360-4898; Kunugi, Hiroshi/0000-0002-7209-3790 NR 51 TC 179 Z9 188 U1 2 U2 6 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 OCT 15 PY 2006 VL 15 IS 20 BP 3024 EP 3033 DI 10.1093/hmg/ddl244 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 092JV UT WOS:000241093700006 PM 16959794 ER PT J AU Kelada, SNP Checkoway, H Kardia, SLR Carlson, CS Costa-Mallen, P Eaton, DL Firestone, J Powers, KM Swanson, PD Franklin, GM Longstreth, WT Weller, TS Afsharinejad, Z Costa, LG AF Kelada, Samir N. P. Checkoway, Harvey Kardia, Sharon L. R. Carlson, Christopher S. Costa-Mallen, Paola Eaton, David L. Firestone, Jordan Powers, Karen M. Swanson, Phillip D. Franklin, Gary M. Longstreth, W. T., Jr. Weller, Terri-Smith Afsharinejad, Zahra Costa, Lucio G. TI 5 ' and 3 ' region variability in the dopamine transporter gene (SLC6A3), pesticide exposure and Parkinson's disease risk: a hypothesis-generating study SO HUMAN MOLECULAR GENETICS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; VARIABLE NUMBER; ALPHA-SYNUCLEIN; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; TRANSCRIPTIONAL REGULATION; TRANSFERASE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; SEQUENCE VARIATION; BIPOLAR DISORDER AB The dopamine transporter gene (SLC6A3) is a candidate gene for Parkinson's disease (PD) on the basis of its critical role in dopaminergic neurotransmission. Previously, we identified 22 SNPs in the 5' region of SLC6A3, which segregate as eight haplotypes that differ in transcriptional activity when transfected in rat dopamine-producing cells. In the present work from a case-control study size of 293 cases and 395 controls, we employed a cladistic approach to examine gene-disease association. First, we found strong evidence of balancing selection in this region, as determined by a Tajima's D statistic of 2.97 (P < 0.001). Second, we found that the eight haplotypes fit into two main clades and that diplotypes of these clades were marginally associated with PD. Then, after we classified cases and controls by the number of risk alleles, accounting for the well-known 3' region VNTR polymorphism, we found that having two or more risk alleles resulted in a modest but significant increase in PD risk [odds ratio=1.58; 95% confidence interval (CI): 1.03-2.40]. Finally, we detected a significant interaction between occupational pesticide exposure in men and the number of risk alleles. Among pesticide-exposed subjects, the odds ratio for having two or more risk alleles was 5.66 (95% CI: 1.73-18.53). Thus, allelic variants in SLC6A3, which affect gene expression, are associated with PD in this population and may interact with occupational pesticide exposure to increase PD risk. C1 Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98105 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. Univ Washington, Dept Neurol, Seattle, WA 98105 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Parma, Sch Med, Dept Human Anat Pharmacol & Forens Sci, I-43100 Parma, Italy. RP Kelada, SNP (reprint author), NHGRI, NIH, Bldg 50,Room 5310,50 S Dr MSC 8004, Bethesda, MD 20892 USA. EM keladas@mail.nih.gov FU NIEHS NIH HHS [ES 07032, P30 ES 07033, P42 ES 04696, R01 ES 10750] NR 83 TC 30 Z9 30 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2006 VL 15 IS 20 BP 3055 EP 3062 DI 10.1093/hmg/ddl247 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 092JV UT WOS:000241093700009 PM 16963468 ER PT J AU Pittman, AM Fung, HC de Silva, R AF Pittman, Alan M. Fung, Hon-Chung de Silva, Rohan TI Untangling the tau gene association with neurodegenerative disorders SO HUMAN MOLECULAR GENETICS LA English DT Review ID PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN GENE; FAMILIAL PARKINSONS-DISEASE; ARGYROPHILIC GRAIN DISEASE; PAIRED HELICAL FILAMENT; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; PROTEIN-TAU; FRONTOTEMPORAL DEMENTIA; LINKAGE DISEQUILIBRIUM AB Pathological tau protein inclusions have long been recognized to define the diverse range of neurodegenerative disorders called the tauopathies, which include Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration. Mutations in the tau gene, MAPT, cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and common variation in MAPT is strongly associated with the risk of PSP, corticobasal degeneration and, to a lesser extent, AD and Parkinson's disease (PD), implicating the involvement of tau in common neurodegenerative pathway(s). This review will discuss recent work towards the unravelling of the functional basis of this MAPT gene association. The region of chromosome 17q21 containing MAPT locus is characterized by the complex genomic architecture, including a large inversion that leads to a bipartite haplotype architecture, an inversion-mediated deletion and multiplications resulting from non-allelic homologous recombination between the MAPT family of low-copy repeats. C1 UCL, Reta Weston Inst Neurol Studies, London WC1N 1PJ, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. RP de Silva, R (reprint author), UCL, Reta Weston Inst Neurol Studies, 1 Wakefield St, London WC1N 1PJ, England. EM rsilva@ion.ucl.ac.uk RI de Silva, Rohan/C-1734-2008; Pittman, Alan/D-6231-2012 OI de Silva, Rohan/0000-0002-5052-5775; FU Medical Research Council [G0501560, G0501560(76517)] NR 86 TC 53 Z9 54 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2006 VL 15 SI 2 BP R188 EP R195 DI 10.1093/hmg/ddl190 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 095SX UT WOS:000241329700012 PM 16987883 ER PT J AU Zabel, EW Alexander, BH Mongin, SJ Doody, MM Sigurdson, AJ Linet, MS Freedman, DM Hauptmann, M Mabuchi, K Ron, E AF Zabel, Erik W. Alexander, Bruce H. Mongin, Steven J. Doody, Michele M. Sigurdson, Alice J. Linet, Martha S. Freedman, D. Michal Hauptmann, Michael Mabuchi, Kiyohiko Ron, Elaine TI Thyroid cancer and employment as a radiologic technologist SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ionizing radiation; thyroid cancer; occupational exposure; epidemiology ID POOLED ANALYSIS; RADIATION-EXPOSURE; BREAST-CANCER; CHILDHOOD; RISK; CONSUMPTION; CARCINOMA; SURVIVAL; ALCOHOL; SMOKING AB The association between chronic occupational ionizing radiation exposure in the medical field and thyroid cancer is not well characterized. Thyroid cancer incidence was ascertained for 2 periods in a cohort of radiologic technologists certified for a minimum 2 years and enumerated in 1983: (i) cases identified prospectively in 73,080 radiologic technologists who were free of thyroid cancer at the baseline survey and completed a second questionnaire a decade later (N = 121), and (ii) cases occurring prior to cohort enumeration among 90,245 technologists who completed the baseline survey and were thyroid cancer free 2 years after certification (N = 148). Survival analyses estimated risks associated with employment as a radiologic technologist, including duration of employment, period of employment, types of procedures and work practices. The only occupational history characteristic associated with prospectively identified thyroid cancer was a history of holding patients for X-ray procedures at least 50 times (HR = 1.47, 95% CI = 1.01-2.15). Total years worked as a radiologic technologist, years performing diagnostic, therapeutic, and nuclear medicine procedures, employment under age 20 and calendar period of first employment were not associated with thyroid cancer risk. Risk of thyroid cancers diagnosed before the baseline questionnaire was inversely associated with decade first employed as a technologist, and was elevated, albeit imprecisely, among those working more than 5 years prior to 1950 (HR = 3.04, 95% CI = 1.01-10.78). These data provide modest evidence of an association between employment as a radiologic technologist and thyroid cancer risk; however, the findings require confirmation with more accurate exposure models. (c) 2006 Wiley-Liss, Inc. C1 Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN 55455 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. RP Alexander, BH (reprint author), Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, MMC 807,Mayo Bldg,420 Delaware St SE, Minneapolis, MN 55455 USA. EM balex@umn.edu NR 28 TC 23 Z9 24 U1 1 U2 8 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 OCT 15 PY 2006 VL 119 IS 8 BP 1940 EP 1945 DI 10.1002/ijc.22065 PG 6 WC Oncology SC Oncology GA 084EF UT WOS:000240514100026 PM 16736495 ER PT J AU Lissowska, J Brinton, LA Zatonski, W Blair, A Bardin-Mikolajczak, A Peplonska, B Sherman, ME Szeszenia-Dabrowska, N Chanock, S Garcia-Closas, M AF Lissowska, Jolanta Brinton, Louise A. Zatonski, Witold Blair, Aaron Bardin-Mikolajczak, Alicja Peplonska, Beata Sherman, Mark E. Szeszenia-Dabrowska, Neonila Chanock, Stephen Garcia-Closas, Montserrat TI Tobacco smoking, NAT2 acetylation genotype and breast cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE breast cancer; smoking; hormone receptor status; NAT2 ID PROGESTERONE-RECEPTOR STATUS; ACETYLTRANSFERASE 2 GENOTYPE; AROMATIC DNA-ADDUCTS; WOMEN UNITED-STATES; CIGARETTE-SMOKING; PASSIVE SMOKING; GENETIC POLYMORPHISMS; ACTIVE SMOKING; ASSOCIATION; POPULATION AB The role of active and passive cigarette smoking in breast cancer etiology remains controversial. Using data from a large population-based case-control study in Poland (2386 cases, 2502 controls) conducted during 2000-2003, we examined the associations between active and passive smoking overall and for different age categories. We also evaluated differences in risk by estrogen receptor (ER) and progesterone receptor (PR) status in tumors, and the potential modification of the smoking association by N-acetyl transferase 2 (NAT2) genotype. Women ever exposed to passive smoking at home or at work had a risk of breast cancer similar to those never exposed to active or passive smoking (OR (95%CI) = 1.11 (0.85-1.46), and no trends were observed with increasing hours/day-years of passive smoking exposure. Active smoking was associated with a significant increase in risk only among women younger than 45 years of age (OR (95%CI) = 1.95 (1.38-2.76); 1.15 (0.93-1.40); 0.91 (0.77-1.09) for < 45, 45-55 and > 55 years of age, respectively; p-heterogeneity < 0.001 for < 45 vs. > 55 years) and prevailed for both ER+ and ER- tumors. The smoking association among women < 45 years was stronger for current than former smokers, and a significant trend was observed with duration of smoking (p = 0.04). NAT2 slow vs. rapid/intermediate acetylation genotype was not related to breast cancer risk (0.99 (0.87-1.13)), and did not significantly modify the smoking relationships. In conclusion, our data indicate that passive smoking is not associated with breast cancer risk; however, active smoking might be associated with an increased risk for early onset breast cancers. (c) 2006 Wiley-Liss, Inc. C1 Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Nofer Inst Occupat Med, Lodz, Poland. NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. RP Lissowska, J (reprint author), Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. EM lissowsj@coi.waw.pl RI Peplonska, Beata/F-6004-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 NR 56 TC 35 Z9 36 U1 0 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 OCT 15 PY 2006 VL 119 IS 8 BP 1961 EP 1969 DI 10.1002/ijc.22044 PG 9 WC Oncology SC Oncology GA 084EF UT WOS:000240514100029 PM 16721725 ER PT J AU Baccarelli, A Hou, L Chen, J Lissowska, J El-Omar, EM Grillo, P Giacomini, SM Yaeger, M Bernig, T Zatonski, W Fraumeni, JF Chanock, SJ Chow, WH AF Baccarelli, Andrea Hou, Lifang Chen, Jinbo Lissowska, Jolanta El-Omar, Emad M. Grillo, Paolo Giacomini, Sara M. Yaeger, Meredith Bernig, Toralf Zatonski, Witold Fraumeni, Joseph F., Jr. Chanock, Stephen J. Chow, Wong-Ho TI Mannose-binding lectin-2 genetic variation and stomach cancer risk SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE stomach cancer; mannose-binding lectin; immunologic deficiency syndromes; haplotypes ID HELICOBACTER-PYLORI INFECTION; GASTRIC-CANCER; INTERLEUKIN-1 POLYMORPHISMS; DISEASE; PROTEIN; EPIDEMIOLOGY; CHILDREN AB Deficiency of the mannose-binding lectin (MBL) protein, an antigen-recognition molecule involved in systemic and mucosal innate immunity, is determined by variant alleles in MBL2 gene promoter and exon-1 regions. We conducted a population-based study on 305 stomach cancer cases and 427 controls in Warsaw, Poland to determine whether MBL2 gene variants predispose to stomach cancer. Single nucleotide polymorphisms (SNPs) in MBL2 were determined by TaqMan (TM). The 5 tested MBL2 variants are in complete linkage disequilibrium and comprise 6 different haplotypes. The risk of stomach cancer was increased in subjects carrying the H/H promoter genotype (OR = 1.8, 95%CI 1.1-2.9; p = 0.020) relative to L/L carriers, after adjustment for age, gender, education and smoking. Carrying at least one D exon-1 allele was associated with nonsignificant excess risk (OR = 1.5, 95% CI 0.9-2.4; p = 0.081). In haplotype analysis, the HYD haplotype was associated with increased risk of stomach cancer when compared with HYA, the most common haplotype (OR = 1.9, 95 % CI 1.1-3.2; p = 0.021). In diplotype analysis, subjects carrying the YA/D haplotype combination showed the highest risk (OR = 3.0, 95% CI 1.2-7.1; p = 0.015), compared with YA/YA. Further analyses to examine the joint effect of MBL2 and IL-1B polymorphisms, previously shown to predispose to stomach cancer, indicated that the combination of at-risk IL-1B genotypes (CT or TT at location -511) and HYD MBL2 haplotype was associated with a 3.5-fold risk (OR = 3.5, 95% CI 1.6-7.6; p = 0.001). Our findings suggest that the codon 52 D MBL2 variant causing a cysteine > arginine replacement, but not B and C variants producing glycine substitutions, is specifically associated with gastric cancer risk. (c) 2006 Wiley-Liss, Inc. C1 Univ Milan, Maggiore Hosp IRCCS Fdn, EPOCA, Epidemiol Res Ctr, Milan, Italy. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Univ Aberdeen, Dept Med & Therapeut, Inst Med Sci, Aberdeen, Scotland. NCI, Core Genotyping Facil, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pediat Oncol Branch, Sect Gen Variat,HIH, Bethesda, MD 20892 USA. RP Baccarelli, A (reprint author), Harvard Univ, Sch Publ Hlth, Epidemiol & Risk Program, 401 Pk Dr,Landmark Ctr,Suite 412F W,POB 15698, Boston, MA 02215 USA. EM abaccare@hsph.harvard.edu OI Baccarelli, Andrea/0000-0002-3436-0640; Lissowska, Jolanta/0000-0003-2695-5799 NR 32 TC 36 Z9 37 U1 0 U2 4 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 OCT 15 PY 2006 VL 119 IS 8 BP 1970 EP 1975 DI 10.1002/ijc.22075 PG 6 WC Oncology SC Oncology GA 084EF UT WOS:000240514100030 PM 16721783 ER PT J AU Ko, JH Son, W Bae, GY Kang, JH Oh, W Yoo, OJ AF Ko, Jung Ho Son, Wonseok Bae, Gab Yong Kang, Joo Hyun Oh, Wonjun Yoo, Ook Joon TI A new hepatocytic isoform of PLZF lacking the BTO domain interacts with ATP7B, the Wilson disease protein, and positively regulates ERK signal transduction SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE PLZF; ATP7B; ERK signal transcluction ID ZINC-FINGER GENE; ADENOSINE-TRIPHOSPHATASE ATP7B; COPPER TRANSPORTING ATPASE; AIRWAY EPITHELIAL-CELLS; PROMYELOCYTIC LEUKEMIA; DROSOPHILA EYE; TRANSCRIPTIONAL REPRESSOR; CAENORHABDITIS-ELEGANS; TERMINAL FRAGMENT; BROAD-COMPLEX AB The promyelocytic leukemia zinc finger (PLZF) protein has been described as a transcriptional repressor of the BTB-domain/zinc-finger family, and shown to regulate the expression of Hox genes during embryogenesis and the expression of cyclin A in the cell cycle progression. Here, a 45-kDa isoform of PLZF without a BTB domain was identified via yeast two-hybrid screening using the C-terminal region of ATP7B as bait in our determination of the biological roles of the Wilson disease protein outside of its copper-binding domain. Our immunoprecipitation experiments showed that the hepatocytic isoform of PLZF could specifically interact with the C-terminal region of ATP7B. The immunostaining of HepG2 cells revealed that the ATP7B and PLZF proteins were apparently colocalized into the trans-Golgi complexes. It was also determined that disruption of PLZF expression in the HepG2 cells affected an attenuation of ERK activity in a dose-dependent manner. The hepatocytic activities of ERK kinase were found to be enhanced as the result of PLZF or ATP7B expression, but this enhancement was abrogated by the deletion of the C-terminal region of ATP7B. Furthermore, a transgenic Drosophila strain that ectopically expressed the hepatocytic Delta BTB-PLZF exhibited phenotypic changes in eye and wing development, and these alterations were fully recovered as the result of ATP7B expression, indicating the obvious in vivo interaction between the two proteins. Those PLZF-induced abnormalities were attributed to the enhancement of ERK signaling, as was shown by phenotypic reversions with loss-of-function mutations in ERK signal transduction in Drosophila. These data suggest the existence of a mechanism that regulates ERK signaling via the C-terminus of ATP7B and the ATP7B-interacting hepatocytic PLZF. C1 Korea Adv Inst Sci & Technol, Dept Biol Sci, Biomed Res Ctr, Lab Mol Biol, Taejon 305701, South Korea. Seoul Natl Univ, Coll Med, Dept Nucl Med, Seoul 110744, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110744, South Korea. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Yoo, OJ (reprint author), Korea Adv Inst Sci & Technol, Dept Biol Sci, Biomed Res Ctr, Lab Mol Biol, 373-1 Kusong Dong, Taejon 305701, South Korea. EM ojyoo@kaist.ac.kr RI Yoo, Ook Joon/C-1860-2011 NR 63 TC 13 Z9 14 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 15 PY 2006 VL 99 IS 3 BP 719 EP 734 DI 10.1002/jcb.20980 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 088BZ UT WOS:000240787800006 PM 16676348 ER PT J AU Lee, MK Choi, H Gil, M Nikodem, VM AF Lee, Mi Kyeong Choi, Hosoon Gil, Minchan Nikodem, Vera M. TI Regulation of osteoblast differentiation by Nurr1 in MC3T3-E1 cell line and mouse calvarial osteoblasts SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Nurr1; osteoblast differentiation; osteocalcin; collagen type I alpha 1; ALP ID ORPHAN RECEPTOR NURR1; NUCLEAR RECEPTORS; NGFI-B; TRANSCRIPTION FACTORS; NURR1/NUR77 SUBFAMILY; BONE-FORMATION; IN-VITRO; EXPRESSION; GENE; INDUCTION AB The orphan nuclear receptor Nurr1 is primarily expressed in the central nervous system. It has been shown that Nurr1 is necessary for terminal differentiation of dopaminergic (DA) neurons in ventral midbrain. The receptor, however, is also expressed in other organs including bone, even though the role of Nurr1 is not yet understood. Therefore, we investigated the role of Nurr1 in osteoblast differentiation in MC3T3-E1 cells and calvarial osteoblasts derived from Nurr1 null newborn pups. Our results revealed that reduced Nurr1 expression, using Nurr1 siRNA in MC3T3-E1 cells, affected the expression of osteoblast differentiation marker genes, osteocalcin (OCN) and collagen type I alpha 1 (COL1A1), as measured by quantitative real-time PCR. The activity of alkaline phosphatase (ALP), another osteoblast differentiation marker gene, was also decreased in Nurr1 siRNA-treated MC3T3-E1 cells. In addition, Nurr1 overexpression increased OCN and COL1A1 expression. Furthermore, consistent with these results, during osteoblast differentiation, the expression of osteoblast marker genes was decreased in primary cultured mouse calvarial osteoblasts derived from Nurr1 null mice. Collectively, our results suggest that Nurr1 is important for osteoblast differentiation. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Nikodem, VM (reprint author), NIDDK, NIH, Bldg 8,Rm 106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM veran@intra.niddk.nih.gov FU Intramural NIH HHS NR 43 TC 15 Z9 16 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 15 PY 2006 VL 99 IS 3 BP 986 EP 994 DI 10.1002/jcb.20990 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 088BZ UT WOS:000240787800029 PM 16741951 ER PT J AU Lukashev, D Klebanov, B Kojima, H Grinberg, A Ohta, A Berenfeld, L Wenger, RH Ohta, A Sitkovsky, M AF Lukashev, Dmitriy Klebanov, Boris Kojima, Hidefumi Grinberg, Alex Ohta, Akiko Berenfeld, Ludmilla Wenger, Roland H. Ohta, Akio Sitkovsky, Michail TI Cutting edge: Hypoxia-inducible factor 1 alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4(+) and CD8(+) T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADENOSINE RECEPTORS; IMMUNE-RESPONSE; FACTOR-I; CELLS; EXPRESSION; GENE; INFLAMMATION; HIF-1-ALPHA; RAPAMYCIN; GROWTH AB To evaluate the role of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and its TCR activation-inducible short isoform L I in T cell functions, we genetically engineered unique mice with: 1) knockout of L 1 isoform of HIF-1 alpha; 2) T cell-targeted HIF-1 a knockdown; and 3) chimeric mice with HIF-1 a gene deletion in T and B lymphocytes. In all three types of mice, the HIF-1 alpha-deficient T lymphocytes, which were TCR-activated in vitro, produced more proinflammatory cytokines compared with HIF-1 alpha-expressing control T cells. Surprisingly, deletion of the L I isoform, which represents < 30% of total HIF-1 alpha mRNA in activated T cells, was sufficient to markedly enhance TCR-triggered cytokine secretion. These data suggest that HIF-1 alpha not only plays a critical role in oxygen homeostasis but also may serve as a negative regulator of T cells. C1 Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. Dokkyo Univ, Inst Med Sci, Div Immunol, Sch Med, Tochigi, Japan. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Physiol, Zurich, Switzerland. Univ Zurich, CIHP, Zurich, Switzerland. RP Sitkovsky, M (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, 360 Huntington Ave,113MU, Boston, MA 02115 USA. EM m.sitkovsky@neu.edu RI Lukashev, Dmitriy/F-8133-2010; Wenger, Roland/B-7953-2009 OI Wenger, Roland/0000-0001-7592-4839 NR 31 TC 97 Z9 100 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 OCT 15 PY 2006 VL 177 IS 8 BP 4962 EP 4965 PG 4 WC Immunology SC Immunology GA 092JP UT WOS:000241093100004 PM 17015677 ER PT J AU Kamperschroer, C Dibble, JP Meents, DL Schwartzberg, PL Swain, SL AF Kamperschroer, Cris Dibble, John P. Meents, Dana L. Schwartzberg, Pamela L. Swain, Susan L. TI SAP is required for Th cell function and for immunity to influenza SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; IG CLASS SWITCH; HUMORAL IMMUNITY; MICE DEFICIENT; B-CELLS; VIRUS-INFECTION; ANTIBODY-RESPONSE; ENCODING GENE; CD40 LIGAND; SH2 DOMAIN AB Ab is a crucial component of protective immunity to infection, but Ab responses do not proceed normally when defects occur in a protein called signaling lymphocytic activation molecule-associated protein (SAP). To explain this Ab defect, we analyzed B cell and plasma cell responses under conditions of SAP deficiency. Our results demonstrate that SAP-deficient (SAP knockout (KO)) mice have a profound CD4 T cell-intrinsic defect in generating Ag-specific plasma cells following challenge with model Ags or influenza virus, resulting in low Ag-specific Ab titers. We also show that SAP is required in CD4 T cells for normal division and expansion of B cells. These B cell and plasma cell defects were observed during the expansion phase of the primary immune response, indicating early defects in Th cell activity. In fact, additional experiments revealed a nearly complete lack of T cell help for B cells in SAP KO mice. Our work suggests that the ability of SAP to promote T-dependent humoral immune responses is important for antiviral immunity because mice lacking SAP are unable to prevent high dose secondary influenza infection, and because passive transfer of IgG in immune serum from wild-type, but not SAP KO mice can protect mice from an otherwise lethal influenza infection. Overall, our results demonstrate that SAP is required in CD4 T cells for their ability to help B cell responses and promote influenza-specific immunity. C1 Trudeau Inst Inc, Saranac Lake, NY 12983 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Kamperschroer, C (reprint author), Trudeau Inst Inc, 154 Algonquin Ave, Saranac Lake, NY 12983 USA. FU NIAID NIH HHS [AI22125-17, AI066684-01, AI46530] NR 42 TC 37 Z9 41 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 OCT 15 PY 2006 VL 177 IS 8 BP 5317 EP 5327 PG 11 WC Immunology SC Immunology GA 092JP UT WOS:000241093100044 PM 17015717 ER PT J AU Poloso, NJ Denzin, LK Roche, PA AF Poloso, Neil J. Denzin, Lisa K. Roche, Paul A. TI CDw78 defines MHC class II-peptide complexes that require Ii chain-dependent lysosomal tracking, not localization to a specific tetraspanin membrane microdomain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HLA-DR MOLECULES; B-CELL LINE; ANTIGEN-PROCESSING MUTANT; INVARIANT CHAIN; LIPID RAFTS; DENDRITIC CELLS; INTRACELLULAR-TRANSPORT; IMMUNOLOGICAL SYNAPSE; HUMAN MONOCYTES; COMPARTMENTS AB MHC class II molecules (MHC-II) associate with detergent-resistant membrane microdomains, termed lipid rafts, which affects the function of these molecules during Ag presentation to CD4(+) T cells. Recently, it has been proposed that MHC-II also associates with another type of membrane microdomain, termed tetraspan microdomains. These microdomains are defined by association of molecules to a family of proteins that contain four-transmembrane regions, called tetraspanins. It has been suggested that MHC-II associated with tetraspanins are selectively identified by a mAb to a MHC-II determinant, CDw78. In this report, we have re-examined this issue of CDw78 expression and MHC-II-association with tetraspanins in human dendritic cells, a variety of human B cell lines, and MHC-II-expressing HeLa cells. We find no correlation between the expression of CDw78 and the expression of tetraspanins CD81, CD82, CD53, CD9; and CD37. Furthermore, we find that the relative amount of tetraspanins bound to CDw78-reactive MHC-II is indistinguishable from the amount bound to peptide-loaded MHC-II. We found that expression of CDw78 required coexpression of MHC-II together with its chaperone Ii chain. In addition, analysis of a panel of MHC-II-expressing B cell lines revealed that different alleles of HLA-DR express different amounts of CDw78 reactivity. We conclude that CDw78 defines a conformation of MHC-II bound to peptides that are acquired through trafficking to lysosomal Ag-processing compartments and not MHC-II-associated with tetraspanins. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Program Immunol, New York, NY 10021 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI046202] NR 50 TC 13 Z9 13 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 OCT 15 PY 2006 VL 177 IS 8 BP 5451 EP 5458 PG 8 WC Immunology SC Immunology GA 092JP UT WOS:000241093100058 PM 17015731 ER PT J AU Little, RF Yarchoan, R AF Little, Richard F. Yarchoan, Robert TI Poor specific T cell responses to human herpesvirus 8: A key to unleashing Kaposi sarcoma? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID EPSTEIN-BARR-VIRUS; HERPESVIRUS; DISEASE; PROTEIN; INFECTION; LYMPHOMA; BLOOD C1 Natl Canc Inst, HIV & AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD USA. RP Little, RF (reprint author), 10 Ctr Dr,MSC 1868, Bethesda, MD 20892 USA. EM littler@mail.nih.gov FU Intramural NIH HHS NR 17 TC 4 Z9 4 U1 0 U2 0 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 OCT 15 PY 2006 VL 194 IS 8 BP 1030 EP 1031 DI 10.1086/507649 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 084QC UT WOS:000240548500002 PM 16991076 ER PT J AU Pacheco, SE McIntosh, K Lu, M Mofenson, LM Diaz, C Foca, M Frederick, M Handelsman, E Hayani, K Shearer, WT AF Pacheco, Susan E. McIntosh, Kenneth Lu, Ming Mofenson, Lynne M. Diaz, Clemente Foca, Marc Frederick, Margaret Handelsman, Edward Hayani, Karen Shearer, William T. CA Women and Infants Transmi TI Effect of perinatal antiretroviral drug exposure on hematologic values in HIV-uninfected children: An analysis of the women and infants transmission study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND ID IMMUNODEFICIENCY-VIRUS TYPE-1; ZIDOVUDINE AZT TREATMENT; IN-UTERO EXPOSURE; MITOCHONDRIAL TOXICITY; HIV-1-INFECTED MOTHERS; NUCLEOSIDE ANALOGS; INFECTED MOTHERS; IMMUNE-SYSTEM; T-LYMPHOCYTES; CELL COUNTS AB Background. With the increasing use of antiretroviral (ARV) drugs to prevent mother-to-child transmission of human immunodeficiency virus (HIV), large numbers of infants are exposed, with possible consequent toxicity. Methods. Hematologic values in 1820 uninfected HIV- and ARV-exposed children were compared with those in 351 ARV-unexposed children from the Women and Infants Transmission Study. Hemoglobin concentrations and platelet, neutrophil, lymphocyte, and CD4(+) and CD8(+) cell counts were analyzed at birth and ages 2, 6, 12, 18, and 24 months. Multivariate analysis was conducted age 0-2 and 6-24 months, with adjustment for multiple cofactors. Results. Hemoglobin concentrations and neutrophil, lymphocyte, and CD4(+) cell counts were significantly lower at age 0-2 months in infants exposed to ARV drugs than in those who were not. At 6-24 months, differences in hemoglobin concentrations and neutrophil counts were no longer significant, whereas differences in platelet, lymphocyte, and CD4(+) cell counts persisted and CD8(+) cell counts became significantly lower. In comparison with ARV monotherapy, combination therapy was associated with larger decreases in neutrophil, lymphocyte, and CD8(+) cell counts at age 0-2 months but with only differences in CD8(+) cell counts at age 6 - 24 months. Clinically significant abnormalities were rare and did not differ by exposure to ARV drugs. Conclusion. Infants exposed to ARV drugs have small but significant differences in several hematologic parameters for the first 24 months of life. These results indicate the need for long-term follow-up of uninfected infants with ARV exposure. C1 Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Baylor Coll Med, Houston, TX 77030 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Puerto Rico, San Juan, PR 00936 USA. Columbia Presbyterian Med Ctr, New York, NY USA. Suny Downstate Med Ctr, Columbia Presbyterian Hosp, Brooklyn, NY 11203 USA. Univ Illinois, Chicago, IL USA. RP McIntosh, K (reprint author), Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. EM Kenneth.mcintosh@childrens.harvard.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR00188, RR00645, RR02172] NR 29 TC 68 Z9 69 U1 0 U2 5 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 OCT 15 PY 2006 VL 194 IS 8 BP 1089 EP 1097 DI 10.1086/507645 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 084QC UT WOS:000240548500009 PM 16991083 ER PT J AU Schou, M Pike, VW Varrone, A Gulyas, B Farde, L Halldin, C AF Schou, Magnus Pike, Victor W. Varrone, Andrea Gulyas, Balazs Farde, Lars Halldin, Christer TI Synthesis and PET evaluation of (R)-[S-methyl-C-11]thionisoxetine, a candidate radioligand for imaging brain norepinephrine transporters SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE norepinephrine transporter; PET; monkey; radioligand; carbon-11 ID H-3 NISOXETINE; UPTAKE SITES; BIOLOGICAL EVALUATION; REBOXETINE ANALOGS; LOCUS-COERULEUS; BINDING; AUTORADIOGRAPHY; INHIBITOR; C-11; NORADRENALINE AB Introduction. (R)-3-(2-(methylthio)phenoxy)-N-methyl-3-phenylpropan-l-amine [(R)-thionisoxetine; 1] is a potent inhibitor of the norepinephrine transporter (NET). We aimed to label 1 with carbon-11 (t(1/2) = 20.4 min) for evaluation as a radioligand for imaging NET in living brain with positron emission tomography (PET). Methods: Methyl 3-(2-((R)-3-(methylamino)-l-phenylpropoxy)phenylthio)-propanoate (MPPP) and 1 were each prepared from o-hydroxythiophenol in three steps. Treatment of MPPP with potassium t-butoxide and [C-11]methyl iodide in tetrahydrofuran gave [S-methyl-C-11]thionisoxetine ([C-11]1), which was purified with HPLC. The distribution of radioactivity in brain after intravenous injection of [C-11]1 into cynomolgus monkey was followed with PET and the appearance of radiometabolites in plasma monitored with radio-HPLC. Results: [C-11]1 was obtained in high yield from [C-11]methyl iodide. Of the radioactivity injected into monkey, 2.4% entered brain. Ratios of radioactivity in thalamus, mesencephalon, occipital cortex and caudate to that in cerebellum at 93 min were 1.3, 1.2, 1.2 and 1.1, respectively. The radioactivity in plasma corresponding to unchanged radioligand decreased to 53% at 45 min, with the remainder represented by hydrophilic radiometabolites. Conclusions: MPPP is an effective precursor for C-11-methylation to [C-11]1, suggesting that the S-y-propionic acid methyl ester protecting group may have wider value in the C-11-labeling of aryl methyl sulfides. However, the relatively low ratios of radioactivity to the cerebellum together with an unexpected accumulation of radioactivity in the caudate, makes [C-11]1 an unpromising NET radioligand. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Karolinska Hosp, S-17176 Stockholm, Sweden. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Schou, M (reprint author), Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Karolinska Hosp, S-17176 Stockholm, Sweden. EM magnus.schou@ki.se NR 44 TC 14 Z9 14 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD OCT 15 PY 2006 VL 49 IS 11 BP 1007 EP 1019 DI 10.1002/jlcr.1128 PG 13 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 108EO UT WOS:000242223300011 ER PT J AU Guo, J Chen, HM Puhl, HL Ikeda, SR AF Guo, Juan Chen, Huanmian Puhl, Henry L., III Ikeda, Stephen R. TI Fluorophore-assisted light inactivation produces both targeted and collateral effects on N-type calcium channel modulation in rat sympathetic neurons SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID METABOTROPIC GLUTAMATE-RECEPTOR; LASER INACTIVATION; PROTEIN FUNCTION; CA2+ CHANNELS; FLUORESCENT PROTEIN; EXPRESSION; SUBUNITS; SPECIFICITY; EGFP AB Fluorophore-assisted light inactivation (FALI) is a method to inactivate specific proteins on a time scale of seconds to minutes using either diffuse or coherent light. Here we examine a novel FALI modality that utilizes a fluorescein-conjugated polypeptide, alpha-bungarotoxin (BTX) and a 13 amino acid BTX-binding site engineered into the N-terminus of metabotropic glutamate receptor 8a (mGluR8a), a class C G-protein-coupled receptor (GPCR). The tagged mGluR8a was expressed in rat sympathetic neurons and labelled with fluorescein-conjugated BTX (FL-BTX). The efficacy of FALI was evaluated by monitoring mGluR8a-mediated inhibition of calcium currents (I-Ca) using whole-cell voltage-clamp techniques. Following either wide-field or laser illumination of FL-BTX-labelled neurons, mGluR8a-mediated I-Ca inhibition was greatly attenuated whereas holding current and basal I-Ca, measures of non-specific effects, were minimally affected. Sodium azide, a collision quencher of singlet oxygen, reduced the magnitude of FALI-mediated effects supporting a role for reactive oxygen species in the process. Although these results were consistent with an acute inactivation of mGluR8a, the intended target, two findings confounded this interpretation. First, effects on a natively expressed signalling pathway, alpha(2)-adrenergic receptor-mediated I-Ca modulation, were observed following illumination of neurons expressing FL-BTX-labelled sodium channel beta 2 subunits or ionotropic 5-HT3 receptors, proteins with no overt relationship to GPCR signalling pathways. Second, GPCR-independent I-Ca modulation induced with intracellular guanylyl imidophosphate was also attenuated by FALI. These data challenge the assumption that the fluorophore-tagged protein is the sole target of FALI and provide evidence that collateral damage to proximal proteins occurs following fluorophore illumination. C1 NIAAA, Lab Mol Physiol, Sect Transmitter Signalling, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, Sect Transmitter Signalling, NIH, 5625 Fishers Lane,Room TS-06,MSC9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508; Puhl, Henry/0000-0003-3095-7201 FU Intramural NIH HHS NR 34 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 15 PY 2006 VL 576 IS 2 BP 477 EP 492 DI 10.1113/jphysiol.2006.113068 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 091AW UT WOS:000240999100012 PM 16873413 ER PT J AU Choi, IY Lee, SP Merkle, H Shen, J AF Choi, In-Young Lee, Sang-Pil Merkle, Hellmut Shen, Jun TI In vivo detection of gray and white matter differences in GABA concentration in the human brain SO NEUROIMAGE LA English DT Article DE GABA; gray and white matter; human brain in vivo; MRS; CSI ID GAMMA-AMINOBUTYRIC-ACID; MAGNETIC-RESONANCE-SPECTROSCOPY; HUMAN CEREBRAL GABA; FREE AMINO-ACIDS; QUANTUM FILTER; SINGLE-SHOT; NMR-SPECTROSCOPY; MR SPECTROSCOPY; HIGH-FIELD; SCHIZOPHRENIA AB A novel selective multiple quantum filtering-based chemical shift imaging method was developed for acquiring GABA images in the human brain at 3 T. This method allows a concomitant acquisition of an interleaved total creatine image with the same spatial resolution. Using T-1-based image segmentation and a nonlinear least square regression analysis of GABA-to-total creatine concentration ratios in frontal and parietal lobes of healthy adult volunteers as a function of the tissue gray matter fraction, the mean GABA concentration in gray and white matter was determined to be 1.30 +/- 0.36 mu mol/g and 0.16 +/- 0.16 mu mol/g (mean +/- SD, n=13), respectively. It is expected that this method will become a useful tool for studying GABAergic function in the human brain in vivo. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66160 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NINDS, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Choi, IY (reprint author), Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Mail Stop 1052,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM ichoi@kumc.edu OI Lee, Phil/0000-0002-2087-8887 FU Intramural NIH HHS; NIA NIH HHS [R03AG022193]; NIBIB NIH HHS [8R01EB00315] NR 51 TC 44 Z9 45 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2006 VL 33 IS 1 BP 85 EP 93 DI 10.1016/j.neuroimage.2006.06.016 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 093ZW UT WOS:000241209800011 PM 16884929 ER PT J AU Finger, EC Marsh, AA Kamel, N Mitchell, DGV Blair, JR AF Finger, Elizabeth C. Marsh, Abigail A. Kamel, Niveen Mitchell, Derek G. V. Blair, James R. TI Caught in the act: The impact of audience on the neural response to morally and socially inappropriate behavior SO NEUROIMAGE LA English DT Article DE social response reversal; ventrolateral prefrontal cortex; guilt; embarrassment; moral transgression; social transgression ID MEDIAL FRONTAL-CORTEX; EVENT-RELATED FMRI; FRONTOTEMPORAL DEMENTIA; PREFRONTAL CORTEX; ACQUIRED SOCIOPATHY; DECISION-MAKING; LOBE DAMAGE; EYE GAZE; REVERSAL; EMOTION AB We examined the impact of witnesses on the neural response to moral and social transgressions using fMRI. In this study, participants (N = 16) read short vignettes describing moral and social transgressions in the presence or absence of an audience. In line with our hypothesis, ventrolateral (BA 47) and dorsomedial (BA 8) frontal cortex showed increased BOLD responses to moral transgressions regardless of audience and to social transgressions in the presence of an audience relative to neutral situations. These findings are consistent with the suggestion that these regions of prefrontal cortex modify behavioral responses in response to social cues. Greater activity was observed in left temporal-parietal junction, medial prefrontal cortex and temporal poles to moral and to a lesser extent social transgressions relative to neutral stories, regardless of audience. These regions have been implicated in the representation of the mental states of others (Theory of Mind). The presence of an audience was associated with increased left amygdala activity across all conditions. Published by Elsevier Inc. C1 NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Finger, EC (reprint author), NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, NIH, 15K N Dr,MSC 2670, Bethesda, MD 20892 USA. EM fingere@mail.nih.gov RI Finger, Elizabeth/B-6453-2015 FU Intramural NIH HHS NR 66 TC 46 Z9 47 U1 6 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2006 VL 33 IS 1 BP 414 EP 421 DI 10.1016/j.neuroimage.2006.06.011 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 093ZW UT WOS:000241209800041 PM 16891125 ER PT J AU Liu, YZ Amarnath, S Chen, WJ AF Liu, Yongzhong Amarnath, Shoba Chen, WanJun TI Requirement of CD28 signaling in homeostasis/survival of TGF-beta converted CD4(+)CD25(+) tregs from thymic CD4(+)CD25(-) single positive T cells SO TRANSPLANTATION LA English DT Article DE alloantigen specific treg; Foxp3; interleukin-2; CD2; natural CD4(+)CD25(+) treg; apoptosis ID TRANSCRIPTION FACTOR FOXP3; GROWTH-FACTOR BETA-1; DOWN-REGULATION; CUTTING EDGE; TOLERANCE; COSTIMULATION; EXPRESSION; INDUCTION; SELF; DIFFERENTIATION AB Background. The thymus is a major organ that generates "natural" CD4(+)CD25(+) T regulatory cells (Tregs). However, the detailed pathway(s) by which Tregs are developed remain a mystery. CD28-/- mice have profound decrease in Tregs, but the underlying molecular events remain largely undefined. Methods. CD4(+)CD25(-) thymocytes from wildtype and CD28-/- mice were cultured with T-cell receptor (TCR) and transforming growth factor (TGF)-beta stimulation to generate CD25(+) Tregs and their phenotype and function were studied in vitro and in vivo. Results. TGF-beta induced Foxp3 expression in thymic CD4(+)CD25(-) cells and converted them to CD25(+) Tregs. The converted Tregs expressed high levels of CD25, whereas the non-suppressive CD4(+) T cells from the control cultures expressed CD25(low). CD28-/- thymic CD4(+)CD25(-) cells showed transit lower levels of Foxp3 upon TCR and TGF-beta stimulation early in culture, but the defect in Foxp3 expression was restored to normal levels after 60-72 hr. Consequently, TGF-beta converted CD28-/- CD25(-) cells to CD25(+) Tregs that were indistinguishable from those of the wildtype mice. However, the total number of TGF-beta converted CD28-/- Tregs was significantly lower than that of wildtype mice. In vivo, TGF-beta converted CD28-/- CD25(+) Tregs were less viable than those from the wildtype mice. Importantly, TGF-beta induced alloantigen specific CD4(+)CD25(+) Tregs from thymic CD25(-)SP cells which also required CD28 to maintain their survival. Conclusions. TGF-beta and TCR co-stimulation converts thymic CD4(+)CD25(-) T cells into CD4+CD25+ Tregs by inducing Foxp3, and the contribution of CD28 stimulation to this process is mainly through maintaining survival of the induced Tregs. C1 NIDCR, NIH, Mucosal Immunol Unit, Oral Infect & Immunol Branch, Bethesda, MD 20895 USA. RP Chen, WJ (reprint author), NIDCR, NIH, Mucosal Immunol Unit, Oral Infect & Immunol Branch, Bldg 30,Room 304, Bethesda, MD 20895 USA. EM wchen@mail.nih.gov NR 33 TC 16 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2006 VL 82 IS 7 BP 953 EP 964 DI 10.1097/01.tp.0000232330.46688.37 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 096IF UT WOS:000241370100016 PM 17038912 ER PT J AU Klauda, JB Brooks, BR Pastor, RW AF Klauda, Jeffery B. Brooks, Bernard R. Pastor, Richard W. TI Dynamical motions of lipids and a finite size effect in simulations of bilayers SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PERIODIC BOUNDARY-CONDITIONS; FIELD-CYCLING NMR; MOLECULAR-DYNAMICS; PHOSPHOLIPID-BILAYERS; ELECTROSTATIC INTERACTIONS; COMPUTER-SIMULATIONS; RIPPLE PHASE; TRANSLATIONAL DIFFUSION; LECITHIN BILAYERS; SYSTEM-SIZE AB Molecular dynamics (MD) simulations of dipalmitoylphosphatidylcholine bilayers composed of 72 and 288 lipids are used to examine system size dependence on dynamical properties associated with the particle mesh Ewald (PME) treatment of electrostatic interactions. The lateral diffusion constant D-... is 2.92x10(-7) and 0.95x10(-7) cm(2)/s for 72 and 288 lipids, respectively. This dramatic finite size effect originates from the correlation length of lipid diffusion, which extends to next-nearest neighbors in the 288 lipid system. Consequently, diffusional events in smaller systems can propagate across the boundaries of the periodic box. The internal dynamics of lipids calculated from the PME simulations are independent of the system size. Specifically, reorientational correlation functions for the slowly relaxing phosphorus-glycerol hydrogen, phosphorus-nitrogen vectors, and more rapidly relaxing CH vectors in the aliphatic chains are equivalent for the 72 and 288 lipid simulations. A third MD simulation of a bilayer with 72 lipids using spherical force-shift electrostatic cutoffs resulted in interdigitated chains, thereby rendering this cutoff method inappropriate. (c) 2006 American Institute of Physics. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Klauda, JB (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008 FU Intramural NIH HHS; NHLBI NIH HHS [Z01 HL001050-08] NR 43 TC 72 Z9 73 U1 2 U2 21 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 OCT 14 PY 2006 VL 125 IS 14 AR 144710 DI 10.1063/1.2354486 PG 8 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 094OI UT WOS:000241248400065 PM 17042634 ER PT J AU Vijayasarathy, C Gawinowicz, MA Zeng, Y Takada, Y Bush, RA Sieving, PA AF Vijayasarathy, Camasamudram Gawinowicz, Mary Ann Zeng, Yong Takada, Yuichiro Bush, Ronald A. Sieving, Paul A. TI Identification and characterization of two mature isoforms of retinoschisin in murine retina SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE retina; retinoschisin; post-translational modifications; isoforms; signal sequence; signal peptidase; processing; X-linked retinoschisis; missense mutations ID LINKED JUVENILE RETINOSCHISIS; SIGNAL SEQUENCES; CLEAVAGE; GENE; PEPTIDES; PROTEINS; SITE; SPECIFICITY; MUTAGENESIS; EFFICIENCY AB Retinoschisin (RS) is a 24 kDa secreted protein expressed in retina and is required for the structural and functional integrity of the retina. RS has been predicted to serve as an adhesive protein but the precise molecular mechanism by which it functions in retina is not yet known. During investigations on structural and functional aspects of RS in murine retina using proteomic tools, we identified two isoforms of RS that differed in mass by 200 Da with no apparent change in charge. Mass spectra and amino acid sequence analysis of the tryptic peptides revealed that these isoforms differed by two amino acids at the N-terminus which suggested processing of RS signal sequence at two cleavage sites by signal peptidase as the basic mechanism underlying the occurrence of two mature RS isoforms in retina. Bioinformatic analysis identified two potential cleavage sites (between amino acids 21-22 and 23-24) in RS signal sequence. The flexibility of the signal peptidase to cleave at two sites is correlated to the amino acid composition of the RS signal sequence. This finding represents a rare example of a naturally occurring signal sequence cleavage at more than one site in vivo. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Inst Deafness & Other Commun DIsorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Prot Core Facil, New York, NY 10032 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), Natl Inst Deafness & Other Commun DIsorders, Sect Translat Res Retinal & Macular Degenerat, NIH, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000065-04] NR 25 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 13 PY 2006 VL 349 IS 1 BP 99 EP 105 DI 10.1016/j.bbrc.2006.07.202 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 086CF UT WOS:000240650000013 PM 16930543 ER PT J AU Feng, Y Yuan, JH Maloid, SC Fisher, R Copeland, TD Longo, DL Conrads, TP Veenstra, TD Ferris, A Hughes, S Dimitrov, DS Ferris, DK AF Feng, Yang Yuan, Jin Hui Maloid, Sharon C. Fisher, Rebecca Copeland, Terry D. Longo, Dan L. Conrads, Thomas P. Veenstra, Timothy D. Ferris, Andrea Hughes, Steve Dimitrov, Dimiter S. Ferris, Douglass K. TI Polo-like kinase 1-mediated phosphorylation of the GTP-binding protein Ran is important for bipolar spindle formation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cytokinesis; mitosis; GTP-binding proteins; Plk1; polo-like kinases; Ran ID CELL-CYCLE; CHECKPOINT; MITOSIS; PLK1; CYTOKINESIS; ASSOCIATION; PHOSPHATASE; MATURATION; INTERACTS; COMPLEX AB Polo-like kinase functions are essential for the establishment of a normal bipolar mitotic spindle, although precisely how Plk1 regulates the spindle is uncertain. In this study, we report that the small GTP/GDP-binding protein Ran is associated with Plk1. Plk1 is capable of phosphorylating co-immunoprecipitated Ran in vitro on serine-135 and Ran is phosphorylated in vivo at the same site during mitosis when Plk1 is normally activated. Cell cultures over-expressing a Ran S135D mutant have significantly higher numbers of abnormal mitotic cells than those over-expressing either wild-type or S135A Ran. The abnormalities in S135D mutant cells are similar to cells over-expressing Plk1. Our data suggests that Ran is a physiological substrate of Plk1 and that Plk1 regulates the spindle organization partially through its phosphorylation on Ran. Published by Elsevier Inc. C1 NCI, Lab Canc Prevent, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC Federick Inc, Frederick, MD 21701 USA. NCI, Nanobiol Program, CCR, Frederick, MD 21701 USA. NCI, Mass Spectrometry Ctr, SAIC Federick Inc, Frederick, MD 21701 USA. NCI, Retroviral Replicat Lab, HIV Drug Resistance Program, Frederick, MD 21701 USA. NIA, Baltimore, MD 21224 USA. RP Feng, Y (reprint author), NCI, Lab Canc Prevent, Frederick, MD 21701 USA. EM yfeng@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 34 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 13 PY 2006 VL 349 IS 1 BP 144 EP 152 DI 10.1016/j.bbrc.2006.08.028 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 086CF UT WOS:000240650000019 PM 16930555 ER PT J AU Ma, HT Lin, WW Zhao, B Wu, WT Huang, W Li, Y Jones, NL Kruth, HS AF Ma, Hong-Tao Lin, Wan-Wan Zhao, Bin Wu, Wen-Tung Huang, Wei Li, Yifu Jones, Nancy L. Kruth, Howard S. TI Protein kinase C beta and delta isoenzymes mediate cholesterol accumulation in PMA-activated macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE macrophages; LDL; activation; cholesterol; PKC isoenzymes; atherosclerosis; macropinocytosis ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; COLONY-STIMULATING FACTOR; FOAM CELL-FORMATION; SELECTIVE INHIBITORS; DOWN-REGULATION; MACROPINOCYTOSIS; PATHWAY; SURFACE; ACTIN AB Previously, we showed that PMA activation of human monocyte-derived macrophages stimulates macropinocytosis (i.e., fluid-phase endocytosis) of LDL and transforms these macrophages into foam cells. The current study aimed to learn which PKC isoenzymes mediate cholesterol accumulation in PMA-activated human macrophages incubated with LDL. Cholesterol accumulation by PMA-activated macrophages incubated with LDL was nearly completely inhibited (> 85%) by the pan PKC inhibitors Go6850, Go6983, and RO 320432, but only was inhibited about 50% by the classical group PKC inhibitor, Go6976. This indicated that cholesterol accumulation was mediated by both a classical group and some other PKC isoenzyme. PKC P was determined to be the classical group isoenzyme that mediated PMA-stimulated cholesterol accumulation. A pseudosubstrate myristoylated peptide inhibitor of PKC alpha and beta showed partial inhibition (congruent to 50%) of cholesterol accumulation. However, a small molecule inhibitor of PKC alpha, HBDDE, show minimal inhibition of cholesterol accumulation while a small molecule inhibitor of PKC beta, LY333513, could completely account for the inhibition of cholesterol. accumulation by the classical group PKC isoenzyme. Thus, our findings show that beta and some other PKC isoenzyme, most likely delta, mediate cholesterol accumulation when macropinocytosis of LDL is stimulated in PMA-activated human monocyte-derived macrophages. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 100, Taiwan. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov RI Huang, Wei/E-3270-2011 FU Intramural NIH HHS NR 41 TC 25 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 13 PY 2006 VL 349 IS 1 BP 214 EP 220 DI 10.1016/j.bbrc.2006.08.018 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 086CF UT WOS:000240650000029 PM 16930534 ER PT J AU Liang, MH Chuang, DM AF Liang, Min-Huei Chuang, De-Maw TI Differential roles of glycogen synthase kinase-3 isoforms in the regulation of transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; TISSUE-PLASMINOGEN ACTIVATOR; CELL-SURVIVAL; NEUROBLASTOMA-CELLS; BRAIN-INJURY; C-JUN; PHOSPHORYLATION; APOPTOSIS; EGR-1; BETA AB Glycogen synthase kinase-3 (GSK-3) exists as two structurally similar isoforms, alpha and beta, whose activities are negatively regulated by serine phosphorylation but positively controlled by tyrosine phosphorylation. We used GSK-3 isoform-specific small interfering RNAs, dominant negative mutants, and pharmacological inhibitors to search for the differential roles for both GSK-3 isoforms in regulating transcriptional activation in cultured rat cerebral cortical neurons. GSK-3 alpha and GSK-3 beta were shown to have differentially regulated transactivation such that GSK-3 alpha silencing/inhibition was more robust than GSK-3 beta silencing/inhibition in causing cAMP-responsive element-and NF-kappa B-dependent transactivation. Moreover, protein-DNA array studies identified two novel GSK-3-regulated transcription factors, early growth response 1 and Smad3/4, which were oppositely affected by GSK-3 alpha or GSK-3 beta silencing or inhibition. Taken together, our results underscore critical variations in the function and regulation of GSK-3 alpha and GSK-3 beta. The development of GSK-3 isoform-specific inhibitors is thus crucial for therapeutic intervention of GSK-3-related neuropathological conditions. C1 Natl Inst Mental Hlth, Mol Neurobiol Sect, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), Natl Inst Mental Hlth, Mol Neurobiol Sect, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU NIMH NIH HHS [Z01MH002468-18] NR 46 TC 87 Z9 89 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2006 VL 281 IS 41 BP 30479 EP 30484 DI 10.1074/jbc.M607468200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092CZ UT WOS:000241075900023 PM 16912034 ER PT J AU Zhao, H Kim, A Song, SH Dean, A AF Zhao, Hui Kim, AeRi Song, Sang-Hyun Dean, Ann TI Enhancer blocking by chicken beta-globin 5 '-HS4 - Role of enhancer strength and insulator nucleosome depletion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; RNA-POLYMERASE-II; TRANSCRIPTIONALLY SILENT CHROMATIN; HISTONE ACETYLATION PATTERN; HYPERSENSITIVE SITE 2; INTERGENIC TRANSCRIPTION; PROMOTER COMMUNICATION; BARRIER FUNCTION; IN-VIVO; GENE AB The 5'-HS4 chicken beta-globin insulator functions as a positional enhancer blocker on chromatinized episomes in human cells, blocking the HS2 enhancer of the human beta-globin locus control region from activating a downstream epsilon-globin gene. 5'-HS4 interrupted formation of a domain of histone H3 and H4 acetylation encompassing the 6-kb minilocus and inhibited transfer of RNA polymerase from the enhancer to the gene promoter. We found that the enhancer blocking phenotype was amplified when the insulated locus contained a weakened HS2 enhancer in which clustered point mutations eliminated interaction of the transcription factor GATA-1. The GATA-1 mutation compromised recruitment of histone acetyltransferases and RNA polymerase II to HS2. Enhancer blocking correlated with a significant depletion of nucleosomes in the core region of the insulator as revealed by micrococcal nuclease and DNase I digestion studies. Nucleosome depletion at 5'-HS4 was dependent on interaction of the insulator protein CCCTC-binding factor (CTCF) and was required for enhancer blocking. These findings provide evidence that a domain of active chromatin is formed by spreading from an enhancer to a target gene and can be blocked by a nucleosome-free gap in an insulator. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea. RP Dean, A (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 50,Rm 3154,50 South Dr,MSC 8028, Bethesda, MD 20892 USA. EM anndean@helix.nih.gov FU Intramural NIH HHS NR 61 TC 17 Z9 18 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 OCT 13 PY 2006 VL 281 IS 41 BP 30573 EP 30580 DI 10.1074/jbc.M606803200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092CZ UT WOS:000241075900033 PM 16877759 ER PT J AU Takemura, H Rao, VA Sordet, O Furuta, T Miao, ZH Meng, L Zhang, HL Pommier, Y AF Takemura, Haruyuki Rao, V. Ashutosh Sordet, Olivier Furuta, Takahisa Miao, Ze-Hong Meng, LingHua Zhang, Hongliang Pommier, Yves TI Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID S-PHASE CHECKPOINT; MISMATCH REPAIR PROTEINS; RECURRENT OVARIAN-CANCER; TOPOISOMERASE-I POISONS; CLEAVAGE COMPLEXES; COVALENT COMPLEX; DAMAGE RESPONSE; MRE11 COMPLEX; ATM; PHOSPHORYLATION AB The Mre11(.)Rad50(.)Nbs1 (MRN) complex binds DNA double strand breaks to repair DNA and activate checkpoints. We report MRN deficiency in three of seven colon carcinoma cell lines of the NCI Anticancer Drug Screen. To study the involvement of MRN in replication-mediated DNA double strand breaks, we examined checkpoint responses to camptothecin, which induces replication-mediated DNA double strand breaks after replication forks collide with topoisomerase I cleavage complexes. MRN-deficient cells were deficient for Chk2 activation, whereas Chk1 activation was independent of MRN. Chk2 activation was ataxia telangiectasia mutated (ATM)-dependent and associated with phosphorylation of Mre11 and Nbs1. Mre11 complementation in MRN-deficient HCT116 cells restored Chk2 activation as well as Rad50 and Nbs1 levels. Conversely, Mre11 down-regulation by small interference RNA ( siRNA) in HT29 cells inhibited Chk2 activation and down-regulated Nbs1 and Rad50. Proteasome inhibition also restored Rad50 and Nbs1 levels in HCT116 cells suggesting that Mre11 stabilizes Rad50 and Nbs1. Chk2 activation was also defective in three of four MRN-proficient colorectal cell lines because of low Chk2 levels. Thus, six of seven colon carcinoma cell lines from the NCI Anticancer Drug Screen are functionally Chk2-deficient in response to replication-mediated DNA double strand breaks. We propose that Mre11 stabilizes Nbs1 and Rad50 and that MRN activates Chk2 downstream from ATM in response to replication-mediated DNA double strand breaks. Chk2 deficiency in HCT116 is associated with defective S-phase checkpoint, prolonged G(2) arrest, and hypersensitivity to camptothecin. The high frequency of MRN and Chk2 deficiencies may contribute to genomic instability and therapeutic response to camptothecins in colorectal cancers. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Convent Dr,Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 NR 75 TC 79 Z9 80 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 13 PY 2006 VL 281 IS 41 BP 30814 EP 30823 DI 10.1074/jbc.M603747200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092CZ UT WOS:000241075900057 PM 16905549 ER PT J AU Kovalevsky, AY Liu, FL Leshchenko, S Ghosh, AK Louis, JM Harrison, RW Weber, IT AF Kovalevsky, Andrey Y. Liu, Fengling Leshchenko, Sofiya Ghosh, Arun K. Louis, John M. Harrison, Robert W. Weber, Irene T. TI Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1 protease; drug resistance; darunavir; allosteric binding site; ultra-high resolution crystal structure ID ELECTRON-DENSITY MAPS; SUBSTRATE-ANALOGS; KINETIC-ANALYSIS; RESISTANCE; INTERFACE; INDINAVIR; MODE; L90M AB TMC114 (darunavir) is a promising clinical inhibitor of HIV-1 protease (PR) for treatment of drug resistant HlV/AIDS. We report the ultra-high 0.84 angstrom resolution crystal structure of the TMC114 complex.with PR containing the drug-resistant mutation V321 (PR(V321)), and the 1.22 angstrom resolution structure of a complex with PR(M46L). These structures show TMC114 bound at two distinct sites, one in the active-site cavity and the second on the surface of one of the flexible flaps in the PR dimer. Remarkably, TMC114 binds at these two sites simultaneously in two diastereomers related by inversion of the sulfonamide nitrogen. Moreover, the flap site is shaped to accommodate the diastereomer with the S-enantiomeric nitrogen rather than the one with the R-enantiomeric nitrogen. The existence of the second binding site and two diastereomers suggest a mechanism for the high effectiveness of TMC114 on drug-resistant HIV and the potential design of new. Published by Elsevier Ltd. C1 Georgia State Univ, Dept Biol Mol Basis Dis, Atlanta, GA 30303 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. RP Weber, IT (reprint author), Georgia State Univ, Dept Biol Mol Basis Dis, Atlanta, GA 30303 USA. EM iweber@gsu.edu OI Kovalevsky, Andrey/0000-0003-4459-9142 FU FIC NIH HHS [R03 TW001001]; Intramural NIH HHS; NIGMS NIH HHS [GM53386, GM62920, U01 GM062920, R01 GM062920] NR 37 TC 88 Z9 89 U1 0 U2 5 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 OCT 13 PY 2006 VL 363 IS 1 BP 161 EP 173 DI 10.1016/j.jmb.2006.08.007 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094PB UT WOS:000241250300014 PM 16962136 ER PT J AU Gagnon, SJ Borbulevych, OY Davis-Harrison, RL Turner, RV Damirjian, M Wojnarowicz, A Biddison, WE Baker, BM AF Gagnon, Susan J. Borbulevych, Oleg Y. Davis-Harrison, Rebecca L. Turner, Richard V. Damirjian, Marale Wojnarowicz, Alison Biddison, William E. Baker, Brian M. TI T cell receptor recognition via cooperative conformational plasticity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE T cell receptor; MHC; crystallography; binding; cross-reactivity ID CAPSID PROTEIN P24; ANTIGEN RECOGNITION; MOLECULAR MIMICRY; CROSS-REACTIVITY; STRUCTURAL BASIS; CRYSTAL-STRUCTURE; SELF-PEPTIDE; SEQUENCE HOMOLOGY; ELECTRON-DENSITY; HLA-B27 SUBTYPE AB Although T cell receptor cross-reactivity is a fundamental property of the immune system and is implicated in numerous autoimmune pathologies, the molecular mechanisms by which T cell receptors can recognize and respond to diverse ligands are incompletely understood. In the current study we examined the response of the human T cell lymphotropic virus-1 (HTLV-1) Tax-specific T cell receptor (TCR) A6 to a panel of structurally distinct haptens coupled to the Tax 11-19 peptide with a lysine substitution at position 5 (Tax5K, LLFG[K-hapten]PVYV). The A6 TCR could crossreactively recognize one of these haptenated peptides, Tax-5K-4-(3-1ndolyl)* butyric acid (IBA), presented by HLA-A*0201. The crystal structures of Tax5K-IBA/HLA-A2 free and in complex with A6 reveal that binding is mediated by a mechanism of cooperative conformational plasticity involving conformational changes on both sides of the protein-protein interface, including the TCR complementarity determining region (CDR) loops, V alpha/V beta domain orientation, and the hapten-modified peptide. Our findings illustrate the complex role that protein dynamics can play in TCR cross-reactivity and highlight that T cell receptor recognition of ligand can be achieved through diverse and complex molecular mechanisms that can occur simultaneously in the interface, not limited to molecular mimicry and CDR loop shifts. Published by Elsevier Ltd. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. Natl Inst Neurol Disorders & Stroke, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. RP Baker, BM (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. EM bbaker2@nd.edu RI Baker, Brian/B-4584-2009 OI Baker, Brian/0000-0002-0864-0964 FU NCI NIH HHS [Y1-CO-1020]; NIGMS NIH HHS [GM067079, Y1-GM-1104] NR 69 TC 46 Z9 46 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 OCT 13 PY 2006 VL 363 IS 1 BP 228 EP 243 DI 10.1016/j.jmb.2006.08.045 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 094PB UT WOS:000241250300019 PM 16962135 ER PT J AU Karbowski, M Norris, KL Cleland, MM Jeong, SY Youle, RJ AF Karbowski, Mariusz Norris, Kristi L. Cleland, Megan M. Jeong, Seon-Yong Youle, Richard J. TI Role of Bax and Bak in mitochondrial morphogenesis SO NATURE LA English DT Article ID CELL-SURVIVAL; APOPTOSIS; FUSION; DYNAMICS; DIVISION; FISSION; DEATH; ACTIVATION; PROTEIN; ABSENCE AB Bcl-2 family proteins are potent regulators of programmed cell death. Although their intracellular localization to mitochondria and the endoplasmic reticulum has focused research on these organelles, how they function remains unknown. Two members of the Bcl-2 family, Bax and Bak, change intracellular location early in the promotion of apoptosis to concentrate in focal clusters at sites of mitochondrial division. Here we report that in healthy cells Bax or Bak is required for normal fusion of mitochondria into elongated tubules. Bax seems to induce mitochondrial fusion by activating assembly of the large GTPase Mfn2 and changing its submitochondrial distribution and membrane mobility properties that correlate with different GTP-bound states of Mfn2. Our results show that Bax and Bak regulate mitochondrial dynamics in healthy cells and indicate that Bcl-2 family members may also regulate apoptosis through organelle morphogenesis machineries. C1 NINCDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. RP Karbowski, M (reprint author), Univ Maryland, Inst Biotechnol, Ctr Med Biotechnol, UMBI Bldg,725 W Lombard St, Baltimore, MD 21201 USA. EM karbowsm@ninds.nih.gov; youler@ninds.nih.gov OI Harwig, Megan/0000-0003-2140-5739 FU Intramural NIH HHS NR 24 TC 386 Z9 399 U1 3 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 12 PY 2006 VL 443 IS 7112 BP 658 EP 662 DI 10.1038/nature05111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093HX UT WOS:000241160500038 PM 17035996 ER PT J AU Chavez, AE Singer, JH Diamond, JS AF Chavez, Andres E. Singer, Joshua H. Diamond, Jeffrey S. TI Fast neurotransmitter release triggered by Ca influx through AMPA-type glutamate receptors SO NATURE LA English DT Article ID MAMMALIAN RIBBON SYNAPSE; ROD BIPOLAR CELLS; AMACRINE CELLS; RAT RETINA; ACCUMULATING NEURONS; RABBIT RETINA; CALCIUM; A17; INHIBITION; TERMINALS AB Feedback inhibition at reciprocal synapses between A17 amacrine cells and rod bipolar cells (RBCs) shapes light-evoked responses in the retina(1-3). Glutamate-mediated excitation of A17 cells elicits GABA (gamma-aminobutyric acid)-mediated inhibitory feedback onto RBCs4-6, but the mechanisms that underlie GABA release from the dendrites of A17 cells are unknown. If, as observed at all other synapses studied, voltage-gated calcium channels (VGCCs) couple membrane depolarization to neurotransmitter release(7), feedforward excitatory postsynaptic potentials could spread through A17 dendrites to elicit 'surround' feedback inhibitory transmission at neighbouring synapses. Here we show, however, that GABA release from A17 cells in the rat retina does not depend on VGCCs or membrane depolarization. Instead, calcium-permeable AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs), activated by glutamate released from RBCs, provide the calcium influx necessary to trigger GABA release from A17 cells. The AMPAR-mediated calcium signal is amplified by calcium-induced calcium release (CICR) from intracellular calcium stores. These results describe a fast synapse that operates independently of VGCCs and membrane depolarization and reveal a previously unknown form of feedback inhibition within a neural circuit. C1 NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU Intramural NIH HHS; NINDS NIH HHS [K22 NS043365] NR 30 TC 89 Z9 92 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 12 PY 2006 VL 443 IS 7112 BP 705 EP 708 DI 10.1038/nature05123 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093HX UT WOS:000241160500049 PM 17036006 ER PT J AU Schneider, LS Tariot, PN Dagerman, KS Davis, SM Hsiao, JK Ismail, MS Lebowitz, BD Lyketsos, CG Ryan, JM Stroup, TS Sultzer, DL Weintraub, D Lieberman, JA AF Schneider, Lon S. Tariot, Pierre N. Dagerman, Karen S. Davis, Sonia M. Hsiao, John K. Ismail, M. Saleem Lebowitz, Barry D. Lyketsos, Constantine G. Ryan, J. Michael Stroup, T. Scott Sultzer, David L. Weintraub, Daniel Lieberman, Jeffrey A. CA CATIE-AD Study Grp TI Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIALS; DIAGNOSTIC-CRITERIA; INTERNATIONAL WORKSHOP; CEREBROVASCULAR EVENTS; NEUROLEPTIC TREATMENT; DEMENTIA TRIALS; METAANALYSIS; DEPRESSION; PSYCHOSIS; RISK AB BACKGROUND Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. C1 Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Banner Alzheimers Inst, Phoenix, AZ USA. Quintiles, Res Triangle Pk, NC USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Johns Hopkins Univ, Johns Hopkins Bayview, Dept Psychiat, Baltimore, MD USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Coll Phys & Surg, New York, NY USA. RP Schneider, LS (reprint author), Univ So Calif, Keck Sch Med, 1510 San Pablo St,HCC 600, Los Angeles, CA 90033 USA. EM lschneid@usc.edu RI Stroup, Thomas/F-9188-2014 OI Adler, Lawrence/0000-0002-6619-2493; Stroup, Thomas/0000-0002-3123-0672 NR 33 TC 556 Z9 562 U1 3 U2 29 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 OCT 12 PY 2006 VL 355 IS 15 BP 1525 EP 1538 DI 10.1056/NEJMoa061240 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 093HW UT WOS:000241160400004 PM 17035647 ER PT J AU Mulherkar, N Ramaswamy, M Mordi, DC Prabhakar, BS AF Mulherkar, N. Ramaswamy, M. Mordi, D. C. Prabhakar, B. S. TI MADD/DENN splice variant of the IG20 gene is necessary and sufficient for cancer cell survival SO ONCOGENE LA English DT Article DE IG20pa; MADD; DENN-SV; shRNA; alternative-splicing; apoptosis ID GDP/GTP EXCHANGE PROTEIN; SMALL INTERFERING RNAS; DEATH DOMAIN PROTEIN; INDUCED APOPTOSIS; NEOPLASTIC-CELLS; MAMMALIAN-CELLS; DENN-SV; MADD; EXPRESSION; RECEPTOR AB The IG20 gene is overexpressed in human tumors and cancer cell lines, and encodes at least four splice variants (SVs) namely, IG20pa, MADD, IG20-SV2 and DENNSV. Earlier, gain-of-function studies showed that IG20SVs can exhibit diverse functions and play a critical role in cell proliferation and apoptosis. Expression of exogenous IG20pa or DENN-SV rendered cells either susceptible or resistant to induced apoptosis, respectively, whereas MADD and IG20-SV2 had no apparent effect. In order to understand the contrasting effects of the IG20-SVs in a physiologically more relevant system, we expressed exon-specific small hairpin RNAs (shRNAs) to selectively knockdown specific IG20-SVs. Consistent with an earlier study, knockdown of all IG20-SVs resulted in spontaneous apoptosis of HeLa and PA-1 cells. In addition, we unambiguously demonstrated that knockdown of MADD can render cells susceptible to spontaneous apoptosis but had no discernible effect on cell proliferation, colony size or cell cycle progression. Moreover, expression of MADD alone, and not DENN-SV, in the absence of endogenous IG20-SVs was sufficient to prevent spontaneous apoptosis. Our results show the utility of shRNAs for selective knockdown of particular IG20-SVs and their potential therapeutic value in cancer. Further, they demonstrate that MADD alone is sufficient and necessary for cancer cell survival. C1 Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Prabhakar, BS (reprint author), Univ Illinois, Coll Med, Dept Microbiol & Immunol, M-C 790,Room E-705,835 S Wolcott Ave, Chicago, IL 60612 USA. EM bprabhak@uic.edu FU NCI NIH HHS [5R01CA107506] NR 35 TC 22 Z9 25 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 12 PY 2006 VL 25 IS 47 BP 6252 EP 6261 DI 10.1038/sj.onc.1209650 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 094CY UT WOS:000241218200003 PM 16682944 ER PT J AU Vannada, J Bennett, EM Wilson, DJ Boshoff, HI Barry, CE Aldrich, CC AF Vannada, Jagadeshwar Bennett, Eric M. Wilson, Daniel J. Boshoff, Helena I. Barry, Clifton E., III Aldrich, Courtney C. TI Design, synthesis, and biological evaluation of beta-ketosulfonamide adenylation inhibitors as potential antitubercular agents SO ORGANIC LETTERS LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; SIDEROPHORE BIOSYNTHESIS; IRON ACQUISITION; SULFONAMIDES; MACROPHAGES; DIANIONS; REAGENTS; GROWTH AB The antitubercular nucleoside antibiotics 1 and 2 were recently described that inhibit the adenylate-forming enzyme MbtA and disrupt biosynthesis of the virulence-conferring siderophore known as mycobactin in Mycobacterium tuberculosis. Herein, we report efforts to refine this inhibitor scaffold by replacing the labile acylsulfamate linkage (highlighted) with the more chemically robust beta-ketosulfonamide linkage of 3 and 4. C1 Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. NIAID, TB Res Sect, Rockville, MD 20852 USA. RP Vannada, J (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA. EM aldri015@umn.edu RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-15]; NIAID NIH HHS [R01 AI070219, R01 AI070219-01, R01AI070219] NR 27 TC 37 Z9 38 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD OCT 12 PY 2006 VL 8 IS 21 BP 4707 EP 4710 DI 10.1021/ol0617289 PG 4 WC Chemistry, Organic SC Chemistry GA 091LS UT WOS:000241030900010 PM 17020283 ER PT J AU Baughman, RW Farkas, R Guzman, M Huerta, MF AF Baughman, Robert W. Farkas, Rebecca Guzman, Marlene Huerta, Michael F. TI The National Institutes of Health Blueprint for Neuroscience Research SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material C1 Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. NIMH, Rockville, MD 20852 USA. RP Baughman, RW (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. EM rb175y@nih.gov RI Baughman, Robert/O-9078-2014 OI Baughman, Robert/0000-0002-8557-9458 NR 0 TC 14 Z9 14 U1 0 U2 0 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 OCT 11 PY 2006 VL 26 IS 41 BP 10329 EP 10331 DI 10.1523/JNEUROSCI.3979-06.2006 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 093TO UT WOS:000241192800002 PM 17035514 ER PT J AU Morrison, JH Brinton, RD Schmidt, PJ Gore, AC AF Morrison, John H. Brinton, Roberta D. Schmidt, Peter J. Gore, Andrea C. TI Estrogen, menopause, and the aging brain: How basic neuroscience can inform hormone therapy in women SO JOURNAL OF NEUROSCIENCE LA English DT Review DE estradiol; mood; cognition; cerebral cortex; hippocampus; hypothalamus; neuroprotection ID GONADOTROPIN-RELEASING-HORMONE; METHYL-D-ASPARTATE; DENDRITIC SPINE DENSITY; RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; CONJUGATED EQUINE ESTROGENS; MILD COGNITIVE IMPAIRMENT; MIDDLE-AGED RATS; RECEPTOR-DEPENDENT MECHANISM; HIPPOCAMPAL PYRAMIDAL CELLS C1 Mt Sinai Sch Med, Fishberg Dept Neurosci, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. Univ So Calif, Neurosci Program, Dept Biomed Engn, Sch Pharm, Los Angeles, CA 90033 USA. Univ So Calif, Neurosci Program, Dept Mol Pharmacol, Sch Pharm, Los Angeles, CA 90033 USA. Univ So Calif, Neurosci Program, Dept Toxicol, Sch Pharm, Los Angeles, CA 90033 USA. NIMH, Behav Endocrinol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Texas, Div Pharmacol Toxicol, Coll Pharm, Inst Neurosci, Austin, TX 78712 USA. Inst Cell & Mol Biol, Austin, TX 78712 USA. RP Morrison, JH (reprint author), Mt Sinai Sch Med, Fishberg Dept Neurosci, Kastor Neurobiol Aging Labs, Box 1065, New York, NY 10029 USA. EM john.morrison@mssm.edu RI Morrison, John/F-9229-2012; OI Gore, Andrea/0000-0001-5549-6793 FU NIA NIH HHS [AG026572, AG06647, AG14751, AG16765]; NIMH NIH HHS [MH67159] NR 188 TC 138 Z9 148 U1 4 U2 10 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 OCT 11 PY 2006 VL 26 IS 41 BP 10332 EP 10348 DI 10.1523/JNEUROSCI.3369-06.2006 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 093TO UT WOS:000241192800003 PM 17035515 ER PT J AU Antonellis, A Lee-Lin, SQ Wasterlain, A Leo, P Quezado, M Goldfarb, LG Myung, K Burgess, S Fischbeck, KH Green, ED AF Antonellis, Anthony Lee-Lin, Shih-Queen Wasterlain, Amy Leo, Paul Quezado, Martha Goldfarb, Lev G. Myung, Kyungjae Burgess, Shawn Fischbeck, Kenneth H. Green, Eric D. TI Functional analyses of glycyl-tRNA synthetase mutations suggest a key role for tRNA-charging enzymes in peripheral axons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Charcot-Marie-Tooth disease; spinal muscular atrophy; peripheral neuropathy; axonopathy; tRNA synthetase; axonal translation ID MARIE-TOOTH-DISEASE; SPINAL MUSCULAR-ATROPHY; SACCHAROMYCES-CEREVISIAE; PARKIN SUBSTRATE; CHROMOSOME 7P; MOTOR; PROTEIN; NEUROPATHY; NEURON; COMPLEX AB Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal neuropathies characterized by a phenotype that is more severe in the upper extremities. We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. GARS is a member of the family of aminoacyl-tRNA synthetases responsible for charging tRNA with cognate amino acids; GARS ligates glycine to tRNAGly. Here, we present functional analyses of disease-associated GARS mutations and show that there are not any significant mutation-associated changes in GARS expression levels; that the majority of identified GARS mutations modeled in yeast severely impair viability; and that, in most cases, mutant GARS protein mislocalizes in neuronal cells. Indeed, four of the five mutations studied show loss-of-function features in at least one assay, suggesting that tRNA-charging deficits play a role in disease pathogenesis. Finally, we detected endogenous GARS-associated granules in the neurite projections of cultured neurons and in the peripheral nerve axons of normal human tissue. These data are particularly important in light of the recent identification of CMT-associated mutations in another tRNA synthetase gene [YARS(tyrosyl-tRNA synthetase gene)]. Together, these findings suggest that tRNA-charging enzymes play a key role in maintaining peripheral axons. C1 NHGRI, Gen Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Green, ED (reprint author), NHGRI, Gen Technol Branch, NIH, 50 S Dr,Bldg 50,Room 5222, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov RI Leo, Paul/B-3470-2011; OI Leo, Paul/0000-0001-8325-4134; Burgess, Shawn/0000-0003-1147-0596 FU Intramural NIH HHS NR 35 TC 61 Z9 64 U1 0 U2 5 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 OCT 11 PY 2006 VL 26 IS 41 BP 10397 EP 10406 DI 10.1523/JNEUROSCI.1671-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 093TO UT WOS:000241192800012 PM 17035524 ER PT J AU Dzirasa, K Ribeiro, S Costa, R Santos, LM Lin, SC Grosmark, A Sotnikova, TD Gainetdinov, RR Caron, MG Nicolelis, MAL AF Dzirasa, Kafui Ribeiro, Sidarta Costa, Rui Santos, Lucas M. Lin, Shih-Chieh Grosmark, Andres Sotnikova, Tatyana D. Gainetdinov, Raul R. Caron, Marc G. Nicolelis, Miguel A. L. TI Dopaminergic control of sleep-wake states SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; sleep; REM; psychosis; schizophrenia; Parkinson's ID DEFICIT HYPERACTIVITY DISORDER; FREELY MOVING RATS; PARKINSONS-DISEASE; REM-SLEEP; NUCLEUS-ACCUMBENS; BEHAVIORAL STATES; TRANSPORTER GENE; LOCUS-COERULEUS; MICE LACKING; RECEPTOR AB Dopamine depletion is involved in the pathophysiology of Parkinson's disease, whereas hyperdopaminergia may play a fundamental role in generating endophenotypes associated with schizophrenia. Sleep disturbances are known to occur in both schizophrenia and Parkinson's disease, suggesting that dopamine plays a role in regulating the sleep-wake cycle. Here, we show that novelty-exposed hyperdopaminergic mice enter a novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during rapid-eye-movement (REM) sleep. Treatment with haloperidol, a D(2) dopamine receptor antagonist, reduces this abnormal intrusion of REM-like activity during wakefulness. Conversely, mice acutely depleted of dopamine enter a different novel awake state characterized by spectral patterns of hippocampal local field potentials that resemble electrophysiological activity observed during slow-wave sleep (SWS). This dopamine-depleted state is marked by an apparent suppression of SWS and a complete suppression of REM sleep. Treatment with D(2) (but not D(1)) dopamine receptor agonists recovers REM sleep in these mice. Altogether, these results indicate that dopamine regulates the generation of sleep-wake states. We propose that psychosis and the sleep disturbances experienced by Parkinsonian patients result from dopamine-mediated disturbances of REM sleep. C1 Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biomed Engn, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychol & Brain Sci, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Neuroengn, Durham, NC 27710 USA. NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Nicolelis, MAL (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Bryan Res Bldg, Durham, NC 27710 USA. EM nicoleli@neuro.duke.edu RI Gainetdinov, Raul/G-5875-2011; OI Costa, Rui/0000-0003-0495-8374; Lin, Shih-Chieh/0000-0003-3693-5476; Gainetdinov, Raul/0000-0003-2951-6038 NR 65 TC 144 Z9 152 U1 0 U2 25 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 OCT 11 PY 2006 VL 26 IS 41 BP 10577 EP 10589 DI 10.1523/JNEUROSCI.1767-06.2006 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 093TO UT WOS:000241192800032 PM 17035544 ER PT J AU Bennett, M Stroncek, DF AF Bennett, Michael Stroncek, David F. TI Recent advances in the bcr-abl negative chronic myeloproliferative diseases SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID COLONY-STIMULATING-FACTOR; POLYCYTHEMIA RUBRA VERA; TYROSINE KINASE JAK2; ESSENTIAL THROMBOCYTHEMIA; STEM-CELL; THROMBOPOIETIN RECEPTOR; MYELOID METAPLASIA; PROGENITOR CELLS; MEGAKARYOCYTE GROWTH; ACTIVATING MUTATION AB The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders of unknown etiology. In one of these ( chronic myeloid leukemia), there is an associated pathognomonic chromosomal abnormality known as the Philadelphia chromosome. This leads to constitutive tyrosine kinase activity which is responsible for the disease and is used as a target for effective therapy. This review concentrates on the search in the other conditions (polycythemia vera, essential thrombocythemia and idiopathic mylofibrosis) for a similar biological marker with therapeutic potential. There is no obvious chromosomal marker in these conditions and yet evidence of clonality can be obtained in females by the use of X-inactivation patterns. PRV-1 mRNA over expression, raised vitamin B-12 levels and raised neutrophil alkaline phosphatase scores are evidence that cells in these conditions have received excessive signals for proliferation, maturation and reduced apoptosis. The ability of erythroid colonies to grow spontaneously without added external erythropoietin in some cases, provided a useful marker and a clue to this abnormal signaling. In the past year several important discoveries have been made which go a long way in elucidating the involved pathways. The recently discovered JAK2 V617F mutation which occurs in the majority of cases of polycythemia vera and in about half of the cases with the two other conditions, enables constitutive tyrosine kinase activity without the need for ligand binding to hematopoietic receptors. This mutation has become the biological marker for these conditions and has spurred the development of a specific therapy to neutralize its effects. The realization that inherited mutations in the thrombopoietin receptor (c-Mpl) can cause a phenotype of thrombocytosis such as in Mpl Baltimore (K39N) and in a Japanese family with S505A, has prompted the search for acquired mutations in this receptor in chronic myeloproliferative disease. Recently, two mutations have been found; W515L and W515K. These mutations have been evident in patients with essential thrombocythemia and idiopathic myelofibrosis but not in polycythemia vera. They presumably act by causing constitutional, activating conformational changes in the receptor. The discovery of JAK2 and Mpl mutations is leading to rapid advancements in understanding the pathophysiology and in the treatment of these diseases. C1 HaEmek Med Ctr, Dept Hematol, Afula, Israel. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Bennett, M (reprint author), HaEmek Med Ctr, Dept Hematol, Afula, Israel. EM benet_m@clalit.org.il; dstroncek@mail.cc.nih.gov NR 69 TC 9 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 11 PY 2006 VL 4 AR 41 DI 10.1186/1479-5876-4-41 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 103HB UT WOS:000241875200001 PM 17032464 ER PT J AU Gurarie, D McKenzie, FE AF Gurarie, David McKenzie, F. Ellis TI Dynamics of immune response and drug resistance in malaria infection SO MALARIA JOURNAL LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; POPULATION-DYNAMICS; CHLOROQUINE; MODELS; CLEARANCE; PARASITES; CHILDREN; GROWTH AB Background: Malaria parasites that concurrently infect a host compete on the basis of their intrinsic growth rates and by stimulating cross-reactive immune responses that inhibit each others' growth. If the phenotypes also show different drug sensitivities ('sensitive' vs. 'resistant' strains), drug treatment can change their joint dynamics and the long-term outcome of the infection: most obviously, persistent drug pressure can permit the more resistant, but otherwise competitively-inferior, strains to dominate. Methods: Here a mathematical model is developed to analyse how these and more subtle effects of antimalarial drug use are modulated by immune response, repeated re-inoculation of parasites, drug pharmacokinetic parameters, dose and treatment frequency. Results: The model quantifies possible effects of single and multiple (periodic) treatment on the outcome of parasite competition. In the absence of further inoculation, the dosage and/or treatment frequency required for complete clearance can be estimated. With persistent superinfection, time-average parasite densities can be derived in terms of the basic immune-regulating parameters, the drug efficacy and treatment regimen. Conclusion: The functional relations in the model are applicable to a wide range of conditions and transmission environments, allowing predictions to be made on both the individual and the community levels, and, in particular, transitions from drug-sensitive to drug-resistant parasite dominance to be projected on both levels. C1 Case Western Reserve Univ, Dept Math, Cleveland, OH 44106 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Gurarie, D (reprint author), Case Western Reserve Univ, Dept Math, Cleveland, OH 44106 USA. EM dxg5@case.edu; em225k@nih.gov OI Gurarie, David/0000-0002-5314-7888 FU Intramural NIH HHS [Z99 TW999999] NR 29 TC 11 Z9 11 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD OCT 11 PY 2006 VL 5 AR 86 DI 10.1186/1475-2875-5-86 PG 15 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 103HK UT WOS:000241876100001 PM 17034637 ER PT J AU Do Carmo, GP Mello, NK Rice, KC Folk, JE Negus, SS AF Do Carmo, Gail Pereira Mello, Nancy K. Rice, Kenner C. Folk, John E. Negus, S. Stevens TI Effects of the selective delta opioid agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE delta opioid receptor agonist; SNC80; cocaine self-administration; rhesus monkey ID DISCRIMINATIVE STIMULUS PROPERTIES; D-AMPHETAMINE TREATMENT; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; RECEPTOR AGONIST; PROGRESSIVE-RATIO; RAPID ASSESSMENT; MU; ABUSE; DPDPE AB Delta agonists such as SNC80 ((+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) produce some cocaine-like behavioral effects and warrant evaluation as candidate "agonist" medications for cocaine abuse. The present study examined acute and chronic effects of the systemically active delta agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys. Acute SNC80 (0.32-3.2 mg/kg, i.m.) pretreatment dose-dependently decreased cocaine self-administration (0.0032 mg/kg/injection), but doses of SNC80 that decreased cocaine self-administration also decreased food-maintained responding. In chronic studies, SNC80 (0.32-3.2 mg/kg/h, i.v.) was delivered for 7 days, and food or cocaine (0.01 mg/kg/injection) was available during 4 daily components of food availability and 4 daily components of drug availability. Chronic SNC80 (1.8 mg/kg/h) tended to decrease cocaine self-administration but produced greater reductions in food-maintained responding. A higher dose of 3.2 mg/kg/h SNC80 eliminated both cocaine- and food-maintained responding and produced profound sedation in one monkey and was not tested in other monkeys. These findings indicate that SNC80 produced dose-dependent and nonselective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Negus, SS (reprint author), Harvard Univ, Sch Med, McLean Hosp, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. EM negus@mclean.org FU Intramural NIH HHS; NIDA NIH HHS [K05 DA000101, R01-DA02519, R01 DA011460, R01 DA002519, K05-DA 00101, R01-DA 11460] NR 57 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 10 PY 2006 VL 547 IS 1-3 BP 92 EP 100 DI 10.1016/j.ejphar.2006.06.075 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 093MM UT WOS:000241172400012 PM 16934797 ER PT J AU Hirai, Y Kodama, Y Moriwaki, SI Noda, A Cullings, HM MacPhee, DG Kodama, K Mabuchi, K Kraemer, KH Land, CE Nakamura, N AF Hirai, Yuko Kodama, Yoshiaki Moriwaki, Shin-Ichi Noda, Asao Cullings, Harry M. MacPhee, Donald G. Kodama, Kazunori Mabuchi, Kiyohiko Kraemer, Kenneth H. Land, Charles E. Nakamura, Nori TI Heterozygous individuals bearing a founder mutation in the XPA DNA repair gene comprise nearly 1% of the Japanese population SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE xeroderma pigmentosum A (XPA); founder mutation; heterozygous carriers; Japanese population ID PIGMENTOSUM GROUP-A; CONGENITAL MUSCULAR-DYSTROPHY; XERODERMA-PIGMENTOSUM; RETROTRANSPOSAL INSERTION; CANCER; POLYMORPHISMS; FAMILIES; ORIGIN; RISK AB Individuals who are homozygotes for mutations in DNA repair genes are at high risk for cancer. It is not well documented, however, if the heterozygous carriers of the mutation are also predisposed to cancer. To address the issue, xeroderma pigmentosum (XP) in Japan is an interesting candidate because of three major reasons: XP is an autosomal recessive disorder with an enormously elevated risk of skin cancer, the frequency of XP patients is higher in Japan than in other parts of the world, and more than half of Japanese XP patients are homozygous for the same founder mutation in the XPA gene. We screened archival blood samples from Japanese individuals who resided in Hiroshima or Nagasaki. A simple PCR-RFLP method was developed that is highly specific for detection of XPA heterozygotes carrying the founder mutation. We identified nine XPA heterozygotes among 1020 individuals screened for a prevalence of 0.88%. This rate, if representative, implies that there are about I million carriers of the XPA founder mutation in the Japanese population. Thus, investigation of their cancer risk may be warranted. (c) 2006 Elsevier B.V. All rights reserved. C1 Radiat Effects Res Fdn, Dept Genet, Minami Ku, Hiroshima 7320815, Japan. Osaka Med Coll, Dept Dermatol, Takatsuki, Osaka 5698686, Japan. Radiat Effects Res Fdn, Dept Stat, Minami Ku, Hiroshima 7320815, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, Hiroshima 7320815, Japan. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Hirai, Y (reprint author), Radiat Effects Res Fdn, Dept Genet, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM hirai@rerf.or.jp FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [N01-CP-31012] NR 26 TC 51 Z9 52 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 10 PY 2006 VL 601 IS 1-2 BP 171 EP 178 DI 10.1016/j.mrfmmm.2006.06.010 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 100XY UT WOS:000241704700019 PM 16905156 ER PT J AU Nash, TE Singh, G White, AC Rajshekhar, V Loeb, JA Proano, JV Takayanagui, OM Gonzalez, AE Butman, JA DeGiorgio, C Del Brutto, OH Delgado-Escueta, A Evans, CAW Gilman, RH Martinez, SM Medina, MT Pretell, EJ Teale, J Garcia, HH AF Nash, T. E. Singh, G. White, A. C. Rajshekhar, V. Loeb, J. A. Proano, J. V. Takayanagui, O. M. Gonzalez, A. E. Butman, J. A. DeGiorgio, C. Del Brutto, O. H. Delgado-Escueta, A. Evans, C. A. W. Gilman, R. H. Martinez, S. M. Medina, M. T. Pretell, E. J. Teale, J. Garcia, H. H. TI Treatment of neurocysticercosis - Current status and future research needs SO NEUROLOGY LA English DT Review ID COMPUTED TOMOGRAPHIC LESIONS; TAENIA-SOLIUM TAENIASIS; TEMPORAL-LOBE EPILEPSY; ALBENDAZOLE THERAPY; CEREBRAL CYSTICERCOSIS; CALCIFIED NEUROCYSTICERCOSIS; MURINE CYSTICERCOSIS; CEREBROSPINAL-FLUID; MAGNETIC-RESONANCE; PERILESIONAL EDEMA AB Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Dayanand Med Coll & Hosp, Ludhiana, Punjab, India. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Christian Med Coll & Hosp, Dept Neurol Sci, Vellore 632004, Tamil Nadu, India. Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Hosp Especial, Ctr Med Nacl Siglo 21, Mexican Inst Social Secur, Med Res Unit Neurol Dis, Mexico City, DF, Mexico. Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Neurol, BR-14049 Ribeirao Preto, Brazil. Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru. Johns Hopkins Univ, Bloomberg Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90024 USA. VA Epilepsy Ctr Excellence, Los Angeles, CA USA. Hosp Clin Kennedy, Dept Neurol Sci, Guayaquil, Ecuador. Univ Cambridge, Sch Clin, Cambridge, England. Univ London Imperial Coll Sci & Technol, Dept Infect Dis & Microbiol, London, England. Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru. Inst Especializado Ciencias Neurol, Cysticercosis Unit, Lima, Peru. Univ Texas, Hlth Sci Ctr, Dept Microbiol & Immunol, San Antonio, TX 78285 USA. Univ Nacl Autonoma Honduras, Tegucigalpa, Honduras. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov RI Butman, John/A-2694-2008; Takayanagui, Osvaldo/C-8159-2013; OI Takayanagui, Osvaldo/0000-0002-8190-0275; White, A Clinton/0000-0002-9668-4632; Butman, John/0000-0002-1547-9195 FU Wellcome Trust [057434] NR 68 TC 98 Z9 102 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 10 PY 2006 VL 67 IS 7 BP 1120 EP 1127 DI 10.1212/01.wnl.0000238514.51747.3a PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 092DL UT WOS:000241077100004 PM 17030744 ER PT J AU Voon, V Hassan, K Zurowski, M de Souza, M Thomsen, T Fox, S Lang, AE Miyasaki, J AF Voon, V. Hassan, K. Zurowski, M. de Souza, M. Thomsen, T. Fox, S. Lang, A. E. Miyasaki, J. TI Prevalence of repetitive and reward-seeking behaviors in Parkinson disease SO NEUROLOGY LA English DT Article ID HEDONISTIC HOMEOSTATIC DYSREGULATION AB We surveyed 297 patients with Parkinson disease (PD) with systematic screens and rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was 2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data, the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in patients on dopamine agonists. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Voon, V (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Rm 5S213,10 Ctr Dr, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov RI zurowski, mateusz/D-1536-2010; OI zurowski, mateusz/0000-0002-6407-4629; Miyasaki, Janis/0000-0002-6372-6007 NR 10 TC 230 Z9 234 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 10 PY 2006 VL 67 IS 7 BP 1254 EP 1257 DI 10.1212/01.wnl.0000238503.20816.13 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 092DL UT WOS:000241077100027 PM 16957130 ER PT J AU Iwahara, J Zweckstetter, M Clore, GM AF Iwahara, Junji Zweckstetter, Markus Clore, G. Marius TI NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dynamics; nonspecific binding; protein-DNA interactions; structure ID PARAMAGNETIC RELAXATION ENHANCEMENT; NUCLEAR MAGNETIC RESONANCE; DIPOLAR COUPLINGS; ANTENNAPEDIA HOMEODOMAIN; CRYSTAL-STRUCTURE; BINDING; COMPLEXES; PROTEINS; RECOGNITION; REFINEMENT AB Nonspecific protein-DNA interactions are inherently dynamic and involve both diffusion of the protein along the DNA and hopping of the protein from one DNA molecule or segment to another. Understanding how gene regulatory proteins interact nonspecifically with DNA in terms of both structure and dynamics is challenging because the experimental, observables are an ensemble average of many rapidly exchanging states. By using a variety of NMR spectroscopic techniques, including relaxation analysis, paramagnetic relaxation enhancement, and residual dipolar couplings, we have characterized structural and kinetic aspects of the interaction of the HoxD9 homeodomain with a nonspecific, 24-bp DNA duplex in a system in which the protein is not constrained to any particular site. The data reveal that HoxD9 binds to nonspecific DNA with the same binding mode and orientation as that observed in the specific complex. The mobility, however, of Arg side-chains contacting the DNA is increased in the nonspecific complex relative to the specific one. The kinetics of intermolecular translocation between two different nonspecific DNA molecules have also been analyzed and reveal that at high DNA concentrations (such as those present in vivo) direct transfer from one nonspecific complex to another nonspecific DNA molecule occurs without going through the intermediary of free protein. This finding provides a simple mechanism for accelerating the target search in vivo for the specific site in a sea of nonspecific sites by permitting more effective sampling of available DNA sites as the protein jumps from one segment to another. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany. RP Clore, GM (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008; OI Clore, G. Marius/0000-0003-3809-1027; Iwahara, Junji/0000-0003-4732-2173 FU Intramural NIH HHS NR 31 TC 120 Z9 121 U1 1 U2 19 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 OCT 10 PY 2006 VL 103 IS 41 BP 15062 EP 15067 DI 10.1073/pnas.0605868103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300016 PM 17008406 ER PT J AU Eller, MS Liao, XD Liu, SY Hanna, K Backvall, H Opresko, PL Bohr, VA Gilchrest, BA AF Eller, Mark S. Liao, Xiaodong Liu, SuiYang Hanna, Kendra Backvall, Helena Opresko, Patricia L. Bohr, Vilhelm A. Gilchrest, Barbara A. TI A role for WRN in telomere-based DNA damage responses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE exonuclease; gamma-H2AX foci; Werner syndrome; senescence; oligonucleotide ID WERNER-SYNDROME PROTEIN; HUMAN CELLULAR SENESCENCE; DOUBLE-STRAND BREAKS; S-PHASE CHECKPOINT; REPLICATIVE SENESCENCE; MAMMALIAN TELOMERES; SYNDROME CELLS; LIFE-SPAN; D-LOOPS; TRF2 AB Telomeres cap the ends of eukaryotic chromosomes and prevent them from being recognized as DNA breaks. We have shown that certain DNA damage responses induced during senescence and, at times of telomere uncapping, also can be induced by treatment of cells with small DNA oligonucleoticles homologous to the telomere 3' single-strand overhang (T-oligos), implicating this overhang in generation of these telomere-based damage responses. Here, we show that T-oligo-treated fibroblasts contain gamma H2AX foci and that these foci colocalize with telomeres. T-oligos with nuclease-resistant 3' ends are inactive, suggesting that a nuclease initiates T-oligo responses. We therefore examined WRN, a 3' -> 5' exonuclease and helicase mutated in Werner syndrome, a disorder characterized by aberrant telomere maintenance, premature aging, chromosomal rearrangements, and predisposition to malignancy. Normal fibroblasts and U20S osteosarcoma cells rendered deficient in WRN showed reduced phosphorylation of p53 and histone H2AX in response to T-oligo treatment. Together, these data demonstrate a role for WRN in processing of telomeric DNA and subsequent activation of DNA damage responses. The T-oligo model helps define the role of WRN in telomere maintenance and initiation of DNA damage responses after telomere disruption. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15219 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gilchrest, BA (reprint author), Boston Univ, Sch Med, Dept Dermatol, 609 Albany St, Boston, MA 02118 USA. EM bgilchre@bu.edu OI Backvall, Helena/0000-0002-1531-9271; Opresko, Patricia/0000-0002-6470-2189 NR 62 TC 44 Z9 46 U1 1 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 OCT 10 PY 2006 VL 103 IS 41 BP 15073 EP 15078 DI 10.1073/pnas.0607332103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300018 PM 17015833 ER PT J AU Sabaawy, HE Azuma, M Embree, LJ Tsai, HJ Starost, MF Hickstein, DD AF Sabaawy, Hatem E. Azuma, Mizuki Embree, Lisa J. Tsai, Huai-Jen Starost, Matthew F. Hickstein, Dennis D. TI TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE stem cell; translocation; childhood cancer; genetics ID CHROMOSOME TRANSLOCATIONS; FUSION PROTEIN; HIGH-FREQUENCY; IN-UTERO; EXPRESSION; GENE; TEL/AML1; TEL; DIFFERENTIATION; LEUKEMOGENESIS AB Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The TEL-AML1 (ETV6-RUNX1) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of TEL-AML1-induced leukemia have not been identified. To study the origin of TEL-AML1-induced ALL, we generated transgenic zebrafish expressing TEL-AML1 either ubiquitously or in lymphoid progenitors. TEL-AML1 expression in all lineages, but not lymphoid-restricted expression, led to progenitor cell expansion that evolved into oligoclonal B-lineage ALL in 3% of the transgenic zebrafish. This leukemia was transplantable to conditioned wildtype recipients. We demonstrate that TEL-AML1 induces a B cell differentiation arrest, and that leukemia development is associated with loss of TEL expression and elevated Bcl2/Bax ratio. The TEL-AML1 transgenic zebrafish models human pre-B ALL, identifies the molecular pathways associated with leukemia development, and serves as the foundation for subsequent genetic screens to identify modifiers and leukemia therapeutic targets. C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Natl Taiwan Univ, Inst Mol & Cellular Biol, Taipei 10617, Taiwan. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Sabaawy, HE (reprint author), NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. EM sabaawyh@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [K22 CA120626] NR 48 TC 96 Z9 100 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2006 VL 103 IS 41 BP 15166 EP 15171 DI 10.1073/pnas.0603349103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300034 PM 17015828 ER PT J AU Hansson, AC Cippitelli, A Sommer, WH Fedeli, A Bjork, K Soverchia, L Terasmaa, A Massi, M Heilig, M Ciccocioppo, R AF Hansson, A. C. Cippitelli, A. Sommer, W. H. Fedeli, A. Bjork, K. Soverchia, L. Terasmaa, A. Massi, M. Heilig, M. Ciccocioppo, R. TI Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE alcoholism; reinstatement; self-administration; corticotropin-releasing hormone ID CORTICOTROPIN-RELEASING-FACTOR; OPIOID RECEPTOR GENE; ANIMAL-MODEL; PREFERRING RATS; ANXIETY; REINSTATEMENT; DEPENDENCE; DRINKING; HISTORY; BINDING AB Alcoholism is a chronic relapsing disorder with substantial heritability. Uncovering gene-environment interactions underlying this disease process can aid identification of novel treatment targets. Here, we found a lowered threshold for stress-induced reinstatement of alcohol seeking in Marchigian-Sardinian Preferring (msP) rats genetically selected for high alcohol preference. In situ hybridization for a panel of 20 stress-related genes in 16 brain regions was used to screen for differential gene expression that may underlie this behavioral phenotype. An innate up-regulation of the Crhr1 transcript, encoding the corticotropin-releasing hormone receptor 1 (CRH-R1), was found in several limbic brain areas of msP rats genetically selected for high alcohol preference, was associated with genetic polynnorphism of the Crhr1 promoter, and was accompanied by increased CRH-R1 density. A selective CRH-R1 antagonist (antalarmin, 10-20 mg/kg) was devoid of effects on operant alcohol self-administration in unselected Wistar rats but significantly suppressed this behavior in the msP line. Stress-induced reinstatement of alcohol seeking was not significantly affected by antalarmin in Wistar rats but was fully blocked in msP animals. These data demonstrate that Crhr1 genotype and expression interact with environmental stress to reinstate alcohol-seeking behavior. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy. Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden. RP Heilig, M (reprint author), 10 Ctr Dr,10-1-5334, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Terasmaa, Anton/I-3312-2015 OI Terasmaa, Anton/0000-0002-5139-1764 FU Intramural NIH HHS NR 33 TC 150 Z9 151 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2006 VL 103 IS 41 BP 15236 EP 15241 DI 10.1073/pnas.0604419103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300046 PM 17015825 ER PT J AU Dang, MT Yokoi, F Yin, HH Lovinger, DM Wang, YY Li, YQ AF Dang, Mai T. Yokoi, Fumiaki Yin, Henry H. Lovinger, David M. Wang, Yanyan Li, Yuqing TI Disrupted motor learning and long-term synaptic plasticity in mice lacking NMDAR1 in the striatum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE long-term potentiation; NMDA receptor; knockout; RGS9-2 ID PRECLINICAL HUNTINGTONS-DISEASE; NUCLEUS-ACCUMBENS; DORSOMEDIAL STRIATUM; NEURONAL PATTERNS; DEFICIENT MICE; DEPRESSION; RECEPTORS; MEMORY; EXPRESSION; MOUSE AB Much research has implicated the striatum in motor learning, but the underlying mechanisms have not been identified. Although NMDA receptor (NMDAR)-dependent long-term potentiation has been observed in the striatum, its involvement in motor learning remains unclear. To examine the role of striatal NMDAR in motor learning, we created striatum-specific NMDAR1 subunit knockout mice, analyzed the striatal anatomy and neuronal morphology of these mice, evaluated their performance on well established motor tasks, and performed electrophysiological recordings to assay striatal NMDAR function and long-term synaptic plasticity. Our results show that deleting the NMDAR1 subunit of the NMDAR specifically in the striatum, which virtually abolished NMDAR-mediated currents, resulted in only small changes in striatal neuronal morphology but severely impaired motor learning and disrupted dorsal striatal long-term potentiation and ventral striatal long-term depression. C1 Univ Illinois, Beckman Inst Adv Sci & Technol, NeuroTech Grp, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. Univ Illinois, Med Scholars Program, Urbana, IL 61801 USA. Univ Illinois, Dept Pharmacol, Urbana, IL 61801 USA. Univ Illinois, Neurosci Program, Urbana, IL 61801 USA. NIAAA, NIH, Bethesda, MD 20892 USA. RP Li, YQ (reprint author), 3347 Beckman Inst,405 N Mathews Ave, Urbana, IL 61801 USA. EM y-li4@uiuc.edu RI Li, Yuqing/G-1596-2011 OI Li, Yuqing/0000-0003-1211-5529 FU Intramural NIH HHS; NIA NIH HHS [AG17291]; NINDS NIH HHS [NS42356, NS47692, R21 NS042356, R21 NS047692] NR 58 TC 115 Z9 122 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2006 VL 103 IS 41 BP 15254 EP 15259 DI 10.1073/pnas.0601758103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300049 PM 17015831 ER PT J AU Gallazzini, M Ferraris, JD Kunin, M Morris, RG Burg, MB AF Gallazzini, Morgan Ferraris, Joan D. Kunin, Margarita Morris, Ryan G. Burg, Maurice B. TI Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE diisopropyl fluorophosphate; phospholipase B ID ORGANIC OSMOLYTE GLYCEROPHOSPHORYLCHOLINE; COLLECTING DUCT CELLS; MDCK CELLS; CHOLINE PHOSPHODIESTERASE; SACCHAROMYCES-CEREVISIAE; OSMOTIC REGULATION; MAMMALIAN-CELLS; MEDULLARY CELLS; BINDING PROTEIN; PHOSPHATIDYLCHOLINE AB Glycerophosphocholine (GPC) is an osmoprotective compatible and counteracting organic osmolyte that accumulates in renal inner medullary cells in response to high NaCl and urea. We previously found that high NaCl increases GPC in renal [Madin-Darby canine kidney (MDCK)] cells. The GPC is derived from phosphatidylcholine, catalyzed by a phospholipase that was not identified at that time. Neuropathy target esterase (NTE) was recently shown to be a phospholipase B that catalyzes production of GPC from phosphatidylcholine. The purpose of the present study was to test whether NTE contributes to the high NaCl-induced increase of GPC synthesis in renal cells. We find that in mouse inner medullary collecting duct cells, high NaCl increases NTE mRNA within 8 h and NTE protein within 16 h. Diisopropyl fluorophosphate, which inhibits NTE esterase activity, reduces GPC accumulation, as does an siRNA that specifically reduces NTE protein abundance. The 20-h half-life of NTE mRNA is unaffected by high NaCl. TonEBP/OREBP is a transcription factor that is activated by high NaCl. Knockdown of TonEBP/OREBP by a specific siRNA inhibits the high NaCl-induced increase of NTE mRNA. Further, the lower renal inner medullary interstitial NaCl concentration that occurs chronically in ClCK1(-/-) mice and acutely in normal mice given furosemide is associated with lower NTE mRNA and protein. We conclude that high NaCl increases transcription of NTE, likely mediated by TonEBP/OREBP, and that the resultant increase of NTE expression contributes to increased production and accumulation of GPC in mammalian renal cells in tissue culture and in vivo. C1 NHLBI, Kidney & Electrolyte Metab Lab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Gallazzini, M (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM gallazzinim@nhlbi.nih.gov; maurice_burg@nih.gov RI Gallazzini, Morgan/E-5465-2011 NR 33 TC 33 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2006 VL 103 IS 41 BP 15260 EP 15265 DI 10.1073/pnas.0607133103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 094NX UT WOS:000241247300050 PM 17015841 ER PT J AU Kaleeba, JAR Berger, EA AF Kaleeba, Johnan A. R. Berger, Edward A. TI Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry SO VIROLOGY LA English DT Article DE human herpesvirus 8; host range; virus glycoprotein; cell fusion assay; virus entry assay; vaccinia virus expression system; beta-galactosidase; enhanced green fluorescent protein; virus receptor; integrin ID SIMPLEX-VIRUS TYPE-1; SURFACE HEPARAN-SULFATE; MEMBRANE-FUSION; GENE-EXPRESSION; HUMAN-HERPESVIRUS-8; GH; RECEPTOR; GL; GB; GD AB The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of alpha 3 beta 1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor. Published by Elsevier Inc. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 237, Bethesda, MD 20892 USA. EM edward_berger@nih.gov FU Intramural NIH HHS NR 41 TC 13 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2006 VL 354 IS 1 BP 7 EP 14 DI 10.1016/j.virol.2006.06.009 PG 8 WC Virology SC Virology GA 093OV UT WOS:000241178500002 PM 16889811 ER PT J AU Javanbakht, H An, P Gold, B Petersen, DC O'Huigin, C Nelson, GW O'Brien, SJ Kirk, GD Detels, R Buchbinder, S Donfield, S Shulenin, S Song, B Perron, MJ Stremlau, M Sodroski, J Dean, M Winkler, C AF Javanbakht, Hassan An, Ping Gold, Bert Petersen, Desiree C. O'Huigin, Cohn Nelson, George W. O'Brien, Stephen J. Kirk, Gregory D. Detels, Roger Buchbinder, Susan Donfield, Sharyne Shulenin, Sergey Song, Byeongwoon Perron, Michel J. Stremlau, Matthew Sodroski, Joseph Dean, Michael Winkler, Cheryl TI Effects of human TRIM5 alpha polymorphisms on antiretroviral function and susceptibility to human immunodeficiency virus infection SO VIROLOGY LA English DT Article DE TRIM5 alpha; single nucleotide polymorphism; HIV-1; HIV infections; disease susceptibility; genetics; haplotype ID RESTRICTION FACTOR TRIM5-ALPHA; BROAD-HOST-RANGE; HIV-1 INFECTION; RETROVIRUS RESTRICTION; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; TYPE-1 INFECTION; DRUG-USERS; OLD-WORLD; AIDS AB TRIM5 alpha acts on several retroviruses, including human immunodeficiency virus (HIV-1), to restrict cross-species transmission. Using natural history cohorts and tissue culture systems, we examined the effect of polymorphism in human TRIM5 alpha on HIV-1 infection. in African Americans, the frequencies of two non-coding SNP variant alleles in exon 1 and intron 1 of TRIM5 were elevated in HIV-1-infected persons compared with uninfected subjects. By contrast, the frequency of the variant allele encoding TRIM5 alpha 136Q was relatively elevated in uninfected individuals, suggesting a possible protective effect. TRIM5 alpha 136Q protein exhibited slightly better anti-HIV-1 activity in tissue culture than the TRIM5 alpha R136 protein. The 43Y variant of TRIM5 alpha was less efficient than the H43 variant at restricting HIV-1 and murine leukemia virus infections in cultured cells. The ancestral TRIM5 haplotype specifying no observed variant alleles appeared to be protective against infection, and the corresponding wild-type protein partially restricted HIV-1 replication in vitro. A single logistic regression model with a permutation test indicated the global corrected P value of < 0.05 for both SNPs and haplotypes. Thus, polymorphism in human TRIM5 may influence susceptibility to HIV-1 infection, a possibility that merits additional evaluation in independent cohorts. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Mol Genet Epidemiol Sec, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Lab Genom Divers, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Div AIDS, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Stellenbosch, Tygerberg Med Sch, Dept Med Virol, ZA-7505 Tygerberg, South Africa. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rho Inc, Chapel Hill, NC 27514 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Winkler, C (reprint author), NCI, Mol Genet Epidemiol Sec, Bldg 560,Room 21-19, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI063987, AI28691] NR 53 TC 81 Z9 87 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2006 VL 354 IS 1 BP 15 EP 27 DI 10.1016/j.virol.2006.06.031 PG 13 WC Virology SC Virology GA 093OV UT WOS:000241178500003 PM 16887163 ER PT J AU Peterson, KE Evans, LH Wehrly, K Chesebro, B AF Peterson, Karin E. Evans, Leonard H. Wehrly, Kathy Chesebro, Bruce TI Increased proinflammatory cytokine and chemokine responses and microglial infection following inoculation with neural stem cells infected with polytropic murine retroviruses SO VIROLOGY LA English DT Article DE chemokines; cytokines; brain; neuropathogenesis; microglia; retrovirus; mouse ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CENTRAL-NERVOUS-SYSTEM; ENDOPLASMIC-RETICULUM STRESS; MULTIPLE-SCLEROSIS LESIONS; LEUKEMIA VIRUSES; ALZHEIMERS-DISEASE; ENVELOPE PROTEIN; SURFACE RECEPTOR; BRAIN DISEASE; AIDS DEMENTIA AB Proinflammatory cytokines and chemokines are often detected in brain tissue of patients with neurological diseases such as multiple sclerosis (MS), HIV-associated dementia (HAD) and Alzheimer's disease (AD). We have utilized a mouse model of retrovirus-induced neurological disease to examine how these proinflammatory responses contribute to neuropathogenesis. In previous studies with this model, a correlation was found between neurovirulence and cytokine and chemokine expression. However, it was unclear whether the induction of these cytokines and chemokines was in response to specific virus envelope determinants or was regulated by the level of virus infection in the brain. In the current study, we demonstrated that multiple polytropic retroviruses induced cytokine and chemokine mRNA expression following increased virus levels in the brain. Increased virus levels of polytropic viruses also correlated with increased neuropathogenesis. In contrast, the ecotropic retrovirus, FB29, did not induce cytokine or chemokine mRNA expression or neurological disease, despite virus levels either similar to or higher than the polytropic retroviruses. As polytropic and ecotropic viruses utilize different receptors for entry, these receptors may play a critical role in the induction of these innate immune responses in the brain. (c) 2006 Elsevier Inc. All rights reserved. C1 Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Peterson, KE (reprint author), Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Skip Bertman Dr, Baton Rouge, LA 70803 USA. EM kpeterson@vetmed.lsu.edu RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU NCRR NIH HHS [1P20RR020159] NR 39 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2006 VL 354 IS 1 BP 143 EP 153 DI 10.1016/j.virol.2006.06.016 PG 11 WC Virology SC Virology GA 093OV UT WOS:000241178500014 PM 16875710 ER PT J AU McDermott, MM Sufit, R Nishida, T Guralnik, JM Ferrucci, L Tian, L Liu, K Tan, J Pearce, WH Schneider, JR Sharma, L Criqui, MH AF McDermott, Mary M. Sufit, Robert Nishida, Takashi Guralnik, Jack M. Ferrucci, Luigi Tian, Lu Liu, Kiang Tan, Jin Pearce, William H. Schneider, Joseph R. Sharma, Leena Criqui, Michael H. TI Lower extremity nerve function in patients with lower extremity ischemia SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; ANKLE BRACHIAL INDEX; INTERMITTENT CLAUDICATION; CARDIOVASCULAR-DISEASE; VASCULAR DISEASE; NATURAL-HISTORY; LEG SYMPTOMS; NEUROPATHY; CONDUCTION; PREVALENCE AB Background: We determined whether lower extremity ischemia, as measured by the ankle brachial index (ABI), is associated with impaired lower extremity nerve function. Methods: Participants included 478 persons with peripheral arterial disease (PAD) identified from noninvasive vascular laboratories and 292 persons without PAD identified from a general medicine practice and noninvasive vascular laboratories. Peripheral arterial disease was defined as an ABI lower than 0.90 ( mild PAD: ABI, 0.70 to < 0.90; moderate PAD: ABI, 0.50 to < 0.70; and severe PAD: ABI, < 0.50). The ABI and electrophysiologic measures of the peroneal, sural, and ulnar nerves were obtained. Results: Among 546 participants without diabetes, PAD participants had significantly impaired peripheral nerve function in the upper and lower extremities compared with non-PAD participants. After adjusting for age, sex, race, smoking, height, body mass index, recruitment source, alcohol use, disk disease, spinal stenosis, cardiac disease, and cerebrovascular disease, these associations were not statistically significant. After adjusting for confounders among nondiabetic participants, those with severe PAD (ABI, < 0.50) had poorer peroneal nerve conduction velocity (NCV) compared with participants without PAD (42.6 vs 44.8 m/s; P=.003) and poorer peroneal NCV compared with participants with mild PAD(42.6 vs 45.0 m/s; P=.001) or moderate PAD (42.6 vs 44.1 m/s; P=.03). Among 224 participants with diabetes, after adjusting for confounders, PAD was associated with poorer peroneal NCV (40.8 vs 43.5 m/s; P=.01), sural nerve amplitude (3.1 vs 4.8 mu V; P=.045), and ulnar NCV (47.6 vs 50.2 m/s; P=.03) compared with those without PAD. Conclusions: Our findings suggest that leg ischemia impairs peroneal nerve function. This association is less strong in patients with diabetes, perhaps because of the overriding influence of diabetes on peripheral nerve function. Clinicians should consider screening for PAD in patients with idiopathic peroneal nerve dysfunction. Peripheral arterial disease-associated nerve dysfunction may contribute to PAD-associated functional impairment. C1 Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Prevent Med, Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Neurol, Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Surg, Sch Med, Chicago, IL 60611 USA. Evanston NW Hosp, Dept Surg, Div Vasc Surg, Evanston, IL USA. NIA, Lab Clin Epidemiol, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000048, RR00048]; NHLBI NIH HHS [R01 HL064739, R01 HL071223, R01-HL58099, R01-HL64739, R01-HL71223] NR 28 TC 26 Z9 31 U1 0 U2 0 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 OCT 9 PY 2006 VL 166 IS 18 BP 1986 EP 1992 DI 10.1001/archinte.166.18.1986 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 091VV UT WOS:000241057300008 PM 17030832 ER PT J AU Cellai, I Benvenuti, S Luciani, P Galli, A Ceni, E Simi, L Baglioni, S Muratori, M Ottanelli, B Serio, M Thiele, CJ Peri, A AF Cellai, I. Benvenuti, S. Luciani, P. Galli, A. Ceni, E. Simi, L. Baglioni, S. Muratori, M. Ottanelli, B. Serio, M. Thiele, C. J. Peri, A. TI Antineoplastic effects of rosiglitazone and PPAR gamma transactivation in neuroblastoma cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE PPAR gamma; rosiglitazone; neuroblastoma ID ACTIVATED RECEPTOR-GAMMA; HUMAN PROSTATE-CANCER; PHASE-II; LIGAND TROGLITAZONE; ENDOTHELIAL-CELLS; COLON-CANCER; IN-VITRO; EXPRESSION; LINES; GENE AB Neuroblastoma ( NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor g (PPAR gamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARg. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 mu M RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARg as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARg responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARg activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARg transactivation. This finding indicates that PPARg activity may be useful to select those patients, for whom PPARg agonists may have a beneficial therapeutic effect. C1 Univ Florence, Dept Clin Physiopathol, Endocrine Unit, DENOThe,Ctr Res Transfer & Highe Educ Chron Infla, I-50139 Florence, Italy. Univ Florence, Dept Clin Physiopathol, Gastroenterol Unit, DENOThe,Ctr Res Transfer & Highe Educ Chron Infla, I-50139 Florence, Italy. Univ Florence, Dept Clin Physiopathol, Clin Biochem Unit, DENOThe,Ctr Res Transfer & Highe Educ Chron Infla, I-50139 Florence, Italy. Univ Florence, Dept Clin Physiopathol, Androl Unit, DENOThe,Ctr Res Transfer & Highe Educ Chron Infla, I-50139 Florence, Italy. NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Peri, A (reprint author), Univ Florence, Dept Clin Physiopathol, Endocrine Unit, DENOThe,Ctr Res Transfer & Highe Educ Chron Infla, VIale Pieraccini 6, I-50139 Florence, Italy. EM a.peri@dfc.unifi.it OI Galli, Andrea/0000-0001-5416-6290; Muratori, Monica/0000-0003-0925-0009 NR 49 TC 24 Z9 24 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 9 PY 2006 VL 95 IS 7 BP 879 EP 888 DI 10.1038/sj.bjc.6603344 PG 10 WC Oncology SC Oncology GA 092EL UT WOS:000241079700017 PM 16969347 ER PT J AU Gan, BY Peng, X Nagy, T Alcaraz, A Gu, H Guan, JL AF Gan, Boyi Peng, Xu Nagy, Tamas Alcaraz, Ana Gu, Hua Guan, Jun-Lin TI Role of FIP200 in cardiac and liver development and its regulation of TNF alpha and TSC-mTOR signaling pathways SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NF-KAPPA-B; FOCAL ADHESION KINASE; TUMOR-NECROSIS-FACTOR; HUMAN BREAST-CANCER; EMBRYONIC LETHALITY; CELL-GROWTH; TUBEROUS-SCLEROSIS; TRANSGENIC MICE; SIZE CONTROL; MAP KINASES AB Focal adhesion kinase family interacting protein of 200 kD (FIP200) has been shown to regulate diverse cellular functions such as cell size, proliferation, and migration in vitro. However, the function of FIP200 in vivo has not been investigated. We show that targeted deletion of FIP200 in the mouse led to embryonic death at mid/late gestation associated with heart failure and liver degeneration. We found that FIP200 knockout (KO) embryos show reduced S6 kinase activation and cell size as a result of increased tuberous sclerosis complex function. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver. Consistent with this, FIP200 KO mouse embryo fibroblasts and liver cells showed increased apoptosis and reduced c-Jun N-terminal kinase phosphorylation in response to tumor necrosis factor (TNF) alpha stimulation, which might be mediated by FIP200 interaction with apoptosis signal - regulating kinase 1 (ASK1) and TNF receptor - associated factor 2 (TRAF2), regulation of TRAF2 - ASK1 interaction, and ASK1 phosphorylation. Together, our results reveal that FIP200 functions as a regulatory node to couple two important signaling pathways to regulate cell growth and survival during mouse embryogenesis. C1 Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. RP Guan, JL (reprint author), Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. EM jlguan@umich.edu FU NHLBI NIH HHS [HL73394, R01 HL073394]; NIGMS NIH HHS [GM52890, R01 GM052890] NR 45 TC 86 Z9 86 U1 1 U2 6 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 OCT 9 PY 2006 VL 175 IS 1 BP 121 EP 133 DI 10.1083/jcb.200604129 PG 13 WC Cell Biology SC Cell Biology GA 096MT UT WOS:000241382000012 PM 17015619 ER PT J AU Chiang, YH Chen, GJ Shen, H Chou, J Wang, Y AF Chiang, Y. H. Chen, G. J. Shen, H. Chou, J. Wang, Y. TI Histogranin reduced brain injury after transient focal ischemia in rats SO NEUROSCIENCE LETTERS LA English DT Article DE glutamate; histogranin; neuroprotection; stroke ID CEREBRAL-ARTERY LIGATION; RECEPTOR ANTAGONIST; HYPOXIA-ISCHEMIA; GLUTAMATE; NEUROPROTECTION; MODEL; INHIBITION; CASPASE-3; PROTECTS; RELEASE AB Excitatory amino acids (EAAs) play an important role during ischemic brain injury. In this study we examined the protective effect of histogranin (HN), an endogenous peptide that antagonizes excitatory amino acids-mediated activity noncompetitively, in an animal model of cerebral ischemia. Adult rats were anesthetized with chloral hydrate. Histogranin was given intracerebroventricularly before a 60-min middle cerebral artery occlusion (MCAo). Animals were examined for their locomotor activity 2 days after MCAo. Histogranin significantly increased locomotor activity in the stroke rats. Histogranin pretreatment reduced the volume of cerebral infarction and the caspase-3 immunoreactivity in the stroke animals. Taken together, our data suggest that histogranin is protective against ischemic brain injury. The protective effect may involve anti-apoptotic mechanisms. Published by Elsevier Ireland Ltd. C1 Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch, NIH, Baltimore, MD 21124 USA. Natl Def Med Ctr, Tri Serve Gen Hosp, Dept Neurol Surg, Taipei, Taiwan. RP Wang, Y (reprint author), Natl Inst Drug Abuse, Neural Protect & Regenerat Sect, Mol Neuropsychiat Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21124 USA. EM ywang@intra.nida.nih.gov NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 9 PY 2006 VL 406 IS 3 BP 211 EP 215 DI 10.1016/j.neulet.2006.07.048 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 091AU UT WOS:000240998700012 PM 16904827 ER PT J AU Derman, RJ Kodkany, BS Goudar, SS Geller, SE Naik, VA Bellad, MB Patted, SS Patel, A Edlavitch, SA Hartwell, T Chakraborty, H Moss, N AF Derman, Richard J. Kodkany, Bhalchandra S. Goudar, Shivaprasad S. Geller, Stacie E. Naik, Vijaya A. Bellad, M. B. Patted, Shobhana S. Patel, Ashlesha Edlavitch, Stanley A. Hartwell, Tyler Chakraborty, Hrishikesh Moss, Nancy TI Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial SO LANCET LA English DT Article ID 3RD STAGE; CLINICAL-TRIAL; LABOR; MANAGEMENT; OXYTOCIN; STATEMENT; 3RD-STAGE; SETTINGS; DELIVERY; HEALTH AB Background Postpartum haemorrhage is a major cause of maternal mortality in the developing world. Although effective methods for prevention and treatment of such haemorrhage exist-such as the uterotonic drug oxytocin - most are not feasible in resource-poor settings where many births occur at home. We aimed to investigate whether oral misoprostol, a potential alternative to oxytocin, could prevent postpartum haemorrhage in a community home-birth setting. Methods In a placebo-controlled trial undertaken between September, 2002, and December, 2005, 1620 women in rural India were randomised to receive oral misoprostol (n=812) or placebo (n=808) after delivery. 25 auxiliary nurse midwives undertook the deliveries, administered the study drug, and measured blood loss. The primary outcome was the incidence of acute postpartum haemorrhage (defined as >= 500 mL bleeding) within 2 h of delivery. Analysis was by intention-to-treat. The trial was registered with the US clinical trials database (http://www.clinicaltrials.gov) as number NCT00097123. Findings Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage (12.0% to 6.4%, p < 0.0001; relative risk 0.53 [95% CI 0.39-0.74]) and acute severe postpartum haemorrhage (1.2% to 0.2%, p < 0.0001; 0.20 [0.04-0.91]. One case of postpartum haemorrhage was prevented for every 18 women treated. Misoprostol was also associated with a decrease in mean postpartum blood loss (262.3 mL to 214.3 mL, p < 0.0001). Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group. Women taking misoprostol. had a higher rate of transitory symptoms of chills and fever than the control. Interpretation Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss. The drug's low cost, ease of administration, stability, and a positive safety profile make it a good option in resource-poor settings. C1 Univ Illinois, Coll Med, Dept Obstet & Gynecol MC 808, Chicago, IL 60612 USA. Univ Missouri, Sch Med, Kansas City, MO 64108 USA. Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India. John H Stroger Jr Hosp Cook Cty, Chicago, IL USA. RTI Int, Stat & Epidemiol, Res Triangle Pk, NC USA. NICHHD, Bethesda, MD 20892 USA. RP Geller, SE (reprint author), Univ Illinois, Coll Med, Dept Obstet & Gynecol MC 808, 820 S Wood St, Chicago, IL 60612 USA. EM SGeller@uic.edu OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053 FU NICHD NIH HHS [1U01HD42372-01] NR 41 TC 165 Z9 167 U1 1 U2 11 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 7 PY 2006 VL 368 IS 9543 BP 1248 EP 1253 DI 10.1016/S0140-6736(06)69522-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 091WF UT WOS:000241058300031 PM 17027730 ER PT J AU Le Menach, A Vergu, E Grais, RF Smith, DL Flahault, A AF Le Menach, Arnaud Vergu, Elisabeta Grais, Rebecca F. Smith, David L. Flahault, Antoine TI Key strategies for reducing spread of avian influenza among commercial poultry holdings: lessons for transmission to humans SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE avian influenza; prevention and control; epidemiology; mathematical model; Netherlands ID A VIRUS; PANDEMIC INFLUENZA; H5N1 INFLUENZA; HONG-KONG; NETHERLANDS; EPIDEMIC; OUTBREAK; RISK; DISEASE; VACCINE AB Recent avian flu epidemics (A/H5N1) in Southeast Asia and case reports from around the world have led to fears of a human pandemic. Control of these outbreaks in birds would probably lead to reduced transmission of the avian virus to humans. This study presents a mathematical model based on stochastic farm-to-farm transmission that incorporates flock size and spatial contacts to evaluate the impact of control strategies. Fit to data from the recent epidemic in the Netherlands, we evaluate the efficacy of control strategies and forecast avian influenza dynamics. Our results identify high-risk areas of spread by mapping of the farm level reproductive number. Results suggest that an immediate depopulation of infected flocks following an accurate and quick diagnosis would have a greater impact than simply depopulating surrounding flocks. Understanding the relative importance of different control measures is essential for response planning. C1 Univ Paris 06, INSERM, U707, F-75012 Paris, France. INRA, Unite Math & Informat Appl, F-78350 Jouy En Josas, France. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Le Menach, A (reprint author), Univ Paris 06, INSERM, U707, 27 Rue Chaligny, F-75012 Paris, France. EM arnaud.lemenach@u707.jussieu.fr RI Smith, David/L-8850-2013; Barley, Kamal/F-9579-2011 OI Smith, David/0000-0003-4367-3849; Barley, Kamal/0000-0003-1874-9813 NR 30 TC 33 Z9 34 U1 0 U2 7 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P R SOC B JI Proc. R. Soc. B-Biol. Sci. PD OCT 7 PY 2006 VL 273 IS 1600 BP 2467 EP 2475 DI 10.1098/rspb.2006.3609 PG 9 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA 087GC UT WOS:000240729900009 PM 16959637 ER PT J AU Chen, CL Shim, MS Chung, J Yoo, HS Ha, JM Kim, JY Choi, J Zang, SL Hou, X Carlson, BA Hatfield, DL Lee, BJ AF Chen, Chang Lan Shim, Myoung Sup Chung, Jiyeol Yoo, Hyun-Seung Ha, Ji Min Kim, Jin Young Choi, Jinmi Zang, Shu Liang Hou, Xiao Carlson, Bradley A. Hatfield, Dolph L. Lee, Byeong Jae TI G-rich, a Drosophila selenoprotein, is a Golgi-resident type III membrane protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Drosophila; G-rich; Golgi; microsomal membrane protein; selenium; selenoprotein; SelK; type III ID ENDOPLASMIC-RETICULUM; TOPOLOGY PREDICTION; SELENOCYSTEINE; EXPRESSION; GLYCOPROTEIN; LIGAND; CELLS AB G-rich is a Drosophila melanogaster selenoprotein, which is a homologue of human and mouse SelK. Subcellular localization analysis using GFP-tagged G-rich showed that G-rich was localized in the Golgi apparatus. The fusion protein was co-localized with the Golgi marker proteins but not with an endoplasmic reticulum (ER) marker protein in Drosophila SL2 cells. Bioinformatic analysis of G-rich suggests that this protein is either type II or type III transmembrane protein. To determine the type of transmembrane protein experimentally, GFP-G-rich in which GFP was tagged at the N-terminus of G-rich, or G-rich-GFP in which GFP was tagged at the C-terminus of G-rich, were expressed in SL2 cells. The tagged proteins were then digested with trypsin, and analyzed by Western blot analysis. The results showed that the C-terminus of the G-rich protein was exposed to the cytoplasm indicating it is a type III microsomal membrane protein. G-rich is the first selenoprotein identified in the Golgi apparatus. Published by Elsevier Inc. C1 Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. Liaoning Univ, Acad Environm & Life Sci, Shenyang 110036, Peoples R China. NCI, Lab Canc Prevent, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Lee, BJ (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. EM imbglmg@plaza.snu.ac.kr NR 23 TC 20 Z9 26 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 6 PY 2006 VL 348 IS 4 BP 1296 EP 1301 DI 10.1016/j.bbrc.2006.07.203 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 082ZL UT WOS:000240425600012 PM 16920070 ER PT J AU Horwitz, J Ding, LL Vasiliou, V Cantore, M Piatigorsky, J AF Horwitz, Joseph Ding, Linlin Vasiliou, Vasilis Cantore, Miriam Piatigorsky, Joram TI Scallop lens Omega-crystallin (ALDH1A9): A novel tetrameric aldehyde dehydrogenase SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE lens crystallin; scallop; Omega-crystallin; aldehyde dehydrogenase; molecular mass; multi-angle laser light scattering; mitochondria ID MULTIPLE SEQUENCE ALIGNMENT; EYE LENS; BACULOVIRUS EXPRESSION; DETOXIFICATION ENZYMES; STRUCTURAL PROTEIN; MOLECULAR-CLONING; ETA-CRYSTALLIN; OCTOPUS LENS; GENE; RECRUITMENT AB Scallop eye lens Omega-crystallin is an inactive aldehyde dehydrogenase (ALDH1A9) related to cytoplasmic ALDH1A1 and mitochondrial ALDH2 that migrates by gel filtration chromatography as a homodimer. Because mammalian ALDH1A1 and ALDH2 are homotetramers, we investigated the native molecular mass of scallop Omega-crystallin by multi-angle laser light scattering. The results indicate that the scallop Omega-crystallin is a tetrameric, not a dimeric protein. Moreover, phylogenetic tree analysis shows that scallop Omega-crystallin clusters with the mitochondrial ALDH2 and ALDH1B1 rather than the cytoplasmic ALDH1A, yet it lacks the mitochondrial N-terminal leader sequence characteristic of the mitochondrial ALDHs. The mitochondrial grouping, enzymatic inactivity, and anomalous gel filtration behavior make scallop cytoplasmic Omega-crystallin an interesting protein for structural studies of evolutionary adaptations to become an enzyme-crystallin. Published by Elsevier Inc. C1 NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Colorado, Hlth Sci Ctr, Mol Toxicol & Environm Hlth Sci Program, Dept Pharmaceut Sci, Denver, CO 80262 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov FU NEI NIH HHS [R01 EY3897, R01 EY11490] NR 47 TC 6 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 6 PY 2006 VL 348 IS 4 BP 1302 EP 1309 DI 10.1016/j.bbrc.2006.07.197 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 082ZL UT WOS:000240425600013 PM 16919242 ER PT J AU Yoo, S AF Yoo, Siuk TI Characterization of Drosophila Rad51/SpnA protein in DNA binding and embryonic development SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Drosophila Rad51; SpnA; DNA binding activity; embryogenesis; spermatocyte; RNAi ID MEIOTIC CHROMOSOME SYNAPSIS; RECA-LIKE GENE; SACCHAROMYCES-CEREVISIAE; SYNAPTONEMAL COMPLEXES; TARGETED DISRUPTION; MOUSE SPERMATOCYTES; RNA INTERFERENCE; STRAND EXCHANGE; YEAST RAD51; RECOMBINATION AB The Rad51 is a highly conserved protein throughout the eukaryotic kingdom and an essential enzyme in DNA repair and recombination. It possesses DNA binding activity and ATPase activity, and interacts with meiotic chromosomes during prophase I of meiosis. Drosophila Rad51, Spindle-A (SpnA) protein has been shown to be involved in repair of DNA damage in somatic cells and meiotic recombination in female germ cells. In this study, DNA binding activity of SpnA is demonstrated by both agarose gel mobility shift assay and restriction enzyme protection assay. SpnA is also shown to interact with meiotic chromosomes during prophase I in the primary spermatocytes of hsp26-spnA transgenic flies. In addition, SpnA is highly expressed in embryos, and the depletion of SpnA by RNA interference (RNAi) leads to embryonic lethality implying that SpnA is involved in early embryonic development. Therefore, these results suggest that Drosophila SpnA protein possesses properties similar to mammalian Rad51 homologs. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Yoo, S (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10,Room 7N321,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yoos@nhlbi.nih.gov NR 39 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 6 PY 2006 VL 348 IS 4 BP 1310 EP 1318 DI 10.1016/j.bbrc.2006.07.021 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 082ZL UT WOS:000240425600014 PM 16919604 ER PT J AU Chien, YC Kim, S Bumeister, R Loo, YM Kwon, SW Johnson, CL Balakireva, MG Romeo, Y Kopelovich, L Gale, M Yeaman, C Camonis, JH Zhao, YM White, MA AF Chien, Yuchen Kim, Sungchan Bumeister, Ron Loo, Yueh-Ming Kwon, Sung Won Johnson, Cynthia L. Balakireva, Mirey G. Romeo, Yves Kopelovich, Levy Gale, Michael, Jr. Yeaman, Charles Camonis, Jacques H. Zhao, Yingming White, Michael A. TI RaIB GTPase-mediated activation of the I kappa B family kinase TBK1 couples innate immune signaling to tumor cell survival SO CELL LA English DT Article ID INTERFERON ANTIVIRAL RESPONSE; DOUBLE-STRANDED-RNA; RAL-GTPASES; REGULATORY FACTOR-3; MEMBRANE-PROTEINS; EPITHELIAL-CELLS; SEC6/8 COMPLEX; IKK-EPSILON; EXOCYST; TRANSCRIPTION AB The monomeric RaIGTPases, RaIA and RalB are recognized as components of a regulatory framework supporting tumorigenic transformation. Specifically, RaIB is required to suppress apoptotic checkpoint activation, the mechanistic basis of which is unknown. Reported effector proteins of RaIB include the Sec5 component of the exocyst, an octameric protein complex implicated in tethering of vesicles to membranes. Surprisingly, we find that the RaIB/Sec5 effector complex directly recruits and activates the atypical I kappa B kinase family member TBK1. In cancer cells, constitutive engagement of this pathway, via chronic RalB activation, restricts initiation of apoptotic programs typically engaged in the context of oncogenic stress. Although dispensable for survival in a nontumorigenic context, this pathway helps mount an innate immune response to virus exposure. These observations define the mechanistic contribution of RaIGTPases to cancer cell survival and reveal the RaIB/Sec5 effector complex as a component of TBK1-dependent innate immune signaling. C1 Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX 75390 USA. Inst Curie, INSERM, U548, Paris, France. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Anat & Cell Biol, Iowa City, IA 52242 USA. RP Chien, YC (reprint author), Univ Texas, SW Med Ctr, Dept Cell Biol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM michael.white@utsouthwestern.edu FU NCI NIH HHS [CA107943, CA71443, CN35132, R01 CA071443]; NIGMS NIH HHS [R01 GM067002] NR 51 TC 187 Z9 195 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 6 PY 2006 VL 127 IS 1 BP 157 EP 170 DI 10.1016/j.cell.2006.08.034 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 097KJ UT WOS:000241445800021 PM 17018283 ER PT J AU Franco, R Cidlowski, JA AF Franco, Rodrigo Cidlowski, John A. TI SLCO/OATP-like transport of glutathione in FasL-induced apoptosis - Glutathione efflux is coupled to an organic anion exchange and is necessary for the progression of the execution phase of apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; REDUCED GLUTATHIONE; INTRACELLULAR GLUTATHIONE; CELL-DEATH; MEMBRANE-TRANSPORT; REDOX-REGULATION; MEDIATED APOPTOSIS; VOLUME DECREASE; LEUKEMIA-CELLS; GSH EXTRUSION AB Apoptosis is characterized by the activation of specific biochemical pathways that lead to the organized demise of cells. Intracellular GSH depletion has been observed during apoptosis; however, neither the mechanisms involved in the reduction of the intracellular GSH concentration, [ GSH] i, nor its link to the progression of apoptosis have been elucidated. We have studied this issue using Fas ligand ( FasL)- induced apoptosis in Jurkat cells where changes in [GSH](i) can be analyzed biochemically and at the single cell level by flow cytometry. A reduction in the total [ GSH](i) in response to FasL occurs in two distinct stages prior to the loss of membrane integrity. Jurkat cells express several members of the multidrug resistance protein ( ABCC/ MRP), and the organic anion- transporting polypeptide protein ( SLCO/ OATP) families of GSH efflux pumps at the mRNAlevel. Glutathione loss and its accumulation in the extracellular medium, induced by FasL, was trans- stimulated by the organic substrates MK571, probenecid, taurocholic acid, estrone sulfate, and bromosulfophthalein and inhibited by high concentrations of extracellular GSH. Single cell analysis demonstrated that intracellular GSH loss was paralleled by the activation of an organic anion uptake process, supporting the role of an anion exchange mechanism ( SLCO/ OATP- like transport) in GSH efflux induced by FasL. Additionally, high extracellular GSH inhibited the activation of the execution caspases, the cleavage of their substrates poly(ADP-ribose) polymerase ( PARP) and alpha-fodrin, and DNA degradation. In contrast, the trans- stimulation of GSH efflux by MK571 increased the cleavage of the execution caspases and their substrates. Together these results suggest that GSH efflux during FasL- induced apoptosis is mediated by a SLCO/ OATP- like transport mechanism that modulates the progression of the execution phase of apoptosis. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@mail.nih.gov RI Franco, Rodrigo/D-9470-2013 OI Franco, Rodrigo/0000-0003-3241-8615 FU Intramural NIH HHS NR 54 TC 76 Z9 77 U1 2 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 OCT 6 PY 2006 VL 281 IS 40 BP 29542 EP 29557 DI 10.1074/jbc.M602500200 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 089QT UT WOS:000240896300016 PM 16857677 ER PT J AU An, E Lu, XN Flippin, J Devaney, JM Halligan, B Hoffman, E Csaky, K Hathout, Y AF An, Eunkyung Lu, Xiaoning Flippin, Jessica Devaney, Joseph M. Halligan, Brian Hoffman, Eric Csaky, Karl Hathout, Yetrib TI Secreted proteome profiling in human RPE cell cultures derived from donors with age related macular degeneration and age matched healthy donors SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE AMD; retinal pigment epithelial cells; drusen; SILAC; secreted proteins; clusterin; complement factor H; SPARC ID PIGMENT EPITHELIAL-CELLS; ENDOTHELIAL GROWTH-FACTOR; FACTOR-H POLYMORPHISM; AMINO-ACIDS; MATRIX METALLOPROTEINASES; QUANTITATIVE PROTEOMICS; EXTRACELLULAR-MATRIX; BINDING-PROTEIN; BRUCHS MEMBRANE; DRUSEN AB Age-related macular degeneration (AMD) is characterized by progressive loss of central vision, which is attributed to abnormal accumulation of macular deposits called "drusen" at the interface between the basal surface of the retinal pigment epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits are accompanied by the growth of new blood vessels that breach the RPE layer and invade photoreceptors. In this study, we hypothesized that RPE secreted proteins are responsible for drusen formation and choroidal neovascularization. We used stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS/MS analysis and ZoomQuant quantification to assess differential protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD donors (diagnosed by histological examinations of the macula and genotyped for the Y402H-complement factor H variant) and age-matched healthy control donors. In general, RPE cells were found to secrete a variety of extracellular matrix proteins, complement factors, and protease inhibitors that have been reported to be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein, fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived factor than RPE cells from age-matched healthy donors. Conversely, secreted protein acidic and rich in cysteine (SPARC) was found to be down regulated by 2-fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis grouped these differentially secreted proteins into two groups; those involved in tissue development and angiogenesis and those involved in complement regulation and protein aggregation such as clusterin. Overall, these data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of AMD. C1 Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. George Washington Univ, Inst Biomed Sci, Program Biochem & Mol Genet, Washington, DC 20052 USA. Med Coll Wisconsin, Bioinformat Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. NIH, NEI, Bethesda, MD 20892 USA. RP Hathout, Y (reprint author), Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. EM yhathout@cnmcresearch.org RI Halligan, Brian/N-5166-2015 OI Halligan, Brian/0000-0002-9553-4253 FU Intramural NIH HHS NR 64 TC 78 Z9 79 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT 6 PY 2006 VL 5 IS 10 BP 2599 EP 2610 DI 10.1021/pr060121j PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 091UF UT WOS:000241053100012 PM 17022631 ER PT J AU Stella, C Beckwith-Hall, B Cloarec, O Holmes, E Lindon, JC Powell, J van der Ouderaa, F Bingham, S Cross, AJ Nicholson, JK AF Stella, Cinzia Beckwith-Hall, Bridgette Cloarec, Olivier Holmes, Elaine Lindon, John C. Powell, Jonathan van der Ouderaa, Frans Bingham, Sheila Cross, Amanda J. Nicholson, Jeremy K. TI Susceptibility of human metabolic phenotypes to dietary modulation SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE metabonomics; protein; diet; vegetarian; human metabolism; NMR; pattern recognition; metabotype; phenotype ID ORTHOGONAL SIGNAL CORRECTION; NMR SPECTROSCOPIC DATA; COLORECTAL-CANCER; H-1-NMR SPECTROSCOPY; URINE COLLECTIONS; PATTERN-RECOGNITION; PROSPECTIVE COHORT; VEGETARIAN DIET; FIBER INTAKE; PLASMA AB Dietary composition has been shown to influence metabolism and to impact on the prevalence and risk for certain diseases, but hitherto, there have been no systematic studies on the effects of dietary modulation of human metabolic phenotype (metabotype). Here, we have applied H-1 NMR spectroscopy in combination with multivariate statistical analysis to characterize the effects of three diets: "vegetarian", "low meat", and "high meat" on the metabotype signature of human participants. Twelve healthy male participants (age range of 25-74 years) consumed each of these diets, in a randomized order, for continuous 15-day-periods with an intervening washout period between each diet of 7 days duration. Each participant provided three consecutive 24-hour urine collections on days 13, 14, and 15 of each dietary period, and H-1 NMR spectra were acquired on all samples. Pattern recognition analysis allowed differentiation of the characteristic metabolic signatures of the diets with creatine, carnitine, acetylcarnitine, and trimethylamine-N-oxide (TMAO) being elevated in the high-meat consumption period. Application of orthogonal projection to latent structure discriminant analysis (O-PLS-DA) allowed the low-meat diet and vegetarian diet signatures to be characterized, and p-hydroxyphenylacetate (a microbial mammalian cometabolite) was higher in the vegetarian than meat diet samples, signaling an alteration of the bacterial composition or metabolism in response to diet. This work shows the potential for the routine use of metabonomics in nutritional and epidemiological studies, in characterizing and predicting the metabolic effects and the influence of diet on human metabotypes. C1 Unilever Corp Res, Sharnbrook MK44 1LQ, Beds, England. Univ London Imperial Coll Sci & Technol, Fac Med, SORA, London SW7 2AZ, England. Addenbrookes Hosp, MRC Dunn Human Nutr Unit, Cambridge CB2 2XY, England. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Nicholson, JK (reprint author), Unilever Corp Res, Colworth House, Sharnbrook MK44 1LQ, Beds, England. EM j.nicholson@imperial.ac.uk RI Nicholson, Jeremy/B-3395-2012 OI Nicholson, Jeremy/0000-0002-8123-8349 NR 60 TC 189 Z9 203 U1 5 U2 45 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT 6 PY 2006 VL 5 IS 10 BP 2780 EP 2788 DI 10.1021/pr060265y PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 091UF UT WOS:000241053100030 PM 17022649 ER PT J AU Yoshimura, M Kohzaki, M Nakamura, J Asagoshi, K Sonoda, E Hou, E Prasad, R Wilson, SH Tano, K Yasui, A Lan, L Seki, M Wood, RD Arakawa, H Buerstedde, JM Hochegger, H Okada, T Hiraoka, M Takeda, S AF Yoshimura, Michio Kohzaki, Masaoki Nakamura, Jun Asagoshi, Kenjiro Sonoda, Eiichiro Hou, Esther Prasad, Rajendra Wilson, Samuel H. Tano, Keizo Yasui, Akira Lan, Li Seki, Mineaki Wood, Richard D. Arakawa, Hiroshi Buerstedde, Jean-Marie Hochegger, Helfrid Okada, Takashi Hiraoka, Masahiro Takeda, Shunichi TI Vertebrate POLQ and POL beta cooperate in base excision repair of oxidative DNA damage SO MOLECULAR CELL LA English DT Article ID HUMAN-CELLS; POLYMERASE-THETA; SOMATIC HYPERMUTATION; MAMMALIAN-CELLS; MULTIPLE ROLES; STRAND BREAKS; PROTEIN; INSTABILITY; RECOMBINATION; MUTANTS AB Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLO is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLO, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H2O2, but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLO. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLO, like POLO, accumulated rapidly at sites of base damage. Accordingly, POLO and POLO share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLO in BER. C1 Kyoto Univ, Dept Radiat Genet, CREST,Sakyo Ku, Japan Sci & Technol Lab,Grad Sch Med, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Med, Dept Radiat Oncol & Image Appl Therapy, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Res Reactor Inst, Osaka 5900494, Japan. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Tohoku Univ, Dept Mol Genet, Inst Dev Aging & Canc, Sendai, Miyagi 9808575, Japan. Univ Pittsburgh, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. GSF, Inst Mol Radiobiol, D-85764 Munich, Germany. Kyoto Univ, Grad Sch Med, Dept Urol, Sakyo Ku, Kyoto 6068507, Japan. RP Takeda, S (reprint author), Kyoto Univ, Dept Radiat Genet, CREST,Sakyo Ku, Japan Sci & Technol Lab,Grad Sch Med, Kyoto 6068501, Japan. EM stakeda@rg.med.kyoto-u.ac.jp RI Wood, Richard/E-7855-2011 OI Wood, Richard/0000-0002-9495-6892 FU Intramural NIH HHS; NCI NIH HHS [R01 CA101980, CA 101980]; NIEHS NIH HHS [P30 ES 10126, P30 ES010126] NR 33 TC 75 Z9 78 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 6 PY 2006 VL 24 IS 1 BP 115 EP 125 DI 10.1016/j.molcel.2006.07.032 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 096WI UT WOS:000241407100010 PM 17018297 ER PT J AU Hatziioannou, T Princiotta, M Piatak, M Yuan, F Zhang, FW Lifson, JD Bieniasz, PD AF Hatziioannou, Theodora Princiotta, Michael Piatak, Michael, Jr. Yuan, Fang Zhang, Fengwen Lifson, Jeffrey D. Bieniasz, Paul D. TI Generation of simian-tropic HIV-1 by restriction factor evasion SO SCIENCE LA English DT Article ID INFECTION; VIF C1 Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Rockefeller Univ, New York, NY 10016 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bieniasz, PD (reprint author), Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. EM pbienias@adarc.org RI Liu, FL/D-1795-2009 NR 4 TC 97 Z9 101 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 6 PY 2006 VL 314 IS 5796 BP 95 EP 95 DI 10.1126/science.1130994 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 091LU UT WOS:000241031200042 PM 17023652 ER PT J AU Morgan, RA Dudley, ME Wunderlich, JR Hughes, MS Yang, JC Sherry, RM Royal, RE Topalian, SL Kammula, US Restifo, NP Zheng, ZL Nahvi, A de Vries, CR Rogers-Freezer, LJ Mavroukakis, SA Rosenberg, SA AF Morgan, Richard A. Dudley, Mark E. Wunderlich, John R. Hughes, Marybeth S. Yang, James C. Sherry, Richard M. Royal, Richard E. Topalian, Suzanne L. Kammula, Udai S. Restifo, Nicholas P. Zheng, Zhili Nahvi, Azam de Vries, Christiaan R. Rogers-Freezer, Linda J. Mavroukakis, Sharon A. Rosenberg, Steven A. TI Cancer regression in patients after transfer of genetically engineered lymphocytes SO SCIENCE LA English DT Article ID T-CELLS; ANTIGEN; TUMOR; TCR; IMMUNOTHERAPY; AUTOIMMUNITY; RECOGNITION; MELANOMA; THERAPY; GENES AB Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM SAR@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 SC003811-32, Z01 BC010763-01, Z99 CA999999] NR 19 TC 1310 Z9 1376 U1 18 U2 133 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 6 PY 2006 VL 314 IS 5796 BP 126 EP 129 DI 10.1126/science.1129003 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 091LU UT WOS:000241031200051 PM 16946036 ER PT J AU Zandi, P Zoellner, S McMahon, F Nurnberger, J Kelsoe, J Cichon, S AF Zandi, P. Zoellner, S. McMahon, F. Nurnberger, J. Kelsoe, J. Cichon, S. TI 8q24 Bipolar Disorder Symposium SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Univ Michigan, Ann Arbor, MI 48109 USA. NIMH, Bethesda, MD USA. Indiana Univ, Bloomington, IN 47405 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Bonn, D-5300 Bonn, Germany. RI McMahon, Francis/A-7290-2009; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014 OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 685 EP 686 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700005 ER PT J AU Pollock, J AF Pollock, J. TI The NIH knockout mouse project (KOMP) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Natl Inst Drug Abuse, Bethesda, MD 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 686 EP 686 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700007 ER PT J AU Meyer-Lindenberg, A AF Meyer-Lindenberg, A. TI Identification of neural risk mechanisms for psychiatric disorders using imaging genetics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 687 EP 687 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700011 ER PT J AU McMahon, FJ AF McMahon, F. J. TI A pharmacogenetic study of treatment outcome and adverse effects in the STAR*D cohort SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 689 EP 690 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700026 ER PT J AU Detera-Wadleigh, SD Liu, CY Cardona, I Corona, W Akula, N Steele, CJM Kundu, M Bonner, TI Badner, JA Maheshwari, M Gibbs, R Gershon, ES McMahon, FJ AF Detera-Wadleigh, Sevilla D. Liu, Chun-Yu Cardona, Imer Corona, Winston Akula, Nirmala Steele, C. J. M. Kundu, Mukta Bonner, Tom I. Badner, Judith A. Maheshwari, Manjula Gibbs, Richard Gershon, Elliot S. McMahon, Francis J. TI DOCK9 variants are associated with several bipolar disorder phenotypes and interact with G72 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NIMH, Genet Lab, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. RI McMahon, Francis/A-7290-2009; Liu, Chunyu/G-7561-2012 OI Liu, Chunyu/0000-0002-5986-4415 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 696 EP 697 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700055 ER PT J AU Straub, R Nicodemus, K Egan, M Goldberg, T Honea, R Callicott, J Weinberger, D AF Straub, Richard Nicodemus, Kristin Egan, Michael Goldberg, Terry Honea, Robyn Callicott, Joseph Weinberger, Daniel TI DTNBP1, muted, and BLOC1S2: Multiple susceptibility genes in the BLOC-1 complex implicates vesicular trafficking defects in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, NIH, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 697 EP 698 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700059 ER PT J AU Kempf, L Straub, R Kolachana, B Verchinski, B Callicott, J Egan, M Mattay, V Weinberger, D Meyer-Lindenberg, A AF Kempf, Lucas Straub, Richard Kolachana, Bhaskar Verchinski, Beth Callicott, Joseph Egan, Michael Mattay, Venkata Weinberger, Daniel Meyer-Lindenberg, Andreas TI Genetic variation in PRODH and ZDHHC8 on 22q11 impacts on brain structure and cortical function in healthy humans SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Bethesda, MD USA. Merck & Co Inc, Philadelphia, PA USA. RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 702 EP 702 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700077 ER PT J AU Straub, R Sei, Y Li, Z Weinberger, D Iizuka, Y AF Straub, Richard Sei, Yoshitasu Li, Zhen Weinberger, Daniel Iizuka, Yukihiko TI BLOC-1 components dysbindin (DTNBP1) and muted can modulate dopamine D2 receptor endocytosis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 702 EP 703 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700080 ER PT J AU Harold, D Paracchini, S Scerri, T Dennis, M Cope, N Hill, G Moskvina, V Walter, J Richardson, A Owen, M Stein, J Green, E O'Donovan, M Williams, J Monacco, A AF Harold, Denise Paracchini, Silvia Scerri, Thomas Dennis, Mcgan Cope, Natalie Hill, Gary Moskvina, Valentina Walter, Janet Richardson, Alex Owen, Michael Stein, John Green, Eric O'Donovan, Michael Williams, Julie Monacco, Anthony TI Further evidence that KIAA0319 is associated with developmental dyslexia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Univ Cardiff Wales, Cardiff, Wales. Univ Oxford, Oxford OX1 2JD, England. NHGRI, 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 704 EP 704 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700088 ER PT J AU Malhotra, A Szeszko, P Hodgkinson, C Lencz, T DeRosse, P Burdick, K Kane, J Goldman, D AF Malhotra, Anil Szeszko, Philip Hodgkinson, Colin Lencz, Todd DeRosse, Pamela Burdick, Katherine Kane, John Goldman, David TI Structural and functional implications of DISC1 genotype in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Bethesda, MD USA. RI Hodgkinson, Colin/F-9899-2010 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 704 EP 704 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700089 ER PT J AU Goes, F Zandi, PZ Miao, KY McMahon, FJ Steele, J Willour, VL MacKinnon, DF Mondimore, FM Schweizer, B Nurnberger, JI Rice, JP Scheftner, W Coryell, W Berrettini, WH Kelsoe, JR Byerley, W Murphy, DL Gershon, ES DePaulo, JR McInnis, MG Potash, JB AF Goes, Fernando Zandi, Peter Z. Miao, Kuangyi McMahon, Francis J. Steele, Jo Willour, Virginia L. MacKinnon, Dean F. Mondimore, Francis M. Schweizer, Barbara Nurnberger, John I. Rice, John P. Scheftner, William Coryell, William Berrettini, Wade H. Kelsoe, John R. Byerley, William Murphy, Dennis L. Gershon, Elliot S. DePaulo, J. Raymond McInnis, Melvin G. Potash, James B. TI Mood-incongruent psychotic features in bipolar disorder: Familial aggregation and suggestive linkage to 2p11-q14 and 13q21-33 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Washington Univ, Sch Med, St Louis, MO USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O131 BP 712 EP 712 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700124 ER PT J AU Weickert, C Miranda-Angulo, A Perlman, W Ward, S Kleinman, J Radhakrishna, V Straub, R Weinberger, D AF Weickert, Cynthia Miranda-Angulo, Ana Perlman, William Ward, Sarah Kleinman, Joel Radhakrishna, Vakkalanca Straub, Richard Weinberger, Daniel TI Variants in the estrogen receptor alpha gene its mRNA isoforms contribute to schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O161 BP 717 EP 717 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700145 ER PT J AU Myers, A Rohrer, K Zhao, A Marlowe, L Kaleem, M Bryden, L Leung, D Hardy, J AF Myers, Amanda Rohrer, Kristen Zhao, Alice Marlowe, Lauren Kaleem, Mona Bryden, Leslie Leung, Doris Hardy, John TI Genome-wide correlation of DNA variation and RNA expression within human cortex SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIA, NAS, NIH, Bethesda, MD 20892 USA. RI Myers, Amanda/B-1796-2010 OI Myers, Amanda/0000-0002-3100-9396 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O212 BP 723 EP 723 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700174 ER PT J AU Laje, G Buervenich, S Manji, H Rush, AJ Wilson, A Charney, D Francis, M AF Laje, Gonzalo Buervenich, Silvia Manji, Husseini Rush, A. John Wilson, Alexander Charney, Dennis Francis, McMahon TI Genetic markers of suicidal ideation emerging during antidepressant treatment SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Bethesda, MD 20892 USA. Karolinska Inst, Stockholm, Sweden. SW Texas State Univ, Dallas, TX USA. NHGRI, Baltimore, MD 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O223 BP 724 EP 725 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700180 ER PT J AU Sodhi, M Hazelwood, L Li, C Airey, D Sanders-Bush, E Meltzer, HY AF Sodhi, Monsheel Hazelwood, Lisa Li, Chun Airey, David Sanders-Bush, Elaine Meltzer, Herbert Y. TI Genetic variation of serotonin receptors predicts psychic anxiety in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Vanderbilt Univ, Nashville, TN USA. NINDS, Rockville, MD USA. RI Meltzer, Herbert/E-8131-2013 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O233 BP 727 EP 727 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700190 ER PT J AU Lencz, T Lipsky, R DeRosse, P Burdick, K Jaeger, J Kane, J Goldman, D Malhotra, A AF Lencz, Todd Lipsky, Robert DeRosse, Pamela Burdick, Katherine Jaeger, Judith Kane, John Goldman, David Malhotra, Anil TI BDNF haplotype differentiates schizoaffective disorder and major affective disorders from schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIAAA, Bethesda, MD USA. NR 0 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA 0253 BP 731 EP 731 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700209 ER PT J AU Nicodemus, K Kolachana, B Vakkalanka, R Straub, RE Weinberger, DR AF Nicodemus, Kristin Kolachana, Bhaskar Vakkalanka, Radhakrishna Straub, Richard E. Weinberger, Daniel R. TI Statistical epistasis between NRG1, ERBB4, AKT1 and capon influences risk for schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 Johns Hopkins SPH, GCAP, CBDB, NIMH,NIH, Bethesda, MD 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 MA O257 BP 732 EP 732 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700213 ER PT J AU Ducci, F Newman, TK Funt, S Virkkunen, M Goldman, D AF Ducci, Francesca Newman, Timothy K. Funt, Sam Virkkunen, Matti Goldman, David TI A functional polymorphism in the MAOA gene promoter predicts central dopamine function and BMI SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIAAA, NIH, Rockville, MD USA. NIAAA, LNG, Rockville, MD USA. Univ Helsinki, Helsinki, Finland. 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 754 EP 755 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700313 ER PT J AU Shaw, P Lerch, J Taylor, K Seal, J Evans, A Rapoport, J Giedd, J AF Shaw, Philip Lerch, Jason Taylor, Kristen Seal, Jeffrey Evans, Alan Rapoport, Judith Giedd, Jay TI Cognitively intact children carrying the apolipoprotein E epsilon (E)4 allele have a thinner mesial temporal cortex SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, Bethesda, MD 20892 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 768 EP 768 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700372 ER PT J AU Seal, J Addington, A Gornick, M Gogtay, N Shaw, P Greenstein, D Gochman, P Coffey, M Fabienne, WD Brooks, J Chen, Z Merriman, B Nelson, S Hardy, J Rapoport, J AF Seal, Jeffrey Addington, Anjene Gornick, Michele Gogtay, Nitin Shaw, Philip Greenstein, Deanna Gochman, Peter Coffey, Marge Fabienne, Wavrant-De Vrieze Brooks, Janet Chen, Zugen Merriman, Barry Nelson, Stanley Hardy, John Rapoport, Judith TI Segmental uniparental isodisomy on 5q32-qter in a patient with childhood-onset schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Meeting Abstract CT 14th World Congress on Psychiatric Genetics CY OCT 28-NOV 01, 2006 CL Cagliari, ITALY SP Int Soc Psychiat Genet C1 NIMH, CHP, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. UCLA Sch, Dept Human Genet, Los Angeles, CA USA. RI Gogtay, Nitin/A-3035-2008 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 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT 5 PY 2006 VL 141B IS 7 BP 770 EP 770 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 089JW UT WOS:000240877700383 ER PT J AU Zhou, S Kern, ER Gullen, E Cheng, YC Drach, JC Tamiya, S Mitsuya, H Zemlicka, J AF Zhou, Shaoman Kern, Earl R. Gullen, Elizabeth Cheng, Yung-Chi Drach, John C. Tamiya, Sadahiro Mitsuya, Hiroaki Zemlicka, Jiri TI 9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. Synthesis and antiviral activity of all stereoisomers SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID METHYLENECYCLOPROPANE ANALOGS; NUCLEOSIDES; PYRIMIDINES; ELIMINATION AB All stereoisomers of adenine and guanine methylene-3-fluoromethylenecyclopropane analogues of nucleosides 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b were synthesized and their antiviral activities were evaluated. A highly convergent approach permitted the synthesis of all these analogues using a single intermediate 15. Reaction of aldehyde 13 with fluorotrichloromethane and tri-n-butylphosphine gave fluoroalkenes 14a+14b (83:17). Addition of carbene derived from ethyl diazoacetate gave cyclopropane 15 as the major product. Reduction (19), bromination (20), and phenylselenenylation (21), followed by Se oxidation and beta-elimination gave cis-methylenecyclopropane 22. Addition of bromine provided the reagent 23 for alkylation-elimination. Reaction of 23 with adenine led to an isomeric mixture 25a+26a that after deprotection afforded analogues 9a and 10a. The 2-amino-6-chloropurine furnished 25e+26e and after deblocking (9e and 10e) and hydrolysis gave targets 9b and 10b. Intermediate 15 provided, after debenzylation (27), 2-nitrophenylselenenylation (28), reduction (29), benzylation (30), and oxidation-elimination trans-methylenecyclopropane 31. Addition of bromine gave reagent 32. Further transformations followed the sequence outlined for analogues 9a, 9b, 10a, and 10b. Analogue 9b was effective against human cytomegalovirus (HCMV; Towne) with EC50 2.9 AM. The trans-isomer 10b inhibited AD169 strain of HCMV (EC50 15 mu M) and the murine virus MCMV (EC50 2.5 mu M). Compound 12a was effective against Epstein-Barr virus (EC50 < 0.03 mu M). Analogue 9a inhibited varicella zoster virus (EC50 5.9 mu M) and human immunodeficiency virus type 1 (EC50 5.2 mu M). Analogues 9a, 10a, and 11a are moderate substrates for adenosine deaminase. The structure-activity relationships will be discussed in context with other methylenecyclopropane analogues. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. Univ Alabama, Sch Med, Dept Pediat, Birmingham, AL 35233 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 860, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Zemlicka, J (reprint author), Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Dept Chem,Dev Therapeut Program, Detroit, MI 48201 USA. EM zemlicka@kci.wayne.edu FU NCI NIH HHS [R35 CA044358, R01 CA032779, R01 CA032779-20, R01-CA32779, R01-CA44358, R35 CA044358-10]; NIAID NIH HHS [N01 AI030049, N01 AI085347, N01 AI085347-005, N01-AI30049, N01-AI85347, N01AI30049, P01 AI046390-040002, P01-AI46390] NR 19 TC 16 Z9 18 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 5 PY 2006 VL 49 IS 20 BP 6120 EP 6128 DI 10.1021/jm0607404 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 088QM UT WOS:000240826200027 PM 17004726 ER PT J AU Hardy, J AF Hardy, John TI A hundred years of Alzheimer's disease research SO NEURON LA English DT Editorial Material ID AMYLOID-PRECURSOR-PROTEIN; PAIRED HELICAL FILAMENTS; HEREDITARY CEREBRAL-HEMORRHAGE; GAMMA-SECRETASE ACTIVITY; LONG-TERM POTENTIATION; DEMENTED OLD PEOPLE; BETA-PROTEIN; TRANSGENIC MICE; ALPHA-SYNUCLEIN; APOLIPOPROTEIN-E AB On the 100(th) anniversary of Alzheimer's lecture describing the clinicopathological entity which bears his eponym, this article reviews the major areas of progress in our understanding of the disease and outlines the many gaps still remaining. The progress toward effective mechanistic therapy is reviewed. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. UCL, Inst Neurol, Reta Lila Weston Inst, London WC2, England. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyJ@mail.nih.gov RI Blossey, Erich/A-9696-2011; Hardy, John/C-2451-2009 OI Blossey, Erich/0000-0002-8189-766X; FU Intramural NIH HHS; Medical Research Council [G0701075] NR 164 TC 236 Z9 247 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 5 PY 2006 VL 52 IS 1 BP 3 EP 13 DI 10.1016/j.neuron.2006.09.016 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 096WS UT WOS:000241408100001 PM 17015223 ER PT J AU Komiya, T Park, Y Modi, S Coxon, AB Oh, H Kaye, FJ AF Komiya, T. Park, Y. Modi, S. Coxon, A. B. Oh, H. Kaye, F. J. TI Sustained expression of Mect1-Mam12 is essential for tumor cell growth in salivary gland cancers carrying the t(11 ; 19) translocation SO ONCOGENE LA English DT Article DE mucoepidermoid cancer; salivary gland cancer; chromosomal translocation; RNAi ID MUCOEPIDERMOID CARCINOMA; GENE FUSION; IDENTIFICATION; FAMILY; COACTIVATORS; ACTIVATION; BENIGN AB Mucoepidermoid (MEC) salivary gland tumors arise from a t(11; 19) rearrangement which generates a fusion oncogene, Mect1-Maml2, that functions to activate CREB-responsive target genes. To determine if sustained expression of Mect1-Maml2 is required for tumor cell growth, we first showed that ectopic expression of Mect1-Maml2 in rat epithelial RK3E cells is tumorigenic in vivo in nude mice and that excised xenografts continue to express the fusion oncogene. We then generated a hairpin RNAi vector that selectively suppressed the fusion peptide and showed that ectopic expression in either parotid or pulmonary MEC tumor cell lines containing the t(11; 19) rearrangement resulted in at least 90% colony growth inhibition. In contrast, single nucleotide changes within this RNAi sequence abolished the ability to suppress Mect1-Maml2 protein and abolished all growth inhibition of these MEC tumor lines. In addition, the RNAi-specific vector had no effect on colony growth of non-MEC tumors including a lung tumor or two other salivary gland cell lines that do not express Mect1-Maml2. We also generated a mutant Mect1-Maml2 expression plasmid that carried silent nucleotide changes within the RNAi target sequence and observed that co-transfection of this mutant, but not wild-type Mect1-Maml2, could partially rescue RNAi growth inhibition in the MEC tumor line. The recent detection of acquired fusion oncogenes in epithelial solid tumors has suggested new possibilities for the diagnosis and therapy of these cancers. Our data show that the 'gain-of-function' activity from aberrant Mect1-Maml2 expression is a candidate therapeutic target for this group of malignant salivary gland tumors. C1 NCI, Canc Res Ctr, Genat Branch, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. RP Kaye, FJ (reprint author), Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 FU Intramural NIH HHS NR 20 TC 37 Z9 39 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 5 PY 2006 VL 25 IS 45 BP 6128 EP 6132 DI 10.1038/sj.onc.1209627 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 092MN UT WOS:000241101200010 PM 16652146 ER PT J AU Vickers, AJ Kramer, BS Baker, SG AF Vickers, Andrew J. Kramer, Barry S. Baker, Stuart G. TI Selecting patients for randomized trials: a systematic approach based on risk group SO TRIALS LA English DT Article ID CANCER-RISK; PROSTATE; BENEFITS; LUNG AB Background: A key aspect of randomized trial design is the choice of risk group. Some trials include patients from the entire at-risk population, others accrue only patients deemed to be at increased risk. We present a simple statistical approach for choosing between these approaches. The method is easily adapted to determine which of several competing definitions of high risk is optimal. Method: We treat eligibility criteria for a trial, such as a smoking history, as a prediction rule associated with a certain sensitivity ( the number of patients who have the event and who are classified as high risk divided by the total number patients who have an event) and specificity ( the number of patients who do not have an event and who do not meet criteria for high risk divided by the total number of patients who do not have an event). We then derive simple formulae to determine the proportion of patients receiving intervention, and the proportion who experience an event, where either all patients or only those at high risk are treated. We assume that the relative risk associated with intervention is the same over all choices of risk group. The proportion of events and interventions are combined using a net benefit approach and net benefit compared between strategies. Results: We applied our method to design a trial of adjuvant therapy after prostatectomy. We were able to demonstrate that treating a high risk group was superior to treating all patients; choose the optimal definition of high risk; test the robustness of our results by sensitivity analysis. Our results had a ready clinical interpretation that could immediately aid trial design. Conclusion: The choice of risk group in randomized trials is usually based on rather informal methods. Our simple method demonstrates that this decision can be informed by simple statistical analyses. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Vickers, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. EM vickersa@mskcc.org; KramerB@OD.NIH.GOV; sb16i@nih.gov OI Vickers, Andrew/0000-0003-1525-6503 FU NCI NIH HHS [P50 CA092629] NR 9 TC 12 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1745-6215 J9 TRIALS JI Trials PD OCT 5 PY 2006 VL 7 AR 30 DI 10.1186/1745-6215-7-30 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 096OD UT WOS:000241385800001 PM 17022818 ER PT J AU Gami, MS Iser, WB Hanselman, KB Wolkow, CA AF Gami, Minaxi S. Iser, Wendy B. Hanselman, Keaton B. Wolkow, Catherine A. TI Activated AKT/PKB signaling in C-elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID 3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1; AGE-1 PI3 KINASE; LIFE-SPAN; C-ELEGANS; TRANSCRIPTION FACTOR; INTERACTING GENES; DAUER FORMATION; FAMILY-MEMBER; LONGEVITY; DIAPAUSE AB Background: In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. Results: This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109); akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109); pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1( mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. Conclusion: A screen for suppressors of PI3K mutant phenotypes identified activating mutations in two known pathway components, providing insights into their regulation. In particular, the interdependence of akt-1 and pdk-1, even in activated forms, supports the existence of AGE-1-independent pathways for these phospholipid-dependent kinases. Phenotypic analysis of these alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable in these mutants. C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. EM gamimi@grc.nia.nih.gov; iserwe@grc.nia.nih.gov; keaton.hanselman@duke.edu; wolkowca@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000320-06, NIH0011061953] NR 38 TC 27 Z9 32 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD OCT 4 PY 2006 VL 6 AR 45 DI 10.1186/1471-213X-6-45 PG 14 WC Developmental Biology SC Developmental Biology GA 095BX UT WOS:000241284300001 PM 17020605 ER PT J AU Schneider, ME Dose, AC Salles, FT Chang, WS Erickson, FL Burnside, B Kachar, B AF Schneider, Mark E. Dose, Andrea C. Salles, Felipe T. Chang, Weise Erickson, Floyd L. Burnside, Beth Kachar, Bechara TI A new compartment at stereocilia tips defined by spatial and temporal patterns of myosin IIIa expression SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hair cells; myosin IIIa; stereocilia; hearing; myosin XVa; myosin Ic ID VESTIBULAR HAIR-CELLS; UNCONVENTIONAL MYOSIN; PROTEIN-KINASE; PDZ PROTEIN; NINAC; MOTOR; PHOTORECEPTORS; LOCALIZATION; ADAPTATION; BUNDLES AB Class III myosins are motor proteins that contain an N-terminal kinase domain and a C-terminal actin-binding domain. We show that myosin IIIa, which has been implicated in nonsyndromic progressive hearing loss, is localized at stereocilia tips. Myosin IIIa progressively accumulates during stereocilia maturation in a thimble-like pattern around the stereocilia tip, distinct from the cap-like localization of myosin XVa and the shaft localization of myosin Ic. Overexpression of deletion mutants for functional domains of green fluorescent protein (GFP)-myosin IIIa shows that the motor domain, but not the actin-binding tail domain, is required for stereocilia tip localization. Deletion of the kinase domain produces stereocilia elongation and bulging of the stereocilia tips. The thimble-like localization and the influence myosin IIIa has on stereocilia shape reveal a previously unrecognized molecular compartment at the distal end of stereocilia, the site of actin polymerization as well as operation of the mechanoelectrical transduction apparatus. C1 NIDOCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Salisbury Univ, Dept Biol Sci, Salisbury, MD 21801 USA. RP Kachar, B (reprint author), NIDOCD, Sect Struct Cell Biol, NIH, Bldg 50,Room 4249,50 S Dr, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov RI Salles, Felipe/H-7544-2013 NR 40 TC 76 Z9 76 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 4 PY 2006 VL 26 IS 40 BP 10243 EP 10252 DI 10.1523/JNEUROSCI.2812-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 093TN UT WOS:000241192700018 PM 17021180 ER PT J AU Fojo, T AF Fojo, Tito TI Can mutations in gamma-actin modulate the toxicity of microtubule targeting agents? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RHO-GTPASES; BETA-ACTIN; CELLS; FIBROBLASTS; EXPRESSION; RESISTANT; DFNA20/26; BINDING; MYOSIN; GENES C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 25 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2006 VL 98 IS 19 BP 1345 EP 1347 DI 10.1093/jnci/djj408 PG 3 WC Oncology SC Oncology GA 101EH UT WOS:000241721200001 PM 17018774 ER PT J AU Lacey, JV Brinton, LA Leitzmann, MF Mouw, T Hollenbeck, A Schatzkin, A Hartge, P AF Lacey, James V., Jr. Brinton, Louise A. Leitzmann, Michael F. Mouw, Traci Hollenbeck, Albert Schatzkin, Arthur Hartge, Patricia TI Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; WOMEN; PROGESTERONE; EXPRESSION; RECEPTOR; CARCINOMA; SYMPTOMS; TRIAL AB Background. Recent studies offer conflicting data on risks of ovarian cancer in users of menopausal hormone therapy. Some findings of increased risks associated with unopposed estrogen use are based on older studies of women with intact uteri, and small sample size and incomplete exposure information have limited the data on estrogen plus progestin associations. Methods: The National Institutes of Health-AARP Diet and Health Study Cohort included 97638 women aged 50-71 years at baseline who completed two questionnaires (1995-1996 and 1996-1997). We identified 214 incident ovarian cancers among these women through the year 2000 using data from state cancer registries and mortality indexes. We estimated relative risks (RRs) of ovarian cancer for detailed hormone therapy exposures using multivariable proportional hazards regression models. All statistical tests were two-sided. Results: Use of unopposed estrogen for fewer than 10 years was not associated with ovarian cancer. Compared with use of no hormone therapy, use of unopposed estrogen for 10 or more years was statistically significantly associated with ovarian cancer among all women (RR = 1.89,95% confidence interval [CI] = 1.22 to 2.95; P =.004; 56 versus 72 ovarian cancers per 100000 person-years, respectively) and, albeit not statistically significantly, among women with hysterectomy (n = 19 359, RR = 1.70, 95% CI = 0.87 to 3.31; P =.06). Among the 73 483 women with intact uteri, 51698 had used no hormone therapy or only estrogen plus progestin. Compared with no hormone therapy use, 5 or more years of use of sequential (progestin for < 15 days per cycle; RR = 3.09, 95% CI = 1.68 to 5.68; P <.001; 49 versus 108 per 100000 person-years) or continuous (progestin for >= 15 days per cycle; RR = 1.82, 95% CI = 1.03 to 3.23; P = .02; 49 versus 66 per 100000 person-years) estrogen plus progestin regimens were statistically significantly associated with ovarian cancer. Conclusions: Long durations of use of unopposed estrogen and of estrogen plus progestin, especially sequential regimens, are associated with increased ovarian cancer risk. These data expand the range of possible risks associated with menopausal hormone therapy. C1 Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Nutr Epidemiol Branch, NIH, Rockville, MD 20852 USA. Natl Canc Inst, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP Lacey, JV (reprint author), 6120 Execut Blvd,Room 5030, Rockville, MD 20852 USA. EM jimlacey@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS NR 42 TC 64 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2006 VL 98 IS 19 BP 1397 EP 1405 DI 10.1093/jnci/djj375 PG 9 WC Oncology SC Oncology GA 101EH UT WOS:000241721200013 PM 17018786 ER PT J AU Schairer, C Brown, LM Chen, BE Howard, R Lynch, CF Hall, P Storm, H Pukkala, E Anderson, A Kaijser, M Andersson, M Joensuu, H Fossa, SD Ganz, PA Travis, LB AF Schairer, Catherine Morris Brown, Linda Chen, Bingshu E. Howard, Regan Lynch, Charles F. Hall, Per Storm, Hans Pukkala, Eero Anderson, Auge Kaijser, Magnus Andersson, Michael Joensuu, Heikki Fossa, Sophie D. Ganz, Patricia A. Travis, Lois B. TI Suicide after breast cancer: An international population-based study of 723 810 women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LIFE EVENTS; RISK; EPIDEMIOLOGY; DISORDERS; DIAGNOSIS; COHORT AB Few studies have examined long-term suicide risk among breast cancer survivors, and there are no data for women in the United States. We quantified suicide risk through 2002 among 723 810 I-year breast cancer survivors diagnosed between January 1, 1953, and December 31, 2001, and reported to 16 population-based cancer registries in the United States and Scandinavia. Among breast cancer survivors, we calculated standardized mortality ratios (SMRs) and excess absolute risks (EARs) compared with the general population, and the probability of suicide. We used Poisson regression likelihood ratio tests to assess heterogeneity in SMRs; all statistical tests were two-sided, with a .05 cutoff for statistical significance. In total 836 breast cancer patients committed suicide (SMR = 1.37, 95% confidence interval [CI] = 1.28 to 1.47; EAR = 4.1 per 100000 person-years). Although SMRs ranged from 1.25 to 1.53 among registries, with 245 deaths among the sample of US women (SMR = 1.49, 95% CI = 1.32 to 1.70), differences among registries were not statistically significant (P for heterogeneity = .19). Risk was elevated throughout follow-up, including for 25 or more years after diagnosis (SMR = 1.35, 95% Cl = 0.82 to 2.12), and was highest among black women (SMR = 2.88, 95% CI = 1.44 to 5.17) (P for heterogeneity = .06). Risk increased with increasing stage of breast cancer (P for heterogeneity = .08) and remained elevated among women diagnosed between 1990 and 2001 (SMR = 1.36, 95% Cl = 1.18 to 1.57). The cumulative probability of suicide was 0.20% 30 years after breast cancer diagnosis. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA 52242 USA. Karolinska Inst, S-10401 Stockholm, Sweden. Danish Canc Soc, Copenhagen, Denmark. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Canc Registry Norway, Oslo, Norway. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Norwegian Radium Hosp, Oslo 3, Norway. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Schairer, C (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,Rm 8020,MSC 7244, Rockville, MD 20852 USA. EM schairec@exchange.nih.gov OI Storm, Hans/0000-0001-7223-8198 FU Intramural NIH HHS NR 32 TC 52 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 4 PY 2006 VL 98 IS 19 BP 1416 EP 1419 DI 10.1093/jnci/djj377 PG 4 WC Oncology SC Oncology GA 101EH UT WOS:000241721200015 PM 17018788 ER PT J AU Ayache, S Panelli, MC Byrne, KM Slezak, S Leitman, SF Marincola, FM Stroncek, DF AF Ayache, Saleh Panelli, Monica C. Byrne, Karen M. Slezak, Stefanie Leitman, Susan F. Marincola, Francesco M. Stroncek, David F. TI Comparison of proteomic profiles of serum, plasma, and modified media supplements used for cell culture and expansion SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID IN-VITRO CULTURE; DENDRITIC CELLS; CANCER-IMMUNOTHERAPY; GENERATION; TRANSPLANTATION; CHEMOTHERAPY; LEUKEMIA; THERAPY; DISEASE; BLASTS AB Background: The culture and expansion of human cells for clinical use requires the presence of human serum or plasma in culture media. Although these supplements have been extensively characterized in their chemical composition, only recently it has been possible to provide by high throughput protein analysis, a comprehensive profile of the soluble factors contributing to cell survival. This study analyzed and compared the presence of 100 proteins including chemokines, cytokines and soluble factors in six different types of media supplements: serum, plasma, recalcified plasma, heat inactivated serum, heat inactivated plasma and heat inactivated recalcified plasma. Methods: Serum, plasma, recalcified plasma, and heat inactivated supplements were prepared from ten healthy subjects. The levels of 100 soluble factors were measured in each sample using a multiplexed ELISA assay and compared by Eisen hierarchical clustering analysis. Results: A comparison of serum and plasma levels of soluble factors found that 2 were greater in plasma but 18 factors were greater in serum including 11 chemokines. The levels of only four factors differed between recalcified plasma and plasma. Heat inactivation had the greatest effect on soluble factors. Supervised Eisen hierarchical clustering indicated that the differences between heat inactivated supplements and those that were not were greater than the differences within these two groups. The levels of 36 factors differed between heat inactivated plasma and plasma. Thirty one of these factors had a lower concentration in heat inactivated plasma including 12 chemokines, 4 growth factors, 4 matrix metalloproteases, and 3 adhesion molecules. Heat inactivated decalcified plasma is often used in place of heat inactivated serum and the levels of 19 soluble factors differed between these two supplements. Conclusion: Our report provides a comprehensive protein profile of serum, plasma recalcified plasma, and heat inactivated supplements. This profile represents a qualitative and quantitative database that can aid in the selection of the appropriate blood derived supplement for human cell cultures with special requirements. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM Saleh.Ayache@mail.tju.edu; MPanelli@cc.nih.gov; kbyrne@cc.nih.gov; sslezak@cc.nih.gov; sleitman@cc.nih.gov; fmarincola@cc.nih.gov; dstroncek@cc.nih.gov NR 19 TC 26 Z9 26 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 4 PY 2006 VL 4 AR 40 DI 10.1186/1479-5876-4-40 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 093RL UT WOS:000241186200001 PM 17020621 ER PT J AU Horkay, F Han, MH Han, IS Bang, IS Magda, JJ AF Horkay, Ferenc Han, Man-Hee Han, In Suk Bang, In-Seok Magda, Jules J. TI Separation of the effects of pH and polymer concentration on the swelling pressure and elastic modulus of a pH-responsive hydrogel SO POLYMER LA English DT Article DE elastic shear modulus; pH-responsive hydrogel; osmotic pressure ID GELS; EQUILIBRIUM; BEHAVIOR AB The elastic shear modulus G and swelling pressure omega are studied for a basic, pH-responsive hydrogel synthesized by crosslinking copolymerization of co-monomers hydroxypropyl methacrylate and N,N-dimethylaminoethyl methacrylate with crosslinker tetraethylene glycol dimethacrylate. Under normal conditions of use as a "smart" material, hydrogel swelling ratio Q and pH vary simultaneously, but here G and w values are presented as a function of pH with Q held constant and vice versa. At fixed pH, G decreases with increase in Q in a power law dependence, as predicted by the Flory-Rehner model. However, at fixed Q, G increases with decrease in pH (i.e., increase in degree of ionization). The pH effect is more pronounced than the volume effect, thus the hydrogel stiffens as it swells in response to pH change. At high pH, to values of the uncharged hydrogel obey the Flory-Rehner model, whereas explicit ionic contributions can be identified at lower pH values. (c) 2006 Elsevier Ltd. All rights reserved. C1 NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. M Biotech Inc, Salt Lake City, UT 84070 USA. Univ Utah, Dept Chem Engn, Salt Lake City, UT 84112 USA. RP Horkay, F (reprint author), NICHD, Sect Tissue Biophys & Biomimet, NIH, 13 S Dr, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov; jj.magda@m.cc.utah.edu RI magda, jules/A-9715-2009 FU NIBIB NIH HHS [R21 EB004947, R21 EB004947-01A1] NR 20 TC 19 Z9 19 U1 5 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD OCT 4 PY 2006 VL 47 IS 21 BP 7335 EP 7338 DI 10.1016/j.polymer.2006.08.037 PG 4 WC Polymer Science SC Polymer Science GA 097CU UT WOS:000241424800002 PM 17917687 ER PT J AU Stek, AM Mirochnick, M Capparelli, E Best, BM Hu, CC Burchett, SK Elgie, C Holland, DT Smith, E Tuomala, R Cotter, A Read, JS AF Stek, Alice M. Mirochnick, Mark Capparelli, Edmund Best, Brookie M. Hu, Chengcheng Burchett, Sandra K. Elgie, Carol Holland, Diane T. Smith, Elizabeth Tuomala, Ruth Cotter, Amanda Read, Jennifer S. CA PACTG 1026s study team TI Reduced lopinavir exposure during pregnancy SO AIDS LA English DT Article; Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND DE lopinavir pharmacokinetics; pregnancy; HIV ID PHARMACOKINETICS; ZIDOVUDINE; LAMIVUDINE; SAFETY AB Background: Optimal antiretroviral exposure during pregnancy is critical for prevention of mother-to-child HIV transmission and for maternal health. Pregnancy can alter antiretroviral pharmacokinetics. Our objective was to describe lopinavir/ritonavir (LPV/r) pharmacokinetics during pregnancy. Methods: We performed intensive steady-state 12-h pharmacokinetic profiles of lopinavir and ritonavir (three capsules: LPV 400 mg/r 100 mg) at 30-36 weeks gestation and 6-12 weeks postpartum. Maternal and umbilical cord blood samples were obtained at delivery. We measured LPV and ritonavir by reverse-phase high-performance liquid chromatography. Target LPV area under concentration versus time curve (AUC) was >= 52 mu g h/ml, the estimated 10th percentile LPV AUC in non-pregnant historical controls (mean AUC = 83 mu g h/ml). Results: Seventeen women completed antepartum evaluations; average gestational age was 35 weeks. Geometric mean antepartum LPV AUC was 44.4 mu g h/ml [90% confidence interval (CI), 38.7-50.9] and 12-h post-dose concentration (C-12h) was 1.6 mu g/ml (90% CI, 1.1-2.5). Twelve women completed postpartum evaluations; geometric mean LPV AUC was 65.2 mu g h/ml (90% CI, 49.7-85.4) and C-12h was 4.6 mu g/ml (90% CI, 3.7-5.7). The geometric mean ratio of antepartum/postpartum LPV AUC was 0.72 (90% CI, 0.54-0.96). Fourteen of 17 (82%) pregnant and three of 12 (25%) postpartum women did not meet our target LPV AUC. The ratio of cord blood/ maternal LPV concentration in ten paired detectable samples was 0.2 +/- 0.13. Conclusions: LPV/r exposure during late pregnancy was lower compared to postpartum and compared to non-pregnant historical controls. Small amounts of lopinavir cross the placenta. The pharmacokinetics, safety, and effectiveness of increased LPV/r dosing during the third trimester of pregnancy should be investigated. (c) 2006 Lippincott Williams & Wilkins. C1 Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA. Boston Univ, Boston, MA 02215 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Calif San Diego, Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Childrens Hosp Boston, Boston, MA USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. NIAID, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Miami, Miami, FL 33152 USA. NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA. RP Stek, AM (reprint author), Los Angeles Cty & USC Med Ctr, Maternal Child & Adolescent HIV Program, 1640 Marengo St,300, Los Angeles, CA 90033 USA. EM stek@usc.edu RI Hu, Chengcheng/A-8391-2017 FU NCRR NIH HHS [5M01 RR 01271, M01 RR 00533]; NIAID NIH HHS [U01 AI 04189, U01 AI 27560-18, U01 AI 32907, U01 AI 41089]; NICHD NIH HHS [N01 HD 33365] NR 17 TC 122 Z9 122 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 3 PY 2006 VL 20 IS 15 BP 1931 EP 1939 DI 10.1097/01.aids.0000247114.43714.90 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 140MQ UT WOS:000244509800005 PM 16988514 ER PT J AU Gerelsaikhan, T Parvin, MN Turner, RJ AF Gerelsaikhan, Tudevdagva Parvin, Most. Nahid Turner, R. James TI Biogenesis and topology of the secretory Na+-K+-2Cl(-) cotransporter (NKCC1) studied in intact mammalian cells SO BIOCHEMISTRY LA English DT Article ID K-CL COTRANSPORTER; IN-VITRO TRANSLATION; MEMBRANE-PROTEINS; NA-K-2CL COTRANSPORTER; FUNCTIONAL EXPRESSION; ENDOPLASMIC-RETICULUM; MOLECULAR-CLONING; N-GLYCOSYLATION; ION-TRANSPORT; MICE LACKING AB The "secretory" Na+-K+-2Cl(-) cotransporter (NKCC1) is a member of a small gene family with nine homologues in vertebrates. Of these, seven are known to be electroneutral chloride transporters. These transporters play a number of important physiological roles related to salt and water homeostasis and the control of intracellular chloride levels. Hydropathy analyses suggest that all of these transporters have a similar transmembrane topology consisting of relatively large intracellular N and C termini and a central hydrophobic domain containing 12 membrane-spanning segments (MSSs). In recent experiments from our laboratory [Gerelsaikhan, T., and Turner, R. J. ( 2000) J. Biol. Chem. 275, 40471-40477], we employed an in Vitro translation system to confirm that each of the putative MSSs of NKCC1 was capable of membrane integration in a manner consistent with a 12 MSS model. Here, we extend that work to the study of the biogenesis of NKCC1 in intact cells. We employ a truncation mutant approach that allows us to monitor this process quantitatively as successive MSSs are synthesized. While the results presented here confirm the 12 MSS model, they also indicate that the integration of NKCC1 into the membrane does not occur via a simple cotranslational process. In particular, we demonstrate that two MSSs, the second and sixth, require the presence of downstream sequence to efficiently integrate into the membrane. C1 DHHS, Membrane Biol Sect, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res,NIH, Bethesda, MD 20892 USA. RP Turner, RJ (reprint author), DHHS, Membrane Biol Sect, Gene Therapy & Therapeut Branch, Natl Inst Dent & Craniofacial Res,NIH, Bldg 10,Room 1A01,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. EM rjturner@nih.gov FU Intramural NIH HHS NR 36 TC 10 Z9 10 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 3 PY 2006 VL 45 IS 39 BP 12060 EP 12067 DI 10.1021/bi061126x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 087OT UT WOS:000240752400034 PM 17002305 ER PT J AU Karev, GP Novozhilov, AS Koonin, EV AF Karev, Georgy P. Novozhilov, Artem S. Koonin, Eugene V. TI Mathematical modeling of tumor therapy with oncolytic viruses: effects of parametric heterogeneity on cell dynamics SO BIOLOGY DIRECT LA English DT Article ID POPULATION HETEROGENEITY; NECK-CANCER; PROGRESSION; ADENOVIRUS; ONYX-015; CHEMOTHERAPY; GROWTH; CARCINOGENESIS; STRATEGIES; DIVERSITY AB Background: One of the mechanisms that ensure cancer robustness is tumor heterogeneity, and its effects on tumor cells dynamics have to be taken into account when studying cancer progression. There is no unifying theoretical framework in mathematical modeling of carcinogenesis that would account for parametric heterogeneity. Results: Here we formulate a modeling approach that naturally takes stock of inherent cancer cell heterogeneity and illustrate it with a model of interaction between a tumor and an oncolytic virus. We show that several phenomena that are absent in homogeneous models, such as cancer recurrence, tumor dormancy, and others, appear in heterogeneous setting. We also demonstrate that, within the applied modeling framework, to overcome the adverse effect of tumor cell heterogeneity on the outcome of cancer treatment, a heterogeneous population of an oncolytic virus must be used. Heterogeneity in parameters of the model, such as tumor cell susceptibility to virus infection and the ability of an oncolytic virus to infect tumor cells, can lead to complex, irregular evolution of the tumor. Thus, quasi-chaotic behavior of the tumor-virus system can be caused not only by random perturbations but also by the heterogeneity of the tumor and the virus. Conclusion: The modeling approach described here reveals the importance of tumor cell and virus heterogeneity for the outcome of cancer therapy. It should be straightforward to apply these techniques to mathematical modeling of other types of anticancer therapy. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov; novozhil@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013 OI Novozhilov, Artem/0000-0001-5469-2557 NR 66 TC 29 Z9 29 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD OCT 3 PY 2006 VL 1 AR 30 DI 10.1186/1745-6150-1-30 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133TN UT WOS:000244036500001 PM 17018145 ER PT J AU Sack, MN AF Sack, Michael N. TI Exploring mitochondria in the intact ischemic heart - Advancing technologies to image intracellular function SO CIRCULATION LA English DT Editorial Material DE editorials; imaging; ischemia; metabolism ID 2-PHOTON MICROSCOPY; PROTECTION; CELLS C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10-CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU Intramural NIH HHS NR 18 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 3 PY 2006 VL 114 IS 14 BP 1452 EP 1454 DI 10.1161/CIRCULATIONAHA.106.653485 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 090MD UT WOS:000240954500006 PM 17015804 ER PT J AU Lin, JP O'Donnell, CJ Schwaiger, JP Cupples, LA Lingenhel, A Hunt, SC Yang, S Kronenberg, F AF Lin, Jing-Ping O'Donnell, Christopher J. Schwaiger, Johannes P. Cupples, L. Adrienne Lingenhel, Arno Hunt, Steven C. Yang, Song Kronenberg, Florian TI Association between the UGT1A1*28 allele, bilirubin levels, and coronary heart disease in the Framingham heart study SO CIRCULATION LA English DT Article DE cardiovascular diseases; genetics; genes; atherosclerosis; enzymes; epidemiology; survival ID ALBUMIN-BOUND BILIRUBIN; CRIGLER-NAJJAR-SYNDROME; LOW-DENSITY-LIPOPROTEIN; SERUM BILIRUBIN; ARTERY-DISEASE; GILBERTS-SYNDROME; GLUCURONOSYLTRANSFERASE; RISK; GENE; PROMOTER AB Background-Bilirubin is an antioxidant that suppresses lipid oxidation and retards atherosclerosis formation. An inverse association between serum bilirubin and coronary heart disease has been reported. Linkage studies have identified a major locus at the chromosome 2q telomere that affects bilirubin concentrations. A candidate gene in the linkage region encodes hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The insertion of a TA in the TATAA box of the gene, an allele designated UGT1A1*28, decreases gene transcription. Individuals homozygous for UGT1A1*28 (genotype 7/7) have increased serum bilirubin levels compared with carriers of the 6 allele. To date, no significant association between UGT1A1*28 and cardiovascular disease (CVD) events has been reported. We performed an association study in the Framingham Heart Study population to investigate whether UGT1A1*28 is associated with the risk of CVD events. Methods and Results-The study population included 1780 unrelated individuals from the Offspring cohort (49% males, mean age 36 years at entry) who had been followed up for 24 years. Individuals with genotype 7/7 had significantly higher bilirubin levels (mean +/- SD 1.14 +/- 0.44 mg/dL) than those with genotypes 6/6 and 6/7 (mean +/- SD 0.69 +/- 0.27 mg/dL, P < 0.01). Using the Cox proportional hazards model, we found significant associations between the UGT1A1*28 allele and decreased risk of CVD. Individuals with genotype 7/7 ( population frequency of 11%) had approximately one third the risk for CVD and coronary heart disease as carriers of the 6 allele, which resulted in a hazard ratio (95% confidence interval) of 0.36 ( 0.18 to 0.74) and 0.30 ( 0.12 to 0.74), respectively. Conclusions-Homozygote UGT1A1*28 allele carriers with higher serum bilirubin concentrations exhibit a strong association with lower risk of CVD. C1 NHLBI, NIH, Off Biostat Res, Bethesda, MD 20892 USA. NHLBI, NIH, Framingham Heart Study, Bethesda, MD 20892 USA. NHLBI, NIH, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Innsbruck Med Univ, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. RP Lin, JP (reprint author), NHLBI, NIH, Off Biostat Res, 6701 Rockledge Dr,Suite 8110, Bethesda, MD 20892 USA. EM linj@nhlbi.nih.gov RI Kronenberg, Florian/B-1736-2008; OI Kronenberg, Florian/0000-0003-2229-1120; Cupples, L. Adrienne/0000-0003-0273-7965; Schwaiger, Johannes/0000-0003-1960-0631 FU NHLBI NIH HHS [N01-HC-25195] NR 31 TC 161 Z9 170 U1 11 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 3 PY 2006 VL 114 IS 14 BP 1476 EP 1481 DI 10.1161/CIRCULATIONAHA.106.633206 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 090MD UT WOS:000240954500010 PM 17000907 ER PT J AU Bossert, JM Poles, GC Sheffler-Collins, SI Ghitza, UE AF Bossert, Jennifer M. Poles, Gabriela C. Sheffler-Collins, Sean I. Ghitza, Udi E. TI The mGluR(2/3) agonist LY379268 attenuates context- and discrete cue-induced reinstatement of sucrose seeking but not sucrose self-administration in rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE conditioned cues; drug seeking; food reward; metabotropic glutamate receptors; relapse ID NUCLEUS-ACCUMBENS; RECEPTOR AGONIST; DRUG-ADDICTION; ADMINISTERED COCAINE; GENE-EXPRESSION; NEURAL CIRCUITS; INDUCED RELAPSE; HEROIN SEEKING; WITHDRAWAL; DOPAMINE AB We recently reported that systemic injections of the mGluR(2/3) agonist LY379268, which decreases evoked glutamate release, attenuate context-and discrete cue-induced reinstatement of heroin seeking, but not heroin self-administration. Here, we report that systemic injections of LY379268 attenuate context- and discrete cue-induced reinstatement of sucrose seeking, but not sucrose self-administration. These results suggest that similar neuronal mechanisms mediate cue-induced relapse to opiate- and palatable food seeking. Published by Elsevier B.V. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHSS, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHSS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov FU Intramural NIH HHS NR 41 TC 48 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD OCT 2 PY 2006 VL 173 IS 1 BP 148 EP 152 DI 10.1016/j.bbr.2006.06.008 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 086DE UT WOS:000240652500018 PM 16834996 ER PT J AU Petrovas, C Casazza, JP Brenchley, JM Price, DA Gostick, E Adams, WC Precopio, ML Schacker, T Roederer, M Douek, DC Koup, RA AF Petrovas, Constantinos Casazza, Joseph P. Brenchley, Jason M. Price, David A. Gostick, Emma Adams, William C. Precopio, Melissa L. Schacker, Timothy Roederer, Mario Douek, Daniel C. Koup, Richard A. TI PD-1 is a regulator of virus-specific CD8(+) T cell survival in HIV infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; COSTIMULATORY PATHWAYS; VIRAL-INFECTION; RESPONSES; MEMORY; ACTIVATION; PROLIFERATION; EXPRESSION; LYMPHOCYTES; TOLERANCE AB Here, we report on the expression of programmed death (PD)-1 on human virus-specific CD8(+) T cells and the effect of manipulating signaling through PD-1 on the survival, proliferation, and cytokine function of these cells. PD-1 expression was found to be low on naive CD8(+) T cells and increased on memory CD8+ T cells according to antigen specificity. Memory CD8(+) T cells specific for poorly controlled chronic persistent virus (HIV) more frequently expressed PD-1 than memory CD8(+) T cells specific for well-controlled persistent virus (cytomegalovirus) or acute (vaccinia) viruses. PD-1 expression was independent of maturational markers on memory CD8(+) T cells and was not directly associated with an inability to produce cytokines. Importantly, the level of PD-1 surface expression was the primary determinant of apoptosis sensitivity of virus-specific CD8(+) T cells. Manipulation of PD-1 led to changes in the ability of the cells to survive and expand, which, over several days, affected the number of cells expressing cytokines. Therefore, PD-1 is a major regulator of apoptosis that can impact the frequency of antiviral T cells in chronic infections such as HIV, and could be manipulated to improve HIV-specific CD8(+) T cell numbers, but possibly not all functions in vivo. C1 NIAID, Immunol Lab, NIA, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, NIA, Bethesda, MD 20892 USA. NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. RP Koup, RA (reprint author), NIAID, Immunol Lab, NIA, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rkoup@mail.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G108/441] NR 49 TC 519 Z9 546 U1 4 U2 19 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2006 VL 203 IS 10 BP 2281 EP 2292 DI 10.1084/jem.20061496 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 090KY UT WOS:000240951400016 PM 16954372 ER PT J AU Mavilio, D Lombardo, G Kinter, A Fogli, M La Sala, A Ortolano, S Farschi, A Follmann, D Gregg, R Kovacs, C Marcenaro, E Pende, D Moretta, A Fauci, AS AF Mavilio, Domenico Lombardo, Gabriella Kinter, Audrey Fogli, Manuela La Sala, Andrea Ortolano, Saida Farschi, Annahita Follmann, Dean Gregg, Roby Kovacs, Colin Marcenaro, Emanuela Pende, Daniela Moretta, Alessandro Fauci, Anthony S. TI Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in HIV-1 infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NK CELL; ACTIVATING RECEPTORS; INNATE RESISTANCE; EXPRESSION; IL-12; VIRUS; NKP30; IMMUNODEFICIENCY; INTERLEUKIN-12; STIMULATION AB In this study, we demonstrate that the in vitro interactions between a CD56(neg)/CD16(pos) (CD56(neg)) subset of natural killer (NK) cells and autologous dendritic cells (DCs) from HIV-1-infected viremic but not aviremic individuals are markedly impaired and likely interfere with the development of an effective immune response. Among the defective interactions are abnormalities in the process of reciprocal NK-DC activation and maturation as well as a defect in the NK cell-mediated editing or elimination of immature DCs (iDCs). Notably, the lysis of mature DCs (mDCs) by autologous NK cells was highly impaired even after the complete masking of major histocompatibility complex I molecules, suggesting that the defective elimination of autologous iDCs is at the level of activating NK cell receptors. In this regard, the markedly impaired expression/secretion and function of NKp30 and TNF-related apoptosis-inducing ligand, particularly among the CD56(neg) NK cell subset, largely accounts for the highly defective NK cell-mediated lysis of autologous iDCs. Moreover, mDCs generated from HIV-1 viremic but not aviremic patients are substantially impaired in their ability to secrete interleukin (IL)-10 and -12 and to prime the proliferation of neighboring autologous NK cells, which, in turn, fail to secrete adequate amounts of interferon-gamma. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Univ Genoa, Dipartimento Med Sperimentale, I-16132 Genoa, Italy. Ist Sci San Raffaele, Ist Ricovero & Cura & Carattere Sci, I-00163 Rome, Italy. Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada. Ist Nazl Ric Canc, I-16132 Genoa, Italy. RP Mavilio, D (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dmavilio@niaid.nih.gov RI la Sala, Andrea/A-3228-2009; Pende, Daniela/J-7429-2016; OI la Sala, Andrea/0000-0003-1268-6516; Pende, Daniela/0000-0003-1565-451X; Mavilio, Domenico/0000-0001-6147-0952 FU Intramural NIH HHS NR 52 TC 122 Z9 122 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2006 VL 203 IS 10 BP 2339 EP 2350 DI 10.1084/jem.20060894 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 090KY UT WOS:000240951400021 PM 17000867 ER PT J AU Huynh, C Sacks, DL Andrews, NW AF Huynh, Chau Sacks, David L. Andrews, Norma W. TI A Leishmania amazonensis ZIP family iron transporter is essential for parasite replication within macrophage phagolysosomes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID METAL TRANSPORTER; METACYCLIC PROMASTIGOTES; PARASITOPHOROUS VACUOLES; ENDOPLASMIC-RETICULUM; INFECTED MACROPHAGES; MURINE MACROPHAGES; NATURAL-RESISTANCE; VIRULENCE FACTORS; PROTEIN; TRANSFERRIN AB Infection of mammalian hosts with Leishmania amazonensis depends on the remarkable ability of these parasites to replicate within macrophage phagolysosomes. A critical adaptation for survival in this harsh environment is an efficient mechanism for gaining access to iron. In this study, we identify and characterize LIT1, a novel L. amazonensis membrane protein with extensive similarity to IRT1, a ZIP family ferrous iron transporter from Arabidopsis thaliana. The ability of LIT1 to promote iron transport was demonstrated after expression in yeast and in L. amazonensis LIT1-null amastigotes. Endogenous LIT1 was only detectable in amastigotes replicating intracellularly, and its intracellular expression was accelerated under conditions predicted to result in iron deprivation. Although L. amazonensis lacking LIT1 grew normally in axenic culture and had no defects differentiating into infective forms, replication within macrophages was abolished. Consistent with an essential role for LIT1 in intracellular growth as amastigotes, Delta lit1 parasites were avirulent. After inoculation into highly susceptible mice, no lesions were detected, even after extensive periods of time. Despite the absence of pathology, viable Delta lit1 parasites were recovered from the original sites of inoculation, indicating that L. amazonensis can persist in vivo independently of the ability to grow in macrophages. Our findings highlight the essential role played by intracellular iron acquisition in Leishmania virulence and identify this pathway as a promising target for therapeutic intervention. C1 Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Andrews, NW (reprint author), Yale Univ, Sch Med, Sect Microbial Pathogenesis, 333 Cedar St, New Haven, CT 06510 USA. EM norma.andrews@yale.edu FU NIAID NIH HHS [R37AI34867, R37 AI034867, R01 AI067979] NR 56 TC 75 Z9 78 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2006 VL 203 IS 10 BP 2363 EP 2375 DI 10.1084/jem.20060559 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 090KY UT WOS:000240951400023 PM 17000865 ER PT J AU Nakahira, K Kim, HP Geng, XH Nakao, A Wang, X Murase, N Drain, PF Wang, X Sasidhar, M Nabel, EG Takahashi, T Lukacs, NW Ryter, SW Morita, K Choi, AMK AF Nakahira, Kiichi Kim, Hong Pyo Geng, Xue Hui Nakao, Atsunori Wang, Xue Murase, Noriko Drain, Peter F. Wang, Xiaomei Sasidhar, Madhu Nabel, Elizabeth G. Takahashi, Toru Lukacs, Nicholas W. Ryter, Stefan W. Morita, Kiyoshi Choi, Augustine M. K. TI Carbon monoxide differentially inhibits TLR signaling pathways by regulating ROS-induced trafficking of TLRs to lipid rafts SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; INNATE IMMUNE RECOGNITION; HEME OXYGENASE-1; OXIDATIVE STRESS; SUBCELLULAR-LOCALIZATION; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; HUMAN NEUTROPHIL; OXIDASE ACTIVITY AB Carbon monoxide (CO), a byproduct of heme catabolism by heme oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent signaling, in macrophages. Ligand-mediated receptor trafficking to lipid rafts represents an early event in signal initiation of immune cells. Trafficking of TLR4 to lipid rafts in response to LPS was reactive oxygen species (ROS) dependent because it was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase, and in gp91(phox)-deficient macrophages. CO selectively inhibited ligand-induced recruitment of TLR4 to lipid rafts, which was also associated with the inhibition of ligand-induced ROS production in macrophages. TLR3 did not translocate to lipid rafts by polyinosine-polycytidylic acid (poly(I:C)). CO had no effect on poly(I:C)-induced ROS production and TLR3 signaling. The inhibitory effect of CO on TLR-induced cytokine production was abolished in gp91phox-deficient macrophages, also indicating a role for NADPH oxidase. CO attenuated LPS-induced NADPH oxidase activity in vitro, potentially by binding to gp91(phox). Thus, CO negatively controlled TLR signaling pathways by inhibiting translocation of TLR to lipid rafts through suppression of NADPH oxidase-dependent ROS generation. C1 Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA. Yale Univ, Sch Med, Pulm & Crit Care Med Sect, New Haven, CT 06520 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Okayama Univ, Sch Med, Dept Anesthesiol & Resuscitol, Okayama 7008558, Japan. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. RP Choi, AMK (reprint author), Univ Pittsburgh, Sch Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA. EM choiam@upmc.edu FU NHLBI NIH HHS [P01 HL070807, P01HL070807, R01 HL055330, R01 HL060234, R01 HL079904, R01HL055330, R01HL060234, R01HL079904] NR 59 TC 216 Z9 226 U1 1 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2006 VL 203 IS 10 BP 2377 EP 2389 DI 10.1084/jem.20060845 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 090KY UT WOS:000240951400024 PM 17000866 ER PT J AU Meyer, CR Johnson, TD McLennan, G Aberle, DR Kazerooni, EA MacMahon, H Mullan, BF Yankelevitz, DF van Beek, EJR Armato, SG McNitt-Gray, MF Reeves, AP Gur, D Henschke, CI Hoffman, EA Bland, PH Laderach, G Pais, R Qing, D Piker, C Guo, JF Starkey, A Max, D Croft, BY Clarke, LP AF Meyer, Charles R. Johnson, Timothy D. McLennan, Geoffrey Aberle, Denise R. Kazerooni, Ella A. MacMahon, Heber Mullan, Brian F. Yankelevitz, David F. van Beek, Edwin J. R. Armato, Samuel G., III McNitt-Gray, Michael F. Reeves, Anthony P. Gur, David Henschke, Claudia I. Hoffman, Eric A. Bland, Peyton H. Laderach, Gary Pais, Richie Qing, David Piker, Chris Guo, Junfeng Starkey, Adam Max, Daniel Croft, Barbara Y. Clarke, Laurence P. TI Evaluation of lung MDCT nodule annotation across radiologists and methods SO ACADEMIC RADIOLOGY LA English DT Article DE LIDC drawing experiment; lung nodule annotation; edge mask; p-map; volume; linear mixed-effects model ID IMAGE DATABASE CONSORTIUM; COMPUTED-TOMOGRAPHY; CANCER; CT; RESOURCE; ONCOLOGY; SOCIETY; LESIONS AB Rationale and Objectives. Integral to the mission of the National Institutes of Health-sponsored Lung Imaging Database Consortium is the accurate definition of the spatial location of pulmonary nodules. Because the majority of small lung nodules are not resected, a reference standard from histopathology is generally unavailable. Thus assessing the source of variability in defining the spatial location of lung nodules by expert radiologists using different software tools as an alternative form of truth is necessary. Materials and Methods. The relative differences in performance of six radiologists each applying three annotation methods to the task of defining the spatial extent of 23 different lung nodules were evaluated. The variability of radiologists' spatial definitions for a nodule was measured using both volumes and probability maps (p-map). Results were analyzed using a linear mixed-effects model that included nested random effects. Results. Across the combination of all nodules, volume and p-map model parameters were found to be significant at P <.05 for all methods, all radiologists, and all second-order interactions except one. The radiologist and methods variables accounted for 15% and 3.5% of the total p-map variance, respectively, and 40.4% and 31.1% of the total volume variance, respectively. Conclusion. Radiologists represent the major source of variance as compared with drawing tools independent of drawing metric used. Although the random noise component is larger for the p-map analysis than for volume estimation, the p-map analysis appears to have more power to detect differences in radiologist-method combinations. The standard deviation of the volume measurement task appears to be proportional to nodule volume. C1 Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Iowa, Sch Med, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Radiol, Iowa City, IA 52242 USA. Univ Iowa, Coll Engn, Dept Biomed Engn, Iowa City, IA 52242 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Weill Coll Med, Dept Radiol, New York, NY USA. Cornell Univ, Sch EECS, Dept Biomed Engn, Ithaca, NY USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. RP Meyer, CR (reprint author), Univ Michigan, Sch Med, Dept Radiol, 109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM cmeyer@umich.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Aberle, Denise/0000-0002-8858-3401 FU NCI NIH HHS [U01 CA091103, 1U01 CA 091085, 1U01 CA 091090, 1U01 CA 091099, 1U01 CA 091100, 1U01 CA 091103, U01 CA091085, U01 CA091090, U01 CA091099, U01 CA091100] NR 23 TC 44 Z9 45 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2006 VL 13 IS 10 BP 1254 EP 1265 DI 10.1016/j.acra.2006.07.012 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 087SJ UT WOS:000240762300011 PM 16979075 ER PT J AU Donahue, JE Flaherty, SL Johanson, CE Duncan, JA Silverberg, GD Miller, MC Tavares, R Yang, WT Wu, Q Sabo, E Hovanesian, V Stopa, EG AF Donahue, John E. Flaherty, Stephanie L. Johanson, Conrad E. Duncan, John A., III Silverberg, Gerald D. Miller, Miles C. Tavares, Rosemarie Yang, Wentian Wu, Qian Sabo, Edmond Hovanesian, Virginia Stopa, Edward G. TI RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease SO ACTA NEUROPATHOLOGICA LA English DT Article DE Alzheimer's disease; blood-brain barrier; amyloid-beta-protein; receptor for advanced glycation end products; low-density lipoprotein receptor-related protein-1 ID BLOOD-BRAIN-BARRIER; RECEPTOR-RELATED PROTEIN; CEREBROSPINAL-FLUID; PRECURSOR PROTEIN; PEPTIDE; ACCUMULATION; TRANSPORT; NEURONS; LOCALIZATION; ASTROCYTES AB The receptor for advanced glycation end products (RAGE) is thought to be a primary transporter of beta-amyloid across the blood-brain barrier (BBB) into the brain from the systemic circulation, while the low-density lipoprotein receptor-related protein (LRP)-1 mediates transport of beta-amyloid out of the brain. To determine whether there are Alzheimer's disease (AD)-related changes in these BBB-associated beta-amyloid receptors, we studied RAGE, LRP-1, and beta-amyloid in human elderly control and AD hippocampi. In control hippocampi, there was robust RAGE immunoreactivity in neurons, whereas microvascular staining was barely detectable. LRP-1 staining, in contrast, was clearly evident within microvessels but only weakly stained neurons. In AD cases, neuronal RAGE immunoreactivity was significantly decreased. An unexpected finding was the strongly positive microvascular RAGE immunoreactivity. No evidence for colocalization of RAGE and beta-amyloid was seen within either microvessels or senile plaques. A reversed pattern was evident for LRP-1 in AD. There was very strong staining for LRP-1 in neurons, with minimal microvascular staining. Unlike RAGE, colocalization of LRP-1 and beta-amyloid was clearly present within senile plaques but not microvessels. Western blot analysis revealed a much higher concentration of RAGE protein in AD hippocampi as compared with controls. Concentration of LRP-1 was increased in AD hippocampi, likely secondary to its colocalization with senile plaques. These data confirm that AD is associated with changes in the relative distribution of RAGE and LRP-1 receptors in human hippocampus. They also suggest that the proportion of amyloid within the brains of AD patients that is derived from the systemic circulation may be significant. C1 Rhode Isl Hosp, Div Neuropathol, Dept Pathol, Providence, RI 02903 USA. Rhode Isl Hosp, Dept Clin Neurosci, Providence, RI 02903 USA. Brown Med Sch, Providence, RI USA. Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rhode Isl Hosp, Mol Pathol Core, COBRE, CCRD, Providence, RI 02903 USA. Rhode Isl Hosp, Core Image Anal Lab, Providence, RI 02903 USA. RP Donahue, JE (reprint author), Rhode Isl Hosp, Div Neuropathol, Dept Pathol, 593 Eddy St,APC 12115, Providence, RI 02903 USA. EM JDonahue3@Lifespan.org RI Donahue, John/A-3000-2008 OI Donahue, John/0000-0001-7186-2562 FU NIMH NIH HHS [R24MH068855] NR 32 TC 217 Z9 235 U1 3 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD OCT PY 2006 VL 112 IS 4 BP 405 EP 415 DI 10.1007/s00401-006-0115-3 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 089QC UT WOS:000240894600002 PM 16865397 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI A mysterious something: The discovery of insulin and the 1923 Nobel Prize for Frederick G. Banting (1891-1941) and John J. R. Macleod (1876-1935) SO ACTA PAEDIATRICA LA English DT Editorial Material C1 NICHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NICHD, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 3 TC 3 Z9 3 U1 0 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 2006 VL 95 IS 10 BP 1155 EP 1156 DI 10.1080/08035250600930328 PG 2 WC Pediatrics SC Pediatrics GA 084VH UT WOS:000240562000001 PM 16982482 ER PT J AU Hintz, SR Kendrick, DE Vohr, BR Poole, WK Higgins, RD AF Hintz, Susan R. Kendrick, Douglas E. Vohr, Betty R. Poole, W. Kenneth Higgins, Rosemary D. CA NICHD Neonatal Res Network TI Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants SO ACTA PAEDIATRICA LA English DT Article DE cerebral palsy; gender; neurodevelopmental outcome; premature ID NEONATAL RESEARCH NETWORK; WHITE-MATTER INJURY; DEVELOPMENTAL-DISABILITY; NATIONAL INSTITUTE; CHILD HEALTH; PREMATURE-INFANT; AGE; TERM; LESS; PREDICTORS AB Aim: To determine whether gender-specific responses to perinatal and neonatal events and exposures explain the male disadvantage in early childhood outcomes. Methods: Infants were in the National Institute of Child Health and Human Development ( NICHD) Neonatal Research Network, born 1/1/1997 - 12/31/2000, < 28 wk, with neurodevelopmental follow-up at 18 - 22 mo corrected age. We evaluated and compared univariate and multivariate associations of risk factors with neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment ( NDI) was one or more of the following: moderate - severe cerebral palsy ( CP), Bayley Mental ( MDI) or Psychomotor ( PDI) Development Indices < 70, deafness or blindness. Results : Boys ( n = 1216) were more likely than girls ( n = 1337) to have adverse outcomes ( moderate - severe CP: 10.7% vs 7.3%; MDI < 70: 41.9% vs 27.1%; NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys. Independent multivariate associations of risk factors with outcome differed by gender, but not consistently in favor of girls. In multivariate models including both girls and boys, male gender remained an independent risk factor for MDI < 70 ( 2.0, 95% CI 1.6 - 2.5) and NDI ( 1.8, 95% CI 1.5 - 2.2). Conclusion: Perinatal, neonatal and early childhood factors confer similar incremental risk or protection to boys and girls, but boys appear to have inherently greater baseline risk. Unmeasured biological variables likely contribute to the preterm male neurodevelopmental outcome disadvantage. C1 Stanford Univ, Sch Med, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. Women & Infants Hosp Rhode Isl, Providence, RI USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NICHHD, Bethesda, MD 20892 USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Div Neonatal & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. NR 30 TC 112 Z9 118 U1 2 U2 4 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 2006 VL 95 IS 10 BP 1239 EP 1248 DI 10.1080/08035250600599727 PG 10 WC Pediatrics SC Pediatrics GA 084VH UT WOS:000240562000016 PM 16982497 ER PT J AU Shi, J Liu, YL Fang, YX Xu, GZ Zhai, HF Lu, L AF Shi, Jie Liu, Yan-li Fang, Yu-xia Xu, Guo-zhu Zhai, Hai-fen Lu, Lin TI Traditional Chinese medicine in treatment of opiate addiction SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE Chinese medicine; acupuncture; opiate addiction; withdrawal; relapse; treatment ID CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; MORPHINE ADDICTION; DOPAMINE RELEASE; DRUG-ABUSE; ACUPUNCTURE; RATS; HEROIN; REINSTATEMENT AB Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture. Chinese medicine consists of natural products including plants, animals and minerals. TCM has been practiced in China for more than 2000 years, and for the past 200 years has been used in treatment of drug addiction. Ten Chinese medicines for the treatment of opiate addiction have been approved by the Chinese State Food and Drug Administration (SFDA), and at least 6 are in clinical trials. The general therapeutic principle of Chinese medicine developed was based on its unique theory of "reinforcing healthy Qi and resolving and removing effects of toxicity". Acupuncture, another essential part of TCM, which was developed based on the principle that "functions of the human body are controlled by the 'Jing-Luo' and 'Qi-Xue' system", has been used not only in China, but also in Europe, the USA and other countries, for controlling opiate addiction. There are some advantages in using TCM for opiate detoxification, including less harmful side effects, high safety and ideal effects in the inhibition of protracted withdrawal symptoms and relapse. Co-administration of TCM with modern medicine shows some synergistic effects in detoxification. Many TCM for detoxification also have efficacy in the rehabilitation of abnormal body functions induced by chronic drug use, including improving immune function, increasing working memory and preventing neurological disorder. Given that TCM is effective in the prevention of relapse and causes fewer side effects, it may be used widely in the treatment of opiate addiction. C1 Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. Soochow Univ, Coll Pharm, Suzhou 215123, Peoples R China. NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn FU Intramural NIH HHS NR 55 TC 35 Z9 42 U1 4 U2 18 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD OCT PY 2006 VL 27 IS 10 BP 1303 EP 1308 DI 10.1111/j.1745-7254.2006.00431.x PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 086PL UT WOS:000240685400003 PM 17007736 ER PT J AU Anderson, CAM Miller, ER AF Anderson, Cheryl A. M. Miller, Edgar R., III TI Dietary recommendations for obese patients with chronic kidney disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE diet; nutrition; CKD; obesity ID BLOOD-PRESSURE; RENAL-DISEASE; PROTEIN RESTRICTION; DIALYSIS PATIENTS; RISK-FACTORS; PROGRESSION; SURVIVAL; WEIGHT; TRIAL AB For optimal management of chronic kidney disease (CKD), dietary modification should be an integral part of patient care. Dietary considerations for obese patients with CKD are numerous and complicated and involve modification of intake of calories, protein, fat, phosphorus, and electrolytes. General principles for dietary management of obese patients include (1) ensuring adequate monitoring of nutritional status through assessment of diet, nutrition-related laboratory parameters, and anthropometrics; (2) creation of an individualized diet plan that meets clinical guidelines and has favorable effects on obesity-related conditions such as blood pressure and lipids; (3) careful attention to patients' food choices, portion size, and food-prepa ration methods; (4) recommending adjustment of overall energy intake to promote weight loss, yet maintain good nutritional status; and (5) modification of diet as the patient's nutritional status changes and CKD progresses. The basic objectives of dietary modification are to lighten the excretory load of products of metabolism and to help the kidney maintain normal equilibrium of the body's internal environment. Dietary modifications must be individualized and appropriate to the stage of CKD. This review describes dietary factors important in optimizing nutritional status of obese patients with CKD. Additionally, current clinical practice guidelines and strategies for meeting them are discussed. (c) 2006 by the National Kidney Foundation, Inc. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIA, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Anderson, CAM (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 2024 e Monument St, Baltimore, MD 21205 USA. EM chanders@jhsph.edu NR 24 TC 2 Z9 3 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2006 VL 13 IS 4 BP 394 EP 402 DI 10.1053/j.ackd.2006.07.001 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 096SH UT WOS:000241396600009 PM 17045225 ER PT J AU Bandinelli, S Lauretani, F Boscherini, V Gandi, F Pozzi, M Corsi, AM Bartali, B Lova, RM Guralnik, JM Ferrucci, L AF Bandinelli, Stefania Lauretani, Fulvio Boscherini, Vittorio Gandi, Francesca Pozzi, Martina Corsi, Anna Maria Bartali, Benedetta Lova, Raffaello Molino Guralnik, Jack M. Ferrucci, Luigi TI A randomized, controlled trial of disability prevention in frail older patients screened in primary care: the FRASI Study. Design and baseline evaluation SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE disability; frailty; FRASI; prevention ID FUNCTIONAL DECLINE; LOWER-EXTREMITY; HEALTH; ADULTS; RELIABILITY; MOBILITY; PROGRAM; WALK; HOME AB Background and aims: We describe the enrollment and intervention phases of FRASI (FRAilty, Screening and Intervention), a randomized controlled trial aimed at preventing ADL disability in frail older persons screened in primary care. Methods: Patients, 70-85 years old, non-disabled and non-cognitively impaired, were screened for frailty (score <= 9 on the Short Physical Performance Battery, SPPB) during primary care visits. Of 447 eligible persons, 410 came to the study clinic and 251 were randomized into treatment (n=126) and control groups (n=125). The active group received an intensive medical intervention, and sixteen 90-minute supervised exercise sessions over 8 weeks. The primary outcome was time to ADL disability onset or death in the 12-month period after study enrollment. Results: The two study arms were similar for demographics, cognitive function, physical function and health status. Compared with a population-based sample selected according to FRASI inclusion criteria except SPPB score, FRASI participants had significantly worse health and functional status. Restricting the comparison to persons with SPPB <= 9, all differences disappeared. The 99 participants (78.6% of 126) who completed the intervention participated in a mean of 15.3 +/- 1.6 exercise sessions. Conclusions: Screening in primary care for non-disabled, older persons with SPPB <= 9 yields individuals with substantial morbidity, impairments and functional limitations that can be successfully involved in an intensive medical and exercise intervention. (c) 2006, Editrice Kurtis. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. Don Gnocchi Fdn, Florence, Italy. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Cooperat Med Leonardo, Florence, Italy. INRCA, Geriatr Rehabil Unit, ASF, Tuscany Reg Hlth Agcy, Florence, Italy. INRCA, Lab Clin Epidemiol, Florence, Italy. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, ASTRA, Longitudinal Studies Sect,Clin Res Branch, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999] NR 28 TC 29 Z9 30 U1 5 U2 8 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD OCT PY 2006 VL 18 IS 5 BP 359 EP 366 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 125BX UT WOS:000243417600003 PM 17167299 ER PT J AU Yang, H Wu, Z Duan, S Li, Z Li, X Shen, M Mathur, A Stanton, B AF Yang, H. Wu, Z. Duan, S. Li, Z. Li, X. Shen, M. Mathur, A. Stanton, B. TI Living environment and schooling of children with HIV-infected parents in southwest China SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID SUB-SAHARAN AFRICA; AIDS EPIDEMIC; ORPHANS; ADJUSTMENT; COMMUNITY; EDUCATION; MOTHERS; UGANDA; DEATH AB A cross-sectional household survey was conducted in Longchuan County, China, to study the lives of children with HIV-infected parents. Registered HIV-infected drug users and their households were approached and information about the living environment of children <= 15 years of age was collected. Of the 266 households interviewed, there were 213 children <= 15 years old. Forty percent of the children had lost at least one parent. Most of the children resided in a household with low economic status and a high dependency ratio. One-half of the children experienced discordant family relations, family anxiety and shame. Compared to orphans, non-orphans and their families were less likely to receive social support from the community. Orphans and older children were less likely to attend school and more likely to be truant if enrolled in school. Findings in the current study suggest that many children whose parents are infected with HIV or have died from HIV are living in stressful environments with minimal support from the community. Efforts should be taken to provide support and supervision to these children. C1 Wayne State Univ, Sch Med, Prevent Res Ctr, Carman & Ann Adams Dept Pediat, Detroit, MI 48201 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Yang, H (reprint author), Wayne State Univ, Sch Med, Prevent Res Ctr, Carman & Ann Adams Dept Pediat, 4201 St Antoine St,Suite 6D, Detroit, MI 48201 USA. EM hoyan@med.wayne.edu OI Li, Xiaoming/0000-0002-5555-9034 NR 31 TC 18 Z9 18 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT PY 2006 VL 18 IS 7 BP 647 EP 655 DI 10.1080/09540120500282896 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 085RC UT WOS:000240620300002 PM 16971271 ER PT J AU Sawyer, RT Gergen, PJ Minnicozzi, M Plaut, M Dong, G Schwaninger, JM Fenton, MJ AF Sawyer, R. T. Gergen, P. J. Minnicozzi, M. Plaut, M. Dong, G. Schwaninger, J. M. Fenton, M. J. TI The future of immunotherapy. Report of a National Institute of Allergy and Infectious Diseases (NIAID), Division of Allergy, Immunology and Transplantation (DAIT) Workshop SO ALLERGY LA English DT Review DE allergens; clinical trials; immunotherapy; subcutaneous immunotherapy; sublingual immunotherapy ID CHILDREN; ASTHMA AB Recent advances in the molecular sciences make possible new and innovative immunotherapeutic approaches to the treatment of human asthma and allergic disorders. In 2005, the National Institute of Allergy and Infectious Diseases, Division of Allergy, Immunology and Transplantation, sponsored a workshop entitled Immunological Basis of Antigen-specific Asthma/Allergies Therapeutic Strategies Meeting. International experts in the field of asthma and allergy immunotherapy discussed the current state of immunotherapy, and made recommendations for future areas of research aimed at advancing our knowledge and understanding of immunotherapy for asthma and allergic diseases. The workshop recommendations are presented herein. C1 NIAID, DAIT, Asthma Allergy & Inflammat Branch, NIH,DHHS, Bethesda, MD 20892 USA. NIAID, NIH, DHHS, Bethesda, MD 20892 USA. RP Sawyer, RT (reprint author), NIAID, DAIT, Asthma Allergy & Inflammat Branch, NIH,DHHS, 6610 Rockledge Dr, Bethesda, MD 20892 USA. NR 3 TC 5 Z9 5 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-4538 J9 ALLERGY JI Allergy PD OCT PY 2006 VL 61 IS 10 BP 1159 EP 1161 DI 10.1111/j.1398-9995.2006.01239.x PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 079WK UT WOS:000240208400002 PM 16942562 ER PT J AU Freeman, AF Shulman, ST AF Freeman, Alexandra F. Shulman, Stanford T. TI Kawasaki disease: Summary of the American Heart Association guidelines SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID RHEUMATIC-FEVER; DIAGNOSIS AB Kawasaki disease is an acute vasculitis of childhood that predominantly affects the coronary arteries. The etiology of Kawasaki disease remains unknown, although an infectious agent is strongly suspected based on clinical and epidemiologic features. A genetic predisposition is also likely, based on varying incidences among ethnic groups, with higher rates in Asians. Symptoms include fever, conjunctival injection, erythema of the lips and oral mucosa, rash, and cervical lymphadenopathy. Some children with Kawasaki disease develop coronary artery aneurysms or ectasia, ischemic heart disease, and sudden death. Kawasaki disease is the leading cause of acquired heart disease among children in developed countries. This article provides a summary of the diagnostic and treatment guidelines published by the American Heart Association. C1 Childrens Mem Hosp, Div Pediat Infect Dis, Chicago, IL 60614 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Div Pediat Infect Dis, Chicago, IL 60611 USA. NIH, Bethesda, MD USA. RP Shulman, ST (reprint author), Childrens Mem Hosp, Div Pediat Infect Dis, 2300 Childrens Plaza, Chicago, IL 60614 USA. EM sshulman@northwestern.edu NR 15 TC 34 Z9 40 U1 1 U2 1 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT 1 PY 2006 VL 74 IS 7 BP 1141 EP 1148 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 090TS UT WOS:000240975400012 PM 17039750 ER PT J AU Fox, ER Han, H Taylor, HA Walls, UC Samdarshi, T Skelton, TN Pan, J Arnett, D AF Fox, Ervin R. Han, Hui Taylor, Herman A. Walls, Ulysses C. Samdarshi, Tandaw Skelton, Thomas N. Pan, Jun Arnett, Donna TI The prognostic value of the mitral diastolic filling velocity ratio for all-cause mortality and cardiovascular morbidity in African Americans: the atherosclerotic Risks in Communities (ARIC) study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CONGESTIVE-HEART-FAILURE; ELDERLY COHORT; MYOCARDIAL-INFARCTION; STROKE; ECHOCARDIOGRAPHY; DISEASE; HEALTH; MASS; HYPERTENSION AB Background Although recent data suggest that the mitral diastolic early-to-late (E/A) ratio may be prognostic in selected population-based cohorts, its predictive value for morbidity and mortality in African Americans has not yet been well studied. Methods The study population consisted of African American participants from the Jackson cohort of the Atherosclerotic Risks in Community Study. Three subgroups of E/A ratios were defined: E/A < 07, E/A 0.7-1.5, and E/A > 1.5, using the middle group as reference. Cox proportional hazard models were used to assess the association between the E/A ratio and both all-cause mortality and incident cardiovascular disease (CVD). The mean follow-up period was 6.8 +/- 1.3 years. Results Of the 2211 participants in the study population (mean age 62 years, 65.1% women), 8.2% had an E/A ratio < 07, 84.7% had an E/A 0.7-1.5, and 7.1% had an E/A > 1.5. An E/A > 1.5 was independently associated with all-cause mortality (hazard ratio [HR] 2.18, 95% confidence interval [CI] 1.20-4.03) in the multivariable model. An E/A < 07 was associated with higher all-cause mortality (HR 1.79, 95% Cl 1.17-2.73) and incident CVD (HR 1.91, 95% CI 1.29-2.83) compared with a normal E/A in the age and sex adjusted model but was not independently predictive in the multivariable model (P > .05). Conclusions In a population-based cohort of middle-aged African Americans, an E/A > 1.5 independently predicts all-cause mortality. An E/A > 1.5 and an E/A < 0.7 were both associated with incident CVD when adjusted for age and sex alone but were not independently predictive in the multivariable analysis. C1 NHLBI, Atherosclerotic Risk Communities Study, Jackson, MS USA. NHLBI, Jackson Heart Study, Jackson, MS USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Univ Alabama, Birmingham, AL USA. RP Fox, ER (reprint author), Heart Stn, 2500 N State St, Jackson, MS 39216 USA. EM efox@medicine.umsmed.edu FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55022, N01-HC-55018, N01-HC-55016, N01-HC-55020, N01-HC-55019, N01-HC-55021]; NINDS NIH HHS [5R01-NS 17950] NR 27 TC 10 Z9 10 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2006 VL 152 IS 4 BP 749 EP 755 DI 10.1016/j.ahj.2006.04.014 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101DO UT WOS:000241719300031 PM 16996852 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Yau, YY Nguyen, TT Botello, G Sachdev, V Sidenko, S Ernst, I Waclawiw, MA Leitman, SF Rosing, DR AF Shizukuda, Yukitaka Bolan, Charles D. Tripodi, Dorothy J. Yau, Yu-Ying Nguyen, Tammy T. Botello, Gilberto Sachdev, Vandana Sidenko, Stanislav Ernst, Inez Waclawiw, Myron A. Leitman, Susan F. Rosing, Douglas. R. TI Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VENTRICULAR DIASTOLIC DYSFUNCTION; SYSTOLIC FUNCTION; PROGNOSTIC VALUE; HEART-FAILURE; ECHOCARDIOGRAPHY; CARDIOMYOPATHY; PATTERNS; INDEXES; FLOW AB Patients with hereditary hemochromatosis (HH) have been reported to develop diastolic functional abnormalities detectable by echocardiography, but it is unknown whether these occur in asymptomatic subjects. Thus, this study tested whether echocardiographic left ventricular (LV) relaxation abnormalities are detectable in subjects with a,symptomatic HH. Forty-three asymptomatic subjects with HH (C282Y homozygosity in the HFE gene) and, 21 age- and gender-matched control subjects without known HFE mutations underwent echocardiography with comprehensive diastolic functional evaluations. Subjects with HH were in New York Heart Association functional class I and consisted of 22 newly diagnosed patients (group A) and 21 chronically phlebotomized subjects with stable iron levels (group B). Group A subjects showed significant iron overload compared with group B subjects and controls (group C) (ferritin 1,164 +/- 886 [p < 0.05 vs: groups B and C], 128 +/- 262, and 98 +/- 76 mu g/L and transferrin saturation 79 +/- 19% [p < 0.05 vs groups B and C], 42 +/- 21%, and 26 +/- 10% for groups A, B, and C, respectively). Echocardiographic evaluation revealed (1) no statistically significant abnormalities of Doppler LV relaxation in HH groups; (2) significant augmentation of atrial contractile function in subjects with HH compared with controls, which was not correlated with iron levels and treatment status; and (3) the preservation of overall LV systolic function in HH groups. In conclusion, the results of this study suggest that the augmentation of atrial contraction appears to be an early detectable echocardiographic cardiac manifestation of abnormal diastolic function in asymptomatic subjects with HH, which may reflect undetectable subclinical LV relaxation abnormalities. (c) 2006 Elsevier Inc. All rights reserved. C1 NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiovasc Branch, Bldg 10, Bethesda, MD 20892 USA. EM shizukuy@nhlbi.nih.gov FU Intramural NIH HHS NR 25 TC 23 Z9 23 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2006 VL 98 IS 7 BP 954 EP 959 DI 10.1016/j.amjcard.2006.04.040 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 092WU UT WOS:000241128900021 PM 16996882 ER PT J AU Le, DSNT Pannacciulli, N Chen, KW Del Parigi, A Salbe, AD Reiman, EM Krakoff, J AF Le, Duc Son N. T. Pannacciulli, Nicola Chen, Kewei Del Parigi, Angelo Salbe, Arline D. Reiman, Eric M. Krakoff, Jonathan TI Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dorsolateral prefrontal cortex; neuronal activity; feature of obesity; response to food intake; satiety; positron emission tomography; PET ID POSITRON-EMISSION-TOMOGRAPHY; GASTRIC DISTENSION; ORBITOFRONTAL CORTEX; BAYESIAN-INFERENCE; BRAIN RESPONSES; SATIATION; HUMANS; HUNGER; WOMEN; CAPACITY AB Background: In an exploratory positron emission tomography study of postprandial regional cerebral blood flow, which is a marker of neuronal activity. obese men differed from lean men in several brain regions, including the prefrontal cortex. The subjects received a meal proportional to their body size; therefore, the meal volume was different for each person. Objective: We investigated whether differences in the brain responses of obese and lean men to a meal represent satiety or feelings of gastric distension. Design: We studied 9 lean ((x) over bar +/- SD body fat: 15 +/- 5%; age: 33 +/- 10 y) and 9 obese (body fat: 31 +/- 4%; age: 32 +/- 10 y) men given a fixed amount (400 mL) of a liquid meal. We compared their results with those in 11 lean (body fat: 16 +/- 5%; age: 35 +/- 8 y) and 11 obese (body fat: 33 +/- 5%; age: 28 +/- 5 y) previously studied men given a meal proportional to their body size. We performed analyses by using a two-level, random-effects approach in the STATISTICAL PARAMETRIC MAPPING software package and a significance level of P <= 0.001, uncorrected for multiple comparisons. Results: Compared with lean men, obese men had consistently less postprandial activation in the left dorsolateral prefrontal cortex, irrespective of meal size. Conclusion: Because the dorsolateral prefrontal cortex has been implicated in the inhibition of inappropriate behavior, satiety, and meal termination, differential responses of neuronal activity to food intake in this area may contribute to a propensity for obesity or to the difficulty in losing weight experienced by obese men. C1 NIDDK, ODCRS, PECRB, NIH,DHIS, Phoenix, AZ 85016 USA. Banner Good Samaritan Med Ctr, Banner Alzheimer Inst, Banner Posit Emiss Tomog Ctr, Phoenix, AZ USA. RP Le, DSNT (reprint author), NIDDK, ODCRS, PECRB, NIH,DHIS, 4212 N 16th St,Room 5-35, Phoenix, AZ 85016 USA. EM leds@mail.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU Intramural NIH HHS NR 37 TC 75 Z9 77 U1 0 U2 4 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 OCT PY 2006 VL 84 IS 4 BP 725 EP 731 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700008 PM 17023697 ER PT J AU Mirch, MC McDuffie, JR Yanovski, SZ Schollnberger, M Tanofsky-Kraff, M Theim, KR Krakoff, J Yanovski, JA AF Mirch, Margaret C. McDuffie, Jennifer R. Yanovski, Susan Z. Schollnberger, Merel Tanofsky-Kraff, Marian Theim, Kelly R. Krakoff, Jonathan Yanovski, Jack A. TI Effects of binge eating on satiation, satiety, and energy intake of overweight children SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE child; obesity; binge eating; energy intake; satiety; satiation; eating behavior ID DISORDERED BEHAVIORS; WEIGHT PATTERNS; FAST-FOOD; ADOLESCENT GIRLS; OBESE CHILDREN; PORTION SIZE; BODY-FAT; QUESTIONNAIRE; PREVALENCE; WOMEN AB Background: Children who report episodes of binge eating gain more weight than do children not reporting binge eating. However, how binge eating affects children's food intake at meals is unknown. Objective: We compared the energy intake and postmeal satiety of children with and without a history of binge eating during buffet meals. Design: Sixty overweight children aged 6-12 y were categorized into those reporting past binge-eating episodes (n = 10) and those reporting no such episodes (n = 50). Children selected lunch twice from a multiple-item, 9835 kcal, buffet meal: after an overnight fast and after a standardized breakfast. Children ate ad libitum, until they reported they were full. The main outcome measures were energy intake during meals and duration of postmeal satiety, after adjustment for covariates, including age, race, sex, socioeconomic status, and body composition. Results: After the overnight fast, children in the binge-eating group consumed more energy [(x) over bar (+/- SD): 1748 +/- 581 compared with 1309 +/- 595 kcal; P = 0.04] and exhibited a shorter satiety duration (194 +/- 84 compared with 262 +/- 89 min; P = 0.03) than did children in the non-binge-eating group. After the standardized breakfast, binge-eating children reported a shorter satiety duration (75 +/- 62 compared with 132 +/- 62 min; P = 0.01) and consumed more energy at the postbreakfast meal (1874 +/- 560 compared with 1275 +/- 566 kcal; P = 0.004). Conclusion: The ability to consume large quantities of palatable foods, coupled with decreased subsequent satiety, may play a role in the greater weight gain found in binge-eating children. C1 NICHD, Unit Growth & Obes, DEB, NICHD,NIH,CRC, Bethesda, MD 20892 USA. NIDDK, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NIDDK, Dept Nutr, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, DEB, NICHD,NIH,CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z99 HD999999, Z01 HD000641-12]; NICHD NIH HHS [Z01 HD000641] NR 50 TC 38 Z9 38 U1 1 U2 8 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 OCT PY 2006 VL 84 IS 4 BP 732 EP 738 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700009 PM 17023698 ER PT J AU Bleys, J Miller, ER Pastor-Barriuso, R Appel, LJ Guallar, E AF Bleys, Joachim Miller, Edgar R. Pastor-Barriuso, Roberto Appel, Lawrence J. Guallar, Eliseo TI Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE meta-analysis; antioxidants; folate; B vitamins; atherosclerosis; prevention ID TRANSLUMINAL CORONARY ANGIOPLASTY; HOMOCYSTEINE-LOWERING TREATMENT; ACID PLUS VITAMIN-B-6; RAT CAROTID ARTERIES; FOLIC-ACID; CARDIOVASCULAR-DISEASE; ANTIOXIDANT VITAMINS; BALLOON INJURY; BETA-CAROTENE; HEART-DISEASE AB Background: Laboratory and observational studies suggest that antioxidant and B vitamin supplementation may prevent atherosclerosis. Although trials have not shown a benefit of these supplements on clinical cardiovascular events, it is unknown whether they affect the progression of atherosclerosis as measured by imaging techniques. Objective: The objective was to perform a meta-analysis of randomized controlled trials of the effect of vitamin-mineral supplementation on atherosclerosis progression. Design: We searched the MEDLINE, EMBASE, and CENTRAL databases for relevant studies. No language restrictions were applied. We separately analyzed trials using antioxidants (vitamins E and C, beta-carotene, or selenium) and trials using B vitamins (folate, vitamin B-6, or vitamin B-12). The progression of atherosclerosis was evaluated by B-mode ultrasound, intravascular ultrasound, or angiography. Effect sizes were calculated for the difference in slope of atherosclerosis progression between participants assigned to supplements and those assigned to the control group. Results: In trials not involving percutaneous transluminal coronary angioplasty, the pooled effect size was -0.06 (95% Cl: -0.20,0.09; 7 trials) for antioxidants; and -0.93 (95% Cl: -2.11, 0.26; 4 trials) for B vitamins. In trials involving percutaneous transluminal coronary angioplasty, the pooled relative risk of restenosis was 0.82 (95% Cl: 0.54,1.26; 3 trials) for antioxidants and 0.84 (95% Cl: 0.34, 2.07; 2 trials) for B vitamins. Conclusion: Our meta-analysis showed no evidence of a protective effect of antioxidant or B vitamin supplements on the progression of atherosclerosis, thus providing a mechanistic explanation for their lack of effect on clinical cardiovascular events. C1 Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. NIA, NIH, Baltimore, MD 21224 USA. Inst Salud Carlos III, Div Biostat, Natl Ctr Epidemiol, Madrid, Spain. RP Guallar, E (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Room 2-639, Baltimore, MD 21205 USA. EM eguallar@jhsph.edu RI Guallar, Eliseo/D-3807-2014 OI Guallar, Eliseo/0000-0002-4471-9565 NR 52 TC 99 Z9 108 U1 0 U2 4 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 OCT PY 2006 VL 84 IS 4 BP 880 EP 887 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700027 PM 17023716 ER PT J AU Xu, JQ Eilat-Adar, S Loria, C Goldbourt, U Howard, BV Fabsitz, RR Zephier, EM Matti, C Lee, ET AF Xu, Jiaqiong Eilat-Adar, Sigal Loria, Catherine Goldbourt, Uri Howard, Barbara V. Fabsitz, Richard R. Zephier, Ellie M. Matti, Claudia Lee, Elisa T. TI Dietary fat intake and risk of coronary heart disease: the Strong Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary fat intake; fatty acids; cholesterol; coronary heart disease; mortality; American Indians ID MIDDLE-AGED MEN; CARDIOVASCULAR-DISEASE; AMERICAN-INDIANS; FOLLOW-UP; NUTRIENT DATABASE; SERUM-CHOLESTEROL; UNITED-STATES; TRANS FATTY; MORTALITY; PREVALENCE AB Background: The results of previous studies on the association between dietary fat intake and coronary heart disease (CHD) incidence are inconsistent. Objective: The aim of this study was to examine the association between dietary fat intake and CHD incidence in American Indians in the Strong Heart Study. Design: A total of 2938 participants aged 47-79 y and free of CHD at the second examination (1993-1995) were examined and followed for CHD, nonfatal CHD, and fatal CHD events to 31 December 2002. Dietary intake was assessed by using a 24-h diet recall and was calculated as percentages of energy. Results: Participants were followed for a mean (+/- SD) of 7.2 +/- 2.3 y. During follow-up, 436 incident CHD cases (298 nonfatal CHD and 138 fatal CHD events) were ascertained. Participants aged 47-59 y in the highest quartile of intake of total fat, saturated fatty acids, or monounsaturated fatty acids had higher CHD mortality than did those in the lowest quartile [hazard ratio (95% Cl): 3.57 (1.21, 10.49), 5.17 (1.64, 16.36), and 3.43 (1.17, 10.04), respectively] after confounders were controlled for. These associations were not observed for those aged 60-79 y. Conclusions: Total fat, saturated fatty acid, and monounsaturated fatty acid intake were strong predictors of CHD mortality in American Indians aged 47-59 y, independent of other established CHD risk factors. It may be prudent for American Indians to reduce their fat intake early in life to reduce the risk of dying from CHD. C1 Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Coll Publ Hlth, Oklahoma City, OK 73190 USA. Medstar Res Inst, Hyattsville, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Indian Hlth Serv, Aberdeen Area Off, Aberdeen, SD USA. Tel Aviv Univ, Dept Epidemiol & Prevent Med, Sackler Fac Med, IL-69978 Tel Aviv, Israel. RP Xu, JQ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Coll Publ Hlth, 801 NE 13th St,Room 112, Oklahoma City, OK 73190 USA. EM susan-xu@ouhsc.edu FU NHLBI NIH HHS [U01-HL-41654, U01HL-41642, U01HL-41652] NR 41 TC 57 Z9 62 U1 1 U2 4 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 OCT PY 2006 VL 84 IS 4 BP 894 EP 902 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700029 PM 17023718 ER PT J AU Zhang, LA Gail, MH Wang, YQ Brown, LM Pan, KF Ma, JL Amagase, H You, WC Moslehi, R AF Zhang, Lian Gail, Mitchell H. Wang, Yu-que Brown, Linda Morris Pan, Kai-Feng Ma, Jun-Ling Amagase, Harunobu You, Wei-Cheng Moslehi, Roxana TI A randomized factorial study of the effects of long-term garlic and micronutrient supplementation and of 2-wk antibiotic treatment for Helicobacter pylori infection on serum cholesterol and lipoproteins SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE cholesterol; blood lipids; garlic supplementation; vitamin supplementation; cardiovascular disease; Helicobacter pylori antibiotic therapy; China ID PRECANCEROUS GASTRIC-LESIONS; VITAMIN-E; CONTROLLED-TRIAL; DOUBLE-BLIND; CARDIOVASCULAR-DISEASE; HDL-CHOLESTEROL; POWDER TABLETS; CANCER; LIPIDS; METAANALYSIS AB Background: Little is known about the long-term effects of garlic or micronutrient supplementation on total, HDL, and LDL cholesterol in disease-free persons. Objective: We aimed to assess the effects of long-term supplementation with garlic and micronutrients and of short-term amoxicillin and omeprazole treatment on serum total, HDL, and LDL cholesterol in a rural Chinese population. Design: We conducted a randomized, double-blind, placebo-controlled, 2 X 2 X 2 and 2 X 2 factorial study of precancerous gastric lesions in 3411 subjects in Linqu County, Shandong Province, China. Thirty-four subjects were randomly selected from each of 12 treatment strata. Sera were analyzed at 3.3 and 7.3 y to measure effects on total, HDL, and LDL cholesterol after 2-wk twice-daily treatment with I g amoxicillin and 20 mg omeprazole and supplementation throughout the study with 1) 2 capsules twice daily, each containing 200 mg aged garlic extract and I mg steam-distilled garlic oil, or 2) twice-daily micronutrient capsules containing 250 mg vitamin C, 100 IU vitamin E, and 37.5 mg selenium. Results: Regressions adjusted for covariates indicated increases of 0.22 mmol total cholesterol/L (P = 0.01) and 0.19 mmol LDL/L (P = 0.02) after 7.3 y of micronutrient supplementation, but no effect of garlic supplementation or short-term amoxicillin and omeprazole treatment. Conclusions: In this rural Chinese population with low meat intake and moderate cholesterol concentrations, long-term garlic supplementation had no effect on lipid profiles, whereas micronutrient supplementation was associated with small but significant increases in total and LDL-cholesterol concentrations at 7.3 y. C1 NCI, NIH, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. Beijing Inst Canc Res, Beijing, Peoples R China. Wakunaga Amer Co Ltd, Mission Viejo, CA USA. RP Moslehi, R (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Biostat Branch, 6120 Execut Blvd,EPS 8047, Rockville, MD 20852 USA. EM moslehir@mail.nih.gov NR 27 TC 21 Z9 21 U1 0 U2 4 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 OCT PY 2006 VL 84 IS 4 BP 912 EP 919 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700031 PM 17023720 ER PT J AU Weinstein, SJ Stolzenberg-Solomon, R Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Weinstein, Stephanie J. Stolzenberg-Solomon, Rachael Pietinen, Pirjo Taylor, Philip R. Virtamo, Jarmo Albanes, Demetrius TI Dietary factors of one-carbon metabolism and prostate cancer risk SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE prostatic neoplasms; folic acid; vitamin B-6; vitamin B-12; methionine; alcohol ID NUTRITION EXAMINATION SURVEY; COLORECTAL-CANCER; FOLATE METABOLISM; CIGARETTE-SMOKING; DNA METHYLATION; NATIONAL-HEALTH; BREAST-CANCER; PLASMA FOLATE; MALE SMOKERS; COHORT AB Background: Folate is hypothesized to be inversely associated with the risk of several cancers, but such a potential association has not been well studied for prostate cancer. Vitamin B-6, vitamin B-12, methionine. and alcohol can influence folate-related metabolism. Objective: The objective was to investigate the associations between dietary factors of one-carbon metabolism and prostate cancer risk within the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. Design: Of the cohort's 27 111 Finnish male smokers aged 50-69 y who had complete dietary data, 1270 had a diagnosis of incident prostate cancer between 1985 and 2002. Folate, vitamin B-6, vitamin B-12, methionine, and alcohol intakes were estimated from a 276-item modified dietary history questionnaire. Cox proportional hazard models, adjusted for age and vitamin supplement use, estimated relative risks (RR) and 95% CIs. Results: Vitamin B-6 intake was inversely associated with prostate cancer risk (RR for highest versus lowest quintile: 0.88; 95% Cl: 0.72. 1.07; P for trend = 0.045), whereas vitamin B-12 intake was associated with significantly increased risk (RR = 1.36; 95% Cl: 1.14. 1.96: P for trend = 0.01). No association between folate or alcohol intake and prostate cancer risk was observed. No differences were found in the above associations according to stage of disease or subgroups of several potential effect modifiers. Conclusions: We found no convincing evidence for a protective role of one-carbon metabolism against prostate cancer, although these observations can be generalized only to smokers. The possible modest protective association with vitamin B-6 and the significantly elevated risk with vitamin B-12 intake warrant further investigation. C1 NCI, Nutrit Epidemiol Branch, DCEG, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Weinstein, SJ (reprint author), NCI, Nutrit Epidemiol Branch, DCEG, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 320, Bethesda, MD 20892 USA. EM weinstes@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU Intramural NIH HHS NR 57 TC 36 Z9 37 U1 1 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2006 VL 84 IS 4 BP 929 EP 935 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700033 PM 17023722 ER PT J AU Swinburn, BA AF Swinburn, Boyd A. TI Energy intake or energy expenditure? Reply to a Bosy-Westphal and MJ Muller SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID WEIGHT; ADULTS C1 Deakin Univ, Sch Exercise & Nutr Sci, Burwood, Vic 3125, Australia. Monash Univ, Monash Inst Hlth Serv Res, Melbourne, Vic 3004, Australia. Univ Ballarat, Sch Human Movement & Sports Sci, Ballarat, Australia. NIDDKD, NIH, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Swinburn, BA (reprint author), Deakin Univ, Sch Exercise & Nutr Sci, 221 Burwood Highway, Burwood, Vic 3125, Australia. EM boyd.swinburn@deakin.edu.au NR 4 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2006 VL 84 IS 4 BP 945 EP 946 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 093AX UT WOS:000241140700038 ER PT J AU Kurlander, JE Simon-Dack, SL Gorelick, DA AF Kurlander, Jacob E. Simon-Dack, Stephanie L. Gorelick, David A. TI Spending of remuneration by subjects in non-treatment drug abuse research studies SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE drug abuse; in-kind; motivation; payment; research; subjects ID PAYING RESEARCH SUBJECTS; PARTICIPATION; INCENTIVES; PAYMENT AB Background: This study examines remuneration spending by drug-using participants in residential drug abuse research. Methods: Ninety-four adult males who participated in residential, non-treatment drug abuse research studies earned remuneration based on length of stay and specific research procedures. Remuneration could be in cash after discharge or for in-kind purchases and bill payments. Spending of remuneration was extracted from charts and evaluated with multivariate analyses. Results: Participants received average remuneration of $1,454, taking 59% in cash. Other categories included cigarettes (60.6% of subjects), toiletries (60.6%), clothing (54.3%), and housing (52.1%). Primary drug of abuse, total remuneration, monthly income, length of stay on the residential research unit, age, and education were significantly associated with in-kind remuneration choices. Less total remuneration, intoxication in the month prior to study, higher IQ, and non-white race were associated with taking more in cash. Conclusion: Residential drug abuse research participants prefer cash to in-kind research remuneration, and their choices reflected drug use and economic status. C1 NIDA, Intramural Res Program, US Dept HHS, NIH, Baltimore, MD 21224 USA. Columbia Univ, New York, NY 10027 USA. Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, US Dept HHS, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS NR 16 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD OCT-DEC PY 2006 VL 32 IS 4 BP 527 EP 540 DI 10.1080/00952990600919427 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 108CA UT WOS:000242216700005 PM 17127540 ER PT J AU Malcolm, R Swayngim, K Donovan, JL DeVane, CL Elkashef, A Chiang, N Khan, R Mojsiak, J Myrick, DL Hedden, S Cochran, K Woolson, RF AF Malcolm, Robert Swayngim, Karla Donovan, Jennifer L. DeVane, C. Lindsay Elkashef, Ahmed Chiang, Nora Khan, Roberta Mojsiak, Jurij Myrick, Donald L. Hedden, Sarra Cochran, Kristi Woolson, Robert F. TI Modafinil and cocaine interactions SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE cocaine; interactions; modafinil; treatment ID SINGLE-DOSE PHARMACOKINETICS; HEALTHY MALE-VOLUNTEERS; INDUCED WAKEFULNESS; DOUBLE-BLIND; METHYLPHENIDATE; RAT; DEXTROAMPHETAMINE; AMPHETAMINE; COMBINATION; DEPENDENCE AB this Phase I trial evaluated the interaction between modafinil steady-state and cocaine. Twelve non-treatment seeking, cocaine dependent volunteers received four sets of randomized blinded infusions of saline, 20mg IV cocaine, and 40mg IV cocaine. Modafinil was given open label at 0mg, 400mg, or 800mg. Modafinil combined with IV cocaine did not result in any significant hemodynamic interactions. Modafinil significantly dampened scores on Visual Analog Scale measures as compared to baseline cocaine conditions. No significant alterations in labs occurred. Further outpatient trials of modafinil appear to be warranted. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug Program, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Alcohol Program, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Lab Drug Disposit & Pharmacogenet, Charleston, SC 29425 USA. NIDA, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Malcolm, R (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug Program, 67 President St,Rm 459 N, Charleston, SC 29425 USA. EM malcolmr@musc.edu FU NIDA NIH HHS [N01-DA-9-8102] NR 16 TC 56 Z9 56 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD OCT-DEC PY 2006 VL 32 IS 4 BP 577 EP 587 DI 10.1080/00952990600920425 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 108CA UT WOS:000242216700011 PM 17127546 ER PT J AU Bowers, K Albanes, D Limburg, P Pietinen, P Taylor, PR Virtamo, J Stolzenberg-Solomon, R AF Bowers, Katherine Albanes, Demetrius Limburg, Paul Pietinen, Pirjo Taylor, Phil R. Virtamo, Jarmo Stolzenberg-Solomon, Rachael TI A prospective study of anthropometric and clinical measurements associated with insulin resistance syndrome and colorectal cancer in male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; colorectal neoplasms; dyslipidemias; hyperinsulinism; hypertension; insulin resistance; metabolic syndrome X; smoking ID DIABETES-MELLITUS; PHYSICAL-ACTIVITY; COLON-CANCER; GROWTH-FACTOR; ENERGY-BALANCE; RECTAL-CANCER; UNITED-STATES; JAPANESE MEN; RISK-FACTORS; CELL-LINE AB Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer. Anthropometric measures (height, weight, and body mass index (weight (kg)/height (m)(2)) and metabolic abnormalities associated with insulin resistance syndrome (IRS) (abnormalities in measured blood pressure, high density lipoprotein (HDL) cholesterol, and total cholesterol) were prospectively evaluated for associations with incident colon (n = 227), rectal (n = 183), and colorectal (n = 410) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. In comparison with the lowest quintile, the highest quintile of body mass index was significantly associated with colorectal cancer (hazard ratio (HR) = 1.70, 95% confidence interval (CI): 1.01, 2.85; p-trend = 0.01), particularly colon cancer. Subjects with a cluster of three IRS-related conditions (hypertension, body mass index >= 25 kg/m(2), and HDL cholesterol level < 40 mg/dl (< 1.55 mmol/liter)), compared with those with fewer conditions, had a significantly increased risk of colorectal cancer (HR = 1.40, 95% CI: 1.12, 1.74), particularly colon cancer (HR = 1.58, 95% CI: 1.18, 2.10), but not rectal cancer. These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Bowers, K (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20892 USA. EM rs221z@nih.gov RI Albanes, Demetrius/B-9749-2015; Bowers, Katherine/N-5226-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 52 TC 74 Z9 78 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2006 VL 164 IS 7 BP 652 EP 664 DI 10.1093/aje/kwj253 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 086UH UT WOS:000240698000008 PM 16877536 ER PT J AU Hatch, EE Troisi, R Wise, LA Hyer, M Palmer, JR Titus-Ernstoff, L Strohsnitter, W Kaufman, R Adam, E Noller, KL Herbst, AL Robboy, S Hartge, P Hoover, RN AF Hatch, Elizabeth E. Troisi, Rebecca Wise, Lauren A. Hyer, Marianne Palmer, Julie R. Titus-Ernstoff, Linda Strohsnitter, William Kaufman, Raymond Adam, Ervin Noller, Kenneth L. Herbst, Arthur L. Robboy, Stanley Hartge, Patricia Hoover, Robert N. TI Age at natural menopause in women exposed to diethylstilbestrol in utero SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diethylstilbestrol; longitudinal studies; menopause; prenatal exposure delayed effects; survival analysis ID FOLLOW-UP; BREAST-CANCER; ADULT DISEASE; MORTALITY; RISK; MICE; PREGNANCY; PATTERNS; INUTERO; OVARIES AB Age at natural menopause is related to several health outcomes, including cardiovascular disease and overall mortality. Age at menopause may be influenced by the number of follicles formed during gestation, suggesting that prenatal factors could influence menopausal age. Diethylstilbestrol (DES), a nonsteroidal estrogen widely prescribed during the 1950s and 1960s, is related to reproductive tract abnormalities, infertility, and vaginal cancer in prenatally exposed daughters but has not been studied in relation to age at menopause. The authors used survival analyses to estimate the risk of natural menopause in 4,210 DES-exposed versus 1,829 unexposed US women based on responses to questionnaires mailed in 1994, 1997, and 2001. DES-exposed women were 50% more likely to experience natural menopause at any given age (hazard ratio = 1.49, 95% confidence interval: 1.28, 1.74). Among women for whom dose information was complete, there were dose-response effects, with a greater than twofold risk for those exposed to > 10,000 mg. The causal mechanism for earlier menopause may be related to a smaller follicle pool, more rapid follicle depletion, or changes in hormone synthesis and metabolism in DES-exposed daughters. Age at menopause has been related, albeit inconsistently, to several exposures, but, to the authors' knowledge, this is the first study to suggest that a prenatal exposure may influence reproductive lifespan. C1 Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Informat Management Serv Inc, Rockville, MD USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Hatch, EE (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St, Boston, MA USA. EM eehatch@bu.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 NR 34 TC 37 Z9 37 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2006 VL 164 IS 7 BP 682 EP 688 DI 10.1093/aje/kwj257 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 086UH UT WOS:000240698000011 PM 16887893 ER PT J AU Perkins, NJ Schisterman, EF AF Perkins, Neil J. Schisterman, Enrique F. TI Re: "The inconsistency of 'optimal' cutpoints obtained using two criteria based on the receiver operating characteristic curve" - The authors reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. RP Perkins, NJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733 NR 3 TC 0 Z9 0 U1 2 U2 7 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 OCT 1 PY 2006 VL 164 IS 7 BP 708 EP 708 DI 10.1093/aje/kwj293 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 086UH UT WOS:000240698000017 ER PT J AU Cronin, DP Harlan, LC Potosky, AL Clegg, LX Stevens, JL Mooney, MM AF Cronin, Deirdre P. Harlan, Linda C. Potosky, Arnold L. Clegg, Limin X. Stevens, Jennifer L. Mooney, Margaret M. TI Patterns of care for adjuvant therapy in a random population-based sample of patients diagnosed with colorectal cancer SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID III COLON-CANCER; FLUOROURACIL PLUS LEVAMISOLE; RECTAL-CANCER; STAGE-III; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; RADIATION-THERAPY; IMPROVED SURVIVAL; CHEMOTHERAPY USE; ELDERLY-PATIENTS AB OBJECTIVES: Over the past decade, clinical trials have proved the efficacy of treatments for colorectal cancer (CRC). This study tracks dissemination of these treatments for patients diagnosed with stage II and III disease and compares risk of death for those who received guideline therapy to those who did not. METHODS: We conducted a stratified randomly sampled, population-based study of CRC treatment trends in the United States. Multivariate models were used to explore patient characteristics associated with receipt of treatments. We pooled data with a previous study-patients diagnosed in 1987-1991 and 1995. Cox proportional hazards models were used to assess observed cause-specific and all-cause mortality. RESULTS: In 2000, guideline therapy receipt decreased among stage III rectal cancer patients, but increased for stage III colon and stage II rectal cancer patients. As age increased, likelihood of receiving guideline treatment decreased (p < 0.0001). Overall, race/ethnicity was significantly associated with guideline therapy (p = 0.04). Rectal patients were less likely to have received guideline treatment. Consistent with randomized clinical trial findings, all-cause mortality was lower in patients who received guideline therapy, regardless of Charlson comorbidity score. CONCLUSIONS: Mortality was decreased in patients receiving guideline therapy. Although, rates of guideline-concordant therapy are low in community clinical practice, they are apparently increasing. Newer treatment (oxaliplatin, capecitabine) started to disseminate in 2000. Racial disparities, present in 1995, were not detected in 2000. Age disparities remain despite no evidence of greater chemotherapy-induced toxicity in the elderly. More equitable receipt of cancer treatment to all segments of the community will help to reduce mortality. C1 NCI, Surveillance Res Program, DCCPS, Bethesda, MD 20892 USA. NCI, DCCPS, Appl Res Program, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. NCI, CTEP, DCTD, Bethesda, MD 20892 USA. RP Cronin, DP (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Ole Worms 1150, DK-8000 Aarhus C, Denmark. NR 50 TC 60 Z9 61 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2006 VL 101 IS 10 BP 2308 EP 2318 DI 10.1111/j.1572-0241.2006.00775.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 089XL UT WOS:000240915100023 PM 17032196 ER PT J AU McMaster, ML Goldin, LR Bai, Y Ter-Minassian, M Boehringer, S Giambarresi, TR Vasquez, LG Tucker, MA AF McMaster, Mary L. Goldin, Lynn R. Bai, Yan Ter-Minassian, Monica Boehringer, Stefan Giambarresi, Therese R. Vasquez, Linda G. Tucker, Margaret A. TI Genomewide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NON-HODGKIN-LYMPHOMA; MONOCLONAL GAMMOPATHY; AGGREGATION; IDENTIFICATION; ABNORMALITIES; STATISTICS; DISEASE; TUMORS; IGM AB Waldenstroom macroglobulinemia (WM), a distinctive subtype of non-Hodgkin lymphoma that features overproduction of immunoglobulin M (IgM), clearly has a familial component; however, no susceptibility genes have yet been identified. We performed a genomewide linkage analysis in 11 high-risk families with WM that were informative for linkage, for a total of 122 individuals with DNA samples, including 34 patients with WM and 10 patients with IgM monoclonal gammopathy of undetermined significance (IgM MGUS). We genotyped 1,058 microsatellite markers ( average spacing 3.5 cM), performed both nonparametric and parametric linkage analysis, and computed both two-point and multipoint linkage statistics. The strongest evidence of linkage was found on chromosomes 1q and 4q when patients with WM and with IgM MGUS were both considered affected; nonparametric linkage scores were 2.5 (P = .0089) and 3.1 (P = .004), respectively. Other locations suggestive of linkage were found on chromosomes 3 and 6. Results of two- locus linkage analysis were consistent with independent effects. The findings from this first linkage analysis of families at high risk for WM represent important progress toward identifying gene(s) that modulate susceptibility to WM and toward understanding its complex etiology. C1 NCI, DCEG, DHHS, Genet Epidemiol Branch,NIH, Bethesda, MD 20892 USA. NCI, DCEG, DHHS, Biostat Branch,NIH, Bethesda, MD 20892 USA. Univ Klinikum Essen, Inst Human Genet, Essen, Germany. Westat Res Inc, Rockville, MD USA. RP McMaster, ML (reprint author), NCI, DCEG, DHHS, Genet Epidemiol Branch,NIH, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM mcmastem@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS; NCI NIH HHS [N02-CP-01108] NR 36 TC 41 Z9 42 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2006 VL 79 IS 4 BP 695 EP 701 DI 10.1086/507687 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 089BV UT WOS:000240855900010 PM 16960805 ER PT J AU Benameur, K Bykowski, JL Luby, M Warach, S Latour, LL AF Benameur, K. Bykowski, J. L. Luby, M. Warach, S. Latour, L. L. TI Higher prevalence of cortical lesions observed in patients with acute stroke using high-resolution diffusion-weighted imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; MRI; PATTERNS; ECHO AB Ischemic lesion conspicuity on routine diffusion-weighted imaging (DWI, 30 seconds) was compared with an improved sequence (high-resolution DWI [DWI-HR], 256 seconds) having increased spatial resolution and signal to noise and decreased eddy current artifact in 42 patients with acute ischemic stroke. Total lesion volumes were similar; however, twice as many lesions were identified on DWI-HR, predominately in cortical gray matter. Modest improvements to imaging resulted in increased conspicuity, potentially affecting diagnosis, suspected pathogenic mechanism, and therapeutic decision. C1 NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. RP Latour, LL (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, NIH, 10 Ctr Dr,Room B1D733, Bethesda, MD 20892 USA. EM latourl@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 12 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2006 VL 27 IS 9 BP 1987 EP 1989 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 095OE UT WOS:000241316400040 PM 17032880 ER PT J AU Nien, JK Yoon, BH Espinoza, J Kusanovic, JP Erez, O Soto, E Richani, K Gomez, R Hassan, S Mazor, M Edwin, S Bahado-Singh, R Romero, R AF Nien, Jyh Kae Yoon, Bo Hyun Espinoza, Jimmy Kusanovic, Juan Pedro Erez, Offer Soto, Eleazar Richani, Karina Gomez, Ricardo Hassan, Sonia Mazor, Moshe Edwin, Sam Bahado-Singh, Ray Romero, Roberto TI A rapid MMP-8 bedside test for the detection of intra-amniotic inflammation identifies patients at risk for imminent preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE MMP-8; point-of-care test; matrix metalloproteinase; preterm labor; intact membranes; intra-amniotic infection/inflammation; chorioamnionitis; prematurity ID AMNIOTIC-FLUID; PREMATURE RUPTURE; INTACT MEMBRANES; UREAPLASMA-UREALYTICUM; CLINICAL-SIGNIFICANCE; BRONCHOPULMONARY DYSPLASIA; INTRAUTERINE INFECTION; CEREBRAL-PALSY; LABOR; PREGNANCY AB Objective: Matrix metalloproteinase-8 (MMP-8) is an enzyme that is released during neutrophil activation. MMP-8 amniotic fluid concentrations are elevated not only in patients with intra-amniotic infection, but also in patients with negative amniotic fluid cultures who deliver preterm neonates. The objective of this study was to determine whether the results of a rapid MMP-8 bedside test predict imminent preterm delivery. This test can be performed in 15 minutes and without laboratory equipment. Study design: Amniotic fluid was retrieved from 331 patients admitted with increased preterm uterine contractions and intact membranes who met the inclusion criteria. Amniotic fluid was processed for-microbial cultures, Gram stain, glucose concentration, and white blood cell count. Amniotic fluid samples were stored, and the MMP-8 rapid test was performed after delivery. End points included spontaneous preterm delivery within 48 hours, 7 days, and 14 days. Diagnostic indices, predictive values, and likelihood ratios were calculated. Results: The prevalence of spontaneous preterm delivery within 48 hours, 7 days, and 14 days was 11.6% (38/327), 20.2% (66/327), and 24.5% (80/327), respectively (4 patients with augmentation of labor were excluded). A positive MMP-8 rapid test had a positive predictive value of 70% (23/33) for the identification of patients who delivered spontaneously within 48 hours, and 94% (31/33) for patients who were delivered within 7 days and 14 days (likelihood ratios: 17.5 [95% CI, 9-33.9], 61.3 [95% CI, 15.1-250], and 50 [95% CI, 12-196], respectively). Conclusion: The MMP-8 rapid test can identify patients at risk for preterm delivery within 7 days and 14 days. Moreover, a positive MMP-8 rapid test result can identify patients with intraamniotic infection/inflammation with a high sensitivity and specificity. This rapid test will give clinicians a fast and accurate assessment of the inflammatory status of the amniotic cavity and allow for better identification of patients at risk for impending preterm delivery. (c) 2006 Mosby, Inc. All rights reserved. C1 Wayne State Univ, NICHD, Perinatl Res Branch, DHHS,Hutzel Womens Hosp,NIH, Detroit, MI 48201 USA. Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul, South Korea. Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Pontificia Univ Catolica Chile, CEDIP, Sotero Rio Hosp, Puente Alto, Chile. Ben Gurion Univ Negev, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, NICHD, Perinatl Res Branch, DHHS,Hutzel Womens Hosp,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 FU Intramural NIH HHS NR 24 TC 40 Z9 40 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1025 EP 1030 DI 10.1016/j.ajog.2006.06.054 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500021 PM 17000236 ER PT J AU Roberson, R Woodard, JE Toso, L Abebe, D Poggi, SH Spong, CY AF Roberson, Robin Woodard, Jade E. Toso, Laura Abebe, Daniel Poggi, Sarah H. Spong, Catherine Y. TI Postnatal inflammatory rat model for cerebral palsy: Too different from humans SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE cerebral palsy; periventricular leukomalacia; lipopolysaccharide; rat ID PERIVENTRICULAR WHITE-MATTER; INTRAUTERINE INFECTION; BRAIN; MICE; OLIGODENDROCYTE; INJURY AB Objective: In humans, cerebral palsy (CP) may originate from inflammation during the second and third trimesters of gestation when preoligodendrocytes (Pre-OL) are most vulnerable to an inflammatory insult. We studied a postnatal CP model to evaluate injury that would correlate with presence of Pre-OL in,human pregnancy. Study design: On postnatal (P) days 2, 3, 4, 5 and 6, pups were treated with (lipopolysaccharide [LPS]) (n = 7; 30, 30, 60, 60, 120 mu g/Kg) or saline (n = 7). Neonates were tested for motor and cognitive development. Adult offspring performed beam walking and rotarod for motor activity. White matter damage was assessed with immunohistochemical Pre-OL markers (CNP, PLP). Statistical analysis included Mann-Whitney U and analysis of variance. Results: LPS-treated animals performed negative geotaxis (P=.009) and surface righting (P=.01) earlier than controls. No differences were observed for other neonatal tests. Adult LPS-treated offspring performed better in tests of motor control: rotarod (P=.01) and beam walking (P =.02). Pre-OL markers were altered in LPS-treated animals at both P22 (CNP and PLP increased in LPS, P <.01 and P <.001, respectively) and 12 weeks (CNP and PLP decreased in LPS, P <.0001 and P <.03, respectively). Conclusion: Neonatal exposure to LPS induced white matter damage in the brain, accelerated neurodevelopment and motor tasks in adulthood. These are similar to findings from a postnatal hypoxic model suggesting that in the rodent, targeting the Pre-OL does not result in a CP phenotype. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD USA. INOVA Hosp, Dept Obstet & Gynecol, Alexandria, VA USA. RP Roberson, R (reprint author), NICHHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD USA. FU Intramural NIH HHS NR 23 TC 12 Z9 12 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1038 EP 1044 DI 10.1016/j.ajog.2006.06.046 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500023 PM 17000237 ER PT J AU Goldenberg, RL Mudenda, V Read, JS Brown, ER Sinkala, M Kamiza, S Martinson, F Kaaya, E Hoffman, I Fawzi, W Valentine, M Taha, TE AF Goldenberg, Robert L. Mudenda, Victor Read, Jennifer S. Brown, Elizabeth R. Sinkala, Moses Kamiza, Steve Martinson, Francis Kaaya, Ephata Hoffman, Irving Fawzi, Wafaie Valentine, Megan Taha, Taha E. CA HPTN 024 Study Grp TI HPTN 024 study: Histologic chorioamnionitis, antibiotics and adverse infant outcomes in a predominantly HIV-1-infected African population SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE preterm birth; chorioamnionitis; Africa ID PERINATAL HIV-1 TRANSMISSION; IDIOPATHIC PRETERM LABOR; TO-CHILD TRANSMISSION; HISTOPATHOLOGIC CHORIOAMNIONITIS; METRONIDAZOLE; INFECTION; DELIVERY; TRIAL; BIRTH; ERYTHROMYCIN AB Objective: Histologic chorioamnionitis has been associated with preterm birth and low birthweight. Our goal was to evaluate the relationship between polymorphonuclear cell and mononuclear cell placental infiltrations and adverse infant outcomes. Study design: Data from women who were enrolled in a trial of antibiotics for prevention of mother-to-child transmission of HIV-1 and of preterm birth were analyzed. Women who had HIV and women who did not have HIV were assigned randomly to either metronidazole 250 mg and erythromycin 250 mg at 20 to 24 weeks of gestation 3 times daily for 7 days and metronidazole 250 mg and ampicillin 500 mg every 4 hours during labor or identical placebos. Women with HIV were offered nevirapine at delivery for the prevention of mother-to-child transmission. At delivery, various placental sites were evaluated for polymorphonuclear cell and mononuclear cell infiltration. Results: Polymorphonuclear and mononuclear cell infiltrations were common in the decidua (18% and 43%, respectively) and chorioamnion (28% and 34%, respectively). Gestational age and birthweight were lower among women with polymorphonuclear cell infiltrations, with these relationships generally stronger at earlier gestational age and birthweight. Mononuclear infiltrations were not associated with adverse outcomes. Neither polymorphonuclear cell nor mononuclear placental infiltrations were associated with mother-to-child transmission of HIV. Antibiotic use was not associated with reduced polymorphonuclear or mononuclear cell infiltrations. Conclusion: Polymorphonuclear cell infiltrations were associated with preterm birth and decreased birthweight and gestational age. Antibiotic use was not associated with reductions in polymorphonuclear or mononuclear cell infiltrations. In this nevirapine-treated population, neither polymorphonuclear nor mononuclear cell infiltration was associated with the mother-to-child transmission of HIV. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. Univ Teaching Hosp, Dept Pathol, Lusaka, Zambia. NICHHD, Bethesda, MD 20892 USA. Minist Hlth, Lusaka, Zambia. FHCRC, SCHARP, Seattle, WA USA. Malawi Coll Med, Dept Histopathol, Blantyre, Malawi. Kamuzu Cent Hosp, Lilongwe, Malawi. Muhimbili Univ, Dept Pathol, Dar Es Salaam, Tanzania. Univ N Carolina, Ctr Infect Dis, Chapel Hill, NC USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Family Hlth Int, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Goldenberg, RL (reprint author), Univ Alabama, Dept Obstet & Gynecol, 1500 6th Ave S,CRWH 379, Birmingham, AL 35233 USA. EM rlg@uab.edu RI Brown, Elizabeth/A-8984-2008 FU NIAID NIH HHS [U01-AI-480006, N01-AI-35173-117/412, N01-AI-35173, U01-AI-48005, N01-AI-45200, U01-AI-47972] NR 23 TC 17 Z9 17 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1065 EP 1074 DI 10.1016/j.ajog.2006.05.046 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500027 PM 16875654 ER PT J AU Durnwald, CP Rouse, DJ Leveno, KJ Spong, CY MacPherson, C Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sibai, B Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG AF Durnwald, Celeste P. Rouse, Dwight J. Leveno, Kenneth J. Spong, Catherine Y. MacPherson, Cora Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary Jo Sibai, Baha Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. Gabbe, Steven G. CA Natl Inst Child Hlth Human Develop TI The Maternal-Fetal Medicine Units Cesarean Registry: Safety and efficacy of a trial of tabor in preterm pregnancy after a prior cesarean delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE preterm pregnancy; vaginal birth after cesarean; trial of labor; cesarean delivery ID VAGINAL BIRTH; UTERINE RUPTURE; LABOR; INFECTION; WOMEN; OUTCOMES AB Objective: This study was undertaken to compare success rates of vaginal birth after cesarean (VBAC) delivery, and uterine. rupture as well as maternal/perinatal outcomes between women with preterm and term pregnancies undergoing trial of labor (TOL), and to compare maternal and neonatal morbidities in those women with preterm pregnancies undergoing a TOL versus repeat cesarean delivery without tabor (RCD). Study design: Prospective 4-year observational study of women with a singleton gestation and a prior cesarean delivery at 19 academic centers. Clinical characteristics, maternal complications and VBAC delivery success for those with a preterm (24(0)-36(6) weeks) TOL, preterm RCD and term TOL (>= 37 weeks) were analyzed. Results: Among 3119 preterm pregnancies with prior cesarean delivery, 2338 (75%) underwent a TOL. 15,331 women undergoing TOL at term were also analyzed as a-control group. TOL success rates for preterm and term pregnancies were similar (72.8% vs 73.3%, P = .64). Rates of uterine rupture (0.34% vs 0.74%, P = .03) and dehiscence (0.26% vs 0.67%, P = .02) were lower in preterm compared with term TOL. Thromboembolic disease, coagulopathy and transfusion were more common in women undergoing a preterm TOL than those at term. Among women undergoing a preterm TOL, rates of uterine dehiscence, coagulopathy, transfusion, and endometritis were similar to those having a preterm RCD. After controlling for gestational age at delivery and race, neonatal outcomes such as Neonatal Intensive Care Unit (NICU) admission, intraventricular hemorrhage, sepsis, and ventilatory support were similar in both groups except for a higher rate of respiratory distress syndrome in those delivered after a TOL. Conclusion: The likelihood of VBAC success after TOL in preterm pregnancies is comparable to term gestations, with a lower risk of uterine rupture. Perinatal outcomes are similar with preterm TOL and RCD. TOL should be considered as an option for women undergoing preterm delivery with a history of prior cesarean delivery. (c) 2006 Mosby, Inc. All rights reserved. C1 Ohio State Univ, Dept Obstet, Columbus, OH 43210 USA. Ohio State Univ, Dept Gynecol, Columbus, OH 43210 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Durnwald, CP (reprint author), Ohio State Univ, Dept Obstet, Columbus, OH 43210 USA. OI Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD27869, HD21410, HD21414, HD27860, HD27861, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560] NR 12 TC 12 Z9 14 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1119 EP 1126 DI 10.1016/j.ajog.2006.06.047 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500037 PM 17000244 ER PT J AU Peaceman, AM Gersnoviez, R Landon, MB Spong, CY Leveno, KJ Varner, MW Rouse, DJ Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Peaceman, Alan M. Gersnoviez, Rebecca Landon, Mark B. Spong, Catherine Y. Leveno, Kenneth J. Varner, Michael W. Rouse, Dwight J. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Natl Inst Child Hlth Human Develop TI The MFMU Cesarean Registry: Impact of fetal size on trial of labor success for patients with previous cesarean for dystocia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE cesarean delivery; vaginal birth after cesarean; dystocia; birth weight ID VAGINAL BIRTH; DELIVERY; OUTCOMES; SECTION; WOMEN AB Objective: The purpose of this study was to determine the influence of change in infant birth weight between pregnancies on the outcome of a trial of labor for women whose first cesarean delivery was performed for dystocia. Study design: Secondary analysis of 7081 patients with I previous cesarean delivery and no other deliveries after 20 weeks' gestation, undergoing a trial of labor with a singleton gestation. Cases were classified as dystocia, if the listed indication for the cesarean delivery in the first pregnancy was failed induction, cephalo-pelvic disproportion, failure to progress, or failed forceps or vacuum. Outcomes of the trial of labor were correlated with fetal size relative to birth weight in the initial pregnancy for those women whose initial cesarean delivery was for dystocia and those with other indications. Results: For the cohort being studied (n = 708 1), dystocia was the indication for the first cesarean delivery for 3182 (44.9%). Trial of labor resulted in vaginal delivery for 54% of patients whose first cesarean delivery was performed for dystocia, compared with 67% for those with other indications (P < .01). For those whose first cesarean delivery was for dystocia, trial of labor success was correlated with birth weight differences between the pregnancies, with only 38% delivering vaginally if the trial of labor birth weight exceeded the initial pregnancy birth weight by more than 500 g. Using logistic regression and adjusting for other potential confounding factors, the odds of success decreased by 3.8% for each increase of 100 g in birth weight in the trial of labor relative to the first birth weight. Conclusion: For women with previous cesarean delivery for dystocia, increasing birth weight in the subsequent trial of labor relative to the first birth weight diminishes the chances of successful vaginal delivery. (c) 2006 Mosby, Inc. All rights reserved. C1 Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Columbus, OH 43210 USA. NICHHD, Bethesda, MD 20892 USA. Univ Texas San Antonio, SW Med Ctr, Dallas, TX 75230 USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Miami, FL USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas San Antonio, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Peaceman, AM (reprint author), Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. OI Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD40485, HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560] NR 11 TC 15 Z9 16 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1127 EP 1131 DI 10.1016/j.ajog.2006.06.003 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500038 PM 17000245 ER PT J AU Bailit, JL Landon, MB Thom, E Rouse, DJ Spong, CY Varner, MW Moawad, AH Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O AF Bailit, Jennifer L. Landon, Mark B. Thom, Elizabeth Rouse, Dwight J. Spong, Catherine Y. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Harper, Margaret Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded CA Natl Inst Child Hlth Human Develop TI The MFMU Cesarean Registry: Impact of time of day on cesarean complications SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 30-FEB 04, 2006 CL Miami Beach, FL SP Soc Maternal Fetal Med DE cesarean delivery; work shift; maternal morbidity; neonatal morbidity ID SLEEP-DEPRIVATION; PERFORMANCE; TRIAL; NIGHT; CALL AB Objective: Studies suggest that sleep deprivation adversely affects performance. We hypothesized that cesarean delivery complications would be more frequent during the night shift (I I PM-7 AM), and evaluated morbidities by delivery shift. Study design: Eighteen thousand nine hundred and thirty-nine term women undergoing an unscheduled cesarean delivery in 13 centers from 1999 to 2000 within a prospective observational study were included. Maternal/neonatal morbidities and time from decision to cesarean delivery were evaluated by time of delivery (7 AM-3 Pm, 3 PM-11 Pm, I I PM-7 AM). A composite of maternal morbidities was evaluated by logistic regression controlling for potentially confounding factors. Results: Controlling for age, race, insurance, cardiac disease, preeclampsia, diabetes, previous incision type, and prenatal care, shift of delivery had no impact on maternal morbidity (I I PM-7 AM OR 0.9 [95% CI 0.81-1.0]). NICU admissions were slightly increased at night but neonatal complications were not. Conclusion: Maternal and neonatal complications of cesarean delivery do not increase with delivery during the night shift. (c) 2006 Mosby, Inc. All rights reserved. C1 Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL USA. NICHHD, Bethesda, MD 20892 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. RP Bailit, JL (reprint author), Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD27869, HD21410, HD21414, HD27860, HD27861, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801, K12 HD98004] NR 10 TC 18 Z9 18 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2006 VL 195 IS 4 BP 1132 EP 1137 DI 10.1016/j.ajog.2006.06.009 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 092UT UT WOS:000241123500039 PM 16875648 ER PT J AU Petrache, I Fijalkowska, I Medler, TR Skirball, J Cruz, P Zhen, L Petrache, HI Flotte, TR Tuder, RM AF Petrache, Irina Fijalkowska, Iwona Medler, Terry R. Skirball, Jarrett Cruz, Pedro Zhen, Lijie Petrache, Horia I. Flotte, Terence R. Tuder, Rubin M. TI alpha-1 Antitrypsin inhibits caspase-3 activity, preventing lung endothelial cell apoptosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; ISOTHERMAL TITRATION CALORIMETRY; SMOKE-INDUCED EMPHYSEMA; ALPHA-1-PROTEINASE INHIBITOR; GROWTH-FACTOR; Z ALPHA(1)-ANTITRYPSIN; ELASTASE; DEFICIENCY; MICE; MECHANISMS AB alpha-1 Antitrypsin (A1AT) is an abundant circulating serpin with a postulated function in the lung of potently inhibiting neutrophil-derived proteases. Emphysema attributable to A1AT deficiency led to the concept that a protease/anti-protease imbalance mediates cigarette smoke-induced emphysema. We hypothesized that A1AT has other pathobiological relevant functions in addition to elastase inhibition. We demonstrate a direct prosurvival effect of A1AT through inhibition of lung alveolar endothelial cell apoptosis. Primary pulmonary endothelial cells internalized human A1AT, which co-localized with and inhibited staurosporine-induced caspase-3 activation. In cell-free studies, native A1AT, but not conformers lacking an intact reactive center loop, inhibited the interaction of recombinant active caspase-3 with its specific substrate. Furthermore, overexpression of human MAT via replication-deficient adeno-associated virus markedly attenuated alveolar wall destruction and oxidative stress caused by caspase-3 instillation in a mouse model of apoptosis-dependent emphysema. our findings suggest that direct inhibition of active caspase-3 by A1AT may represent a novel anti-apoptotic mechanism relevant to disease processes characterized by excessive structural cell apoptosis, oxidative stress, and inflammation, such as pulmonary emphysema. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Div Cardioulm Pathol, Baltimore, MD 21218 USA. Univ Florida, Sch Med, Dept Pediat, Gainesville, FL 32611 USA. NICHHD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Petrache, I (reprint author), 1481 W 10th St,VA111P-IU, Indianapolis, IN 46202 USA. EM ipetrach@iupui.edu FU NHLBI NIH HHS [K08 HL004396, K08 HL04396-04, R01 HL066554, R01 HL069877, R01-HL69877, R01HL66554]; NIDDK NIH HHS [P01 DK058327, P01-DK58327] NR 44 TC 124 Z9 129 U1 1 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2006 VL 169 IS 4 BP 1155 EP 1166 DI 10.2353/ajpath.2006.060058 PG 12 WC Pathology SC Pathology GA 089HW UT WOS:000240872400007 PM 17003475 ER PT J AU Morrison, RR Teng, B Oldenburg, PJ Katwa, LC Schnermann, JB Mustafa, SJ AF Morrison, R. Ray Teng, Bunyen Oldenburg, Peter J. Katwa, Laxmansa C. Schnermann, Jurgen B. Mustafa, S. Jamal TI Effects of targeted deletion of A(1) adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE gene expression; coronary flow; lactate dehydrogenase ID REPERFUSED MOUSE HEART; CORONARY FLOW; ENDOGENOUS ADENOSINE; A(2A) RECEPTOR; MICE LACKING; TRANSGENIC OVEREXPRESSION; GENE-EXPRESSION; A(2B) RECEPTORS; A(3) RECEPTORS; ISCHEMIA AB To examine ischemic tolerance in the absence of A(1) adenosine receptors (A(1)ARs), isolated wild-type (WT) and A(1)AR knockout (A(1)KO) murine hearts underwent global ischemia-reperfusion, and injury was measured in terms of functional recovery and efflux of lactate dehydrogenase (LDH). Hearts were analyzed by real-time RT-PCR both at baseline and at intervals during ischemia-reperfusion to determine whether compensatory expression of other adenosine receptor subtypes occurs with either A(1)AR deletion and/or ischemia-reperfusion. A(1)KO hearts had higher baseline coronary flow (CF) and left ventricular developed pressure (LVDP) than WT hearts, whereas heart rate was unchanged by A(1)AR deletion. After 20 min of ischemia, CF was attenuated in A(1)KO compared with WT hearts, and this reduction persisted throughout reperfusion. Final recovery of LVDP was decreased in A1KO hearts (54.4 +/- 5.1 vs. WT 81.1 +/- 3.4% preischemic baseline) and correlated with higher diastolic pressure during reperfusion. Postischemic efflux of LDH was greater in A(1)KO compared with WT hearts. Real-time RT-PCR demonstrated the absence of A(1)AR transcript in A(1)KO hearts, and the message for A(2A), A(2B), and A(3) adenosine receptors was similar in uninstrumented A(1)KO and WT hearts. Ischemia-reperfusion increased A(2B) mRNA expression 2.5-fold in both WT and A(1)KO hearts without changing A(1) or A(3) expression. In WT hearts, ischemia transiently doubled A(2A) mRNA, which returned to preischemic level upon reperfusion, a pattern not observed in A(1)KO hearts. Together, these data affirm the cardioprotective role of A(1)ARs and suggest that induced expression of other adenosine receptor subtypes may participate in the response to ischemia-reperfusion in isolated murine hearts. C1 St Jude Childrens Res Hosp, Div Crit Care Med, Memphis, TN 38105 USA. W Virginia Univ, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. Univ Nebraska, Med Ctr, Durham Res Ctr, Omaha, NE 68182 USA. E Carolina Univ, Brody Sch Med, Greenville, NC USA. NIDDK, NIH, Bethesda, MD USA. RP Morrison, RR (reprint author), St Jude Childrens Res Hosp, Div Crit Care Med, 332 N Lauderdale St,MS 734, Memphis, TN 38105 USA. EM ray.morrison@stjude.org FU NHLBI NIH HHS [HL-074001, HL-60047, HL-27339] NR 48 TC 36 Z9 37 U1 0 U2 1 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 OCT PY 2006 VL 291 IS 4 BP H1875 EP H1882 DI 10.1152/ajpheart.00158.2005 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 084CP UT WOS:000240509700046 PM 16679400 ER PT J AU Burch, LH Yang, IV Whitehead, GS Chao, FG Berman, KG Schwartz, DA AF Burch, Lauranell H. Yang, Ivana V. Whitehead, Gregory S. Chao, Frank G. Berman, Katherine G. Schwartz, David A. TI The transcriptional response to lipopolysaccharide reveals a role for interferon-gamma in lung neutrophil recruitment SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE endotoxin; environmental airway disease; murine; microarray; transcription factor ID GENE-EXPRESSION; GRAIN DUST; KAPPA-B; SIGNALING PATHWAYS; CHEMOKINE N51/KC; HUMAN-DISEASE; MICE; ENDOTOXIN; TLR4; MUTATIONS AB Neutrophil recruitment to the lung after lipopolysaccharide (LPS; endotoxin) inhalation is primarily dependent on Toll-like receptor 4 (Tlr4) signaling, because it is virtually absent in mice deficient in Tlr4. However, among strains wild type for Tlr4, the magnitude of neutrophil recruitment to the lung after LPS inhalation is variable, suggesting the involvement of genes other than Tlr4. To identify genes associated with the inflammatory response to inhaled LPS, we evaluated the transcriptional response in lungs of 12 inbred strains of mice, 8 which are wild type for Tlr4 and 4 of which lack functional Tlr4. Using the promoter integration in microarray analysis algorithm, we scanned our gene list for transcription factor-binding sites significantly overrepresented among Tlr4 wild-type strains with high neutrophil influx in the lung after LPS inhalation. This analysis identified the interferon (IFN)-stimulated response element (ISRE) as the most overrepresented transcription factor (present in 24% of the promoters) associated with the neutrophil influx to the lower respiratory tract. To test the validity of this observation, we evaluated IFN-gamma-deficient mice and found that the presence of IFN-gamma is essential for robust neutrophil recruitment to the lower respiratory tract and modulation of key regulatory cytokines and chemokines after LPS inhalation. In conclusion, using a genomic approach, we identified the ISRE as a transcriptional element associated with the neutrophil response to inhaled LPS and demonstrated for the first time that IFN-gamma plays a critical role in LPS-induced neutrophil recruitment to the lower airways. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. Duke Univ, Ctr Med, Div Pulm Allergy & Crit Care Med, Durham, NC USA. Vet Adm Med Ctr, Durham, NC USA. RP Burch, LH (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, Rall Bldg,Rm C204A,POB 12233,MD C2-13,111 Alexand, Res Triangle Pk, NC 27709 USA. EM burchl@niehs.nih.gov FU NIEHS NIH HHS [ES-07498, ES-11375, ES-012496, ES-011961] NR 35 TC 8 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD OCT PY 2006 VL 291 IS 4 BP L677 EP L682 DI 10.1152/ajplung.00523.2005 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 082BF UT WOS:000240360800017 PM 16766576 ER PT J AU Verlander, JW Kim, YH Shin, W Pham, TD Hassell, KA Beierwaltes, WH Green, ED Everett, L Matthews, SW Wall, SM AF Verlander, Jill W. Kim, Young Hee Shin, Wonkyong Pham, Truyen Derek Hassell, Kathryn A. Beierwaltes, William H. Green, Eric D. Everett, Lorraine Matthews, Sharon W. Wall, Susan M. TI Dietary Cl- restriction upregulates pendrin expression within the apical plasma membrane of type B intercalated cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE acid-base and fluid balance; mammalian collecting duct ID COLLECTING DUCT; SYNDROME GENE; MOUSE KIDNEY; RAT-KIDNEY; CHLORIDE; HYPERTENSION; DETERMINANT; TRANSPORT; SECRETION; SUBTYPES AB Pendrin, encoded by Slc26a4, is a Cl-/HCO3- exchanger expressed in the apical region of type B and non-A, non-B intercalated cells, which regulates renal NaCl excretion. Dietary Cl- restriction upregulates total pendrin protein expression. Whether the subcellular expression of pendrin and whether the apparent vascular volume contraction observed in Slc26a4 null mice are Cl- dependent, but Na+ independent, is unknown. Thus the subcellular distribution of pendrin and its role in acid-base and fluid balance were explored using immunogold cytochemistry and balance studies of mice ingesting a NaCl-replete or a Na+-replete, Cl--restricted diet, achieved through substitution of NaCl with NaHCO3. Boundary length and apical plasma membrane pendrin label density each increased by similar to 60-70% in type B intercalated cells, but not in non-A, non-B cells, whereas cytoplasmic pendrin immunolabel increased similar to 60% in non-A, non-B intercalated cells, but not in type B cells. Following either NaCl restriction or Cl- restriction alone, Slc26a4 null mice excreted more Cl- and had a higher arterial pH than pair-fed wild-type mice. In conclusion, 1) following dietary Cl- restriction, apical plasma membrane pendrin immunolabel increases in type B intercalated cells, but not in non-A, non-B intercalated cells; and 2) pendrin participates in the regulation of renal Cl- excretion and arterial pH during dietary Cl- restriction. C1 Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA 30322 USA. Univ Florida, Coll Med, Dept Med, Gainesville, FL 32611 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Houston, TX USA. Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA. Wayne State Univ, Sch Med, Detroit, MI 48202 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Wellcome Trust Sanger Inst, Cambridge, England. RP Wall, SM (reprint author), Emory Univ, Sch Med, Dept Med, Div Renal, WMB Rm 338,1639 Pierce Dr NE, Atlanta, GA 30322 USA. EM smwall@emory.edu RI Verlander, Jill/I-5991-2015 FU NIDDK NIH HHS [DK-52935] NR 23 TC 49 Z9 49 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 OCT PY 2006 VL 291 IS 4 BP F833 EP F839 DI 10.1152/ajprenal.00474.2005 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 081JD UT WOS:000240313000015 PM 16670435 ER PT J AU Yang, TX Zhang, AH Pasumarthy, A Zhang, LH Warnock, Z Schnermann, JB AF Yang, Tianxin Zhang, Aihua Pasumarthy, Anita Zhang, Lihong Warnock, Zachary Schnermann, Jurgen B. TI Nitric oxide stimulates COX-2 expression in cultured collecting duct cells through MAP kinases and superoxide but not cGMP SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cyclooxygenase-2 ID DEPENDENT PROTEIN-KINASES; CYCLOOXYGENASE-2 EXPRESSION; RENAL MEDULLA; MACULA DENSA; BLOOD-PRESSURE; CYCLIC-GMP; IN-VIVO; TYROSINE NITRATION; PROSTAGLANDIN E-2; SODIUM-EXCRETION AB Collecting ducts are a major site of renal production and action of both prostaglandins and nitric oxide. Experiments were undertaken to examine whether nitric oxide regulates cyclooxygenase (COX)-2 expression and PGE(2) release in cultured collecting duct cells. In mIMCD-K2 cells, sodium nitroprusside (SNP) in the 50-to 800-mu M range induced a marked dose-and time-dependent increase in COX-2 protein levels, determined by immunoblotting, and the induction was detectable at 4 h. This was preceded by induction of COX-2 mRNA as determined by real-time-RT-PCR. The COX-2 induction was accompanied by a significant rise in PGE(2) release as determined by enzyme immunoassay. S-nitroso-N-acetylpenicillamine (SNAP) had a similar stimulatory effect on COX-2 expression and PGE(2) release. 8-bromo-cGMP (200 mu M) had no effect on COX-2 expression. The SNP-stimulated COX-2 expression was not affected by the guanylyl cyclase inhibitor methylene blue or the protein kinase G inhibitor KT-5823 (2.0 mu M). In contrast, the SNP-stimulated COX-2 expression was significantly reduced by either the Erk1/ 2 inhibitor PD-98059 or the P38 inhibitor SB-203580 and was abolished by combination of the two kinase inhibitors. The stimulation was also significantly blocked by the SOD mimetic tempol. Thus we conclude that NO stimulates COX-2 expression in collecting duct cells through mechanisms involving MAP kinase and superoxide, but not cGMP. C1 Univ Utah, Dept Internal Med, Res Serv 151 E, Salt Lake City, UT 84148 USA. Vet Affairs Med Ctr, Res Serv 151 E, Salt Lake City, UT 84148 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Yang, TX (reprint author), Univ Utah, Dept Internal Med, Res Serv 151 E, Bldg 2,500 Foothill Dr, Salt Lake City, UT 84148 USA. EM tianxin.yang@hsc.utah.edu FU Intramural NIH HHS; NHLBI NIH HHS [R01-HL-079453]; NIDDK NIH HHS [R01-DK-066592, K01-DK-064981] NR 40 TC 29 Z9 30 U1 0 U2 0 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 OCT PY 2006 VL 291 IS 4 BP F891 EP F895 DI 10.1152/ajpreanal.00512.2005 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 081JD UT WOS:000240313000021 PM 16705145 ER PT J AU Partin, MR An, LC Nelson, DB Nugent, S Snyder, A Fu, SS Willenbring, ML Joseph, AM AF Partin, Melissa R. An, Lawrence C. Nelson, David B. Nugent, Sean Snyder, Annamay Fu, Steven S. Willenbring, Mark L. Joseph, Anne M. TI Randomized trial of an intervention to facilitate recycling for relapsed smokers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NICOTINE; CESSATION; SMOKING AB Background: Tobacco dependence is a chronic condition requiring repeat treatment and long-term follow-up. However, current evidence regarding best approaches to providing these services is fairly limited. This study assessed the effectiveness of an intervention for increasing repeat tobacco-dependence treatment in a population of relapsed smokers. Design: The study was a multicenter randomized controlled trial. Setting/participants: Patients aged 19 and older receiving a prescription for nicotine replacement therapy or bupropion for smoking cessation in 2002 at one of five participating Veterans Affairs (VA) facilities were eligible. Intervention: A total of 1900 eligible veterans were randomized to (1) patient phone call to assess smoking status, quit challenges, and treatment preferences, and computerized progress note to providers communicating this information (intervention); or (2) usual care (control). Main Outcome measures: Outcomes, assessed in 2003, included the proportion of patients receiving repeat pharma cologic or behavioral smoking-cessation treatment in the 6-month follow-up period (assessed from VA pharmacy and outpatient data), 7-day point prevalence abstinence, and satisfaction (assessed by patient survey). Results: Thirty-four percent of intervention participants versus 22% of controls received treatment for tobacco dependence in the follow-up period (p = 0.0001). Thirty-two percent of intervention participants versus 21% of controls received pharmacologic treatment (p = 0.0001), and 12% of intervention subjects versus 8% of controls received behavioral treatment (p = 0.005). Abstinence rates at follow-up were 25% for intervention subjects and 22% for controls (p = 0.15). Intervention subjects were more likely than controls to report being satisfied with the general smoking-cessation help (87% vs 82%, p = 0.01), as well as the pharmacologic help that they received from the VA (89 vs 84%, p = 0.01). Conclusions: The intervention significantly increased repeat treatment rates and satisfaction with services but did not have a significant effect on abstinence rates. C1 Vet Adm Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Internal Med, Minneapolis, MN 55455 USA. NIAAA, Rockville, MD 20852 USA. RP Partin, MR (reprint author), Vet Adm Med Ctr, Ctr Chron Dis Outcomes Res, 152-2E,1 Vet Dr, Minneapolis, MN 55417 USA. EM Melisssa.Partin@va.gov NR 15 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2006 VL 31 IS 4 BP 293 EP 299 DI 10.1016/j.amepre.2006.06.021 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 089JT UT WOS:000240877400004 PM 16979453 ER PT J AU Rabin, BA Brownson, RC Kerner, JF Glasgow, RE AF Rabin, Borsika A. Brownson, Ross C. Kerner, Jon F. Glasgow, Russell E. TI Methodologic challenges in disseminating evidence-based interventions to promote physical activity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Conference on Diffusion and Dissemination of Physical Activity Recommendations and Programs to World Populations CY 2004 CL Dallas, TX SP Cooper Inst ID PRACTICAL CLINICAL-TRIALS; BEHAVIOR-CHANGE RESEARCH; HEALTH-PROMOTION; PREVENTION INTERVENTIONS; TRANSLATING RESEARCH; IMPROVE TRANSLATION; DISEASE PREVENTION; SYSTEMATIC REVIEWS; CANCER CONTROL; DIFFUSION AB During the past decade, numerous intervention studies have been published on the effectiveness of programs to promote active living; however, few studies have addressed the dissemination of effective physical activity interventions. Both community settings and healthcare settings are important locations for dissemination of evidence-based programs and policies. A major gap in the existing literature involves the appropriate methodologic approaches for planning, evaluating, and reporting on dissemination efforts for effective and promising interventions in these locations. To address this gap, two hypothetical dissemination studies are presented: a quasi-experimental study of local health agencies (Scenario 1) and a group-randomized trial of clinical practices (Scenario 2). These studies help to elucidate the barriers and opportunities for implementing evidence-based physical activity interventions across different settings. Based on the scenarios, the existing literature, and the authors' experience, dissemination challenges that researchers and practitioners may experience (i.e., issues of design, measures of outcomes and external validity, the balance between fidelity and adaptation to local settings, and the review and funding of dissemination science) are discussed. Researchers, practitioners, and policy makers are invited to address the issues outlined in this article in order to bridge the gap between the generation of new knowledge on efficacious physical activity interventions and widespread application of these approaches in community and clinical settings. C1 St Louis Univ, Sch Publ Hlth, Dept Community Hlth, St Louis, MO 63104 USA. St Louis Univ, Sch Publ Hlth, Prevent Res Ctr, St Louis, MO 63104 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Kaiser Permanente, Clin Res Unit, Denver, CO USA. RP Rabin, BA (reprint author), St Louis Univ, Sch Publ Hlth, Dept Community Hlth, 3545 Lafayette Ave,Salus Ctr 490 A, St Louis, MO 63104 USA. EM rabinab@slu.edu FU PHS HHS [U48/CCU71086] NR 68 TC 41 Z9 41 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2006 VL 31 IS 4 SU S BP S24 EP S34 DI 10.1016/j.amepre.2006.06.009 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 090ND UT WOS:000240957100005 PM 16979467 ER PT J AU Fenton, WS Chavez, MR AF Fenton, Wayne S. Chavez, Mark R. TI Medication-induced weight gain and dyslipidemia in patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; METABOLIC-SYNDROME; DOUBLE-BLIND; ANTIPSYCHOTIC-DRUGS; GLUCOSE REGULATION; DIABETES-MELLITUS; OLANZAPINE; INTERVENTION; PREVENTION; RISK C1 NIMH, Div Adult Translat Res & treatment Dev, Bethesda, MD 20892 USA. RP Fenton, WS (reprint author), 1000 Wilson Blvd,Suite 1825, Arlington, VA 22209 USA. NR 47 TC 23 Z9 24 U1 2 U2 4 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 OCT PY 2006 VL 163 IS 10 BP 1697 EP 1704 DI 10.1176/appi.ajp.163.10.1697 PG 8 WC Psychiatry SC Psychiatry GA 089UN UT WOS:000240906800009 PM 17012676 ER PT J AU Kassem, L Lopez, V Hedeker, D Steele, J Zandi, P McMahon, FJ AF Kassem, Layla Lopez, Victor Hedeker, Don Steele, Jo Zandi, Peter McMahon, Francis J. CA NIMH Genet Initiative Bipolar Diso TI Familiality of polarity at illness onset in bipolar affective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; GENETICS; PEDIGREES; SEQUENCE; EPISODE; SAMPLE; CHROMOSOME-16; REPLICATION; LINKAGE; PROGRAM AB Objective: Bipolar affective disorder is clinically heterogeneous, and clinical features that run in families may help define more homogeneous phenotypes. The authors sought to establish whether polarity at illness onset, which is related to severity and course, is a familial feature of bipolar affective disorder. Method: The authors studied 971 subjects from 507 families ascertained through sibling pairs with bipolar I or schizoaffective bipolar disorder. Self-reported ages at onset of mania and major depression were used to code polarity at onset as manic, major depressive, or both ( mania and major depression in the same onset year). Familial clustering was estimated by using mixed-effects regression analysis, and the relationship between polarity at onset and several other clinical features was assessed. As a preliminary test of genetic validity, the authors assessed the impact of polarity at onset on genetic linkage findings previously detected in this sample. Results: Polarity at onset was significantly familial in this sample. This largely reflected relative pairs concordant for mania at onset, which occurred significantly more frequently than would be expected by chance. Mania at onset substantially increased the genetic linkage signal on chromosome 16p ( maximum lod score = 4.5) but had no effect on linkage to chromosome 6q. Mania at onset occurred at a later age on average than major depression at onset and was less likely to be complicated by panic attacks or alcoholism. Conclusions: Polarity at illness onset is a familial feature of bipolar affective disorder and is associated with important clinical indicators, which may help define more homogeneous subtypes of bipolar affective disorder. C1 NIMH, Intramural Res Program, Mood & Anxiety Program, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Clin Sci Lab, Bethesda, MD 20892 USA. Univ Illinois, Dept Epidemiol & Biostat, Chicago, IL USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. Univ Calif Irvine, Dept Psychiat, Irvine, CA USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. RP Kassem, L (reprint author), NIH, 35 Convent Dr,Rm 1A202 MSC 3616, Bethesda, MD 20809 USA. EM kasseml@intra.nimh.nih.gov RI McMahon, Francis/A-7290-2009; OI McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS; NCRR NIH HHS [RR03655]; NIMH NIH HHS [K01 MH072866, K01 MH072866-01] NR 25 TC 30 Z9 32 U1 2 U2 3 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 OCT PY 2006 VL 163 IS 10 BP 1754 EP 1759 DI 10.1176/appi.ajp.163.10.1754 PG 6 WC Psychiatry SC Psychiatry GA 089UN UT WOS:000240906800019 PM 17012686 ER PT J AU Parry, M AF Parry, Manon TI Thomas W. Salmon: Advocate of mental hygiene SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 Natl Lib Med, Exhibit Program, Bethesda, MD 20894 USA. RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 6 TC 0 Z9 0 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 OCT PY 2006 VL 96 IS 10 BP 1741 EP 1741 DI 10.2105/AJPH.2006.095794 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 089OX UT WOS:000240891200009 PM 17008565 ER PT J AU Fee, E Brown, TM AF Fee, Elizabeth Brown, Theodore M. TI Freeing the insane SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, NIH, Bethesda, MD USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Rm 1E-21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2006 VL 96 IS 10 BP 1743 EP 1743 DI 10.2105/AJPH.2006.095448 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 089OX UT WOS:000240891200010 PM 17008566 ER PT J AU Kimura, S Kurotani, R AF Kimura, Shioko Kurotani, Reiko TI Periarterial leukocyte accumulation in allergic airway inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 NCI, NIH, Bethesda, MD 20892 USA. RP Kimura, S (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2006 VL 174 IS 7 BP 840 EP 840 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 089PD UT WOS:000240891900018 ER PT J AU Kirk, AD Light, JA AF Kirk, A. D. Light, J. A. TI Of ends and means SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; CHRONIC REJECTION; CAMPATH; THYMOGLOBULIN; MONOTHERAPY; DEPLETION C1 NIDDKD, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Washington Hosp Ctr, Transplantat Serv, Washington, DC 20010 USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 12 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2006 VL 6 IS 10 BP 2228 EP 2229 DI 10.1111/j.1600-6143.2006.01500.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 082DD UT WOS:000240366000002 PM 16925568 ER PT J AU Cheng, O Thuillier, R Sampson, E Schultz, G Ruiz, P Zhang, X Yuen, PST Mannon, RB AF Cheng, O. Thuillier, R. Sampson, E. Schultz, G. Ruiz, P. Zhang, X. Yuen, P. S. T. Mannon, R. B. TI Connective tissue growth factor is a biomarker and mediator of kidney allograft fibrosis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE chronic allograft nephropathy; CTGF; fibrosis; kidney; mouse; TGF-beta; transplantation ID EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC REJECTION; FACTOR-BETA; RENAL-ALLOGRAFTS; MESSENGER-RNA; TUBULOINTERSTITIAL FIBROSIS; EXPRESSION; NEPHROPATHY; CELLS; RATS AB Chronic allograft nephropathy (CAN) is a leading cause of kidney graft failure following transplantation. Its causes are complex and include both immunological and nonimmunological factors. Here we have studied the development of CAN in a mouse model of kidney transplantation comparing isografts and allografts. Unlike the normal histology and normal serum creatinine of the uninephrectomized, nonrejecting isografted mice (0.219 +/- 0.024 mg/dL), allografted mice demonstrated severe renal dysfunction (mean serum creatinine 0.519 +/- 0.061 mg/dL; p < 0.005) with progressive inflammation and fibrosis of the kidney. These animals also showed an increased expression of connective tissue growth factor (CTGF), both systemically and within the graft. CTGF was highly expressed in tubuloepithelial cells of allografts, along with alpha-smooth muscle actin, a marker of myofibroblasts, and transcriptionally associated with other markers of fibrosis. In vitro studies of tubular epithelium indicate that CTGF is capable of inducing EMT, independent of TGF-beta. Finally, in human transplant recipients, serum and urine CTGF levels are significantly elevated compared to naive individuals. Urinary levels correlated with the histological presence of CAN. These studies suggest a critical role of CTGF in graft fibrogenesis, for both mouse and man. Thus, CTGF has potential as a biomarker of CAN, and also a therapeutic target in managing graft fibrosis. C1 NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. Univ Florida, Med Ctr, Dept Cell Biol, Miami, FL USA. Univ Florida, Med Ctr, Dept Pathol, Miami, FL USA. RP Mannon, RB (reprint author), NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. EM rozm@intra.niddk.nih.gov RI Yuen, Peter/B-1954-2008; thuillier, raphael/P-5709-2016 OI Yuen, Peter/0000-0001-9557-3909; thuillier, raphael/0000-0002-7482-0031 FU Intramural NIH HHS NR 49 TC 70 Z9 80 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2006 VL 6 IS 10 BP 2292 EP 2306 DI 10.1111/j.1600-6143.2006.01493.x PG 15 WC Surgery; Transplantation SC Surgery; Transplantation GA 082DD UT WOS:000240366000010 PM 16889607 ER PT J AU Karlsson, RM Holmes, A AF Karlsson, R. -M. Holmes, A. TI Galanin as a modulator of anxiety and depression and a therapeutic target for affective disease SO AMINO ACIDS LA English DT Article; Proceedings Paper CT 9th International Congress on Amino Acids and Proteins CY AUG 08-12, 2005 CL Vienna, AUSTRIA DE galanin; neuropeptides; stress; anxiety; depression; rodent ID LOCUS-COERULEUS NEURONS; CENTRAL-NERVOUS-SYSTEM; OVEREXPRESSING TRANSGENIC MICE; PREPROGALANIN MESSENGER-RNA; CHRONIC RESTRAINT STRESS; DORSAL RAPHE NUCLEUS; ANXIOLYTIC-LIKE; NEUROPEPTIDE-Y; RAT-BRAIN; IN-VIVO AB Galanin is a 29 amino-acid (30 in humans) neuropeptide with a close functional relationship with neurotransmitter systems implicated in the pathophysiology and treatment of depression and anxiety disorders. In rodent models of depression-related behavior, treatment with galanin or compounds with agonist actions at galanin receptors has been shown to affect depression-related behaviors and the behavioral and neurochemical effects of antidepressants. Treatment with clinically efficacious antidepressants alters galanin and galanin receptor gene expression in rodents. Rodent anxiety-like behaviors appear to be modulated by galanin in a complex manner, with studies showing either increases, decreases and no effects of galanin treatments and galanin mutations on anxiety-like behavior in various tasks. One concept to emerge from this literature is that galanin recruitment during extreme behavioral and physiological provocations such as stress and opiate withdrawal may serve to attenuate negative emotional states caused by noradrenergic hyperactivation. The specific galanin receptor subtypes mediating the anxiety- and depression-related effects of galanin remains to be determined, with evidence supporting a possible contribution of GalR1, GalR2 and GalR3. While our understanding of the role of galanin as a modulator of emotion remains at an early stage, recent progress in this rapidly evolving field raise possibility of that galanin may represent a target for the development of novel antidepressant and anxiolytic drug treatments. C1 NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Karlsson, RM (reprint author), NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA. EM karlssonr@mail.nih.gov NR 99 TC 42 Z9 43 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD OCT PY 2006 VL 31 IS 3 BP 231 EP 239 DI 10.1007/s00726-006-0336-8 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 093LJ UT WOS:000241169500003 PM 16733616 ER PT J AU Mossop, BJ Barr, RC Henshaw, JW Zaharoff, DA Yuan, F AF Mossop, Brian J. Barr, Roger C. Henshaw, Joshua W. Zaharoff, David A. Yuan, Fan TI Electric fields in tumors exposed to external voltage sources: Implication for electric field-mediated drug and gene delivery SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE drug and gene delivery; electroporation; electrogenetherapy; electrochemotherapy ID IN-VIVO ELECTROPORATION; FINITE-ELEMENT MODEL; EXTRAVASCULAR SPACE; NONVIRAL VECTORS; TISSUE; CELLS; PERMEABILIZATION; CONDUCTIVITY; FIBROSARCOMA; STIMULATION AB The intratumoral field, which determines the efficiency of electric field-mediated drug and gene delivery, can differ significantly from the applied field. Therefore, we investigated the distribution of the electric field in mouse tumors and tissue phantoms exposed to a large range of electric stimuli, and quantified the resistances of tumor, skin, and electrode-tissue interface. The samples used in the study included 4T1 and B16.F10 tumors, mouse skin, and tissue phantoms constructed with 1% agarose gel with or without 4T1 cells. When pulsed electric fields were applied to samples using a pair of parallel-plate electrodes, we determined the electric field and resistances in each sample as well as the resistance at the electrode-tissue interface. The electric fields in the center region of tissue phantoms and tumor slices ex vivo were macroscopically uniform and unidirectional between two parallel-plate electrodes. The field strengths in tumor tissues were significantly lower than the applied field under both ex vivo and in vivo conditions. During in vivo stimulation, the ratio of intratumoral versus applied fields was approximately either 20% or 55%, depending on the applied field. Meanwhile, the total resistance of skin and electrode-tissue interface was decreased by approximately 70% and the electric resistance at the center of both tumor models was minimally changed when the applied field was increased from 50 to 400 V/cm. These results may be useful for improving electric field-mediated drug and gene delivery in solid tumors. C1 Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Yuan, F (reprint author), Duke Univ, Dept Biomed Engn, 136 Hudson Hall,Box 90281, Durham, NC 27708 USA. EM fyuan@acpub.duke.edu RI Yuan, Fan/A-1287-2011; OI Zaharoff, David/0000-0001-6885-6727 FU NCI NIH HHS [CA94019] NR 31 TC 18 Z9 18 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD OCT PY 2006 VL 34 IS 10 BP 1564 EP 1572 DI 10.1007/s10439-006-9151-3 PG 9 WC Engineering, Biomedical SC Engineering GA 098SL UT WOS:000241543000007 PM 16917743 ER PT J AU Hardy, J Cai, HB Cookson, MR Gwinn-Hardy, K Singleton, A AF Hardy, John Cai, Huaiban Cookson, Mark R. Gwinn-Hardy, Katrina Singleton, Andrew TI Genetics of Parkinson's disease and parkinsonism SO ANNALS OF NEUROLOGY LA English DT Article ID ALPHA-SYNUCLEIN GENE; EARLY-ONSET PARKINSONISM; DROSOPHILA DJ-1 MUTANTS; COMMON LRRK2 MUTATION; OXIDATIVE STRESS; KINASE-ACTIVITY; LEWY BODIES; DOPAMINERGIC-NEURONS; CLINICAL-DIAGNOSIS; LOCUS TRIPLICATION AB Until 10 years ago, conventional wisdom held that Parkinson's disease was not a genetic disorder. Since that time, there have been a plethora of genetic findings, culminating in the cloning of several genes that derive from the loci given the nomenclature PARK1-PARK12 (OMIM 168600). Recently, these research findings have begun to impact clinical practice, and this impact is likely to increase. The primary purpose of this article is to outline these genetic advances, discuss their importance for current practice in clinical and related settings, and outline briefly how they are influencing research into the causes of and possible future treatments for this prevalent disorder. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Cai, Huaibin/H-3359-2013; OI Cai, Huaibin/0000-0002-8596-6108; Gwinn, Katrina/0000-0002-8277-651X FU Intramural NIH HHS; Medical Research Council [G0701075] NR 86 TC 206 Z9 211 U1 2 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2006 VL 60 IS 4 BP 389 EP 398 DI 10.1002/ana.21022 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 105TM UT WOS:000242055200007 PM 17068789 ER PT J AU Oroszi, G Lapteva, L Davis, E Yarboro, CH Weickert, T Roebuck-Spencer, T Bleiberg, J Rosenstein, D Pao, M Lipsky, PE Goldman, D Lipsky, RH Illei, GG AF Oroszi, G. Lapteva, L. Davis, E. Yarboro, C. H. Weickert, T. Roebuck-Spencer, T. Bleiberg, J. Rosenstein, D. Pao, M. Lipsky, P. E. Goldman, D. Lipsky, R. H. Illei, G. G. TI The Met66 allele of the functional Val66Met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID ACTIVITY-DEPENDENT SECRETION; FAMILY-BASED ASSOCIATION; NERVE GROWTH-FACTOR; COGNITIVE IMPAIRMENT; MOLECULAR-CLONING; BIPOLAR DISORDER; HUMAN-MEMORY; BDNF; PREVALENCE; SURVIVAL AB Background: A common functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) was previously associated with diminished episodic memory performance in healthy people. As cognitive function is commonly impaired in patients with systemic lupus erythematosus (SLE), the association of the BDNF Val66Met with neurocognitive function was studied. Objective: To study the association of the BDNF Val66Met with neurocognitive function in a cohort of patients with SLE. Methods: Cognitive function was assessed in 59 patients with SLE with no previous or current central nervous system involvement. Cognitive tests were grouped into five domains (memory, attention/executive function, visuospatial skills, motor function and psychomotor speed) and used to obtain domain Z scores, reflecting the difference between averaged scores of performance on individual tests and published norms in each domain. Genotyping was carried out using a 5'-nuclease assay with 99.9% accuracy. Unpaired t test was used to assess the relationship between genotypes and cognitive function, whereas the effect of possible confounders was assessed in a multivariate analysis. Results: Patients carrying the Met66 allele scored significantly higher on psychomotor, attention/executive and motor function tests, resulting in significantly higher domain Z scores for the psychomotor (p=0.005) and motor (p=0.002) domains. Conclusions: The BDNF Met66 allele was associated with better cognitive functioning in the psychomotor and motor domains, even after controlling for differences in ethnicity, sex, depression status and prednisone treatment. These data suggest that the BDNF Met66 allele confers protection against the decline of motor and psychomotor cognitive functions in patients with longstanding SLE. C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Natl Rehabil Hosp, Washington, DC USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, 10 Ctr Dr,Room 1N114, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 FU Intramural NIH HHS NR 42 TC 33 Z9 33 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD OCT PY 2006 VL 65 IS 10 BP 1330 EP 1335 DI 10.1136/ard.2006.051623 PG 6 WC Rheumatology SC Rheumatology GA 084CF UT WOS:000240508600011 PM 16606648 ER PT J AU Liu, XW Lagenaur, LA Simpson, DA Essenmacher, KP Frazier-Parker, CL Liu, Y Tsai, D Rao, SS Hamer, DH Parks, TP Lee, PP Xu, Q AF Liu, Xiaowen Lagenaur, Laurel A. Simpson, David A. Essenmacher, Kirsten P. Frazier-Parker, Courtney L. Liu, Yang Tsai, Daniel Rao, Srinivas S. Hamer, Dean H. Parks, Thomas P. Lee, Peter P. Xu, Qiang TI Engineered vaginal Lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GENITAL-TRACT INFECTION; LACTIC-ACID BACTERIA; SEXUAL TRANSMISSION; MICROBICIDE DEVELOPMENT; INACTIVATING PROTEIN; TOPICAL MICROBICIDES; COMMENSAL BACTERIA; HIV; WOMEN; EXPRESSION AB Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIVBaL infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women. C1 Stanford Univ, Dept Med, Stanford, CA 94305 USA. Osel Inc, Santa Clara, CA 95054 USA. NIH, Lab Anim Med, Vaccine Res Ctr, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Lee, PP (reprint author), Stanford Univ, Dept Med, Stanford, CA 94305 USA. EM ppl@stanford.edu; qxu@oselinc.com FU NIAID NIH HHS [U19 AI060615, U01 AI066708, U19 AI60615] NR 54 TC 73 Z9 84 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3250 EP 3259 DI 10.1128/AAC.00493-06 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700004 PM 17005802 ER PT J AU Manjunatha, UH Lahiri, R Randhawa, B Dowd, CS Krahenbuhl, JL Barry, CE AF Manjunatha, Ujjini H. Lahiri, Ramanuj Randhawa, Baljit Dowd, Cynthia S. Krahenbuhl, James L. Barry, Clifton E., III TI Mycobacterium leprae is naturally resistant to PA-824 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; COENZYME F-420; BOVIS BCG; TUBERCULOSIS; LEPROSY; BIOSYNTHESIS; R207910; INVITRO; SYSTEM; ACID AB Leprosy responds very slowly to the current multidrug therapy, and hence there is a need for novel drugs with potent bactericidal activity. PA-824 is a 4-nitroimidazo-oxazine that is currently undergoing phase I clinical trials for the treatment of tuberculosis. The activity of PA-824 against Mycobacterium leprae was tested and compared with that of rifampin in axenic cultures, macrophages, and two different animal models. Our results conclusively demonstrate that PA-824 has no effect on the viability of M. leprae in all three models, consistent with the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547 in the M. leprae genome, which is essential for activation of this molecule. C1 NIAID, Tuberculosis Res Sect, Rockville, MD 20852 USA. Louisiana State Univ, Lab Res Branch, Natl Hansens Dis Program, Baton Rouge, LA 70803 USA. RP Barry, CE (reprint author), NIAID, Tuberculosis Res Sect, 12441 Parklawn Dr,Twinbrook 2, Rockville, MD 20852 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [Y1-AI-2004] NR 27 TC 24 Z9 25 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3350 EP 3354 DI 10.1128/AAC.00488-06 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700018 PM 17005816 ER PT J AU Bona, R Andreotti, M Buffa, V Leone, P Galluzzo, CM Amici, R Palmisano, L Mancini, MG Michelini, Z Di Santo, R Costi, R Roux, A Pommier, Y Marchand, C Vella, S Cara, A AF Bona, Roberta Andreotti, Mauro Buffa, Viviana Leone, Pasqualina Galluzzo, Clementina Maria Amici, Roberta Palmisano, Lucia Mancini, Maria Grazia Michelini, Zuleika Di Santo, Roberto Costi, Roberta Roux, Alessandra Pommier, Yves Marchand, Christophe Vella, Stefano Cara, Andrea TI Development of a human immunodeficiency virus vector-based, single-cycle assay for evaluation of anti-integrase compounds SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DIKETO ACID-DERIVATIVES; HIV-1 INTEGRASE; IN-VIVO; TYPE-1 INTEGRASE; HTLV-III; T-LYMPHOCYTES; CELL-CULTURE; INHIBITORS; DNA; REPLICATION AB Therapeutic strategies aimed at inhibiting human immunodeficiency virus type 1 (HIV-1) replication employ a combination of drugs targeted to two viral enzymes (reverse transcriptase and protease) and to the viral entry/fusion step. However, the high propensity of HIV-1 to develop resistance makes the development of novel compounds targeting different steps of the HIV-1 life cycle essential. Among these, integrase (IN) inhibitors have successfully passed the early phases of clinical development. By preventing integration, IN inhibitors preclude viral replication while allowing production of extrachromosomal forms of viral DNA (E-DNA). Here, we describe an improved and standardized assay aimed at evaluating IN inhibitors by taking advantage of the transcriptional activity of E-DNA produced by HIV-derived vectors in the absence of replication-competent virus. In this context, the use of the firefly luciferase gene as a reporter gene provides a rapid and quantitative measure of viral-vector infectivity, thus making it a safe and cost-effective assay for evaluating novel IN inhibitors. C1 Ist Super Sanita, Dept Drug Res & Evaluat, I-00161 Rome, Italy. Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy. Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Studi Farmaceut, I-00185 Rome, Italy. NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Cara, A (reprint author), Ist Super Sanita, Dept Drug Res & Evaluat, Viale Regina Elena 299, I-00161 Rome, Italy. EM acara@iss.it RI palmisano, lucia/G-5577-2011; Cara, Andrea/M-4865-2015; MANCINI, MARIA GRAZIA/D-7960-2016; Marchand, Christophe/D-8559-2016; Vella, Stefano/D-4912-2015; Michelini, Zuleika/J-9003-2016; andreotti, mauro/K-1436-2016; OI Cara, Andrea/0000-0003-4967-1895; Vella, Stefano/0000-0003-2347-5984; Michelini, Zuleika/0000-0001-6841-7396; andreotti, mauro/0000-0001-5168-8624; COSTI, Roberta/0000-0002-1314-9029; Di Santo, Roberto/0000-0002-4279-7666 NR 49 TC 17 Z9 17 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3407 EP 3417 DI 10.1128/AAC.00517-06 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700026 PM 17005823 ER PT J AU Groll, AH Lyman, CA Petraitis, V Petraitiene, R Armstrong, D Mickiene, D Alfaro, RM Schaufele, RL Sein, T Bacher, J Walsh, TJ AF Groll, Andreas H. Lyman, Caron A. Petraitis, Vidmantas Petraitiene, Ruta Armstrong, Derek Mickiene, Diana Alfaro, Raul M. Schaufele, Robert L. Sein, Tin Bacher, John Walsh, Thomas J. TI Compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL ACTIVITY; PULMONARY ASPERGILLOSIS; LIPOSOMAL FORMULATION; ANTIMICROBIAL AGENTS; COLLOIDAL DISPERSION; TISSUE DISTRIBUTION; CANDIDA-ALBICANS; COMPLEX; INFECTION; EFFICACY AB We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations +/- standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 +/- 1.62 versus 2.71 +/- 1.22, 6.29 +/- 1.17, and 6.32 +/- 0.57 mu g/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 +/- 37.0 versus 8.92 +/- 2.89, 5.43 +/- 1.75, and 7.52 +/- 2.50 mu g/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 +/- 1.43 versus 0.44 +/- 0.13, 0.68 +/- 0.27, and 0.90 +/- 0.28 mu g/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 It after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD USA. Warren Grant Magnuson Clin Ctr, Dept Pharm, Pharmacokinet Res Lab, Bethesda, MD USA. NIH, Div Vet Resources, Bethesda, MD USA. Univ Childrens Hosp, Ctr Bone Marrow Transplantat, Infect Dis Res Program, Munster, Germany. Univ Childrens Hosp, Dept Pediat Hematol & Oncol, Munster, Germany. RP Walsh, TJ (reprint author), CRC-1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 31 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3418 EP 3423 DI 10.1128/AAC.00241-06 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700027 PM 17005824 ER PT J AU Kocisko, DA Caughey, B Morrey, JD Race, RE AF Kocisko, David A. Caughey, Byron Morrey, John D. Race, Richard E. TI Enhanced antiscrapie effect using combination drug treatment SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PRION PROTEIN-FORMATION; INHIBITION; INFUSION AB Combination treatment with pentosan polysulfate and Fe(III)meso-tetra(4-sulfonatopbenyl)porphine in mice beginning 14 or 28 days after scrapie inoculation significantly increased survival times. This increase may be synergistic, implying that the compounds act cooperatively in vivo. Combination therapy may therefore be more effective for treatment of transmissible spongiform encephalopathies and other protein-misfolding diseases. C1 NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. Utah State Univ, Inst Antiviral Res Anim Dairy, Logan, UT 84322 USA. Utah State Univ, Dept Vet Sci, Logan, UT 84322 USA. RP Kocisko, DA (reprint author), NIAID, Rocky Mt Lab, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM DKocisko@niaid.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-15435, N01AI15435] NR 11 TC 17 Z9 21 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2006 VL 50 IS 10 BP 3447 EP 3449 DI 10.1128/AAC.00715-06 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 091IX UT WOS:000241021700031 PM 17005828 ER PT J AU Baleja, JD Cherry, JJ Liu, ZG Gao, H Nicklaus, MC Voigt, JH Chen, JJ Androphy, EJ AF Baleja, James D. Cherry, Jonathan J. Liu, Zhiguo Gao, Hua Nicklaus, Marc C. Voigt, Johannes H. Chen, Jason J. Androphy, Elliot J. TI Identification of inhibitors to papillomavirus type 16 E6 protein based on three-dimensional structures of interacting proteins SO ANTIVIRAL RESEARCH LA English DT Article DE papillomavirus; HPV-16; E6; in silico screening; antiviral; protein-protein interaction ID KERATINOCYTE CELL-LINE; CERVICAL-CANCER; UBIQUITIN LIGASE; EPITHELIAL-CELLS; BINDING DOMAIN; ONCOPROTEIN; P53; DIFFERENTIATION; INACTIVATION; ASSOCIATION AB Human papillomaviruses (HPV) cause cutaneous and genital warts. A subset of HPV types is associated with a high-risk for progression to malignancy. The E6 protein from the high-risk HPV types represents an attractive target for intervention because of its roles in viral propagation and cellular transformation. E6 functions in part by interaction with human cellular proteins, several of which possess a helical E6-binding motif. The role for each amino acid in this motif for binding E6 has been tested through structure determination and site-directed mutagenesis. These structural and molecular biological approaches defined the spatial geometry of functional groups necessary for binding to E6. This E6-binding information (the E6-binding pharmacophore) was transferred into a three-dimensional query format suitable for computational screening of large chemical databases. Compounds were identified and tested using in vitro and cell culture-based assays. Several compounds selectively inhibited E6 interaction with the E6-binding protein E6AP and interfered with the ability of E6 to promote p53 degradation. Such compounds provide leads for the development of new pharmacologic agents to treat papillomavirus infections and their associated cancers. (c) 2006 Elsevier B.V. All rights reserved. C1 Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. RP Baleja, JD (reprint author), Tufts Univ, Sch Med, Dept Biochem, 136 Harrison Ave, Boston, MA 02111 USA. EM jim.baleja@tufts.edu; jason.chen@umassmed.edu RI Nicklaus, Marc/N-4183-2014; OI liu, zhiguo/0000-0002-8485-7356; Nicklaus, Marc/0000-0002-4775-7030; Androphy, Elliot/0000-0002-8104-0703 FU NCI NIH HHS [R03 CA92746, R01 CA119904, R01 CA119904-02]; NIAID NIH HHS [R01 AI038001, R01 AI38001] NR 56 TC 38 Z9 40 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 2006 VL 72 IS 1 BP 49 EP 59 DI 10.1016/j.antiviral.2006.03.014 PG 11 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 086YH UT WOS:000240708600006 PM 16690141 ER PT J AU Schultz, MK Hammond, M Cessnaa, JT Plascjak, P Norman, B Szajek, L Garmestani, K Zimmerman, BE Unterweger, M AF Schultz, Michael K. Hammond, Michelle Cessnaa, Jeffrey T. Plascjak, Paul Norman, Bruce Szajek, Lawrence Garmestani, Kayhan Zimmerman, Brian E. Unterweger, Michael TI Assessing the At-210 impurity in the production of At-211 for radiotherapy by Po-210 analysis via isotope dilution alpha spectrometry SO APPLIED RADIATION AND ISOTOPES LA English DT Article; Proceedings Paper CT 15th International Conference on Radionuclide Metrology and Its Applications (ICRM 2005) CY SEP 05-09, 2005 CL Univ Oxford, Oxford, ENGLAND SP Natl Phys Lab HO Univ Oxford DE astatine-211; cyclotron production; radiotherapy; impurity analysis; astatine-210; polonium-210; isotope dilution; alpha spectrometry ID CYCLOTRON PRODUCTION AB A method for assessing the impurity At-210 in cyclotron-produced At-211 via isotope dilution alpha spectrometry is presented. The activity of At-210 is quantified by measuring the activity of daughter nuclide Po-210. Counting sources are prepared by spontaneous deposition of Po on a silver disc. Activity of At-210 (at the time of Po-210 maximum activity) is found to be 83.5 +/- 9.0 Bq, corresponding to an atom ratio (At-210:At-211 at the time of distillation) of 0.010 +/- 0.007% (k = 2). The method produces high-quality alpha spectra, with baseline alpha-peak resolution and chemical yields of greater than 85%. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Inst Stand & Technol, Radioact Grp, Gaithersburg, MD 21702 USA. Natl Inst Hlth, Cyclotron Facil, Bethesda, MD USA. IAEA, Dosimetry & Radiat Phys Sect, A-1400 Vienna, Austria. RP Schultz, MK (reprint author), Natl Inst Stand & Technol, Radioact Grp, 100 Bur Dr,MS8462, Gaithersburg, MD 21702 USA. EM michael.schultz@nist.gov NR 15 TC 8 Z9 8 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD OCT-NOV PY 2006 VL 64 IS 10-11 SI SI BP 1365 EP 1369 DI 10.1016/j.apradiso.2006.02.046 PG 5 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 092LA UT WOS:000241096900054 PM 16563782 ER PT J AU Furey, ML Drevets, WC AF Furey, Maura L. Drevets, Wayne C. TI Antidepressant efficacy of the antimuscarinic drug scopolamine - A randomized, placebo-controlled clinical trial SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BEHAVIORAL DESPAIR TEST; DEPRESSED-PATIENTS; SLEEP-DEPRIVATION; MAJOR DEPRESSION; ANTI-DEPRESSANTS; INDUCTION TEST; RATING-SCALE; ANIMAL-MODEL; CHRM2 GENE; RECEPTOR AB Context: The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide ( 4 mu g/kg intravenously) compared with placebo ( P= .002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. Objective: To evaluate scopolamine as a potential antidepressant agent. Design: Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. Setting: The National Institute of Mental Health. Patients: Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. Interventions: Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 mu g/kg). Individuals were randomized to a placebo/ scopolamine or scopolamine/ placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. Main Outcome Measures: Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. Results: The placebo/ scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores ( P < .001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/ placebo group also showed reductions in depression and anxiety rating scale scores ( P < .001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration ( P <= .002). Conclusion: Rapid, robust antidepressant responses to the scopolamine occurred in currently depressed patients who predominantly had poor prognoses. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Furey, ML (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr,Bldg 15K,Room 115B, Bethesda, MD 20892 USA. EM mfurey@mail.nih.gov RI Furey, Maura/H-5273-2013 FU Intramural NIH HHS [ZIA MH002813-08] NR 68 TC 172 Z9 180 U1 6 U2 17 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 OCT PY 2006 VL 63 IS 10 BP 1121 EP 1129 DI 10.1001/archpsyc.63.10.1121 PG 9 WC Psychiatry SC Psychiatry GA 090FK UT WOS:000240935900008 PM 17015814 ER PT J AU McFarland, HF Jacobson, S AF McFarland, Henry F. Jacobson, Steven TI Natalizumab and immune cells SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP McFarland, HF (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bldg 10,Room 5B16,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. EM mcfarlandh@ninds.nih.gov NR 5 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2006 VL 63 IS 10 BP 1366 EP 1367 DI 10.1001/archneur.63.10.1366 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 091VW UT WOS:000241057400001 PM 17030649 ER PT J AU Misdraji, J Oliva, E Goldblum, JR Lauwers, CY Compton, CC AF Misdraji, Joseph Oliva, Esther Goldblum, John R. Lauwers, Cregory Y. Compton, Carolyn C. CA Coll Amer Pathologists TI Protocol for the examination of specimens from patients with invasive carcinomas of the appendix SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID DISSEMINATED PERITONEAL ADENOMUCINOSIS; INTRAPERITONEAL CHEMOTHERAPY; VERMIFORM APPENDIX; PSEUDOMYXOMA-PERITONEI; CYTOREDUCTIVE SURGERY; CLINICOPATHOLOGICAL ANALYSIS; MUCINOUS CARCINOMATOSIS; PRIMARY ADENOCARCINOMA; TUMORS; PROGNOSIS C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Anat Pathol, Cleveland, OH 44195 USA. NCI, Off Director, Bethesda, MD 20892 USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren Bldg 105F, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 26 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2006 VL 130 IS 10 BP 1433 EP 1439 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 091SS UT WOS:000241049200006 PM 17090183 ER PT J AU Tuan, RS AF Tuan, Rocky S. TI Stemming cartilage degeneration: Adult mesenchymal stem cells as a cell source for articular cartilage tissue engineering SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID GLOW-DISCHARGE PLASMA; CHONDROGENIC DIFFERENTIATION; BONE-MARROW; IN-VIVO; EXPRESSION C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1523,MSC 8022, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov NR 20 TC 56 Z9 65 U1 0 U2 3 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 OCT PY 2006 VL 54 IS 10 BP 3075 EP 3078 DI 10.1002/art.22148 PG 4 WC Rheumatology SC Rheumatology GA 094TB UT WOS:000241260800004 PM 17009225 ER PT J AU Nagai, T Tanaka, M Tsuneyoshi, Y Matsushita, K Sunahara, N Matsuda, T Yoshida, H Komiya, S Onda, M Matsuyama, T AF Nagai, Taku Tanaka, Masashi Tsuneyoshi, Yasuhiro Matsushita, Kakushi Sunahara, Nobuhiko Matsuda, Takemasa Yoshida, Hiroki Komiya, Setsuro Onda, Masanori Matsuyama, Takami TI In vitro and in vivo efficacy of a recombinant immunotoxin against folate receptor beta on the activation and proliferation of rheumatoid arthritis synovial cells SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; PSEUDOMONAS EXOTOXIN; SCID MICE; ADHESION MOLECULE-1; MACROPHAGES; CANCER; EXPRESSION; APOPTOSIS; ANTIBODY AB Objective. To investigate the effects of the recombinant immunotoxin dsFv anti-FR beta-PE38, which consists of the disulfide-stabilized Fv fragment (dsFv) of the anti-folate receptor beta (anti-FR beta) antibody and the 38-kd portion of Pseudomonas exotoxin A (PE38), on the activation and proliferation of cells that function in inflammatory and degradative processes in rheumatoid arthritis (RA) synovial tissue. Methods. The Ig V-H-PE38 fusion protein and the Ig V-L protein were produced in Escherichia coli, and then joined with a disulfide bond by engineering cysteine residues in the framework regions of these proteins. The effects of dsFv anti-FR beta-PE38 on the activation and proliferation of cells in RA synovial tissue were investigated by immunohistochemistry; the numbers of cells expressing CD68, vascular cell adhesion molecule 1, angiopoietin 1, CD34, proliferating cell nuclear antigen, and interleukin-6 and the numbers of apoptotic cells were counted in RA synovial tissue engrafted into SCID mice treated or not treated with dsFv anti-FR beta-PE38. The effects of dsFv anti-FR beta-PE38 on the generation of osteoclasts from RA adherent synovial mononuclear cells in vitro was investigated by counting the number of resorption pits on dentin slices treated or not treated with dsFv anti-FR beta-PE38. Results. Administration of dsFv anti-FR beta-PE38 reduced the numbers of macrophages, activated fibroblast-like cells, endothelial cells, and proliferating cells and increased the numbers of apoptotic cells in RA synovial tissue engrafted into SCID mice. In vitro, the generation of osteoclasts from RA adherent synovial mononuclear cells was largely suppressed by treatment with dsFv anti-FR beta-PE38. Conclusion. Our findings show that dsFv anti-FR beta-PE38 immunotoxin would be a promising tool for the treatment of RA synovitis, especially when administered intraarticularly. C1 Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Immunol, Kagoshima 8908544, Japan. Kagoshima Red Cross Hosp, Kagoshima, Japan. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Matsuyama, T (reprint author), Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Immunol, 8-35-1 Sakuragaoka, Kagoshima 8908544, Japan. EM matuyama@m.kufm.kagoshima-u.ac.jp NR 36 TC 22 Z9 22 U1 0 U2 3 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 OCT PY 2006 VL 54 IS 10 BP 3126 EP 3134 DI 10.1002/art.22082 PG 9 WC Rheumatology SC Rheumatology GA 094TB UT WOS:000241260800011 PM 17009233 ER PT J AU Fukuda, T Roberts, A Ahearn, M Zaal, K Ralston, E Plotz, PH Raben, N AF Fukuda, Tokiko Roberts, Ashley Ahearn, Meghan Zaal, Kristien Ralston, Evelyn Plotz, Paul H. Raben, Nina TI Autophagy and lysosomes in Pompe disease SO AUTOPHAGY LA English DT Article DE glycogen storage disease type II; myopathy; acid alpha-glucosidase; enzyme replacement therapy; lysosomal disorder ID ACID ALPHA-GLUCOSIDASE; ENZYME REPLACEMENT THERAPY; STORAGE-DISEASE; CLINICAL-TRIAL; RECOMBINANT; LC3; GLYCOGEN AB In Pompe disease, a deficiency of lysosomal acid alpha-glucosidase, intralysosomal glycogen accumulates in multiple tissues, with skeletal and cardiac muscle most severely affected.(1) Complete enzyme deficiency results in rapidly progressive infantile cardiomyopathy and skeletal muscle myopathy that is fatal within the first two years of life. Patients with partial enzyme deficiency suffer from skeletal muscle myopathy and experience shortened lifespan due to respiratory failure. The major advance has been the development of enzyme replacement therapy, which recently became available for Pompe patients. However, the effective clearance of skeletal muscle glycogen, as shown by both clinical and preclinical studies, has proven more difficult than anticipated.(2-4) Our recent work published in Annals of Neurology(5) was designed to cast light on the problem, and was an attempt to look beyond the lysosomes by analyzing the downstream events affected by the accumulation of undigested substrate in lysosomes. We have found that the cellular pathology in Pompe disease spreads to affect both endocytic (the route of the therapeutic enzyme) and autophagic (the route of glycogen) pathways, leading to excessive autophagic buildup in therapy-resistant skeletal muscle fibers of the knockout mice. C1 NIAMS, NIH, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. NIAMS, NIH, Light Imaging Sect, Off Sci & Technol, Bethesda, MD 20892 USA. RP Raben, N (reprint author), NIAMS, NIH, Arthritis & Rheumatism Branch, 9000 Rockville Pike,Clin Ctr Bld 10-9N244, Bethesda, MD 20892 USA. EM rabenn@arb.niams.nih.gov FU Intramural NIH HHS NR 16 TC 57 Z9 60 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD OCT-DEC PY 2006 VL 2 IS 4 BP 318 EP 320 PG 3 WC Cell Biology SC Cell Biology GA 080LR UT WOS:000240249800017 PM 16874053 ER PT J AU Fukuda, T Plotz, P Raben, N AF Fukuda, Tokiko Plotz, Paul Raben, Nina TI Autophagy in a metabolic myopathy, Pompe disease (Short talk-9) SO AUTOPHAGY LA English DT Meeting Abstract C1 NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. EM fukudat@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD OCT-DEC PY 2006 VL 2 IS 4 MA 51 BP 362 EP 362 PG 1 WC Cell Biology SC Cell Biology GA 080LR UT WOS:000240249800111 ER PT J AU Maestripieri, D Higley, JD Lindell, SG Newman, TK McCormack, KM Sanchez, MM AF Maestripieri, Dario Higley, J. Dee Lindell, Stephen G. Newman, Timothy K. McCormack, Kai M. Sanchez, Mar M. TI Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta) SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE early experience; monoamine metabolites; development; primates ID MOTHER-INFANT RELATIONSHIPS; TRANSPORTER GENE VARIATION; INDIVIDUAL-DIFFERENCES; EARLY EXPERIENCE; REARING CONDITION; PRIMATES; MONKEYS; PSYCHOPATHOLOGY; CARE; TRANSMISSION AB This study investigated the effects of early exposure to variable parenting style and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine metabolites and examined the role of monoaminergic function in the intergenerational transmission of infant abuse in rhesus monkeys (Macaca mulatto). Forty-three infants reared by their biological mothers and 15 infants that were cross-fostered at birth and reared by unrelated mothers were followed longitudinally through their first 3 years of life or longer. Approximately half of the infants were reared by abusive mothers and half by nonabusive controls. Abused infants did not differ from controls in CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA than low-rejection infants. The abused females who became abusive mothers in adulthood had lower CSF 5-HIAA than the abused females who did not. A similar trend was also observed among the cross-fostered females, suggesting that low serotonergic function resulting from early exposure to high rates of maternal rejection plays a role in the intergenerational transmission of infant abuse. C1 Univ Chicago, Dept Comparat Human Dev, Chicago, IL 60637 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Spelman Coll, Dept Psychol, Atlanta, GA USA. NIAAA, Sect Study Primate Models Psychopathol, Lab Clin & Translat Studies, Poolesville, MD USA. Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Maestripieri, D (reprint author), Univ Chicago, Dept Comparat Human Dev, 5730 S Woodlawn Ave, Chicago, IL 60637 USA. EM dario@uchicago.edu FU NCRR NIH HHS [RR-00165]; NIMH NIH HHS [K02-MH63097, R01-MH57249, R01-MH62577, R21-MH01005] NR 31 TC 67 Z9 68 U1 1 U2 19 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2006 VL 120 IS 5 BP 1017 EP 1024 DI 10.1037/0735-7044.120.5.1017 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 094YC UT WOS:000241274200003 PM 17014253 ER PT J AU LaSalle-Ricci, VH Arnkoff, DB Glass, CR Crawley, SA Ronquillo, JG Murphy, DL AF LaSalle-Ricci, V. Holland Arnkoff, Diane B. Glass, Carol R. Crawley, Sarah A. Ronquillo, Jonne G. Murphy, Dennis L. TI The hoarding dimension of OCD: Psychological comorbidity and the five-factor personality model SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE hoarding; obsessive-compulsive disorder; personality; five-factor model; comorbidity ID OBSESSIVE-COMPULSIVE DISORDER; FACTOR-ANALYZED SYMPTOM; CLINICAL-FEATURES; BEHAVIOR; EPIDEMIOLOGY; RELIABILITY; INTERVIEW; THERAPY; BIPOLAR; IMPACT AB Although hoarding has been associated with several psychological disorders, it is most frequently linked to obsessive-compulsive disorder (OCD). The present study assessed hoarding obsessions and compulsions in 204 individuals with OCD, and evaluated how hoarding was related to obsessive-compulsive symptom severity, psychological comorbidity, and personality as measured by the five-factor model. Results indicated that hoarding in OCD is a dimensional variable that is positively associated with dysphoria, total number of lifetime Axis I disorders, and lifetime histories of bipolar 1, PTSD, and body dysmorpbic disorder. Hoarding was negatively correlated with the NEOPersonality I nven tory- Revised (NEO-PI-R) factor of Conscientiousness and positively associated with the NEO-Pl-R factor of Neuroticism. When all personality and psychopathology variables were entered into a regression equation, dysphoria, bipolar 11 disorder, Conscientiousness, age, and Extraversion emerged as significant predictors of hoarding severity. Recommendations are made for clinicians and for future research. (c) 2005 Elsevier Ltd. All rights reserved. C1 Catholic Univ Amer, NIMH, Adult OCD Unit, NIH, Bethesda, MD 20892 USA. RP LaSalle-Ricci, VH (reprint author), Catholic Univ Amer, NIMH, Adult OCD Unit, NIH, 10 Ctr Dr MDC 1264,10-3D41, Bethesda, MD 20892 USA. EM vholly@aol.com NR 47 TC 31 Z9 31 U1 4 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD OCT PY 2006 VL 44 IS 10 BP 1503 EP 1512 DI 10.1016/j.brat.2005.11.009 PG 10 WC Psychology, Clinical SC Psychology GA 094WK UT WOS:000241269700013 PM 16386705 ER PT J AU Fan, HK Williams, DL Zingarelli, B Breuel, KF Teti, G Tempel, GE Spicher, K Boulay, G Birnbaumer, L Halushka, PV Cook, JA AF Fan, Hongkuan Williams, David L. Zingarelli, Basilia Breuel, Kevin F. Teti, Giuseppe Tempel, George E. Spicher, Karsten Boulay, Guylain Birnbaumer, Lutz Halushka, Perry V. Cook, James A. TI Differential regulation of lipopolysaccharide and Gram-positive bacteria induced cytokine and chemokine production in splenocytes by G alpha(i) proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE G(i) protein deficient mice; endotoxin; Staphylococcus aureus; TLR signaling ID SIGNAL-TRANSDUCTION EVENTS; HUMAN MONOCYTIC CELLS; STAPHYLOCOCCUS-AUREUS; MURINE MACROPHAGES; GENE-EXPRESSION; TLR4 AGONISTS; CUTTING EDGE; IN-VITRO; TYROSINE KINASE; RECEPTOR (TLR)2 AB Heterotrimeric G(i) proteins play a role in lipopolysaccharide (LPS) and Staphylococcus aureus (SA) activated signaling leading to inflammatory mediator production. We hypothesized that genetic deletion of Gi proteins would alter cytokine and chemokine production induced by LPS and SA. LPS- and heat killed SA-induced cytokine and chemokine production in splenocytes from wild type (WT), G alpha(i2) (-/-) or G alpha(i1/3) (-/-) mice were investigated. LPS- or SA-induced production of TNF alpha, IL-6, IFN gamma, IL-12, IL-17, GM-CSF, MIP-1 alpha, MCP-1, MIG and IP-10 were significantly increased (1.2 to 33 fold, p < 0.05) in splenocytes harvested from G alpha(i2)(-/-) mice compared with WT mice. The effect of G alpha(i) protein depletion was remarkably isoform specific. In splenocytes from G alpha(i1/3) (-/-) mice relative to WT mice, SA-induced IL-6, IFN gamma, GM-CSF, and IP-10 levels were decreased (59% to 86%,p < 0.05), whereas other LPS- or SA-stimulated cytokines and chemokines were not different relative to WT mice. LPS- and SA-induced production of KC were unchanged in both groups of the genetic deficient mice. Splenocytes from both G alpha(i2) (-/-)and G alpha(i1/3) (-/-)mice did not exhibit changes in TLR2 and TLR4 expression. Also analysis of splenic cellular composition by flow cytometry demonstrated an increase in splenic macrophages and reduced CD4 T cells in both G alpha(i2) (-/-)and G alpha(i1/3\) (-/-)mice relative to WT mice. The disparate response of splenocytes from the G alpha(i2) (-/-) relative to G alpha(i1/3) (-/-) Mice therefore cannot be attributed to major differences in spleen cellular composition. These data demonstrate that G(i2) and G(i1/3) proteins are both involved and differentially regulate splenocyte inflammatory cytokine and chemokine production in a highly Gi isoform specific manner in response to LPS and Gram-positive microbial stimuli. (c) 2006 Elsevier B.V. All rights reserved. C1 Dept Neurosci, Charleston, SC 29425 USA. E Tennessee State Univ, Dept Surg, Johnson City, TN 37614 USA. Childrens Hosp, Med Ctr, Div Crit Care Med, Cincinnati, OH 45229 USA. E Tennessee State Univ, James H Quillen Coll Med, Johnson City, TN 37614 USA. Med Univ Messina, Dept Expt Pathol & Microbiol, Messina, Italy. Univ Dusseldorf, Inst Biochem & Mol Biol, Sch Med, D-40225 Dusseldorf, Germany. Univ Sherbrooke, Sch Med, Dept Pharmacol, Sherbrooke, PQ J1N 5N4, Canada. Natl Inst Environm Hlth Sci, Transmembrane Signaling Grp, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cook, JA (reprint author), Dept Neurosci, 173 Ashley Ave,BSB Room 403, Charleston, SC 29425 USA. EM cookja@musc.edu FU Intramural NIH HHS; NIDDK NIH HHS [DK19318]; NIGMS NIH HHS [GM27673, GM53522, GM67202] NR 44 TC 10 Z9 11 U1 0 U2 1 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 OCT PY 2006 VL 1763 IS 10 BP 1051 EP 1058 DI 10.1016/j.bbamer.2006.08.003 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 099IO UT WOS:000241587200008 PM 16962188 ER PT J AU Schieke, SM Finkel, T AF Schieke, Stefan M. Finkel, Toren TI Mitochondrial signaling, TOR, and life span SO BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT Mosbach Colloquium of the German-Gesellschaft-fur-Biochemie-und-Molekularbiologie CY APR 06-08, 2006 CL Mosbach, GERMANY SP German Gesell Biochem & Molelularbiol DE aging; metabolism; mitochondria; mTOR pathway; retrograde response ID MTOR PATHWAY; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; RETROGRADE RESPONSE; CALORIE RESTRICTION; ELECTRON-TRANSPORT; CELL-GROWTH; C-ELEGANS; METABOLISM; YEAST AB Growing evidence supports the concept that mitochondrial metabolism and reactive oxygen species (ROS) play a major role in aging and determination of an organism's life span. Cellular signaling pathways regulating mitochondrial activity, and hence the generation of ROS and retrograde signaling events originating in mitochondria, have recently moved into the spotlight in aging research. Involvement of the energy-sensing TOR pathway in both mitochondrial signaling and determination of life span has been shown in several studies. This brief review summarizes the recent progress on how mitochondrial signaling might contribute to the aging process with a particular emphasis on TOR signaling from invertebrates to humans. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 46 TC 70 Z9 72 U1 1 U2 19 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD OCT-NOV PY 2006 VL 387 IS 10-11 BP 1357 EP 1361 DI 10.1515/BC.2006.170 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 102CR UT WOS:000241788900009 PM 17081107 ER PT J AU Kim, YH Park, EJ Park, MH Badarch, U Woldemichael, GM Beutler, JA AF Kim, Young Ho Park, Eun Jung Park, Mi Hyun Badarch, Uranchimeg Woldemichael, Girma Moges Beutler, John Albert TI Crinamine from Crinum asiaticum var.japonicum inhibits hypoxia inducible factor-1 activity but not activity of hypoxia inducible factor-2 SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE crinamine; Crinum asiaticum var. japonicum; HIF1-alpha; HRE assay ID NITRIC-OXIDE SYNTHASE; ANTICANCER DRUG SCREEN; BREAST-TUMOR CELLS; CANCER-THERAPY; ALKALOIDS; AMARYLLIDACEAE; BULBS; GROWTH; HIF-1; CONSTITUENTS AB In a search for natural product inhibitors of hypoxia inducible factor-1 (HIF-1) function, crinamine (1), a crinane type alkaloid, showed potent dose dependent inhibition (IC50 = 2.7 mu m) of HIF-1 alpha in a cell-based reporter gene assay. Crinamine (1) was isolated from the aerial parts of Crinum asiaticum var.japonicum together with ly-corine (2), norgalanthamine (3) and epinorgalanthamine (4). The other components (2-4) showed no significant inhibition of HIF-1 alpha induced transcriptional activity. C1 Chungnam Natl Univ, Coll Pharm, Taejon 305764, South Korea. NCI, Mol Targets Dev Program, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Kim, YH (reprint author), Chungnam Natl Univ, Coll Pharm, Taejon 305764, South Korea. EM yhk@cnu.ac.kr RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU Intramural NIH HHS NR 32 TC 11 Z9 12 U1 0 U2 6 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD OCT PY 2006 VL 29 IS 10 BP 2140 EP 2142 DI 10.1248/bpb.29.2140 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098TV UT WOS:000241546600030 PM 17015967 ER PT J AU Grillon, C Baas, JMP Cornwell, B Johnson, L AF Grillon, Christian Baas, Johanna M. P. Cornwell, Brian Johnson, Linda TI Context conditioning and behavioral avoidance in a virtual reality environment: Effect of predictability SO BIOLOGICAL PSYCHIATRY LA English DT Article DE associative learning; Pavlovian conditioning; predictability; psychophysiology ID POSTTRAUMATIC-STRESS-DISORDER; DIOXIDE-ENRICHED AIR; STARTLE REFLEX; BACKGROUND STIMULI; STRIA TERMINALIS; ACOUSTIC STARTLE; PANIC DISORDER; BED NUCLEUS; FEAR; ANXIETY AB Background: Sustained anxiety can be modeled using context conditioning, which can be studied in a virtual reality environment. Unpredictable stressors increase context conditioning in animals. This study examined context conditioning to predictable and unpredictable shocks in humans using behavioral avoidance, potentiated startle, and subjective reports of anxiety. Methods: Subjects were guided through three virtual rooms (no-shock, predictable, unpredictable contexts). Eight-sec duration colored lights served as conditioned stimuli (CS). During acquisition, no shock was administered in the no-shock context. Shocks were paired with the CS in the predictable context and were administered randomly in the unpredictable context. No shock was administered during extinction. Startle stimuli were delivered during CS and between. CS to assess cued and context conditioning, respectively. To assess avoidance, subjects freely navigated into two of the three contexts to retrieve money. Results: Startle between CS was potentiated in the unpredictable context compared to the two other contexts. Following acquisition, subjects showed a strong preference for the no-shock context and avoidance of the unpredictable context. Conclusions: Consistent with animal data, context conditioning is increased by unpredictability. These data support virtual reality as a tool to extend research on physiological and behavioral signs of fear and anxiety in humans. C1 NIMH, MAP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Utrecht, Netherlands. RP Grillon, C (reprint author), NIMH, MAP, Mood & Anxiety Disorders Program, 15K N Dr,Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM grillonc@intra.nimh.nih.gov OI Baas, Johanna/0000-0001-6267-8712 FU Intramural NIH HHS NR 52 TC 101 Z9 103 U1 2 U2 15 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 OCT 1 PY 2006 VL 60 IS 7 BP 752 EP 759 DI 10.1016/j.biopsych.2006.03.072 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 090TB UT WOS:000240973300012 PM 16950216 ER PT J AU Grillon, C Baas, JMP Pine, DS Lissek, S Lawley, M Ellis, V Levine, J AF Grillon, Christian Baas, Johanna M. P. Pine, Daniel S. Lissek, Shmuel Lawley, Megan Ellis, Valerie Levine, Jessica TI The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alprazolam; anxiety; benzodiazepine; context; fear; startle reflex ID POSTTRAUMATIC-STRESS-DISORDER; LIGHT-ENHANCED STARTLE; BASE-LINE STARTLE; ACOUSTIC STARTLE; BED NUCLEUS; STRIA TERMINALIS; ANTICIPATORY ANXIETY; VIETNAM VETERANS; REFLEX; RESPONSES AB Background: The startle reflex is potentiated by aversive states. it has been, proposed that phasic startle potentiation to a threat cue and sustained startle potentiation to contextual stimuli reflect distinct processes mediated by different brain structures. The present study tested the hypothesis that alprazolam would reduce the sustained startle potentiation to contextual threats but not the startle potentiation to a threat cue. Methods: Sixteen healthy subjects received each of four treatments: placebo, .5 mg of alprazolam, 7 mg of alprazolam, and 50 mg of diphenhydramine (Benadryl) in a crossover design. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which shocks were administered unpredictably, and a third condition in which no shocks were anticipated. Acoustic startle were delivered regularly across conditions. Results: Phasic startle potentiation to the threat cue in the predictable condition was not affected by alprazolam. in contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam. Conclusions: Startle responses to an explicit threat cue and to an aversive context are psychopharmacologically distinct, suggesting that they may represent functionally dissociable aversive states. C1 NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. RP Grillon, C (reprint author), NIMH, Mood & Anxiety Disorder Program, 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA. EM christian.grillon@nih.gov RI Lissek, Shmuel/B-6577-2008; OI Baas, Johanna/0000-0001-6267-8712 FU Intramural NIH HHS NR 42 TC 70 Z9 70 U1 6 U2 10 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 OCT 1 PY 2006 VL 60 IS 7 BP 760 EP 766 DI 10.1016/j.biopsych.2005.11.027 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 090TB UT WOS:000240973300013 PM 16631127 ER PT J AU Pandit, B Sun, YJ Chen, P Sackett, DL Hu, ZG Rich, W Li, CL Lewis, A Schaefer, K Li, PK AF Pandit, Bulbul Sun, Yanjun Chen, Ping Sackett, Dan L. Hu, Zhigen Rich, Wendy Li, Chenglong Lewis, Andrew Schaefer, Kevin Li, Pui-KaI TI Structure-activity-relationship studies of conformationally restricted analogs of combretastatin A-4 derived from SU5416 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE combretastatins; SU5416; antimicrotubule; antitumor agents; cell cycle arrest; colchicine ID RECEPTOR TYROSINE KINASES; VASCULAR-TARGETING AGENT; ANTITUMOR-ACTIVITY; IN-VIVO; TUBULIN POLYMERIZATION; ANTINEOPLASTIC AGENTS; ANTIMITOTIC AGENTS; A4 PHOSPHATE; DERIVATIVES; CANCER AB A series of combretastatin A-4 analogs derived from the ATP competitive, VEGF receptor tyrosine kinase inhibitor, SU5416 were synthesized. The cytotoxic effects of the analogs were evaluated against PC-3 and MDA-MB-231 cancer cell lines, as well as their abilities to inhibit tubulin polymerization. Results are compared to those of compound 1, our lead compound previously reported. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Li, PK (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. EM li.27@osu.edu RI Li, Chenglong/E-7182-2010 OI Li, Chenglong/0000-0003-3174-8719 FU Intramural NIH HHS NR 32 TC 43 Z9 43 U1 0 U2 2 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 OCT 1 PY 2006 VL 14 IS 19 BP 6492 EP 6501 DI 10.1016/j.bmc.2006.06.017 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 086CK UT WOS:000240650500004 PM 16860559 ER PT J AU Jang, H Ma, B Woolf, TB Nussinov, R AF Jang, Hyunbum Ma, Buyong Woolf, Thomas B. Nussinov, Ruth TI Interaction of protegrin-1 with lipid bilayers: Membrane thinning effect SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; SOLID-STATE NMR; INDIVIDUAL ALPHA-HELICES; ANTIMICROBIAL PEPTIDE; PORE FORMATION; ORIENTATION; BACTERIORHODOPSIN; MICELLES; CECROPIN; DIMYRISTOYLPHOSPHATIDYLCHOLINE AB Protegrins (PG) are important in defending host tissues, preventing infection via an attack on the membrane surface of invading microorganisms. Protegrins have powerful antibiotic abilities, but the molecular-level mechanisms underlying the interactions of their beta-sheet motifs with the membrane are not known. Protegrin-1 (PG-1) is composed of 18 amino acids with a high content of basic residues and two disulfide bonds. Here we focused on the stability of PG-1 at the amphipathic interface in lipid bilayers and on the details of the peptide-membrane interactions. We simulated all-atom models of the PG-1 monomer with explicit water and lipid bilayers composed of both homogeneous POPC (palmitoyl-oleylphosphatidylcholine) lipids and a mixture of POPC/POPG (palmitoyl-oleyl-phosphatidylglycerol) (4:1) lipids. We observed that local thinning of the lipid bilayers mediated by the peptide is enhanced in the lipid bilayer containing POPG, consistent with experimental results of selective membrane targeting. The beta-hairpin motif of PG-1 is conserved in both lipid settings, whereas it is highly bent in aqueous solution. The conformational dynamics of PG-1, especially the highly charged beta-hairpin turn region, are found to be mostly responsible for disturbing the membrane. Even though the eventual membrane disruption requires PG-1 oligomers, our simulations clearly show the first step of the monomeric effects. The thinning effects in the bilayer should relate to pore/channel formation in the lipid bilayer and thus be responsible for further defects in the membrane caused by oligomer. C1 SAIC Frederick Inc, NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, B (reprint author), SAIC Frederick Inc, NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. EM mab@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [R01 GM064746] NR 46 TC 52 Z9 53 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2006 VL 91 IS 8 BP 2848 EP 2859 DI 10.1529/biophysj.106.084046 PG 12 WC Biophysics SC Biophysics GA 086VI UT WOS:000240700700013 PM 16861271 ER PT J AU Dunson, DB AF Dunson, David B. TI Bayesian dynamic modeling of latent trait distributions SO BIOSTATISTICS LA English DT Article DE dynamic Dirichlet process; factor analysis; hierarchical model; latent variables; measurement error; random effect; surrogate data ID MULTIPLE CONTINUOUS OUTCOMES; DIRICHLET PROCESS MIXTURE; VARIABLE MODELS; FACTOR ANALYZERS; NONPARAMETRIC PROBLEMS; MEDIAN REGRESSION; LONGITUDINAL DATA; MIXED OUTCOMES; INFERENCE; INDICATORS AB Studies of latent traits often collect data for multiple items measuring different aspects of the trait. For such data, it is common to consider models in which the different items are manifestations of a normal latent variable, which depends on covariates through a linear regression model. This article proposes a flexible Bayesian alternative in which the unknown latent variable density can change dynamically in location and shape across levels of a predictor. Scale mixtures of underlying normals are used in order to model flexibly the measurement errors and allow mixed categorical and continuous scales. A dynamic mixture of Dirichlet processes is used to characterize the latent response distributions. Posterior computation proceeds via a Markov chain Monte Carlo algorithm, with predictive densities used as a basis for inferences and evaluation of model fit. The methods are illustrated using data from a study of DNA damage in response to oxidative stress. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 46 TC 44 Z9 45 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD OCT PY 2006 VL 7 IS 4 BP 551 EP 568 DI 10.1093/biostatistics/kxj025 PG 18 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 090CA UT WOS:000240927000004 PM 16488893 ER PT J AU Mumford, SL Schisterman, EF Vexler, A Liu, AY AF Mumford, Sunni L. Schisterman, Enrique F. Vexler, Albert Liu, Aiyi TI Pooling biospecimens and limits of detection: effects on ROC curve analysis SO BIOSTATISTICS LA English DT Article DE limit of detection; maximum likelihood; pooling design; receiver operating characteristics; sampling ID BREAST-CANCER; EXPOSURE; RISK; AREA AB Frequently, epidemiological studies deal with two restrictions in the evaluation of biomarkers: cost and instrument sensitivity. Costs can hamper the evaluation of the effectiveness of new biomarkers. In addition, many assays are affected by a limit of detection (LOD), depending on the instrument sensitivity. Two common strategies used to cut costs include taking a random sample of the available samples and pooling biospecimens. We compare the two sampling strategies when an LOD effect exists. These strategies are compared by examining the efficiency of receiver operating characteristic (ROC) curve analysis, specifically the estimation of the area under the ROC curve (AUC) for normally distributed markers. We propose and examine a method to estimate AUC when dealing with data from pooled and unpooled samples where an LOD is in effect. In conclusion, pooling is the most efficient cost-cutting strategy when the LOD affects less than 50% of the data. However, when much more than 50% of the data are affected, utilization of the pooling design is not recommended. C1 NICHD, Div Epidemiol Stat & Prevent, NIH, DHHS, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Schisterman, EF (reprint author), NICHD, Div Epidemiol Stat & Prevent, NIH, DHHS, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS NR 17 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD OCT PY 2006 VL 7 IS 4 BP 585 EP 598 DI 10.1093/biostatistics/kxj027 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 090CA UT WOS:000240927000006 PM 16531470 ER PT J AU Donovan, PJ Smith, GT Dove, LF Klose, J Powell, DA AF Donovan, Paul J. Smith, George T. Dove, Lee F. Klose, John Powell, Douglas A. TI HGPRT mutation induction by N-ethyl-N-nitrosourea as measured by 6-thioguanine resistance is higher in male than in female Syrian hamster fetuses SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE HGPRT; male fetuses; female fetuses; N-ethyl-N-nitrosourea; Lyon hypothesis; X-chromosome inactivation ID X-CHROMOSOME INACTIVATION; AGE-DEPENDENT SELECTION; PHOSPHORIBOSYL TRANSFERASE; T-LYMPHOCYTES; MOUSE; CELLS; EXPRESSION; HPRT; RETINOBLASTOMA; DEFICIENT AB BACKGROUND: The consequences of mutations in embryonic and fetal cells are serious and contribute to high prenatal sensitivity to mutagenic agents. An understanding of the factors that influence the yield of such mutations is important for management of adverse effects of perinatal exposures. Resistance to 6-thioguanine (6-TG) can be utilized to study mutational events at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus. HGPRT is X-linked and recessive. According to the Lyon hypothesis, male cells have only one X-chromosome and female cells randomly inactivate the second X-chromosome. This leads to the prediction that X-linked genes should be equally sensitive to the mutagenic effects of toxicants in male and female fetuses. METHODS: We tested this supposition by in utero exposure of Syrian hamster fetuses to N-ethyl-N-nitrosourea (ENU) at day 12 of gestation. ENU is a strong carcinogen and mutagen. HGPRT mutations were detected by selection with 6-TG. RESULTS: Surprisingly. the male cells had 4 to 5 times more 6-TG mutants than female cells, in two separate experiments (p < 0.001). Ouabain resistance, reflecting a co-dominant autosomal locus, was used as a control, and we found that there was no significant difference between male and female cells (p = 0.549). CONCLUSIONS: Possible reasons for the sex difference in mutations include escape of the second X-chromosome from inactivation in some of the female cells, or higher mutability in male cells. In any event, there is a gender difference in vulnerability to mutation of an X-linked gene that has previously not been appreciated, and that may be relevant to toxicological studies of such genes. HGPRT is frequently used to monitor mutagenic events in human fetuses. C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. NCI, SAIC, Frederick, MD 21702 USA. NCI, Data Management Serv Inc, Frederick, MD 21702 USA. RP Donovan, PJ (reprint author), NCI, Lab Comparat Carcinogenesis, Room 205, Frederick, MD 21702 USA. EM donovapa@mail.ncifcrf.gov FU Intramural NIH HHS NR 44 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD OCT PY 2006 VL 77 IS 5 BP 399 EP 404 DI 10.1002/bdrb.20088 PG 6 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 098UR UT WOS:000241548800001 PM 17066413 ER PT J AU Uzel, G AF Uzel, Gum TI That fish (NEMO) again? SO BLOOD LA English DT Editorial Material ID ECTODERMAL DYSPLASIA; ACTIVATION; MUTATIONS C1 NIAID, Bethesda, MD 20892 USA. RP Uzel, G (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2006 VL 108 IS 7 BP 2135 EP 2135 DI 10.1182/blood-2006-07-034637 PG 1 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700003 ER PT J AU Stroncek, DF AF Stroncek, David F. TI Hot on the trail of TRALI SO BLOOD LA English DT Editorial Material ID ACUTE LUNG INJURY C1 NIH, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2006 VL 108 IS 7 BP 2136 EP 2137 DI 10.1182/blood-2006-07-034736 PG 2 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700005 ER PT J AU Pang, LY Xue, HH Szalai, G Wang, X Wang, YH Watson, DK Leonard, WJ Blobel, GA Poncz, M AF Pang, Liyan Xue, Hai-Hui Szalai, Gabor Wang, Xun Wang, Yuhuan Watson, Dennis K. Leonard, Warren J. Blobel, Gerd A. Poncz, Mortimer TI Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; GA-BINDING-PROTEIN; MEGAKARYOCYTE-SPECIFIC GENES; ZINC-FINGER PROTEIN; DEFINITIVE HEMATOPOIESIS; HISTONE ACETYLATION; NEUTROPHIL ELASTASE; GLYCOPROTEIN-IX; DNA-BINDING; EXPRESSION AB Numerous megakaryocyte-specific genes contain signature Ets-binding sites in their regulatory regions. Fli-1 (friend leukemia integration 1), an Ets transcription factor, is required for the normal maturation of megakaryocytes and controls the expression of multiple megakaryocyte-specific genes. However, in Fli-1(-/-) mice, early megakaryopoiesis persists, and the expression of the early megakaryocyte-specific genes, alpha llb and cMpl, is maintained, consistent with functional compensation by a related Ets factor(s). Here we identify the Ets protein GABP alpha (GA-binding protein alpha) as a regulator of early megakaryocyte-specific genes. Notably, GABP alpha, preferentially occupies Ets elements of early megakaryocyte-specific genes in vitro and in vivo, whereas Fli-1 binds both early and late megakaryocyte-specific genes. Moreover, the ratio of GABP alpha/Fli-1 expression declines throughout megakaryocyte maturation. Consistent with this expression pattern, primary fetal liver-derived megakaryocytes from Fli-1-deficient murine embryos exhibit reduced expression of genes associated with late stages of maturation (glycoprotein [GP] Ib alpha, GPIX, and platelet factor 4 [PF4]), whereas GABP alpha-deficient megakaryocytes were mostly impaired in the expression of early megakaryocyte-specific genes (alpha llb and cMpl). Finally, mechanistic experiments revealed that GABP alpha, like Fli-1, can impart transcriptional synergy between the hematopoietic transcription factor GATA-1 and its cofactor FOG-1 (friend of GATA-1). In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Natl Heart Lung & Blood Inst, Lab Mol Immunol, Bethesda, MD USA. Med Univ S Carolina, Hollings Canc Ctr, Dept Pathol & Lab Med, Charleston, SC USA. Med Univ S Carolina, Hollings Canc Ctr, Dept Biochem & Mol Biol, Charleston, SC USA. RP Blobel, GA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, 3165 Civic Ctr Blvd,ARC 316H, Philadelphia, PA 19104 USA. EM blobel@email.chop.edu RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU Intramural NIH HHS; NCI NIH HHS [P01 CA78582]; NHLBI NIH HHS [P01 HL40387]; NIDDK NIH HHS [DK54937, DK58044] NR 58 TC 51 Z9 51 U1 0 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 OCT 1 PY 2006 VL 108 IS 7 BP 2198 EP 2206 DI 10.1182/blood-2006-04-019760 PG 9 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700018 PM 16757682 ER PT J AU Temmerman, ST Ma, CA Borges, L Kubin, M Liu, SY Derry, JMJ Jain, A AF Temmerman, Stephane T. Ma, Chi A. Borges, Louis Kubin, Marek Liu, Shuying Derry, Jonathan M. J. Jain, Ashish TI Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination SO BLOOD LA English DT Article ID B KINASE COMPLEX; HYPER-IGM SYNDROME; IKK-GAMMA; ACTIVATION; CD40; TRAF6; INTERLEUKIN-12; MUTATIONS; IMMUNODEFICIENCY; PHOSPHORYLATION AB Ectodermal dysplasia with immune deficiency (EDI) is caused by alterations in NEMO (nuclear factor [NF]-kappa B essential modulator). Most genetic mutations are located in exon 10 and affect the C-terminal zinc finger domain. However, the biochemical mechanism by which they cause immune dysfunction remains undetermined. In this report, we investigated the effect of a cysteine-to-arginine mutation (C417R) found in the NEMO zinc finger domain on dendritic cell (DC) function. Following CD40 stimulation of DCs prepared from 2 unrelated patients with the NEMO C417R mutation, we found NEMO ubiquitination was absent, and this was associated with preserved ReIA but absent c-Rel activity. As a consequence, CD40 stimulated EDI DCs failed to synthesize the c-Rel-dependent cytokine interleukin-12, had impaired up-regulation of costimulatory molecules, and failed to support allogeneic lymphocyte proliferation in vitro. In contrast, EDI DCs stimulated with the TLR4 ligand lipopolysaccharide (LPS) showed normal downstream NF-kappa B activity, DC maturation, and NEMO ubiquitination. These findings show for the first time how mutations in the zinc finger domain of NEMO can lead to pathway specific defects in NEMO ubiquitination and thus immune deficiency. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Amgen Inc, Seattle, WA USA. RP Jain, A (reprint author), NIAID, Host Def Lab, NIH, Rm 5490,10 Ctr Dr, Bethesda, MD 20892 USA. EM ajain@niaid.nih.gov NR 34 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2006 VL 108 IS 7 BP 2324 EP 2331 DI 10.1182/blood-2006-04-017210 PG 8 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700034 PM 16794254 ER PT J AU Swartz, JM Dyer, KD Cheever, AW Ramalingam, T Pesnicak, L Domachowske, JB Lee, JJ Lee, NA Foster, PS Wynn, TA Rosenberg, HF AF Swartz, Jonathan M. Dyer, Kimberly D. Cheever, Allen W. Ramalingam, Thirumalai Pesnicak, Lesley Domachowske, Joseph B. Lee, James J. Lee, Nancy A. Foster, Paul S. Wynn, Thomas A. Rosenberg, Helene F. TI Schistosoma mansoni infection in eosinophil lineage-ablated mice SO BLOOD LA English DT Article ID INNATE IMMUNE-SYSTEM; IN-VIVO; INTERLEUKIN-5 IL-5; ANTIGEN-PRESENTATION; IL-5-DEFICIENT MICE; HELMINTH-PARASITES; HEPATIC-FIBROSIS; TH2 RESPONSE; EXPRESSION; CELLS AB We explore the controversial issue of the role of eosinophils in host defense against helminthic parasites using the established Schistosoma mansoni infection model in 2 novel mouse models of eosinophil lineage ablation (Delta dblGATA and TgPHIL). No eosinophils were detected in bone marrow of infected Delta dblGATA or TgPHIL mice, despite the fact that serum IL-5 levels in these infected mice exceeded those in infected wild type by approximately 4-fold. Liver granulomata from infected Delta dblGATA and TgPHIL mice were likewise depleted of eosinophils compared with those from their respective wild types. No eosinophil-dependent differences in granuloma number, size, or fibrosis were detected at weeks 8 or 12 of infection, and differential accumulation of mast cells was observed among the Delta dblGATA mice only at week 12. Likewise, serum levels of liver transaminases, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) increased in all mice in response to S mansoni infection, with no eosinophil-dependent differences in hepatocellular damage observed. Finally, eosinophil ablation had no effect on worm burden or on egg deposition. Overall, our data indicate that eosinophil ablation has no impact on traditional measures of disease in the S mansoni infection model in mice. However, eosinophils may have unexplored immunomodulatory contributions to this disease process. C1 NIAID, Lab Allerg Dis, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA. Mayo Clin, Scottsdale, AZ USA. Univ Newcastle, Hunter Med Res Inst, Sch Biomed Sci, Newcastle, NSW 2308, Australia. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, Parasit Dis Lab, NIH, Bldg 10,Rm 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; Foster, Paul/G-5057-2013 FU Intramural NIH HHS NR 59 TC 79 Z9 84 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2006 VL 108 IS 7 BP 2420 EP 2427 DI 10.1182/blood-2006-04-015933 PG 8 WC Hematology SC Hematology GA 088ZD UT WOS:000240848700046 PM 16772607 ER PT J AU Lauretani, F Bandinelli, S Russo, CR Maggio, M Di Iorio, A Cherubini, A Maggio, D Ceda, GP Valenti, G Guralnik, JM Ferrucci, L AF Lauretani, F. Bandinelli, S. Russo, C. R. Maggio, M. Di Iorio, A. Cherubini, A. Maggio, D. Ceda, G. P. Valenti, G. Guralnik, J. M. Ferrucci, L. TI Correlates of bone quality in older persons SO BONE LA English DT Article DE bone geometry and density; pQCT; age-related bone loss; osteoporosis ID RANDOMIZED CONTROLLED-TRIAL; DIFFERENT SKELETAL SITES; QUANTITATIVE COMPUTED-TOMOGRAPHY; SEX STEROID-LEVELS; PARATHYROID-HORMONE; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; STRUCTURAL PARAMETERS; POSTMENOPAUSAL WOMEN; FREE TESTOSTERONE AB Purpose of the study: In a population-based sample of older persons, we studied the relationship between tibial bone density and geometry and factors potentially affecting osteoporosis. Methods: Of the 1260 participants aged 65 years or older eligible for the InCHIANTI study, 1155 received an interview and 915 (79.2%) had complete data on tibial QCT scans and other variables used in the analysis presented here. The final study population included 807 persons (3 72 men and 43 5 women, age range 65-96 years) after exclusion of participants affected by bone diseases or treated with drugs that interfere with bone metabolism. Results: In both sexes, calf cross-sectional muscle area (CSMA) was significantly and independently associated with total bone cross-sectional area (tCSA) and cortical bone cross-sectional area (cCSA) but not with trabecular or cortical volumetric bone mineral density (vBMD). Bioavailable testosterone (Bio-T) was independently associated with both trabecular and cortical vBMD in both sexes. In women, independently of confounders, 25(OH)-vitamin D was positively associated with tCSA and cortical vBMD, while PTH was negatively associated with cortical vBMD. IL-1 beta was negatively correlated with cortical vBMD in women, while TNF-alpha was associated with enhanced bone geometrical adaptation in men. Conclusions: Physiological parameters that are generically considered risk factors for osteoporosis were associated with specific bone parameters assessed by tibial QCT. Factors known to be associated with increased bone reabsorption, such as 25(OH)-vitamin D, PTH and Bio-T, affected mainly volumetric BMD, while factors associated with bone mechanical stimulation, such as CSMA, affected primarily bone geometry. Our results also suggested that pro-inflammatory cytokines might be considered as markers of bone resorption. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Tuscany Reg Hlth Agcy, Florence, Italy. Geriatr Rehabil ASF, Florence, Italy. Univ Florence, Florence, Italy. Univ G DAnnunzio, Lab Clin Epidemiol, Dept Med & Sci Aging, Chieti, Italy. Univ Perugia, Sch Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 21224 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM FerrucciLu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295; Cherubini, Antonio/0000-0003-0261-9897 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-821336, N01-AG-916413]; NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13, R01 MD009164] NR 40 TC 33 Z9 34 U1 0 U2 1 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 OCT PY 2006 VL 39 IS 4 BP 915 EP 921 DI 10.1016/j.bone.2006.03.014 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 088DW UT WOS:000240792700027 PM 16709469 ER PT J AU Peller, M Zeuner, KE Munchau, A Quartarone, A Weiss, M Knutzen, A Hallett, M Deuschl, G Siebner, HR AF Peller, M. Zeuner, K. E. Munchau, A. Quartarone, A. Weiss, M. Knutzen, A. Hallett, M. Deuschl, G. Siebner, H. R. TI The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp SO BRAIN LA English DT Article DE basal ganglia; focal hand dystonia; functional MRI; tactile discrimination; thalamus; writer's cramp ID FOCAL HAND DYSTONIA; PRIMARY SOMATOSENSORY CORTEX; REPETITIVE STRAIN INJURY; SPATIAL DISCRIMINATION; SENSORY DISCRIMINATION; METABOLIC TOPOGRAPHY; GENERALIZED DYSTONIA; NEURONAL-ACTIVITY; VISUAL-CORTEX; HUMAN BRAIN AB Writer's cramp is a focal hand dystonia that specifically affects handwriting. Though writer's cramp has been attributed to a dysfunction of the basal ganglia, the role of the basal ganglia in the pathogenesis of writer's cramp remains to be determined. Seventeen patients with writer's cramp (nine females; age range: 24-71 years) and 17 healthy individuals (six females; age range: 27-68 years) underwent functional MRI (fMRI) while they discriminated the orientation of gratings delivered to the tip of the right index finger. Statistical parametric mapping was used to analyse the fMRI data. The significance level was set at a corrected P-value of 0.05. Relative to healthy controls, patients with writer's cramp showed a widespread bilateral increase in task-related activity in the putamen, caudate nucleus, internal globus pallidus and lateral thalamus. In these areas, hyperactivity was more pronounced in patients who had recently developed writer's cramp. The enhanced response of the basal ganglia to tactile input from the affected hand is compatible with the concept of impaired centre-surround inhibition within the basal ganglia-thalamic circuit and may lead to an excessive activation of sensorimotor cortical areas during skilled movements affected by dystonia. Outside the basal ganglia, dystonic patients showed task-related overactivity in visual cortical areas, left anterior insula and right intraparietal sulcus, but not in the primary or secondary sensory cortex. In addition, task-related activity in the cerebellar nuclei, posterior vermis, right paramedian cerebellar hemisphere and dorsal pons was inversely related with the severity of hand dystonia. Regional activity in these areas may reflect secondary adaptive reorganization at the systems level to compensate for the dysfunction in the basal ganglia-thalamic loop. C1 Univ Kiel, Dept Neurol, D-24105 Kiel, Germany. NeuroImageNord Hamburg Kiel Lubeck, Lubeck, Germany. Univ Hamburg, Dept Neurol, Hamburg, Germany. Univ Messina, Dept Neurosci Psychiat & Anaesthesiol Sci, I-98100 Messina, Italy. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Siebner, HR (reprint author), Univ Kiel, Dept Neurol, Schittenhelmstr 10, D-24105 Kiel, Germany. EM h.siebner@neurologie.uni-kiel.de RI Deuschl, Gunther/A-7986-2010; Siebner, Hartwig/G-4052-2016; OI QUARTARONE, Angelo/0000-0003-1485-6590 NR 66 TC 64 Z9 68 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2006 VL 129 BP 2697 EP 2708 DI 10.1093/brain/awl181 PN 10 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 090BL UT WOS:000240925500018 PM 16854945 ER PT J AU Twiss, JL Chang, JH Schanen, NC AF Twiss, Jeffery L. Chang, Jay H. Schanen, N. Carolyn TI Pathophysiological mechanisms for actions of the neurotrophins SO BRAIN PATHOLOGY LA English DT Review ID NERVE GROWTH-FACTOR; LOCAL PROTEIN-SYNTHESIS; PRADER-WILLI-SYNDROME; DEVELOPING NEUROMUSCULAR SYNAPSES; MYELIN-ASSOCIATED GLYCOPROTEIN; FOREBRAIN CHOLINERGIC NEURONS; ACTIVITY-DEPENDENT SECRETION; TRK PROTOONCOGENE PRODUCT; LONG-TERM POTENTIATION; CYCLIC-AMP CONTROLS AB Neurotrophins provide trophic and tropic support for different neuronal subpopulations in the developing and adult nervous systems. Expression of the neurotrophins and their receptors can be altered in several different disease or injury states that impact upon the functions in the central and peripheral nervous systems. The intracellular signals used by the neurotrophins are triggered by ligand binding to the cell surface Trk and p75(NTR) receptors. In general, signals emanating from Trk receptors support survival, growth and synaptic strengthening, while those emanating from p75(NTR) induce apoptosis, attenuate growth and weaken synaptic signaling. Mature neurotrophins are the preferred ligand for Trk proteins while p75(NTR) binds preferentially to the proneurotrophins and serves as a signaling component of the receptor complex for growth inhibitory molecules of central nervous system myelin [ie, myelin-associated glycoprotein (MAG), oligodendrocyte-myelin glycoprotein (OMgP) and Nogo]. The functional antagonism between Trk and p75(NTR) signaling may significantly impact the pathogenesis of human neurodevelopmental and neurodegenerative diseases and further complicate therapeutic uses of exogenous neurotrophins. The potential for each is discussed in this review. C1 Alfred I DuPont Hosp Children, Wilmington, DE 19803 USA. Univ Delaware, Dept Biol Sci, Newark, DE USA. NICHD, Sect Neural Dev & Plastic, LCSN, NIH, Bethesda, MD USA. RP Twiss, JL (reprint author), Alfred I DuPont Hosp Children, 1600 Rockland Rd,Room H3B 341, Wilmington, DE 19803 USA. EM twiss@medsci.udel.edu FU NICHD NIH HHS [R01-HD037874]; NINDS NIH HHS [R01-NS041596, R01-NS049041] NR 201 TC 29 Z9 30 U1 2 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 2006 VL 16 IS 4 BP 320 EP 332 DI 10.1111/j.1750-3639.2006.00039.x PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 106OT UT WOS:000242111100010 PM 17107602 ER PT J AU Ingle, JN Tu, DS Pater, JL Martino, S Robert, NJ Muss, HB Piccart, MJ Castiglione, M Shepherd, LE Pritchards, KI Livingston, RB Davidsonlo, NE Norton, L Perez, EA Abrams, JS Cameron, DA Palmer, MJ Goss, PE AF Ingle, James N. Tu, Dongsheng Pater, Joseph L. Martino, Silvana Robert, Nicholas J. Muss, Hyman B. Piccart, Martine J. Castiglione, Monica Shepherd, Lois E. Pritchards, Kathleen I. Livingston, Robert B. Davidsonlo, Nancy E. Norton, Larry Perez, Edith A. Abrams, Jeffrey S. Cameron, David A. Palmer, Michael J. Goss, Paul E. TI Duration of letrozole treatment and outcomes in the placebo-controlled NCICCTG MA.17 extended adjuvant therapy trial SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE adjuvant hormonal therapy; early breast cancer ID BREAST-CANCER; RANDOMIZED-TRIAL; UPDATED FINDINGS; TAMOXIFEN AB Purpose. MA. 17 was a double-blind placebo-controlled trial involving 5187 postmenopausal women that established letrozole to be of value in reducing recurrence of breast cancer when given in the extended adjuvant therapy setting after about 5 years of tamoxifen. Analyses were conducted to examine the relationships between duration of treatment on MA.17 and outcomes. Methods. The final MA. 17 database that included all events up to the date of unblinding of the study was interrogated. A non-parametric kernel smoothing method was used to estimate the hazard rates for disease-free survival (DFS),. distant DFS (DDFS) and overall survival (OS) at 6, 12, 24, 36 and 48 months of follow-up and the hazard ratios (HRs) of letrozole to placebo were determined. The trend in HRs over time was tested based on a Cox model with a time-dependent covariate. Results. Considering all patients, HRs for events in DFS and DDFS progressively decreased over time, favoring letrozole. with the trend being significant (p < 0.0001 and p = 0.0013, respectively) whereas the trend for OS was not significant. Considering the 2360 patients with node-positive status, the HRs for DFS, DDFS and OS all decreased over time with tests for trend all showing significance (p = 0.0004, 0.0005 and 0.038, respectively). Considering the 2568 patients with node-negative status, the HRs for DFS decreased over time with the test for trend being significant (p = 0.027) whereas the HRs for DDFS and OS showed no significant change over time. Conclusion. These analyses suggest that, at least out to about 48 months, longer duration of letrozole treatment is associated with greater benefit in the extended adjuvant therapy setting. C1 Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. Natl Canc Inst Canada, Clin Trials Grp, Kingston, ON, Canada. Angeles Clin & Res Inst, Santa Monica, CA USA. Inova Fairfax Hosp, Falls Church, VA USA. Univ Vermont, Burlington, VT USA. Inst Jules Bordet, B-1000 Brussels, Belgium. IBCSG Coordinating Ctr, Bern, Switzerland. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mayo Clin, Jacksonville, FL 32224 USA. NCI, Clin Invest Branch, Rockville, MD USA. Western Gen Hosp, Edinburgh Breast Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ingle, JN (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM ingle.james@mayo.edu OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA25224, CA21115, CA31946, CA32102, CA38926] NR 8 TC 61 Z9 65 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2006 VL 99 IS 3 BP 295 EP 300 DI 10.1007/s10549-006-9207-y PG 6 WC Oncology SC Oncology GA 093UD UT WOS:000241194900007 PM 16541302 ER PT J AU Fan, J McKean-Cowdin, R Bernstein, L Stanczyk, FZ Li, AXJ Ballard-Barbash, R McTiernan, A Baumgartner, R Gilliland, F AF Fan, Jing McKean-Cowdin, Roberta Bernstein, Leslie Stanczyk, Frank Z. Li, Arthur Xuejun Ballard-Barbash, Rachel McTiernan, Anne Baumgartner, Richard Gilliland, Frank TI An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE African-American; breast cancer; IRS-1; polymorphism; sex hormones ID INSULIN-RECEPTOR SUBSTRATE-1; GROWTH-FACTOR-I; DEPENDENT DIABETES-MELLITUS; AMINO-ACID POLYMORPHISM; ACTIVATED PROTEIN-KINASE; CORONARY-ARTERY-DISEASE; ESTROGEN-RECEPTOR; TAIWANESE POPULATION; RACIAL-DIFFERENCES; GLY972ARG VARIANT AB Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating, levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth factor 1 (IGF-1) levels among post-menopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p=0.02), free estradiol (p=0.04), total testosterone (p=0.04), free testosterone (p=0.006) and decreased levels of sex hormone-binding globulin (p=0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors. C1 Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Integated Subst Abuse Program, Neuropsychiat Inst, Los Angeles, CA 90025 USA. Univ So Calif, Dept Obstet & Gynecol, Keck Sch Med, Los Angeles, CA 90033 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Louisville, Dept Epidemiol & Clin Invest Sci, Louisville, KY 40202 USA. RP McKean-Cowdin, R (reprint author), Univ So Calif, Dept Prevent Med, Keck Sch Med, 1441 Eastlake Ave,MS-44, Los Angeles, CA 90033 USA. EM mckeanco@usc.edu RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NCI NIH HHS [PC-67010, N01 PC035138-22, N01 PC067010, N01-PC-35139, N01PC35139]; NICHD NIH HHS [N01 HD 3-3175] NR 66 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2006 VL 99 IS 3 BP 323 EP 331 DI 10.1007/s10549-006-9211-2 PG 9 WC Oncology SC Oncology GA 093UD UT WOS:000241194900011 PM 16752222 ER PT J AU Anderson, WF Jatoi, I Devesa, SS AF Anderson, William F. Jatoi, Ismail Devesa, Susan S. TI Assessing the impact of screening mammography: breast cancer incidence and mortality rates in Connecticut (1943-2002) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE lead time bias; length bias; prognostic factors; calendar-period effects; birth cohort effects; breast cancer incidence; breast cancer mortality ID BIOLOGIC CHARACTERISTICS; IN-SITU; INTERVAL; THERAPY; REGRESSION; SURVIVAL; PROGRAM; TRIALS; TRENDS; WOMEN AB Background Randomized controlled studies demonstrate that early detection and intervention reduce breast cancer mortality by approximately 25%. Though the ultimate goal of screening is to reduce breast cancer deaths, the immediate goal is to detect and treat early-stage tumors before they pose a threat to life. Materials and methods To assess the impact of early detection and intervention in the general population, we analyzed breast cancer incidence and mortality rates in the NCI's Historical Connecticut Tumor Registry (1943-2002). Results Though breast cancer rates increased for the entire study period, overall incidence rates rose faster than previously following, the initiation of mammography screening in the early 1980s in the United States. Of note, stage-specific incidence rates increased 152% (53.2-133.9 per 100,000 woman-years) for early-stage tumors and fell 16% (56.1-47.2 per 100,000 woman-years) for late-stage breast cancers. Period- and cohort-age-specific incidence rates rose dramatically for early-stage tumors among women targeted for screening (ages 40-80 years), whereas rates for regional and distant stages declined modestly among women ages > 50 years. Breast cancer mortality rates fell 31.6%. Conclusions Along with increases in incidence rates for early-stage tumors, rates for late-stage disease and breast cancer mortality declined following widespread screening mammography, consistent with effective early detection and improved treatment over time. However, the disparity between the dramatic rise in early-stage tumors compared to the more modest declines in late-stage disease and mortality suggests that many mammography-derived early-stage lesions may never progress to late-stage cancers and pose a threat to life. C1 NCI, NIH, DHHS, Biostat Branch,Div Canc Epidemiol & Genet,EPS, Rockville, MD 20852 USA. Natl Naval Med Ctr, Breast Care Ctr, Dept Surg, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. RP Anderson, WF (reprint author), NCI, NIH, DHHS, Biostat Branch,Div Canc Epidemiol & Genet,EPS, Room 8036,6120 Execut Blvd, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov; ismail.jatoi@us.army.mil; devesas@mail.nih.gov FU Intramural NIH HHS NR 23 TC 52 Z9 53 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2006 VL 99 IS 3 BP 333 EP 340 DI 10.1007/s10549-006-9214-z PG 8 WC Oncology SC Oncology GA 093UD UT WOS:000241194900012 PM 16703451 ER PT J AU McPherson, T Cowen, EW McBurney, E Klion, AD AF McPherson, T. Cowen, E. W. McBurney, E. Klion, A. D. TI Platelet-derived growth factor receptor-alpha-associated hypereosinophilic syndrome and lymphomatoid papulosis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE eosinophils; imatinib; T-cell lymphoma ID IMATINIB; FUSION AB Fip1-like 1/platelet-derived growth factor receptor-alpha (FIP1L1/PDGFRA)-positive hypereosinophilic syndrome is a rare disorder with a poor prognosis if untreated and for which treatment with imatinib mesilate is highly effective. A 33-year-old man presented with recurrent papular skin lesions and marked peripheral eosinophilia. Skin biopsy revealed proliferation of CD30+ T cells consistent with lymphomatoid papulosis (LyP), whereas molecular analysis of peripheral blood mononuclear cells demonstrated the presence of the FIP1L1/PDGFRA fusion gene. As the presence of this gene has important prognostic and therapeutic implications, this report underscores the importance of molecular testing in the evaluation of patients with LyP and peripheral eosinophilia. C1 NIAID, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, Dept Dermatol, New Orleans, LA 70118 USA. RP Klion, AD (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM aklion@niaid.nih.gov NR 9 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 2006 VL 155 IS 4 BP 824 EP 826 DI 10.1111/j.1365-2133.2006.07416.x PG 3 WC Dermatology SC Dermatology GA 081WS UT WOS:000240348900025 PM 16965435 ER PT J AU Shand, JC Mansky, PJ Brown, MV Fleisher, TA Mackall, CL AF Shand, Jessica C. Mansky, Patrick J. Brown, Margaret V. Fleisher, Thomas A. Mackall, Crystal L. TI Adolescents and young adults successfully restore lymphocyte homeostasis after intensive T-cell depleting therapy for cancer SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE chemotherapy; lymphopenia; immune reconstitution; thymus ID TRANSPLANTATION; RECONSTITUTION C1 Natl Canc Inst, Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Div Intramural Res, Bethesda, MD USA. Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Shand, JC (reprint author), Natl Canc Inst, Ctr Canc Res, Pediat Oncol Branch, 9000 Rockville Pike Bldg 31,Rm 10A03, Bethesda, MD 20892 USA. EM cm35c@nih.gov NR 6 TC 2 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2006 VL 135 IS 2 BP 270 EP 271 DI 10.1111/j.1365-2141.2006.06292.x PG 2 WC Hematology SC Hematology GA 084WZ UT WOS:000240566400019 PM 17010050 ER PT J AU Saw, SM Goh, PP Cheng, A Shankar, A Tan, DTH Ellwein, LB AF Saw, S-M Goh, P-P Cheng, A. Shankar, A. Tan, D. T. H. Ellwein, L. B. TI Ethnicity-specific prevalences of refractive errors vary in Asian children in neighbouring Malaysia and Singapore SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SCHOOL-CHILDREN; VISUAL IMPAIRMENT; MYOPIA; POPULATION; PROGRESSION; NEARWORK; DISTRICT; CHINA AB Aim: To compare the prevalences of refractive errors in Malay, Chinese and Indian children in Malaysia and Singapore. Methods: Children aged 7-9 years from three schools in the Singapore Cohort study of the Risk factors for Myopia (n = 1962) and similarly aged children from a random cluster sample in the metropolitan Kuala Lumpur area in the Malaysia Refractive Error Study in Children (n = 1752) were compared. Cycloplegic autorefraction was conducted in both countries. Results: The prevalence of myopia (spherical equivalent of at least -0.5 diopters (D) in either eye) was higher in Singapore Malays (22.1%) than in Malays in Malaysia (9.2%; 95% confidence interval (CI) 11.2 to 14.7; p < 0.001). Similarly, Singapore Chinese (40.1%) had higher prevalences than Malaysian Chinese (30.9%; 95% CI 1.5 to 16.9). Singapore Indians had a higher prevalence (34.1%) than Malaysian Indians (12.5%; 95% CI 17.4 to 25.9). The multivariate odds ratio of astigmatism (cylinder at least 0.75 D in either eye) in Singapore Malays compared with Malaysian Malays was 3.47 (95% CI 2.79 to 4.32). Ethnicity-specific hyperopia rates did not differ in Singapore and Malaysia. Conclusion: The ethnicity-specific prevalences of myopia in Singapore Malays, Chinese and Indians are higher than those in Malaysian Malays, Chinese and Indians. As Malays, Chinese and Indians in Malaysia have genetic make-up similar to that of Malays, Chinese and Indians in Singapore, environmental factors may contribute to the higher myopia rates. C1 Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117597, Singapore. Hosp Selayang, Dept Ophthalmol, Selangor, Malaysia. Singapore Eye Res Inst, Singapore, Singapore. NEI, NIH, Bethesda, MD 20892 USA. RP Saw, SM (reprint author), Natl Univ Singapore, Dept Community Occupat & Family Med, 16 Med Dr, Singapore 117597, Singapore. EM cofsawsm@nus.edu.sg FU NEI NIH HHS [N01-EY-2103] NR 23 TC 55 Z9 57 U1 1 U2 9 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 2006 VL 90 IS 10 BP 1230 EP 1235 DI 10.1136/bjo.2006.093450 PG 6 WC Ophthalmology SC Ophthalmology GA 084HX UT WOS:000240525100007 PM 16809384 ER PT J AU Dinc, S Ozaslan, C Kuru, B Karaca, S Ustun, H Alagol, H Renda, N Oz, M AF Dinc, Soykan Ozaslan, Cihangir Kuru, Bekir Karaca, Sefa Ustun, Huseyin Alagol, Haluk Renda, Nurten Oz, Murat TI Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing SO CANADIAN JOURNAL OF SURGERY LA English DT Article ID NITRIC-OXIDE SYNTHASE; RAT COLON; ISCHEMIA REPERFUSION; FREE-RADICALS; EXPRESSION; REDUCTION; STRENGTH; MODEL; PATHOPHYSIOLOGY; OBSTRUCTION AB Objectives: Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods: We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results: During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion: MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway. C1 NIDA, NIH, DHHS, Intramural Res Program,Cellular Neurobiol Sect, Baltimore, MD 21224 USA. Univ Hacettepe, Fac Med, Dept Gen Surg, TR-06100 Ankara, Turkey. Univ Hacettepe, Fac Med, Dept Pathol, TR-06100 Ankara, Turkey. Univ Hacettepe, Fac Med, Ankara Oncol Training & Res Hosp, TR-06100 Ankara, Turkey. Univ Hacettepe, Fac Med, Dept Biochem, TR-06100 Ankara, Turkey. RP Oz, M (reprint author), NIDA, NIH, DHHS, Intramural Res Program,Cellular Neurobiol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 42 TC 27 Z9 30 U1 4 U2 6 PU CMA MEDIA INC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0008-428X J9 CAN J SURG JI Can. J. Surg. PD OCT PY 2006 VL 49 IS 5 BP 321 EP 328 PG 8 WC Surgery SC Surgery GA 089GI UT WOS:000240868100006 PM 17152569 ER PT J AU Bleyer, A Budd, T Montello, M AF Bleyer, Archie Budd, Troy Montello, Michael TI Adolescents and young adults with cancer - The scope of the problem and criticality of clinical trials SO CANCER LA English DT Article; Proceedings Paper CT Symposium on Walking Two Worlds - Adolescent and Young Adult CY NOV, 2003 CL Toronto, CANADA SP Pediat Oncol Grp Ontario DE adolescents; young adults; cancer; clinical trials ID LEUKEMIA; SURVIVAL; ACCESS AB In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15-34-year-olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age-dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person-years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults. C1 Univ Texas, MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX USA. Childrens Oncol Grp, Arcadia, CA USA. NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Bleyer, A (reprint author), St Charles Hosp, Canc Treatment Ctr, 2500 NE Neff Rd, Bend, OR 97701 USA. EM ableyer@scmc.org NR 20 TC 140 Z9 142 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 OCT 1 PY 2006 VL 107 IS 7 SU S BP 1645 EP 1655 DI 10.1002/cncr.22102 PG 11 WC Oncology SC Oncology GA 090NU UT WOS:000240958800002 PM 16906507 ER PT J AU Jain, L Venitz, J Figg, WD AF Jain, Lokesh Venitz, Juergen Figg, William D. TI Randomized discontinuation trial of sorafenib (BAY 43-9006) SO CANCER BIOLOGY & THERAPY LA English DT Article DE renal cell carcinoma; cytostatic; kinase inhibitor; phase-II ID PLACEBO-CONTROLLED TRIALS; AGENTS; DESIGN AB With the increasing interest in development of cytostatic anticancer drugs, the randomized discontinuation trial (RDT) design has been proved to be useful in the evaluation of their clinical activity. In the June 1, 2006 issue of the Journal of Clinical Oncology, a study by Ratain et al. uses RDT in a phase-II placebo controlled study to evaluate the efficacy of sorafenib ( BAY 43-9006) in patients with metastatic renal cell carcinoma (RCC). The results from their investigation affirm the merits of the RDT in testing the efficacy of cytostatic drugs and also prove the significant disease-stabilizing activity and tolerability of sorafenib in metastatic renal cell carcinoma. C1 NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Sch Pharm, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 8 TC 4 Z9 5 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD OCT PY 2006 VL 5 IS 10 BP 1270 EP 1272 DI 10.4161/cbt.5.10.3290 PG 3 WC Oncology SC Oncology GA 122VZ UT WOS:000243256600011 PM 16969070 ER PT J AU Zhang, TQ Somasundaram, R Berking, C Caputo, L Van Belle, P Elder, D Czerniecki, B Hotz, S Schuchter, L Spitz, FR Berencsi, K Rani, P Marincola, F Qiu, R Herlyn, D AF Zhang, Tianqian Somasundaram, Rajasekharan Berking, Carola Caputo, Laura Van Belle, Patricia Elder, David Czerniecki, Brian Hotz, Susan Schuchter, Lynn Spitz, Francis R. Berencsi, Klara Rani, Pyapalli Marincola, Francesco Qiu, Ruihua Herlyn, Dorothee TI Preferential involvement of CX chemokine receptor 4 and CX chemokine ligand 12 in T-cell migration toward melanoma cells SO CANCER BIOLOGY & THERAPY LA English DT Article DE apoptosis; chemokine; chemokine receptor; chemotaxis; cytotoxic T lymphocyte; melanoma; tumor immunology ID LYMPHOCYTE-FIBROBLAST INTERACTIONS; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN ENDOTHELIAL-CELLS; ORGANOTYPIC CULTURE; MALIGNANT-MELANOMA; ANTITUMOR IMMUNITY; COLON-CARCINOMA; COLLAGEN MATRIX; GROWTH-FACTOR; CHEMOKINE AB Our previous analysis of the role of chemokines in T lymphocyte trafficking toward human tumor cells revealed the migration of a melanoma patient's cytotoxic T lymphocytes (CTL) toward autologous tumor cells, resulting in tumor cell apoptosis, in an organotypic melanoma culture. CTL migration was mediated by CX chemokine receptor (CXCR) 4 expressed by the CTL and CX chemokine ligand ( CXCL) 12 secreted by the tumor cells, as evidenced by blockage of CTL migration by antibodies to CXCL12 or CXCR4, high concentrations of CXCL12 or small molecule CXCR4 antagonist. Here, we present the results of T cell migration in one additional melanoma patient and T cell and tumor cell analyses for CXCR4 and CXCL12 expression, respectively, in 12 additional melanoma patients, indicating the preferential role of CXCR4 and CXCL12 in CTL migration toward melanoma cells. These studies add to the increasing body of evidence suggesting that CXCL12 is a potent chemoattractant for T cells. C1 Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Sch Med, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD USA. RP Herlyn, D (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM dherlyn@wistar.org FU NCI NIH HHS [CA25874, P50 CA93372, CA10815] NR 44 TC 8 Z9 9 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD OCT PY 2006 VL 5 IS 10 BP 1304 EP 1312 DI 10.4161/cbt.5.10.3153 PG 9 WC Oncology SC Oncology GA 122VZ UT WOS:000243256600018 PM 16929176 ER PT J AU Pinsky, PF AF Pinsky, Paul F. TI Racial and ethnic differences in lung cancer incidence: how much is explained by differences in smoking patterns? (United States) SO CANCER CAUSES & CONTROL LA English DT Review DE ethnicity; lung cancer; race; smoking ID CIGARETTE-SMOKING; RISK; MORTALITY; AMERICANS AB Objectives Lung cancer rates vary considerably among U.S. racial/ethnic groups. We quantitatively analyzed the extent to which these differences can be attributed to differential patterns of smoking. Methods We utilized survey data from the U.S. Census to estimate smoking patterns in the following racial/ethnic groups: non-Hispanic whites, non-Hispanic blacks, Hispanics, Asian/Pacific Islanders and American Indians. We used several dose-response models of smoking and lung cancer to predict relative lung cancer rates in these groups based on reported smoking patterns, specifically, on smoking status (current, former, never), cigarettes per day, age started, and age quit (for former smokers). Predicted rates were compared to observed population rates for these groups. Results Black men had slightly lower predicted lung cancer rates than white men, but had 35-47% higher observed rates. Hispanic men had predicted rates about 25% lower than whites but observed rates 50% lower than whites; predicted rates for Hispanic women were 50% lower than whites compared to observed rates that were 60-70% lower. For Asian/Pacific Islanders, predicted and observed rates relative to whites were comparable. Predicted rates for American Indians were slightly higher than whites while observed rates were about 40% lower. Conclusion Differences in smoking largely explain lower lung cancer rates in Asian/Pacific Islanders relative to whites and partially explain lower rates in Hispanics compared to whites. Increased rates in black men and decreased rates in American Indians are not explained by differences in smoking. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 18 TC 27 Z9 27 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 OCT PY 2006 VL 17 IS 8 BP 1017 EP 1024 DI 10.1007/s10552-006-0038-2 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 077VO UT WOS:000240059600003 PM 16933052 ER PT J AU Hartge, P Lim, U Freedman, DM Colt, JS Cerhan, JR Cozen, W Severson, RK Davis, S AF Hartge, Patricia Lim, Unhee Freedman, D. Michal Colt, Joanne S. Cerhan, James R. Cozen, Wendy Severson, Richard K. Davis, Scott TI Ultraviolet radiation, dietary vitamin D, and risk of non-Hodgkin lymphoma (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE non-Hodgkin lymphoma; sunlight; epidemiology; vitamin D ID OCCUPATIONAL SUNLIGHT EXPOSURE; HISTORY QUESTIONNAIRE; POOLED ANALYSIS; CANCER; WOMEN; MORTALITY; ALCOHOL; EPIDEMIOLOGY; CONNECTICUT; ASSOCIATION AB Objective Because of conflicting findings about the relationship between ultraviolet (UV) radiation and the risk of non-Hodgkin lymphoma (NHL), we evaluated the risk of several indicators related to UV, including two not previously studied: dietary vitamin D, and ambient UV levels by residential location. Methods As part of a case-control study conducted in four Surveillance, Epidemiology, and End Results (SEER) registries, we collected UV information from a self-administered questionnaire and computer-assisted personal interview with 551 NHL cases and 462 controls. We estimated the relative risk (RR) and 95% confidence intervals (CI) from unconditional logistic regression models. Results Eye color, a marker of host susceptibility to UV, showed a decreasing risk gradient for lightest eyes (0.47) compared to darkest. Relative risks were in the range of 0.73-0.78 for participants reporting more hours in the mid-day summer sun. Use of sunlamps or tanning booths was associated with decreased risk (RR = 0.88), as was estimated overall ambient UV (RR = 0.76 per 50 RB-units) overall. Vitamin D intake from diet and supplements was not related to risk. Results were thus consistent for the various indicators, although some estimated risks were not statistically significant. Effects were generally similar for diffuse large B-cell (DLBCL) and follicular lymphomas. Conclusion These data suggest a slight protective effect of sunlight against NHL, and they agree with geographic patterns of NHL incidence observed in the US. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ So Calif, Los Angeles, CA 90089 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. RP Hartge, P (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8090, Rockville, MD 20852 USA. EM hartgep@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [N01-PC-67009, N02-CP-31003, N01-PC-65064, N01-PC-67008, N02-PC-71105, N01-PC-67010] NR 43 TC 51 Z9 52 U1 2 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2006 VL 17 IS 8 BP 1045 EP 1052 DI 10.1007/s10552-006-0040-8 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 077VO UT WOS:000240059600006 PM 16933055 ER PT J AU Guo, ZY Dai, BJ Jiang, TY Xu, KX Xie, YQ Kim, O Nesheiwat, I Kong, XT Melamed, J Handratta, VD Njar, VCO Brodie, AMH Yu, LR Veenstra, TD Chen, HG Qiu, Y AF Guo, Zhiyong Dai, Bojie Jiang, Tianyun Xu, Kexin Xie, Yingqiu Kim, Oekyung Nesheiwat, Issa Kong, Xiangtian Melamed, Jonathan Handratta, Venkatesh D. Njar, Vincent C. O. Brodie, Angela M. H. Yu, Li-Rong Veenstra, Timothy D. Chen, Hegang Qiu, Yun TI Regulation of androgen receptor activity by tyrosine phosphorylation SO CANCER CELL LA English DT Article ID PROSTATE-CANCER CELLS; EPIDERMAL-GROWTH-FACTOR; INDEPENDENT GROWTH; ANTI-ANDROGENS; BREAST-CANCER; LINE LNCAP; FACTOR-I; INTERLEUKIN-6; KINASE; SRC AB The androgen receptor (AR) is essential for the growth of prostate cancer cells. Here, we report that tyrosine phosphorylation of AR is induced by growth factors and elevated in hormone-refractory prostate tumors. Mutation of the major tyrosine phosphorylation site in AR significantly inhibits the growth of prostate cancer cells under androgen-depleted conditions. The Src tyrosine kinase appears to be responsible for phosphorylating AR, and there is a positive correlation of AR tyrosine phosphorylation with Src tyrosine kinase activity in human prostate tumors. Our data collectively suggest that growth factors and their downstream tyrosine kinases, which are elevated during hormone-ablation therapy, can induce tyrosine phosphorylation of AR and such modification may be important for prostate tumor growth under androgen-depleted conditions. C1 Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. NYU, Sch Med, Dept Pathol, New York 10016, NY USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Natl Canc Inst Frederick, Ft Detrick, MD 21702 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Qiu, Y (reprint author), Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. EM yqiu@som.umaryland.edu OI Melamed, Jonathan/0000-0003-2844-7990 FU NCI NIH HHS [CA85380, CA106504, N01-CO-12400, U01-CA86772]; NIEHS NIH HHS [T32ES07263] NR 41 TC 200 Z9 207 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2006 VL 10 IS 4 BP 309 EP 319 DI 10.1016/j.ccr.2006.08.021 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 101BR UT WOS:000241714400007 PM 17045208 ER PT J AU Ostrander, EA Kwon, EM Stanford, JL AF Ostrander, Elaine A. Kwon, Erika M. Stanford, Janet L. TI Genetic susceptibility to aggressive prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID GENOME-WIDE SCAN; LINKAGE ANALYSIS; ALLELIC IMBALANCE; FAMILIES; LOCI; CHROMOSOME; SCREEN; RISK; OVEREXPRESSION; PREDISPOSITION C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [R01 CA080122, R01 CA089600, R01 CA78836] NR 50 TC 9 Z9 9 U1 0 U2 0 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 OCT PY 2006 VL 15 IS 10 BP 1761 EP 1764 DI 10.1158/1055-9965.EPI-06-0730 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800004 PM 17035380 ER PT J AU McGlynn, KA Zhang, YW Sakoda, LC Rubertone, MV Erickson, RL Graubard, BI AF McGlynn, Katherine A. Zhang, Yawei Sakoda, Lori C. Rubertone, Mark V. Erickson, Ralph L. Graubard, Barry I. TI Maternal smoking and testicular germ cell tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-FACTORS; CANCER-PATIENTS; EUROPEAN COUNTRIES; UNITED-STATES; BIRTH COHORT; YOUNG MEN; CRYPTORCHIDISM; HYPOSPADIAS; POPULATION; EXPOSURE AB Testicular germ cell tumors (TGCT) are the most common cancer among men ages 15 to 35 years in the United States. The well-established TGCT risk factors cryptorchism, prior diagnosis of TGCT, and family history of testicular cancer indicate that exposures in early life and/or in the familial setting may be critical to determining risk. Previous reports of familial clustering of lung cancer in mothers and testicular cancers in sons suggest that passive smoking in childhood may be such an exposure. To clarify the relationship of passive smoking exposure to TGCT risk, data from 754 cases and 928 controls enrolled in the Servicemen's Testicular Tumor Environmental and Endocrine Determinants study were analyzed. Data from 1,086 mothers of the cases and controls were also examined. Overall, there was no relationship between maternal [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.9-1.3] or paternal smoking (OR, 1.0; 95% CI, 0.8-1.3) and TGCT risk. Although living with a nonparent smoker was marginally related to risk (OR, 1.4; 95% CI, 1.0-2.1), there was no relationship with number of smokers, amount smoked, or duration of smoking. Responses from both case-control participants and mothers also revealed no relationship between either maternal smoking while pregnant or while breast-feeding. Results did not differ by TGCT histology (seminoma, nonseminoma). These results do not support the hypothesis that passive smoking, either in utero or in childhood, is related to risk of TGCT. Other early life exposures, however, may explain the familial clustering of lung cancer in mothers and TGCT in sons. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. USA, Ctr Hlth Promot & Prevent Med, Silver Spring, MD USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, EPS 7060,6120 Execut Blvd, Rockville, MD 20892 USA. EM mcglynnk@mail.nih.gov FU Intramural NIH HHS NR 50 TC 16 Z9 16 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 OCT PY 2006 VL 15 IS 10 BP 1820 EP 1824 DI 10.1158/1055-9965.EPI-06-0389 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800012 PM 17035387 ER PT J AU Abrahamson, PE Gammon, MD Lund, MJ Flagg, EW Porter, PL Stevens, J Swanson, CA Brinton, LA Eley, JW Coates, RJ AF Abrahamson, Page E. Gammon, Marilie D. Lund, Mary Jo Flagg, Elaine W. Porter, Peggy L. Stevens, June Swanson, Christine A. Brinton, Louise A. Eley, J. William Coates, Ralph J. TI General and abdominal obesity and survival among young women with breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; INSULIN-RESISTANCE; PROGNOSTIC FACTORS; WEIGHT-GAIN; RISK; FAT; DIAGNOSIS; SIZE; AGE; PREMENOPAUSAL AB Among postmenopausal women, obesity is linked to increased risk of breast cancer and poorer subsequent survival. For premenopausal women, obesity may reduce incidence, but less is known about its effect on prognosis, particularly for abdominal obesity. This study investigated whether general or abdominal obesity at diagnosis influenced survival in a cohort of young women with breast cancer. A population-based follow-up study was conducted among 1,254 women ages 20 to 54 who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta or New Jersey. Women were interviewed within several months of diagnosis and asked about their weight and height at age 20 and in the year before diagnosis. Study personnel did anthropometric measures at the interview. With 8 to 10 years of follow-up, all-cause mortality status was determined using the National Death Index (n = 290 deaths). Increased mortality was observed for women who were obese [body mass index (BMI), >= 30] at the time of interview compared with women of ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48; 95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05-2.19). Strong associations with mortality were found for women who were obese at age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, >= 25) at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This study provides evidence that breast cancer survival is reduced among younger women with general or abdominal obesity. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. US Ctr Dis Control & Prevent, Surveillance & Epidemiol Branch, Div Global Migrat & Quarantine, Natl Ctr Infect Dis, Atlanta, GA USA. US Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. NCI, Off Dis Prevent, Off Dietary Supplements, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Abrahamson, PE (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM pabraham@fhcrc.org RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS; NCI NIH HHS [R25 CA94880]; NIEHS NIH HHS [P30ES10126] NR 60 TC 71 Z9 72 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2006 VL 15 IS 10 BP 1871 EP 1877 DI 10.1158/1055-9965.EPI-06-0356 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800020 PM 17035393 ER PT J AU Anderson, WF Pfeiffer, RM Dores, GM Sherman, ME AF Anderson, William F. Pfeiffer, Ruth M. Dores, Graca M. Sherman, Mark E. TI Comparison of age distribution patterns for different histopathologic types of breast carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID END RESULTS DATABASE; HODGKINS DISEASE; CANCER INCIDENCE; UNITED-STATES; IN-SITU; EPIDEMIOLOGY; SURVEILLANCE; EXPRESSION; MORTALITY; MENOPAUSE AB Background: Historically, female breast carcinoma has been viewed as an etiologically homogeneous disease associated with rapidly increasing incidence rates until age 50 years, followed by a slower rate of increase among older women. More recent studies, however, have shown distinct age incidence patterns for female breast cancer when stratified by estrogen receptor (ER) expression and/or histopathologic subtypes, suggesting etiologic heterogeneity. Materials and Methods: To determine if different age incidence patterns reflect etiologic heterogeneity (more than one breast cancer type within the general breast carcinoma), we applied "smoothed" age histograms at diagnosis (density plots) and a two-component statistical mixture model to all breast carcinoma cases (n = 270,124) in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. These overall patterns were then reevaluated according to histopathologic type, race, and ER expression. Results: A bimodal age distribution at diagnosis provided a better fit to the data than a single density for all breast carcinoma populations, except for medullary carcinoma. Medullary carcinomas showed a single age distribution at diagnosis irrespective of race and/or ER expression. Conclusions: Distinct age-specific incidence patterns reflected bimodal breast cancer populations for breast carcinoma overall as well as for histopathologic subtypes, race, and ER expression. The one exception was medullary carcinoma. Of note, medullary carcinomas are rare tumors, which are associated with germ-line mutations in the BRCA1 gene. These descriptive and model-based results support emerging molecular data, suggesting two main types of breast carcinoma in the overall breast cancer population. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,EPS,NIH, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,EPS,NIH, Bethesda, MD 20892 USA. NCI, Off Prevent Oncol, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,EPS,NIH, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,EPS,NIH, Room 8036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM wanderso@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS NR 44 TC 63 Z9 68 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 OCT PY 2006 VL 15 IS 10 BP 1899 EP 1905 DI 10.1158/1055-9965.EPI-06-0191 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800024 PM 17035397 ER PT J AU Kamangar, F Cheng, C Abnet, CC Rabkin, CS AF Kamangar, Farin Cheng, Cindy Abnet, Christian C. Rabkin, Charles S. TI Interleukin-1B polymorphisms and gastric cancer risk - A meta-analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HELICOBACTER-PYLORI INFECTION; CYTOKINE GENE POLYMORPHISMS; RECEPTOR ANTAGONIST GENE; NECROSIS-FACTOR-ALPHA; EPSTEIN-BARR-VIRUS; CHINESE POPULATION; PROMOTER POLYMORPHISM; ATROPHIC GASTRITIS; KOREAN POPULATION; ASSOCIATION AB Some studies have reported that proinflammatory polymorphisms in interleukin-1B (IL-1B) and IL-1 receptor antagonist (IL-1RN) genes are associated with increased gastric cancer risk. However, other studies have shown null or inverse associations. This meta-analysis reviews and summarizes published evidence for these associations. Searching the PubMed Database yielded 35 studies that reported on the association between IL-1B -511 C > T, IL-1B -31 T > C, or IL-1RN variable number tandem repeat polymorphisms and gastric cancer risk. Q-statistics and 12 statistics were calculated to examine heterogeneity. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated in the random-effects model using the DerSimonian-Laird method. For all gastric cancers, the overall ORs (95% CIs) for IL-1B -511 CT versus CC and TT versus CC genotypes were 1.07 (0.91-1.25) and 1.16 (0.95-1.42), respectively. ORs (95% CIs) for the association between IL-1B -31 CT versus TT and CC versus TT genotypes were 0.99 (0.83-1.19) and 0.98 (0.78-1.21), respectively. For the associations between IL-1RN and gastric cancer, ORs (95% CIs) for *2/L versus LL and *2/*2 versus L/L were 1.15 (0.96-1.38) and 1.23 (0.79-1.92). For each of the examined associations, there was significant heterogeneity among studies; P(heterogeneity) <= 0.001 and I(2) ranged from 0.54 to 0.71. Noncardia cancers showed stronger associations with IL-1B -511 CT or TT and IL1-RN *2/*2 genotypes, but limiting the analysis to intestinal-type cancers, studies conducted in Western countries, or studies in which polymorphisms were in Hardy-Weinberg equilibrium, made no material difference in the results. The overall associations between IL-1B or IL-1RN proinflammatory polymorphisms and gastric cancer were null but several studies showed an association. The sources of this variation are unclear. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 3034, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS NR 56 TC 89 Z9 98 U1 0 U2 7 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 OCT PY 2006 VL 15 IS 10 BP 1920 EP 1928 DI 10.1158/1055-9965.EPI-06-0267 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800027 PM 17035400 ER PT J AU Gong, ZH Neuhouser, ML Goodman, PJ Albanes, D Chi, C Hsing, AW Lippman, SM Platz, EA Pollak, MN Thompson, IM Kristal, AR AF Gong, Zhihong Neuhouser, Marian L. Goodman, Phyllis J. Albanes, Demetrius Chi, Chen Hsing, Ann W. Lippman, Scott M. Platz, Elizabeth A. Pollak, Michael N. Thompson, Ian M. Kristal, Alan R. TI Obesity, diabetes, and risk of prostate cancer: Results from the prostate cancer prevention trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; IGF-BINDING PROTEIN-3; SEX STEROID-HORMONES; GROWTH-FACTOR-I; UNITED-STATES; PHYSICAL-ACTIVITY; FOLLOW-UP; WAIST CIRCUMFERENCE; NORWEGIAN MEN; INSULIN AB Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency maybe due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index >= 30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason < 7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason >= 7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Jewish Gen Hosp, Dept Med, Montreal, PQ, Canada. Jewish Gen Hosp, Dept Oncol, Lady Davis Res Inst, Montreal, PQ, Canada. McGill Univ, Montreal, PQ H3A 2T5, Canada. Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78285 USA. RP Gong, ZH (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N M4-B402, Seattle, WA 98109 USA. EM zgong@fhcrc.org RI Kristal, Alan/A-8779-2008; Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015 OI Kristal, Alan/0000-0002-7329-1617; Pollak, Michael/0000-0003-3047-0604; FU NCI NIH HHS [5 U10 CA37429, 1 P01 CA108964-01A1, 5 R01 CA63164] NR 54 TC 185 Z9 192 U1 0 U2 7 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 OCT PY 2006 VL 15 IS 10 BP 1977 EP 1983 DI 10.1158/1055-9965.EPI-06-0477 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800035 PM 17035408 ER PT J AU Ahn, J Weinstein, SJ Snyder, K Pollak, MN Virtamo, J Albanes, D AF Ahn, Jiyoung Weinstein, Stephanie J. Snyder, Kirk Pollak, Michael N. Virtamo, Jarmo Albanes, Demetrius TI No association between serum insulin-like growth factor (IGF)-I, IGF-binding protein-3, and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID FACTOR-I; COHORT; JACC; MEN C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. McGill Univ, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Oncol, Montreal, PQ H3T 1E2, Canada. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, EPS 3044,9000 Rockville Pike, Bethesda, MD 20892 USA. EM daa@nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 12 TC 11 Z9 13 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 OCT PY 2006 VL 15 IS 10 BP 2010 EP 2012 DI 10.1158/1055-9965.EPI-06-0580 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800042 PM 17035415 ER PT J AU Troisi, R Vatten, L Hoover, RN Roberts, JM Cole, BF Potischman, N AF Troisi, Rebecca Vatten, Lars Hoover, Robert N. Roberts, James M. Cole, Bernard F. Potischman, Nancy TI Maternal androgen and estrogen concentrations are not associated with blood pressure changes in uncomplicated pregnancies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BREAST-CANCER RISK; PREECLAMPSIA; SERUM; HYPERTENSION AB Systolic blood pressure increase between the second and third trimester of pregnancy has been associated with a substantially reduced maternal breast cancer risk, and it has been suggested that elevated androgens mediate the association. Androgen and estrogen concentrations were measured in maternal serum collected in 86 uncomplicated, singleton pregnancies. Overall, there were no consistent or statistically significant patterns of association between the hormones and systolic, diastolic, or mean arterial blood pressure or blood pressure change between trimesters. Results were similar with adjustment for factors related to the hormones. These data are not consistent with the hypothesis that elevated androgen concentrations mediate the observed reduction in maternal breast cancer risk associated with increases in blood pressure over the pregnancy. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Norwegian Univ Sci & Technol, Dept Publ Hlth, Trondheim, Norway. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. RP Troisi, R (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM troisir@mail.nih.gov NR 11 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2006 VL 15 IS 10 BP 2013 EP 2015 DI 10.1158/1055-9965.EPI-06-0531 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 099SU UT WOS:000241616800043 PM 17035416 ER PT J AU Helou, K Padilla-Nash, H Wangsa, D Karlsson, E Osterberg, L Karlsson, P Ried, T Knutsen, T AF Helou, Khalil Padilla-Nash, Hesed Wangsa, Danny Karlsson, Elin Osterberg, Lovisa Karlsson, Per Ried, Thomas Knutsen, Turid TI Comparative genome hybridization reveals specific genomic imbalances during the genesis from benign through borderline to malignant ovarian tumors SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COPY NUMBER CHANGES; GRANULOSA-CELL TUMOR; CHROMOSOME-ABNORMALITIES; GENETIC ALTERATIONS; HUMAN CANCER; CARCINOMAS; ABERRATIONS; TRISOMY-12; SEQUENCE; ADENOCARCINOMA AB Ovarian cancer is one of the most common types of malignancy in women throughout the developed world. Despite recent therapeutic advances, long-term survival is poor because ovarian cancer is largely asymptomatic in its early stages. Comparative genomic hybridization (CGH) was applied to a series of 8 benign, 8 borderline, and 17 malignant ovarian to establish genomic imbalances associated with tumor progression. Benign and borderline tumors were characterized by losses at 1p32 similar to p11, 2q14-q34, 4q13-q34, 5q11-q23, and 6q12-q24, as well as gains of 6p and chromosome 12. Similar chromosomal changes were also detected in malignant tumors but included additional chromosomal changes: gains at 1q21-q31, 2p, 3q, 5p, 7, 10p, 12p, 16p, 17, 19q, 20q, and 22q, as well as losses at X, 3p, 8p, 9, 11p, 13, 14, and 18. Some individual cases of benign and borderline tumors revealed no genetic alterations detectable by CGH, suggesting that these tumors may represent a subset of tumors that originate by an alternative mechanism of tumorigenesis. Furthermore, our findings reveal that borderline tumors are more similar to benign tumors than to malignant tumors with respect to their genetic profiles. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Gothenburg, Inst Clin Sci, Dept Oncol, SE-41345 Gothenburg, Sweden. NCI, Genet Branch, Clin Res Ctr, Bethesda, MD 20892 USA. Sahlgrens Univ Hosp, Dept Oncol, Oncol Sect, SE-41345 Gothenburg, Sweden. RP Helou, K (reprint author), Univ Gothenburg, Inst Clin Sci, Dept Oncol, Bla Str 2, SE-41345 Gothenburg, Sweden. EM khalil.helou@oncology.gu.se NR 38 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 2006 VL 170 IS 1 BP 1 EP 8 DI 10.1016/j.cancergencyto.2006.04.010 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 089CG UT WOS:000240857100001 PM 16965948 ER PT J AU Varella-Garcia, M Chen, L Zheng, XL Yu, L Dixon, D AF Varella-Garcia, Marileila Chen, Lin Zheng, Xiaolin Yu, Linda Dixon, Darlene TI Karyotypic characteristics of human uterine leiomyoma and myometrial cell lines following telomerase induction SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HUMAN FIBROBLASTS; LIFE-SPAN; CATALYTIC SUBUNIT; EXPRESSION; IMMORTALIZATION; EXTENSION; GROWTH; HTERT; CHECKPOINT; SENESCENCE AB Uterine leiomyomas are the most frequently diagnosed tumors of the female genital tract and the primary cause of hysterectomy in premenopausal women in the United States. In vitro model systems for studying these tumors are limited, due to poor culture growth. For the present study, myometrial (UtSMC) and uterine leiomyoma (UtLM) cell lines and their human telomerase reverse transcriptase (hTERT) immortalized counterparts were evaluated by GTL-banding and spectral karyotyping. UtSMC, at passage 9 showed the normal female karyotype, 46,XX. UtSMC-hTERT at passage 13 (population doubling [PD] 22 post immortalization) had two cell clones: 46,XX,der(13)t(10;13)(q11.2;p13)]/46,XX. UtLM, at passage 14, and the immortalized counterpart UtLM-hTERT (passage 13, PD 20 post immortalization), had the reciprocal translocation t(12;14)(q14;q23) in all cells and monosomy X in a fraction of cells. UtLM also displayed genomic instability with 15% of cells showing structural abnormalities involving chromosome arms 1p and 5q. UtLM-hTERT was karyotypically more stable than the parental line, thereby reflecting the inhibition of the accumulation of cytogenetic abnormalities by the maintenance of telomere integrity. This phenomenon was not observed in the UtSMC cells. (c) 2006 Elsevier Inc. All rights reserved. C1 NIEHS, NIH, Lab Expt Pathol, US Dept Hlth & Human Serv HHS, Res Triangle Pk, NC 27709 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Med Oncol, Aurora, CO 80045 USA. RP Dixon, D (reprint author), NIEHS, NIH, Lab Expt Pathol, US Dept Hlth & Human Serv HHS, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov FU Intramural NIH HHS NR 30 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 2006 VL 170 IS 1 BP 71 EP 75 DI 10.1016/j.jcancergencyto.2006.05.003 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 089CG UT WOS:000240857100013 PM 16965960 ER PT J AU Lung, HL Cheung, AKL Xie, D Cheng, Y Kwong, FM Murakami, Y Guan, YY Sham, JS Chua, D Protopopov, AI Zabarovsky, ER Tsao, SW Stanbridge, EJ Lung, ML AF Lung, Hong Lok Cheung, Arthur Kwok Leung Xie, Dan Cheng, Yue Kwong, Fung Mei Murakami, Yoshinori Guan, Yin-Yuan Sham, Jonathan Shuntong Chua, Daniel Protopopov, Alexey I. Zabarovsky, Eugene R. Tsao, Sai Wah Stanbridge, Eric J. Lung, Maria Li TI TSLC1 is a tumor suppressor gene associated with metastasis in nasopharyngeal carcinoma SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; EPSTEIN-BARR VIRUS; PROSTATE-CANCER; BREAST-CANCER; EXPRESSION; GROWTH; APOPTOSIS; PROGRESSION; LINES; TUMORIGENESIS AB In up to 87% of nasopharyngeal carcinoma (NPC) clinical tumor specimens, there was either down-regulation or loss of TSLC1 gene expression. Using a tissue microarray and immunohistochemical staining, the frequency of down-regulated or loss of expression of TSLC1 in metastatic lymph node TNPC was 83% and the frequency of loss of expression of TSLC1 was 35%, which was significantly higher than that in primary NPC (12%). To examine the possible growth-suppressive activity of TSLC1 in NPC, three NPC cell lines, HONE1, HNE1, and CNE2, were transfected with the wild-type TSLC1 gene cloned into the pCR3.1 expression vector; a reduction of colony formation ability was observed for all three cell lines. A tetracycline-inducible expression vector, pETE-Bsd, was also used to obtain stable transfectants of TSLC1 There was a dramatic difference between colony formation ability in the presence or absence of doxycycline when the gene is shut off or expressed, respectively, with the tetracycline-inducible system. Tumorigenicity assay results show that the activation of TSLC1 suppresses tumor formation in nude mice and functional inactivation of this gene is observed in all the tumors derived from tumorigenic transfectants. Further studies indicate that expression of TSLC1 inhibits HONE1 cell growth in vitro by arresting cells in G(0)-G(1) phase in normal culture conditions, whereas in the absence of serum, TSLC1 induced apoptosis. These findings suggest that TSLC1 is a tumor suppressor gene in NPC, which is significantly associated with lymph node metastases. C1 Hong Kong Univ Sci & Technol, Dept Biol, Kowloon, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Canc Res Ctr, Kowloon, Hong Kong, Peoples R China. Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Anat, Hong Kong, Hong Kong, Peoples R China. Sun Yat Sen Univ, State Key Lab Oncol So China, Ctr Canc, Guangzhou, Peoples R China. NCI, Genet Branch, Natl Naval Med Ctr, Bethesda, MD 20892 USA. Natl Canc Ctr, Res Inst, Tumor Suppress & Funct Genom Project, Tokyo 104, Japan. Karolinska Inst, Ctr Genom & Bioinformat, Ctr Microbiol & Tumor Biol, Stockholm, Sweden. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. RP Lung, ML (reprint author), Hong Kong Univ Sci & Technol, Dept Biol, Clear Water Bay, Kowloon, Hong Kong, Peoples R China. EM bomaria@ust.hk RI Lung, Hong Lok/C-4494-2009; Cheng, Yue/E-9853-2010; Zabarovsky, Eugene/A-6645-2010; Cheung, Arthur Kwok Leung/H-8940-2013 OI Cheng, Yue/0000-0002-2472-1879; NR 33 TC 65 Z9 75 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 OCT 1 PY 2006 VL 66 IS 19 BP 9385 EP 9392 DI 10.1158/0008-5472.CAN-06-0590 PG 8 WC Oncology SC Oncology GA 091GE UT WOS:000241014200009 PM 17018592 ER PT J AU Kotliarov, Y Steed, ME Christopher, N Walling, J Su, Q Center, A Heiss, J Rosenblum, M Mikkelsen, T Zenklusen, JC Fine, HA AF Kotliarov, Yuri Steed, Mary Ellen Christopher, Neil Walling, Jennifer Su, Qin Center, Angela Heiss, John Rosenblum, Mark Mikkelsen, Tom Zenklusen, Jean C. Fine, Howard A. TI High-resolution global genomic survey of 178 gliomas reveals novel regions of copy number alteration and allelic imbalances SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; ARRAY CGH DATA; GLIOBLASTOMA-MULTIFORME; OLIGODENDROGLIAL TUMORS; OLIGONUCLEOTIDE ARRAYS; EGFR AMPLIFICATION; GENE AMPLIFICATION; MOLECULAR-GENETICS; HYBRIDIZATION; EXPRESSION AB Primary brain tumors are the fourth leading cause of cancer mortality in adults under the age of 54 years and the leading cause of cancer mortality in children in the United States. Therapy for the most common type of primary brain tumors, gliomas, remains suboptimal. The development of new and more effective treatments will likely require a better understanding of the biology of these tumors. Here, we show that use of the high-density 100K single-nucleotide polymorphism arrays in a large number of primary tumor samples allows for a much higher resolution survey of the glioma genome than has been previously reported in any tumor type. We not only confirmed alterations in genomic areas previously reported to be affected in gliomas, but we also refined the location of those sites and uncovered multiple, previously unknown regions that are affected by copy number alterations (amplifications, homozygous and heterozygous deletions) as well as allelic imbalances (loss of heterozygosity/gene conversions). The wealth of genomic data produced may allow for the development of a more rational molecular classification of gliomas and serve as an important starting point in the search for new molecular therapeutic targets. C1 NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Henry Ford Hosp, Dept Neurol, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. Henry Ford Hosp, Dept Neurosurg, Hermelin Brain Tumor Ctr, Detroit, MI 48202 USA. RP Zenklusen, JC (reprint author), NCI, Neurooncol Branch, NIH, 37 Convent Dr,Room 1142B, Bethesda, MD 20892 USA. EM jz44m@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017; OI Heiss, John/0000-0002-3890-0165 FU Intramural NIH HHS [ZIA NS003052-06]; NCI NIH HHS [CA095809, R24 CA095809] NR 34 TC 85 Z9 88 U1 0 U2 2 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 OCT 1 PY 2006 VL 66 IS 19 BP 9428 EP 9436 DI 10.1158/0008-5472.CAN-06-1691 PG 9 WC Oncology SC Oncology GA 091GE UT WOS:000241014200014 PM 17018597 ER PT J AU de Bruijn, DRH Allander, SV van Dijk, AHA Willemse, MP Thijssen, J van Groningen, JJM Meltzer, PS van Kessel, AG AF de Bruijn, Diederik R. H. Allander, Susanne V. van Dijk, Anke H. A. Willemse, Marieke P. Thijssen, Jose van Groningen, Jan J. M. Meltzer, Paul S. van Kessel, Ad Geurts TI The synovial sarcoma-associated SS18-SSX2 fusion protein induces epigenetic gene (De)regulation SO CANCER RESEARCH LA English DT Article ID BINDING-PROTEIN; TRANSCRIPTIONAL ACTIVATION; NUCLEAR-LOCALIZATION; MICROARRAY ANALYSIS; SWI/SNF COMPLEX; ONCOPROTEIN SYT; SSX; EXPRESSION; INTERACTS; METHYLATION AB Fusion of the SS18 and either one of the SSX genes is a hallmark of human synovial sarcoma. The SS18 and SSX genes encode nuclear proteins that exhibit opposite transcriptional activities. The SS18 protein functions as a transcriptional coactivator and is associated with the SWI/SNF complex, whereas the SSX proteins function as transcriptional corepressors and are associated with the polycomb complex. The domains involved in these opposite transcriptional activities are retained in the SS18-SSX fusion proteins. Here, we set out to determine the direct transcriptional consequences of conditional SS18-SSX2 fusion protein expression using complementary DNA microarray-based profiling. By doing so, we identified several clusters of SS18-SSX2-responsive genes, including a group of genes involved in cholesterol synthesis, which is a general characteristic of malignancy. In addition, we identified a group of SS18-SSX2-responsive genes known to be specifically deregulated in primary synovial sarcomas, including IGF2 and CD44. Furthermore, we observed an uncoupling of EGR1, JUNB, and WNT signaling in response to SS18-SSX2 expression, suggesting that the SWI/SNF-associated coactivation functions of the SS18 moiety are impaired. Finally, we found that SS18-SSX2 expression affects histone modifications in the CD44 and IGF2 promoters and DNA methylation levels in the IGF2 imprinting control region. Together, we conclude that the SSIS-SSX2 fusion protein may act as a so-called transcriptional "activator-repressor," which induces downstream target gene deregulation through epigenetic mechanisms. Our results may have implications for both the development and clinical management of synovial sarcomas. C1 Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 855, NL-6500 HB Nijmegen, Netherlands. NIH, Natl Ctr Human Genome Res, Canc Genet Branch, Bethesda, MD 20892 USA. RP van Kessel, AG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet 855, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM a.geurtsvankessel@antrg.umcn.nl RI Geurts van Kessel, Ad/A-2810-2010; Bruijn, D.R.H./L-4233-2015 NR 55 TC 47 Z9 51 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 OCT 1 PY 2006 VL 66 IS 19 BP 9474 EP 9482 DI 10.1158/0008-5472.CAN-05-7326 PG 9 WC Oncology SC Oncology GA 091GE UT WOS:000241014200020 PM 17018603 ER PT J AU Meng, LH Shankavaram, U Chen, C Agama, K Fu, HQ Gonzalez, FJ Weinstein, J Pommier, Y AF Meng, Ling-hua Shankavaram, Uma Chen, Chi Agama, Keli Fu, Hai-qing Gonzalez, Frank J. Weinstein, John Pommier, Yves TI Activation of aminoflavone (NSC 686288) by a sulfotransferase is required for the antiproliferative effect of the drug and for induction of histone gamma-H2AX SO CANCER RESEARCH LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; BREAST-CANCER CELLS; H2AX PHOSPHORYLATION; DIETARY FLAVONOIDS; GENE-EXPRESSION; ANTITUMOR AGENT; TUMOR CELLS; DNA-ADDUCTS; METABOLISM; SULFONATION AB Aminotlavone (AF) is entering clinical trials. We recently reported that AF induces DNA-protein cross-links (DPC) and gamma-H2AX in MCF-7 human breast cancer cells. To elucidate the mechanism of action of AF and provide biomarkers indicative of AF activity, we correlated AF activity profile (GI(50)) with gene expression patterns in the NCI-60 cell lines. Sulfotransferases (SULT) showed the highest positive correlation coefficients among similar to 14,000 probe sets analyzed (r = 0.537, P < 0.001). Stable transfection of SULT1A1 into AF-resistant MDA-MB-231 cells sensitized these cells to AF. AF produced DPCs, gamma-H2AX foci, and S-phase arrest in the SULT1A1-transfected but not in the parent MDA-MB-231 cells. Conversely, cells in which SULT1A1 was knocked down by small interfering RNA failed to induce gamma-H2AY- Inhibition of SULTs and cytochrome P450 (CYP) enzymes by natural flavonoids blocked the antiproliferative activity of AF and the formation of AF-DNA adducts. AF also induces SULT1A1 and CYP expression in MCF-7 cells, suggesting the existence of an aryl hydrocarbon receptor-mediated positive feedback for AF activation by CYP and SULT1A1. Metabolism studies showed that AF can be oxidized by CYP at two amino groups to form N-hydroxyl metabolites that are substrates for bioactivation by SULTs. We propose that both N-sulfoxy-groups can be further converted to nitrenium ions that form adducts with DNA and proteins. The results reported here show the importance of SULT1A1 and CYP for AF activation and anticancer activity. They also suggest using SULT1A1 and gamma-H2AX as biomarkers for prediction of AF activity during patient selection and monitoring of clinical trials. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Room 5068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Chen, Chi/B-4618-2008 NR 36 TC 32 Z9 33 U1 2 U2 2 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 OCT 1 PY 2006 VL 66 IS 19 BP 9656 EP 9664 DI 10.1158/0008-5472.CAN-06-0796 PG 9 WC Oncology SC Oncology GA 091GE UT WOS:000241014200040 PM 17018623 ER PT J AU Wang, SS Cerhan, JR Hartge, P Davis, S Cozen, W Severson, RK Chatterjee, N Yeager, M Chanock, SJ Rothman, N AF Wang, Sophia S. Cerhan, James R. Hartge, Patricia Davis, Scott Cozen, Wendy Severson, Richard K. Chatterjee, Nilanjan Yeager, Meredith Chanock, Stephen J. Rothman, Nathaniel TI Common genetic variants in proinflammatory and other immunoregulatory genes and risk for non-Hodgkin lymphoma SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Association-for-Cancer-Research CY APR 16-20, 2005 CL Anaheim, CA SP Amer Assoc Canc Res ID B-CELL LYMPHOMA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FC-GAMMA-RIIA; FOLLICULAR LYMPHOMA; AFRICAN-AMERICANS; TNF-ALPHA; POLYMORPHISMS; SUSCEPTIBILITY; DISEASE; INFLAMMATION AB Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% Cl) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P-trend = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ Iowa, Iowa City, IA 52242 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Univ So Calif, Los Angeles, CA 90089 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA. Wayne State Univ, Dept Family Med, Detroit, MI 48202 USA. NCI, Core Genotyping Facil, Adv Technol Corp, Gaithersburg, MD USA. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N01-PC-67009, N01-PC-67010, N01-PC-65064, N01-PC-67008, N02-PC-71105] NR 58 TC 101 Z9 103 U1 0 U2 2 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 OCT 1 PY 2006 VL 66 IS 19 BP 9771 EP 9780 DI 10.1158/0008-5472.CAN-06-0324 PG 10 WC Oncology SC Oncology GA 091GE UT WOS:000241014200054 PM 17018637 ER PT J AU Gaudet, MM Chanock, S Lissowska, J Berndt, SI Peplonska, B Brinton, LA Welch, R Yeager, M Mikolajczak, AB Garcia-Closas, M AF Gaudet, Mia M. Chanock, Stephen Lissowska, Jolanta Berndt, Sonja I. Peplonska, Beata Brinton, Louise A. Welch, Robert Yeager, Meredith Mikolajczak, Alicja Bardin Garcia-Closas, Montserrat TI Comprehensive assessment of genetic variation of catechol-O-methyltransferase and breast cancer risk SO CANCER RESEARCH LA English DT Article ID SEQUENCE VALIDATION; ASSAY DEVELOPMENT; PUBLIC RESOURCE; CANDIDATE GENES; HAPLOTYPE; COMT; SCHIZOPHRENIA; SNP500CANCER; ASSOCIATION; VARIANT AB Because catechol-O-methyltransferase (COMT) catalyzes the addition of methyl groups to stabilize catechol estrogens that may induce DNA damage, genetic variants could influence breast cancer risk. To comprehensively characterize genetic variation in this gene, we selected haplotype-tagging single nucleotide polymorphisms (htSNP) in COMT. A total of 11 htSNTs (including COMT Val(158)Met) were selected based on the resequencing and dense genotyping approach of the Breast and Prostate Cancer Cohort Consortium. htSNPs were genotyped in a population-based, case-control study in Poland (1,995 cases and 2,296 controls). Individual SNPs were not significantly associated with risk. Haplotypes were estimated using the expectation-maximization algorithm. Overall differences in the haplotype distribution between cases and controls were assessed using a global score test. The TGAG haplotype (frequent in 4.3% of controls), in a linkage disequilibrium (LD) block that included the 3' untranslated region (UTR) of COMT, was associated with breast cancer risk (odds ratio, 1.29; 95% confidence interval, 1.06-1.58) compared with the most common haplotype TGAA; however, the global test for haplotype associations was not significant (P = 0.09). Haplotypes in another LD block, which included COMT Val(158)Met, were not associated with breast cancer risk (global P = 0.76). Haplotype-breast cancer risk associations were not significantly modified by hormonally related risk factors, family history of breast cancer, or tumor characteristics. in summary, our data does not support a substantial overall association between COMT haplotypes and breast cancer. The suggestion of increased risk associated with a haplotype in the 3' UTR of COMT needs to be confirmed in independent study populations. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Core Genotype Facil, Ctr Adv Technol, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Ctr Canc, Dept Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Gaudet, MM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-7055, Rockville, MD 20852 USA. EM gaudetm@mail.nih.gov RI Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 20 TC 15 Z9 15 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 OCT 1 PY 2006 VL 66 IS 19 BP 9781 EP 9785 DI 10.1158/0008-5472.CAN-06-1294 PG 5 WC Oncology SC Oncology GA 091GE UT WOS:000241014200055 PM 17018638 ER PT J AU Baccarelli, A Hirt, C Pesatori, AC Consonni, D Patterson, DG Bertazzi, PA Dolken, G Landi, MT AF Baccarelli, Andrea Hirt, Carsten Pesatori, Angela C. Consonni, Dario Patterson, Donald G., Jr. Bertazzi, Pier Alberto Doelken, Gottfried Landi, Maria Teresa TI t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy SO CARCINOGENESIS LA English DT Article ID NON-HODGKIN-LYMPHOMA; SOLID-WASTE INCINERATOR; ULTRAVIOLET-LIGHT; PERIPHERAL-BLOOD; BCL-2/J(H) TRANSLOCATION; FOLLICULAR LYMPHOMA; FREQUENCY; ACCIDENT; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; CANCER AB Dioxin exposure has been associated with non-Hodgkin's lymphoma (NHL) in epidemiological investigations. The NHL-related t(14;18) translocations can be detected at a low copy number in lymphocytes from healthy subjects. Exposure to NHL-associated carcinogens, such as dioxin or pesticides, may cause expansion of t(14;18)-positive clones. We investigated prevalence and frequency of circulating t(14;18)-positive lymphocytes in 144 healthy subjects from a population exposed to dioxin [plasma TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) range: < 1.7-475.0 parts per trillion (p.p.t.)] after the Seveso, Italy, accident of 1976. t(14;18) translocations were measured in DNA from peripheral blood lymphocytes by high-sensitivity real-time quantitative polymerase chain reaction. We found that the frequency, but not the prevalence, of t(14;18) translocation-positive cells increased with increasing plasma TCDD. Among t(14;18)-positive subjects (n = 50;34.7%), the mean number of t(14;18) translocations/10(6) lymphocytes was 4.2 [95% confidence interval (CI), 2.9-6.2] in subjects with plasma TCDD < 10.0 p.p.t., 8.1 (95% CI, 4.9-13.3) in subjects with plasma TCDD between 10.0 and 50.0 and 12.5 (95% CI, 7.4-21.1) in subjects with plasma TCDD between 50.0 and 475.0 p.p.t. (P-trend = 0.003). As expected, t(14;18) frequency was associated with cigarette smoking and was highest in subjects who smoked for >= 16 years (mean = 12.6; 95% CI, 7.4-21.3; P = 0.01). Higher t(14;18) prevalence was found among individuals with fair hair color (P = 0.01) and light eye color (P = 0.04). No significant association between t(14;18)-and age was found. Our results show that dioxin exposure is associated with increased number of circulating t(14;18) positive cells. Whether this change in t(14;18) frequency is an indicator of elevated lymphoma risk remains speculative and needs further investigation for its potential impact on public health. C1 Univ Milan, EPOCA Res Ctr Occupat Clin & Environm Epidemiol, Dept Occupat & Environm Hlth, I-20122 Milan, Italy. Osped Maggiore, IRCCS, Policlin, Milan, Italy. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Greifswald, Med Ctr, Dept Hematol & Oncol, D-17487 Greifswald, Germany. Ctr Dis Control & Prevent, Div Environm Hlth Lab Sci, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7114, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; Baccarelli, Andrea/0000-0002-3436-0640; pesatori, angela/0000-0002-0261-3252 FU Intramural NIH HHS NR 47 TC 27 Z9 28 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2006 VL 27 IS 10 BP 2001 EP 2007 DI 10.1093/carcin/bgl011 PG 7 WC Oncology SC Oncology GA 090CF UT WOS:000240927500008 PM 16543249 ER PT J AU Shen, M Lan, Q Zhang, LP Chanock, S Li, GL Vermeulen, R Rappaport, SM Guo, WH Hayes, RB Linet, M Yin, SN Yeager, M Welch, R Forrest, MS Rothman, N Smith, MT AF Shen, Min Lan, Qing Zhang, Luoping Chanock, Stephen Li, Guilan Vermeulen, Roel Rappaport, Stephen M. Guo, Weihong Hayes, Richard B. Linet, Martha Yin, Songnian Yeager, Meredith Welch, Robert Forrest, Matthew S. Rothman, Nathaniel Smith, Martyn T. TI Polymorphisms in genes involved in DNA double-strand break repair pathway and susceptibility to benzene-induced hematotoxicity SO CARCINOGENESIS LA English DT Article ID WERNER-SYNDROME PROTEIN; HEMATOPOIETIC PROGENITOR CELLS; HOMOLOGOUS RECOMBINATION; BONE-MARROW; P53; BRCA2; SUPPRESSION; METABOLITES; STABILITY; VARIANTS AB Benzene is a recognized hematotoxicant and carcinogen that produces genotoxic damage. DNA double-strand breaks (DSB) are one of the most severe DNA lesions caused directly and indirectly by benzene metabolites. DSB may lead to chromosome aberrations, apoptosis and hematopoietic progenitor cell suppression. We hypothesized that genetic polymorphisms in genes involved in DNA DSB repair may modify benzene-induced hematotoxicity. We analyzed one or more single nucleotide polymorphisms (SNPs) in each of seven candidate genes (WRN, TP53, NBS1, BRCA1, BRCA2, XRCC3 and XRCC4) in a study of 250 workers exposed to benzene and 140 controls in China. Four SNPs in WRN (Ex4 -16 G > A, Ex6 +9 C > T, Ex20 -88 G > T and Ex26 -12 T > G), one SNP in TP53 (Ex4 +119 C > G) and one SNP in BRCA2 (Ex11 +1487 A > G) were associated with a statistically significant decrease in total white blood cell (WBC) counts among exposed workers. The SNPs in WRN and TP53 remained significant after accounting for multiple comparisons. One or more SNPs in WRN had broad effects on WBC subtypes, with significantly decreased granulocyte, total lymphocyte, CD4(+)-T cell, CD8(+)-T cell and monocyte counts. Haplotypes of WRN were associated with decreased WBC counts among benzene-exposed subjects. Likewise, subjects with TP53 Ex4 +119 C > G variant had reduced granulocyte, CD4(+)-T cell and B cell counts. The effect of BRCA2 Ex11 +1487 A > G polymorphism was limited to granulocytes. These results suggest that genetic polymorphisms in WRN, TP53 and BRCA2 that maintain genomic stability impact benzene-induced hematotoxicity. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Canc Res Ctr, NIH, DHHS, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP Shen, M (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X; Forrest, Matthew/0000-0002-2141-0303 FU Intramural NIH HHS; NIEHS NIH HHS [P30ES01896, P30ES10126, P42ES04705, P42ES05948, R01ES06721] NR 41 TC 40 Z9 45 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2006 VL 27 IS 10 BP 2083 EP 2089 DI 10.1093/carcin/bgl061 PG 7 WC Oncology SC Oncology GA 090CF UT WOS:000240927500017 PM 16728435 ER PT J AU Colbert, LH Mai, V Tooze, JA Perkins, SN Berrigan, D Hursting, SD AF Colbert, Lisa H. Mai, Volker Tooze, Janet A. Perkins, Susan N. Berrigan, David Hursting, Stephen D. TI Negative energy balance induced by voluntary wheel running inhibits polyp development in APC(Min) mice SO CARCINOGENESIS LA English DT Article ID GROWTH-FACTOR-I; INDUCED COLON CARCINOGENESIS; IGF-BINDING PROTEIN-3; SKIN TUMOR PROMOTION; MAMMARY CARCINOGENESIS; CALORIE RESTRICTION; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; FOOD RESTRICTION; FACTOR (IGF)-I AB Treadmill running of similar to 0.9 km/day has had inconsistent effects on spontaneous intestinal polyp development in C57BL/6J-Apc(Min)/J (Min) mice; the amount of energy expenditure and/or a lack of hormonal changes could account for this variability. The purpose of this study was to examine the effects of a negative energy balance induced by voluntary wheel running on polyps, insulin-like growth factor-1 (IGF-1) and corticosterone in Min mice. Seven-week-old male Min mice were randomly assigned to control (CON, n = 23) or wheel running (EX, n = 24) conditions for a 10-week study period. All mice had water and AIN-76A diet ad libitum for the first similar to 3 weeks on study, after which the EX group was pair-fed to the CON group to maintain a negative energy balance due to the exercise. EX mice voluntarily ran 3.8 km/day (2.7-6.0 km/day) (median, interquartile range) and weighed less than CON mice throughout the study. More CON mice died before the end of the study versus EX mice (26 versus 0%, P < 0.01). CON mice had significantly more polyps versus EX mice (21.6 +/- 1.5 versus 16.9 +/- 2.0, P < 0.01; mean +/- SE), and daily running distance in EX was inversely correlated with total polyp number (r = -0.70, P < 0.01). Urinary corticosterone output (P < 0.01) and serum IGF-1 were significantly higher in EX than CON (P < 0.001); however, total polyp number was unrelated to corticosterone (r = 0.05, P = 0.84) and IGF-1 (r = -0.01, P = 0.93). In this study, a negative energy balance produced by wheel running exercise and restricted feeding decreased polyp burden in male Min mice and appeared to have a dose-response effect on polyp number. Although EX affected IGF-1 and corticosterone, neither marker was related to total polyp number. C1 Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NCI, Bethesda, MD 20892 USA. Univ Texas, Dept Human Ecol, Austin, TX 78712 USA. RP Colbert, LH (reprint author), Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. EM lhcolbert@education.wisc.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 31 TC 26 Z9 27 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2006 VL 27 IS 10 BP 2103 EP 2107 DI 10.1093/carcin/bgl056 PG 5 WC Oncology SC Oncology GA 090CF UT WOS:000240927500020 PM 16699175 ER PT J AU Trostel, SY Sackett, DL Fojo, T AF Trostel, Shana Y. Sackett, Dan L. Fojo, Tito TI Oligomerization of p53 precedes its association with dynein and nuclear accumulation SO CELL CYCLE LA English DT Article DE nuclear localization; p53; tubulin; microtubules; oligomerization; dynein; microtubule transport; p53 tetramerization ID TUMOR-SUPPRESSOR P53; HSP90-BINDING IMMUNOPHILINS; TETRAMERIZATION DOMAIN; MICROTUBULE DYNAMICS; TERMINAL DOMAIN; DNA-REPAIR; PROTEIN; CANCER; LOCALIZATION; TRANSPORT AB Previous studies have identified several proteins that associate with microtubules and the dynein motor complex including p53, the glucocorticoid and the vitamin D receptors, and the APC ( adenomatous polyposis coli) protein; but neither the residues important for this interaction nor the physical state of the proteins involved have been clarified. We observed in SN12C cells harboring a mutant p53 truncated at amino acid 336, impaired nuclear localization and impaired association with dynein. This finding was confirmed and extended by examining a series of truncated p53 proteins that identified residues 336 to 348 as crucial for association with dynein and nuclear transport. Point mutations identified the importance of residues involved in p53 oligomerization in this process, establishing a p53 oligomer as the cargo for dynein transport. The association of cytosolic p53 oligomers with dynein occurs independent of microtubules indicating that following this association, the p53/dynein complex then associates with microtubules and is transported to the peri-nuclear region. These studies suggest that mutations or modifications that affect p53 oligomerization not only interfere with DNA binding but also with its intracellular distribution. They also highlight the importance of an intact microtubule network in the trafficking of crucial cellular proteins. C1 NCI, Canc Res Ctr, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Canc Res Ctr, Med Oncol Branch, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov FU Intramural NIH HHS NR 41 TC 16 Z9 17 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2006 VL 5 IS 19 BP 2253 EP 2259 DI 10.4161/cc.5.19.3291 PG 7 WC Cell Biology SC Cell Biology GA 098KQ UT WOS:000241519800015 PM 16969106 ER PT J AU Wang, BD Butylin, P Strunnikov, A AF Wang, Bi-Dar Butylin, Pavel Strunnikov, Alexander TI Condensin function in mitotic nucleolar segregation is regulated by rDNA transcription SO CELL CYCLE LA English DT Article DE condensin; nucleolus; transcription; chromosome segregation; chromosome condensation; RFB; FOB1 ID RIBOSOMAL-RNA SYNTHESIS; FORK BLOCK PROTEIN; SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONDENSATION; REPLICATION FORK; IN-VIVO; YEAST RDNA; BUDDING YEAST; POLYMERASE-I; ACTIVE GENES AB Chromosome condensation is established and maintained by the condensin complex. The mechanisms governing loading of condensin onto specific chromosomal sites remain unknown. To elucidate the molecular pathways that determine condensin binding to the nucleolar organizer, a key condensin binding site, we analyzed the properties of condensin-bound sites within the rDNA repeat in budding yeast and demonstrated that the bulk of mitotic condensin binding to rDNA is reduced or eliminated when Pol I transcription is elevated. Conversely, when Pol I transcription is repressed either by rapamycin treatment or by promoter shut-off, condensin binding to rDNA is increased. This novel potential role for constitutive and/or periodic repression of Pol I transcription in rDNA condensin loading is an important factor in determining the segregation proficiency of NOR-containing chromosomes. C1 NICHD, LRGD, NIH, Bethesda, MD 20892 USA. RP Strunnikov, A (reprint author), NICHD, LRGD, NIH, 18T Lib Dr,Room 106, Bethesda, MD 20892 USA. EM strunnik@mail.nih.gov OI Strunnikov, Alexander/0000-0002-9058-2256 FU Intramural NIH HHS [Z99 AI999999, Z01 HD001903-11] NR 58 TC 23 Z9 23 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2006 VL 5 IS 19 BP 2260 EP 2267 DI 10.4161/cc.5.19.3292 PG 8 WC Cell Biology SC Cell Biology GA 098KQ UT WOS:000241519800016 PM 16969110 ER PT J AU Muppidi, JR Lobito, AA Ramaswamy, M Yang, JK Wang, L Wu, H Siegel, RM AF Muppidi, J. R. Lobito, A. A. Ramaswamy, M. Yang, J. K. Wang, L. Wu, H. Siegel, R. M. TI Homotypic FADD interactions through a conserved RXDLL motif are required for death receptor-induced apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Fas; apoptosis; FADD; oligomerization; TNF receptor ID EFFECTOR DOMAIN; CASPASE-8 ACTIVATION; SIGNALING COMPLEX; NMR STRUCTURE; FAS; PROTEIN; CD95; MEMBRANE; DISC; OLIGOMERIZATION AB Death receptors in the TNF receptor superfamily signal for apoptosis via the ordered recruitment of FADD and caspase-8 to a death-inducing signaling complex ( DISC). However, the nature of the protein-protein interactions in the signaling complex is not well defined. Here we show that FADD self-associates through a conserved RXDLL motif in the death effector domain (DED). Despite exhibiting similar binding to both Fas and caspase-8 and preserved overall secondary structure, FADD RDXLL motif mutants cannot reconstitute FasL- or TRAIL-induced apoptosis and fail to recruit caspase-8 into the DISC of reconstituted FADD-deficient cells. Abolishing self-association can transform FADD into a dominant-negative mutant that interferes with Fas-induced apoptosis and formation of microscopically visible receptor oligomers. These findings suggest that lateral interactions among adapter molecules are required for death receptor apoptosis signaling and implicate self-association into oligomeric assemblies as a key function of death receptor adapter proteins in initiating apoptosis. C1 NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. HHMI, NIH, Res Scholoars Program, Bethesda, MD 20814 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Siegel, RM (reprint author), NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, 9000 Rockville Pk,Bldg 10,Room 9N238, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU NIEHS NIH HHS [T32-ES007079] NR 33 TC 30 Z9 30 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2006 VL 13 IS 10 BP 1641 EP 1650 DI 10.1038/sj.cdd.4401855 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 095IM UT WOS:000241301400003 PM 16410793 ER PT J AU Franke, JD Boury, AL Gerald, NJ Kiehart, DP AF Franke, Josef D. Boury, Amanda L. Gerald, Noel J. Kiehart, Daniel P. TI Native nonmuscle myosin II stability and light chain binding in Drosophila melanogaster SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE essential light chain; regulatory light chain; protein complex stability ID SMOOTH-MUSCLE MYOSIN; IQGAP-LIKE PROTEIN; HEAVY-CHAIN; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; ACTIN CYTOSKELETON; EFFECT CYTOKINESIS; MITOTIC SPINDLE; ATPASE ACTIVITY AB Native nonmuscle myosin IIs play essential roles in cellular and developmental processes throughout phylogeny. Individual motor molecules consist of a hetero-hexameric complex of three polypeptides which, when properly assembled, are capable of force generation. Here, we more completely characterize the properties, relationships and associations that each subunit has with one another in Drosophila melanogaster. All three native nonmuscle myosin 11 polypeptide subunits are expressed in close to constant stoichiometry to each other throughout development. We find that the stability of two subunits, the heavy chain and the regulatory light chain, depend on one another whereas the stability of the third subunit, the essential light chain, does not depend on either the heavy chain or regulatory light chain. We demonstrate that heavy chain aggregates, which form in when regulatory light chain is lacking, associate with the essential light chain vivo-thus showing that regulatory light chain association is required for heavy chain solubility. By immunodepletion we find that the majority of both light chains are associated with the nonmuscle myosin 11 heavy chain but pools of free light chain and/or light chain bound to other proteins are present. We identify four myosins (myosin 11, myosin V, myosin VI and myosin VIIA) and a microtubule-associated protein (asp/Abnormal spindle) as binding partners for the essential light chain (but not the regulatory light chain) through mass spectrometry and co-precipitation. Using an in silico approach we identify six previously uncharacterized genes that contain IQ-motifs and may be essential light chain binding partners. C1 Duke Univ, Dept Biol, Durham, NC 27708 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Kiehart, DP (reprint author), Duke Univ, Dept Biol, Durham, NC 27708 USA. EM dkiehart@duke.edu FU NIDCD NIH HHS [DC007673]; NIGMS NIH HHS [GM07184, GM33830, GM61240] NR 88 TC 20 Z9 20 U1 0 U2 0 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 OCT PY 2006 VL 63 IS 10 BP 604 EP 622 DI 10.1002/cm.20148 PG 19 WC Cell Biology SC Cell Biology GA 086KC UT WOS:000240671200002 PM 16917818 ER PT J AU Wuest, T Farber, J Luster, A Carr, DJJ AF Wuest, Todd Farber, Joshua Luster, Andrew Carr, Daniel J. J. TI CD4(+) T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection SO CELLULAR IMMUNOLOGY LA English DT Article DE HSV-1; chemokines; CXCL9; CXCL10; knockout mice; cornea; T lymphocyte ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INDUCED STROMAL KERATITIS; NATURAL-KILLER-CELLS; IFN-GAMMA; INDUCIBLE PROTEIN-10; INTERFERON-GAMMA; TRIGEMINAL GANGLION; CYTOKINE PRODUCTION; CHEMOKINE LIGAND-9 AB The role of CXCL9 and CXCL10 in the ocular immune response to herpes simplex virus type I (HSV-1) infection was investigated using mice deficient in either CXCL9 or CXCL10. CXCL10 but not CXCL9 deficient mice showed an increase in sensitivity to ocular virus infection as measured by an elevation in virus titer recovered in the tear film and corneal tissue. The increase in virus was associated with an increase in the expression of the chemokine CCL2 but no significant change in the infiltration of CD4(+) T cells or NK cells into the corneal stroma. In contrast, a significant reduction in CD4(+) T cell infiltration into the cornea was found in CXCL9 deficient mice following HSV-1 infection consistent with the absence of CXCL9 expression and reduction in expression of other chemokines including CCL3, CCL5, CXCL1, and CXCL10. Collectively, the results suggest a non-redundant role for CXCL9 and CXCL10 in response to ocular HSV-1 infection in terms of controlling virus replication and recruitment of CD4(+) T cells into the cornea. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. Natl Inst Allergy & Infect Dis, Lab Clin Invest, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK 73104 USA. RP Carr, DJJ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. EM dan-carr@oulisc.edu FU NEI NIH HHS [EY12190, EY015566, P30 EY012190, R21 EY015566] NR 43 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT PY 2006 VL 243 IS 2 BP 83 EP 89 DI 10.1016/j.cellimm.2007.01.001 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 152VV UT WOS:000245391000003 PM 17296171 ER PT J AU Qin, XB Gao, B AF Qin, Xuebin Gao, Bin TI The Complement System in Liver Diseases SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE immunity; complement; liver disease AB The complement system plays an important role in mediating both acquired and innate responses to defend against microbial infection, and in disposing immunoglobins and apoptotic cells. The liver (mainly hepatocytes) is responsible for biosynthesis of about 80-90% of plasma complement components and expresses a variety of complement receptors. Recent evidence from several studies suggests that the complement system is also involved in the pathogenesis of a variety of liver disorders including liver injury and repair, fibrosis, viral hepatitis, alcoholic liver disease, and liver ischemia/reperfusion injury. In this review, we will discuss the potential role of the complement system in the pathogenesis of liver diseases. C1 [Qin, Xuebin] Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. [Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Qin, XB (reprint author), Harvard Univ, Sch Med, Lab Translat Res, One Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM xuebin_qin@hms.harvard.edu NR 83 TC 66 Z9 71 U1 1 U2 1 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD OCT PY 2006 VL 3 IS 5 BP 333 EP 340 PG 8 WC Immunology SC Immunology GA V32BL UT WOS:000208926600002 PM 17092430 ER PT J AU Lin, L AF Lin, Li TI RAGE on the Toll Road? SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE TLR; RAGE; NF-kappa B; innate immunity; inflammation; noncanonical Toll AB Mammalian Toll-like receptors (TLRs) are cellular pattern-recognizing receptors (PRRs) that recognize the molecular patterns of pathogens. After engaging the pathogenic patterned ligands, the cytosolic portion of the TLRs in monocytes and macrophages, recruits adaptor proteins, via a receptor-driven signaling cascade, activates the transcription factor NF-kappa B, leading to the expression of proinflammatory cytokines, which trigger inflammation. Such rapid, innate cellular responses serve as the first line of host defense against infection by pathogens, and also stimulate the adaptive immune system to clear the invading microbes. Increasing evidence suggests that TLRs also recognize host-derived ligands, linking this group of PRRs to diseases that may not have an etiology that is associated directly with infections. Advanced glycation end products (AGEs) are nonenzymatically glycated or oxidated proteins, lipids and nucleic acids that are formed in the environment of oxidant stress and hyperglycemia. Binding of AGEs to their receptor RAGE initiates cellular signals that activate NF-kappa B, which results in transcription of proinflammatory factors. RAGE can also interact with other endogenous ligands generated by cell death and tissue injuries. RAGE has been implicated in chronic diseases such as diabetes, atherosclerosis, neurodisorders, cancers, as well as aging. This review discusses the possible role of RAGE as a PRR that may use signaling mechanisms parallel to TLRs', to solicit inflammatory reactions. Thus, in this scenario, RAGE may play a prominent role in the regulation of cellular homeostasis in the context of complex disease progression. C1 Natl Inst Aging, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Lin, L (reprint author), Natl Inst Aging, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM linli@mail.nih.gov FU NIH [RO1CA104912]; National Institute on Aging FX I thank Drs. Edward Lakatta, Rui-Ping Xiao, Steven Sollott, and Gianfranco Pintus for their critique and discussion of this review. My work is supported by NIH grant RO1CA104912 and the intramural funding from the National Institute on Aging. NR 54 TC 85 Z9 94 U1 0 U2 2 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD OCT PY 2006 VL 3 IS 5 BP 351 EP 358 PG 8 WC Immunology SC Immunology GA V32BL UT WOS:000208926600004 PM 17092432 ER PT J AU Liu, XF Ohno, S Miki, T AF Liu, Xiu Fen Ohno, Shigeo Miki, Toru TI Nucleotide exchange factor ECT2 regulates epithelial cell polarity SO CELLULAR SIGNALLING LA English DT Article DE Rho GTPases; DBL family; cyst formation; MDCK cells; morphogenesis ID GTP-BOUND RHOA; PROTEIN COMPLEX; G2/M PHASE; KINASE-C; CYTOKINESIS; CONTACT; PHOSPHORYLATION; MORPHOGENESIS; ACCUMULATION; CULTURE AB Cell polarity regulates diverse biological events such as localization of embryonic determinants and establishment of tissue and organ architecture. Epithelial cell polarity is regulated by the polarity complex Par6/Par3/atypical protein kinase C (aPKC). We previously found that the nucleotide exchange factor ECT2 associates with this polarity complex and regulates aPKC activity, but the role of ECT2 in cell polarity is still unclear. Here we show that expression of a dominant negative (ECT2-N2) or constitutively active (ECT2-Delta N5) form of ECT2 inhibits normal cyst formation of MDCK cells in 3-dimensional collagen gels. Central lumens were not observed in cysts formed by cells expressing either ECT2-Delta N5 or ECT2-N2. Apical localization of ZO-1 and basolateral localization of beta-catenin were no longer observed in these cells. Interestingly, cells expressing ECT2-N2 did form normal cysts when cultured in the basement membrane matrix Matrigel instead of collagen gels. Addition of a major Matrigel component, laminin, partially rescued the normal cyst formation inhibited by ECT2-N2 in 3-dimensional collagen gels. Thus, signaling through laminin might override the defects of signaling through collagen and ECT2. Whereas ECT2-N2 inhibited the lumen formation of MDCK cysts, caspase-3, which is reportedly involved in lumen formation through apoptosis, was activated at various locations of cells in the cysts. It is likely that perturbation of ECT2 signaling inhibits the establishment of epithelial cell polarity leading to the inhibition of selected elimination of cells at the center of cysts. Thus, ECT2 appears to play a critical role in epithelial cell polarity. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Cell Biol Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. Yokohama City Univ, Sch Med, Dept Mol Biol, Yokohama, Kanagawa 2360004, Japan. RP Miki, T (reprint author), NCI, Cell Biol Lab, Mol Tumor Biol Sect, Bldg 37,Room 2144,37 Convent Dr MSC 4256, Bethesda, MD 20892 USA. EM toru@helix.nih.gov RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 FU Intramural NIH HHS NR 37 TC 21 Z9 22 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 OCT PY 2006 VL 18 IS 10 BP 1604 EP 1615 DI 10.1016/j.cellsig.2006.01.007 PG 12 WC Cell Biology SC Cell Biology GA 082MQ UT WOS:000240391300007 PM 16495035 ER PT J AU Nilsson, R Ahmad, F Sward, K Andersson, U Weston, M Manganiello, V Degerman, E AF Nilsson, Rebecka Ahmad, Faiyaz Sward, Karl Andersson, Ulrika Weston, Marie Manganiello, Vincent Degerman, Eva TI Plasma membrane cyclic nucleotide phosphodiesterase 3B (PDE3B) is associated with caveolae in primary adipocytes SO CELLULAR SIGNALLING LA English DT Article DE PDE3B; caveolae; caveolin-1; adipocytes; insulin; GLUT-4 ID INSULIN-RECEPTOR SUBSTRATE-1; PRIMARY RAT ADIPOCYTES; PROTEIN-KINASE; CAVEOLIN-1-DEFICIENT MICE; ADIPOSE-CELLS; FAT CELLS; IDENTIFICATION; TRANSLOCATION; LOCALIZATION; LIPOLYSIS AB Caveolae, plasma membrane invaginations particularly abundant in adipocytes, have been suggested to be important in organizing insulin signalling. Insulin-induced activation of the membrane bound cAMP degrading enzyme, phosphodiesterase 3B (PDE3B) is a key step in insulin-mediated inhibition of lipolysis and is also involved in the regulation of insulin-mediated glucose uptake and lipogenesis in adipocytes. The aim of this work was to evaluate whether PDE3B is associated with caveolae. Subcellular fractionation of primary rat and mouse adipocytes demonstrated the presence of PDE3B in endoplasmic reticulum and plasma membrane fractions. The plasma membrane PDE3B was further analyzed by detergent treatment at 4 degrees C, which did not solubilize PDE3B, indicating an association of PDE3B with lipid rafts. Detergent-treated plasma membranes were studied using Superose-6 chromatography which demonstrated co-elution of PDE3B with caveolae and lipid raft markers (caveolin-1, flotillin-1 and cholesterol) at a Mw of > 4000 kDa. On sucrose density gradient centrifugation of sonicated plasma membranes, a method known to enrich caveolae, PDE3B co-migrated with the caveolae markers. Immunoprecipitation of caveolin-1 using anti caveolin-1 antibodies co-immunoprecipitated PDE3B and immunoprecipitation of flag-PDE3B from adipocytes infected with a flag-PDE3B adenovirus resulted in co-immunoprecipitation of caveolin-1. Studies on adipocytes with disrupted caveolae, using either caveolin-1 deficient mice or treatment of adipocytes with methyl-beta-cyclodextrin, reduced the membrane associated PDE3B activity. Furthermore, inhibition of PDE3 in primary rat adipocytes resulted in reduced insulin stimulated glucose transporter-4 translocation to caveolae, isolated by immunoprecipitation using caveolin-1 antibodies. Thus, PDE3B, a key enzyme in insulin signalling, appears to be associated with caveolae in adipocytes and this localization seems to be functionally important. (c) 2006 Elsevier Inc. All rights reserved. C1 Lund Univ, Dept Expt Med Sci, S-22184 Lund, Sweden. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Nilsson, R (reprint author), Lund Univ, Dept Expt Med Sci, BMC C11, S-22184 Lund, Sweden. EM rebecka.nilsson@med.lu.se RI sward, karl/J-5798-2012; OI Sward, Karl/0000-0002-7255-5510 NR 37 TC 33 Z9 35 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 OCT PY 2006 VL 18 IS 10 BP 1713 EP 1721 DI 10.1016/j.cellsig.2006.01.010 PG 9 WC Cell Biology SC Cell Biology GA 082MQ UT WOS:000240391300019 PM 16503395 ER PT J AU Grissom, CK Morris, AH Lanken, PN Ancukiewicz, M Orme, J Schoenfeld, DA Thompson, BT AF Grissom, Colin K. Morris, Alan H. Lanken, Paul N. Ancukiewicz, Marek Orme, James, Jr. Schoenfeld, David A. Thompson, B. T. TI Correlation of clinical exam findings and cardiac index in patients with the acute respiratory distress syndrome SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 NHLBI, NIH, ARDS Netwok LDS Hosp, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 SU S BP 87S EP 87S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288000017 ER PT J AU Barnett, CF Tran, K Calvo, KR Machado, RF AF Barnett, Christopher F. Tran, Khoi Calvo, Katherine R. Machado, Roberto F. TI A case of pulmonary venoocclusive disease treated with sildenafil SO CHEST LA English DT Meeting Abstract CT CHEST 2006 Conference CY OCT 21-26, 2006 CL Salt Lake City, UT C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RI Calvo, Katherine/A-8109-2009 NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2006 VL 130 IS 4 SU S BP 307S EP 307S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 095DI UT WOS:000241288001422 ER PT J AU Schrump, DS Fischette, MR Nguyen, DM Zhao, M Li, XM Kunst, TF Hancox, A Hong, JA Chen, GA Pishchik, V Figg, WD Murgo, AJ Steinberg, SM AF Schrump, David S. Fischette, Maria R. Nguyen, Dao M. Zhao, Ming Li, Xinmin Kunst, Tricia F. Hancox, Ana Hong, Julie A. Chen, G. Aaron Pishchik, Vitaliy Figg, William D. Murgo, Anthony J. Steinberg, Seth M. TI Phase I study of decitabine-mediated gene expression in patients with cancers involving the lungs, esophagus, or pleura SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; REFRACTORY SOLID TUMORS; DNA METHYLATION; 5-AZA-2'-DEOXYCYTIDINE DECITABINE; TESTIS GENES; CELLS; NY-ESO-1; PROMOTER; ANTIGENS; IMMUNOTHERAPY AB Purpose: The DNA methylation paradox, manifested as derepression of cancer-testis antigens, and silencing of tumor suppressors during malignant transformation, provides the rationale for the utilization of chromatin remodeling agents for cancer therapy. A phase I trial was done to examine pharmacokinetics, toxicities, and gene expression mediated by 5-aza-2'-deoxycytidine (DAC) in patients with thoracic malignancies. Experimental Design: Thirty-five patients with cancers refractory to standard therapy received continuous 72-hour DAC infusions using a phase I dose-escalation schema. Each full course of therapy consisted of two identical 35-day cycles. Plasma DAC levels were evaluated by liquid chromatography-mass spectrometry techniques. Quantitative reverse transcription-PCR, methylation-specific PCR, and immunohistochemical techniques were used to evaluate NY-ESO-1, MAGE-3, and p16 expression in tumor biopsies. Long oligonucleotide arrays were used to evaluate gene expression profiles in laser-captured tumor cells before and after DAC exposure. Results: Thirty-five patients were evaluable for toxicities; 25 were evaluable for treatment response. Myelosuppression constituted dose-limiting toxicity. The maximum tolerated dose of DAC was 60 to 75 mg/m(2) depending on the number of prior cytotoxic chemotherapy regimens. No objective responses were observed. Plasma DAC concentrations approximated thresholds for gene induction in cultured cancer cells. Target gene induction was observed in 36% of patients. Posttreatment antibodies to NY-ESO-1 were detected in three patients exhibiting NY-ESO-1 induction in their tumor tissues. Complex, heterogeneous gene expression profiles were observed in pretreatment and posttreatment tissues. Conclusion: Prolonged DAC infusions can modulate gene expression in primary thoracic malignancies. These findings support further evaluation of DNA-demethylating agents alone or in combination with other regimens targeting induced gene products for the treatment of these neoplasms. C1 NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Chicago, Funct Genom Facil, Chicago, IL 60637 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bldg 10,Room 4-3942,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM davidschrump@nih.gov RI Figg Sr, William/M-2411-2016 NR 45 TC 133 Z9 138 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2006 VL 12 IS 19 BP 5777 EP 5785 DI 10.1158/1078-0432.CCR-06-0669 PG 9 WC Oncology SC Oncology GA 092LL UT WOS:000241098100026 PM 17020984 ER PT J AU Grover, A Kim, GJ Lizee, G Tschoi, M Wang, G Wunderlich, JR Rosenberg, SA Hwang, ST Hwu, P AF Grover, Amelia Kim, Grace J. Lizee, Gregory Tschoi, Mary Wang, Gang Wunderlich, John R. Rosenberg, Steven A. Hwang, Sam T. Hwu, Patrick TI Intralymphatic dendritic cell vaccination induces tumor antigen-specific, skin-homing T lymphocytes SO CLINICAL CANCER RESEARCH LA English DT Article ID CC-CHEMOKINE RECEPTOR; INFLAMMATORY PROTEIN 3-ALPHA; REGIONAL IMMUNITY; IN-VITRO; TRAFFICKING; MICROENVIRONMENT; IMMUNOTHERAPY; EXPRESSION; INJECTION; RESPONSES AB Purpose: The identification of tumor antigens recognized by cytotoxic and T helper lymphocytes has led to the development of specific cancer vaccines. Immunization with tumor antigen-pulsed dendritic cells has proved effective at eliciting elevated levels of tumor antigen - specific T cells in patient blood, but objective clinical responses remain rare, suggesting that vaccine-induced T cells are not trafficking optimally to site(s) of tumor burden. Accumulating evidence from animal models suggests that route of immunization can have a substantial influence on the subsequent migration of primed, activated T cells in vivo. Experimental Design: In a clinical trial designed to elicit more effective cytotoxic T-cell mediated antitumor responses, metastatic melanoma patients were immunized directly via a peripheral intralymphatic route with autologous dendritic cells pulsed with HLA-A*0201-restricted melanoma-associated peptide antigens derived from MART-1 and gp100. Results: Within 10 days of intralymphatic dendritic cell vaccination, four of six patients developed dramatic and diffuse erythematous rashes in sun-exposed areas of skin that showed extensive T-cell infiltration. CTLs grown from rash biopsies were strongly enriched for tumor antigen specific T cells that had elevated expression of cutaneous lymphocyte antigen and chemokine receptor-6, consistent with a skin-homing phenotype. Of note, the only patient in the study with cutaneously localized disease showed a significant regression of metastatic lesions following the development of a surrounding rash. Conclusions: The evidence presented here is consistent with immunization studies in animal models and supports the concept that T cells are "imprinted" in peripheral lymph node sites to express specific ligands and chemokine receptors that allow them to migrate to skin. Furthermore, the preferential migration of the T cells to sun-exposed cutaneous sites suggests that inflammation plays a critical role in this migration. These observations suggest that further study of the effects of immunization route and inflammation on T-cell migration in humans is warranted, and could lead to vaccination approaches that would more reliably direct trafficking of activated T cells to diverse sites of metastatic disease. C1 Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Hwu, P (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Unit 430,1515 Holcombe Blvd, Houston, TX 77030 USA. EM phwu@mdanderson.org FU Intramural NIH HHS [Z01 SC003811-32] NR 32 TC 36 Z9 43 U1 1 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 OCT 1 PY 2006 VL 12 IS 19 BP 5801 EP 5808 DI 10.1158/1078-0432.CCR-05-2421 PG 8 WC Oncology SC Oncology GA 092LL UT WOS:000241098100029 PM 17020987 ER PT J AU Roberts, JD Smith, MR Feldman, EJ Cragg, L Millenson, MM Roboz, GJ Honeycutt, C Thune, R Padavic-Shaller, K Carter, WH Ramakrishnan, V Murgo, AJ Grant, S AF Roberts, John D. Smith, Mitchell R. Feldman, Eric J. Cragg, Louise Millenson, Michael M. Roboz, Gail J. Honeycutt, Connie Thune, Rose Padavic-Shaller, Kristin Carter, W. Hans Ramakrishnan, Viswanathan Murgo, Anthony J. Grant, Steven TI Phase I study of bryostatin 1 and fludarabine in patients with chronic lymphocytic leukemia and indolent (Non-Hodgkin's) lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; COLONY-STIMULATING FACTOR; LOW-GRADE LYMPHOMA; HEMATOPOIETIC PROGENITOR CELLS; PHORBOL ESTER; CLONOGENIC RESPONSE; MACROCYCLIC LACTONE; AGENT BRYOSTATIN-1; EXPRESSION; INDUCTION AB Purpose: Preclinical studies suggested that bryostatin 1 might potentiate the therapeutic effects of fludarabine in the treatment of hematologic malignancies. We undertook a phase I study to identify appropriate schedules and doses of bryostatin 1 and fludarabine to be used in phase 11 studies. Experimental Design: Patients with chronic lymphocytic leukemia (CLL) or indolent lymphoma received fludarabine daily for 5 days and a single dose of bryostatin 1 via a 24-hour continuous infusion either before or after the fludarabine course. Doses were escalated in successive patients until recommended phase II doses for each sequence were identified on the basis of dose-limiting toxic events. Results: Bryostatin 1 can be administered safely and tolerably with full dose fludarabine (25 mg/m(2) /d x 5). The recommended bryostatin 1 phase II dose is 50 mu g/m(2) for both sequences, bryostatin 1 --> fludarabine and fludarabine --> bryostatin 1. The combination is active against both CLL and indolent lymphomas with responses seen in patients who had been previously treated with fludarabine. Correlative studies do not support the hypothesis that bryostatin 1 potentiates fludarabine activity through down-regulation of protein kinase C in target cells. Conclusions: Bryostatin 1 can be administered with full dose fludarabine, and the combination is moderately active in patients with persistent disease following prior treatment. In view of the activity of monoclonal antibodies such as the anti-CD20 monoclonal antibody rituximab in the treatment of CLL and indolent lymphomas, the concept of combining bryostatin 1 and fludarabine with rituximab warrants future consideration. C1 Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Internal Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol & Immunol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Microbiol & Immunol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Biostat, Richmond, VA 23298 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Mercy Canc Ctr, Mason City, IA USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Grant, S (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Massey Canc Ctr, POB 980230, Richmond, VA 23298 USA. EM stgrant@vcu.edu OI Smith, Mitchell/0000-0003-1428-8765 FU NCI NIH HHS [P30 CA 16059, R21 CA 87056, CA 63753, P30 CA 06927]; NCRR NIH HHS [M01 RR 00065] NR 50 TC 32 Z9 38 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 OCT 1 PY 2006 VL 12 IS 19 BP 5809 EP 5816 DI 10.1158/1078-0432.CCR-05-2730 PG 8 WC Oncology SC Oncology GA 092LL UT WOS:000241098100030 PM 17020988 ER PT J AU Beumer, JH Joseph, E Egorin, MJ Parker, RS Dargenio, DZ Covey, JM Eiseman, JL AF Beumer, Jan H. Joseph, Erin Egorin, Merrill J. Parker, Robert S. Dargenio, David Z. Covey, Joseph M. Eiseman, Julie L. TI A mass balance and disposition study of the DNA methyltransferase inhibitor zebularine (NSC 309132) and three of its metabolites in mice SO CLINICAL CANCER RESEARCH LA English DT Article ID ALDEHYDE OXIDASE; URIDINE PHOSPHORYLASE; CYTIDINE DEAMINASE; PRODRUG; RESCUE; PLASMA; 5-FLUOROURACIL; METHYLATION; TOXICITY; THERAPY AB Purpose:To elucidate the in vivo metabolic fate of zebularine (NSC 309132), a DNA methyltransferase inhibitor proposed for clinical evaluation in the treatment of cancer. Experimental Design: Male, CD2F1 mice were dosed i.v. with 100 mg/kg 2- [C-14] zebularine. At specified times between 5 and 1,440 minutes, mice were euthanized. Plasma, organs, carcass, urine, and feces were collected and assayed for total radioactivity. Plasma and urine were also analyzed for zebularine and its metabolites with a previously validated high-pressure liquid chromatography assay. A similar experiment was done with 2- [C-14] uridine, the proposed primary metabolite of zebularine. Results: Maximum plasma concentrations were 462, 306, 33.6, 21.7, and 11.5 mu mol/L for total radioactivity, zebularine, uridine, uracil (each at 5 minutes), and dihydrouracil (at 15 minutes), respectively. Total radioactivity, zebularine, uridine, uracil, and dihydrouracil were rapidly eliminated from plasma, and after 45 minutes, none of the individual compounds could be quantitated by high-pressure liquid chromatography. Plasma data were consistent with sequential conversion of zebularine to uridine, uracil, and dihydrouracil. 2-Pyrimidinone was not observed. Prolonged retention of radioactivity, at concentrations higher than in plasma, was observed in tissues. Recovery of given radioactivity in urine (30.3% of dose), feces (0.4% of dose), cage wash (7.9% of dose), and tissues and carcass (6.1% of dose) after 24 hours implied that up to 55% of radioactivity was expired as (CO2)-C-14. Comparison of zebularine and uridine pharmacokinetic data indicated that similar to 40% of the zebularine dose was converted to uridine. Conclusions: Zebularine is extensively and rapidly metabolized into endogenous compounds that are unlikely to have effects at the concentrations observed. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Engn, Dept Chem & Petr Engn, Pittsburgh, PA 15261 USA. Univ So Calif, Los Angeles, CA USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G28,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerjh@upmc.edu OI Beumer, Jan/0000-0002-8978-9401 FU NCI NIH HHS [P30 CA 47904, N01 CM 52202]; NIBIB NIH HHS [P41 EB 001978] NR 32 TC 5 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2006 VL 12 IS 19 BP 5826 EP 5833 DI 10.1158/1078-0432.CCR-06-1234 PG 8 WC Oncology SC Oncology GA 092LL UT WOS:000241098100032 PM 17020990 ER PT J AU Ghany, MG Seeff, LB AF Ghany, Marc G. Seeff, Leonard B. TI Efforts to define the natural history of chronic hepatitis C continue SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID LIVER FIBROSIS PROGRESSION; SINGLE-SOURCE OUTBREAK; NON-B-HEPATITIS; TERM FOLLOW-UP; NON-A; POSTTRANSFUSION HEPATITIS; CLINICAL-OUTCOMES; VIRUS; INFECTION; TRANSFUSION C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2006 VL 4 IS 10 BP 1190 EP 1192 DI 10.1016/j.cgh.2006.07.024 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 097KZ UT WOS:000241447700004 PM 17045209 ER PT J AU Sidransky, E AF Sidransky, E. TI Heterozygosity for a Mendelian disorder as a risk factor for complex disease SO CLINICAL GENETICS LA English DT Review DE Gaucher disease; glucocerebrosidase; heterozygotes; Mendelian disorders; modifier genes; multifactorial disorders; parkinsonism; risk factors ID CYSTIC-FIBROSIS MUTATION; GAUCHER-DISEASE; PARKINSONS-DISEASE; GLUCOCEREBROSIDASE GENE; SYNERGISTIC HETEROZYGOSITY; MARFAN-SYNDROME; MODIFIER GENES; ASHKENAZI-JEWS; TRAFFIC JAMS; DEFICIENCY AB While genetic diseases are generally classified as being either 'simple' monogenic or 'complex' polygenic, the distinction between Mendelian and complex disorders is becoming increasingly blurred. Mendelian disorders may demonstrate qualities more typical of multifactorial diseases through shared clinical presentations, the effect of genetic modifiers, moonlighting proteins, synergistic heterozygosity, disease manifestations in heterozygotes and situations where heterozygosity for a 'simple' disorder proves to be a risk factor for seemingly unrelated complex diseases. A recent example of the last instance is the observation that mutations in glucocerebrosidase, the enzyme deficient in Gaucher disease, may be a risk factor for the development of Parkinson disease and other synucleinopathies. Insights gleaned from the study of Mendelian disorders may ultimately lead to a better understanding of factors influencing complex diseases. C1 NHGRI, Sect Mol Neurogenet, Clin Genet Branch, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Clin Genet Branch, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU Intramural NIH HHS NR 72 TC 35 Z9 37 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2006 VL 70 IS 4 BP 275 EP 282 DI 10.1111/j.1399-0004.2006.00688.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 081JB UT WOS:000240312600002 PM 16965318 ER PT J AU Gillim-Ross, L Subbarao, K AF Gillim-Ross, Laura Subbarao, Kanta TI Emerging respiratory viruses: Challenges and vaccine strategies SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID INFLUENZA-A VIRUS; FELINE INFECTIOUS PERITONITIS; HUMAN CORONAVIRUS NL63; A/DUCK/SINGAPORE/97 H5N3 VACCINE; ANTIBODY-DEPENDENT ENHANCEMENT; HUMAN MONOCLONAL-ANTIBODIES; COLD-ADAPTED REASSORTANT; JANUARY-FEBRUARY 1976; AVIAN INFLUENZA; HONG-KONG AB The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratoty syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from cut-rent vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), 50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 247 TC 77 Z9 83 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2006 VL 19 IS 4 BP 614 EP + DI 10.1128/CMR.00005-06 PG 24 WC Microbiology SC Microbiology GA 097KW UT WOS:000241447400002 PM 17041137 ER PT J AU Meletiadis, J Chanock, S Walsh, TJ AF Meletiadis, Joseph Chanock, Stephen Walsh, Thomas J. TI Human pharmacogenomic variations and their implications for antifungal efficacy SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID HUMAN SERUM-ALBUMIN; B LIPID COMPLEX; SINGLE NUCLEOTIDE POLYMORPHISMS; INVASIVE FUNGAL-INFECTIONS; PLASMA-PROTEIN BINDING; DUBIN-JOHNSON-SYNDROME; MULTIDRUG-RESISTANCE PROTEIN-2; CATECHOL O-METHYLTRANSFERASE; HUMAN-IMMUNODEFICIENCY-VIRUS; ORGANIC ANION TRANSPORTERS AB Pharmacogenomics is defined as the study of the impacts of heritable traits on pharmacology and toxicology. Candidate genes with potential pharmacogenomic importance include drug transporters involved in absorption and excretion, phase I enzymes (e.g., cytochrome P450-dependent mixed-function oxidases) and phase II enzymes (e.g., glucuronosyl-transferases) contributing to metabolism, and those molecules (e.g., albumin, A1-acid glycoprotein, and lipoproteins) involved in the distribution of antifungal compounds. By using the tools of population genetics to define interindividual differences in drug absorption, distribution, metabolism, and excretion, pharmacogenomic models for genetic variations in antifungal pharmacokinetics can be derived. Pharmacogenomic factors may become especially important in the treatment of immunocompromised patients or those with persistent or refractory mycoses that cannot be explained by elevated MICs and where rational dosage optimization of the antifungal agent may be particularly critical. Pharmacogenomics has the potential to shift the paradigm of therapy and to improve the selection of antifungal compounds and adjustment of dosage based upon individual variations in drug absorption, metabolism, and excretion. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, 1-5750 10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 286 TC 19 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD OCT PY 2006 VL 19 IS 4 BP 763 EP + DI 10.1128/CMR.00059-05 PG 26 WC Microbiology SC Microbiology GA 097KW UT WOS:000241447400008 PM 17041143 ER PT J AU Jiang, B Zhu, ZZ Liu, F Hou, LF Gu, J Chen, E Tzeng, CM Zhu, G AF Jiang, B. Zhu, Z. -Z. Liu, F. Hou, L. -F. Gu, J. Chen, E. Tzeng, C. -M. Zhu, G. TI Prevalence of mutation in the epidermal growth factor receptor gene in Chinese patients with non-small cell lung cancer SO CLINICAL ONCOLOGY LA English DT Letter ID GEFITINIB; RESPONSIVENESS C1 Shanghai Med Univ 2, Baogang Hosp, Dept Oncol, Shanghai 201900, Peoples R China. 113 Hosp PLA, Dept Pathol, Ningbo 315040, Peoples R China. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Shanghai GeneCore Biotechnol Co, Shanghai 201203, Peoples R China. RP Jiang, B (reprint author), Shanghai Med Univ 2, Baogang Hosp, Dept Oncol, Shanghai 201900, Peoples R China. NR 5 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD OCT PY 2006 VL 18 IS 8 BP 635 EP 635 DI 10.1016/j.clon.2006.06.001 PG 1 WC Oncology SC Oncology GA 088ED UT WOS:000240793400010 PM 17051955 ER PT J AU Proschan, MA Leifer, ES AF Proschan, Michael A. Leifer, Eric S. TI Comparison of two or more measurement techniques to a standard SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE measurement error; bias; Bland-Altman plot AB With advancing medical technology come new and less invasive ways to measure the extent of a patient's disease. These techniques may be preferred to an invasive standard even if they are not quite as accurate. They may also be the only available tools because some patients are not sufficiently stable to be measured the standard way. The question then becomes, does one newer method more closely match the standard than another? For comparison of a single new method to a standard, one measures patients using each method and assesses the distribution of differences. But how does one compare the distributions of differences when there are multiple newer techniques? At least two components of these distributions are important. One is the mean difference or bias, but its absolute value is what is most relevant; a bias of -3 is better than a bias of +4. Another important component is the variance of the differences. If two methods have similar and small absolute bias, the one yielding a smaller variance of differences is preferred. We derive methods of comparing absolute biases, variances of errors, and parameters that combine biases and variances. Published by Elsevier Inc. C1 NHLBI, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD OCT PY 2006 VL 27 IS 5 BP 472 EP 482 DI 10.1016/j.cct.2006.02.008 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 079FD UT WOS:000240160000008 PM 16750939 ER PT J AU Nelson, JE Angus, DC Weissfeld, LA Puntillo, KA Danis, M Deal, D Levy, MM Cook, DJ AF Nelson, Judith E. Angus, Derek C. Weissfeld, Lisa A. Puntillo, Kathleen A. Danis, Marion Deal, David Levy, Mitchell M. Cook, Deborah J. CA Critical Care Peer Workgroup Promo TI End-of-life care for the critically ill: A national intensive care unit survey SO CRITICAL CARE MEDICINE LA English DT Review DE intensive care; intensive care units; critical care; healthcare surveys; palliative care; communication ID DECISION-MAKING; SUSTAINING TREATMENTS; FAMILY MEMBERS; NEEDS; MEDICINE; QUALITY; CANCER; ICU; QUESTIONNAIRE; PERSPECTIVES AB Objective: One in five Americans dies following treatment in an intensive care unit (ICU), and evidence indicates the need to improve end-of-life care for ICU patients. We conducted this study to elicit the views and experiences of ICU directors regarding barriers to optimal end-of-life care and to identify the type, availability, and perceived benefit of specific strategies that may improve this care. Design. Self-administered mail survey. Setting: Six hundred intensive care units. Participants. A random, nationally representative sample of nursing and physician directors of 600 adult ICUs in the United States. Interventions: Mail survey. Measurements and Main Results. We asked participants about barriers to end-of-life care (1 = huge to 5 = not at all a barrier), perceived benefit of strategies to improve end-of-life care, and availability of these strategies. From 468 ICUs (78.0% of sample), 590 ICU directors participated (406 nurses [65.1% response] and 184 physicians [31.7% response]). Respondents had a mean of 16.6 yrs (SD 7.6 yrs) of ICU experience. Important barriers to better end-of-life care included patient/family factors, including unrealistic patient/family expectations 2.5 (1.0), inability of patients to participate in discussions 2.7 (0.9), and lack of advance directives 2.9 (1.0); clinician factors, which included insufficient physician training in communication 2.9 (1.1) and competing demands on physicians' time 3.0 (1.1); and institution/ICU factors, such as suboptimal space for family meetings 3.5 (1.2) and lack of a palliative care service 3.4 (1.2). More than 80% of respondents rated 14 of 14 strategies as likely to improve end-of-life care, including trainee role modeling by experienced clinicians, clinician training in communication and symptom management, regular meetings of senior clinicians with families, bereavement programs, and end-of-life care quality monitoring. However, few of these strategies were widely available. Conclusions: Intensive care unit directors perceive important barriers to optimal end-of-life care but also universally endorse many practical strategies for quality improvement. C1 NIH, Bethesda, MD 20892 USA. Abt Associates Inc, Cambridge, MA 02138 USA. Rhode Isl Hosp, Crit Care Serv, Providence, RI USA. Rhode Isl Hosp, MICU, Providence, RI USA. Brown Med Sch, Providence, RI USA. McMaster Univ, Dept Clin Epidemiol, Acad Chair, Hamilton, ON L8S 4L8, Canada. McMaster Univ, Dept Clin Epidemiol, Canada Res Chair, Hamilton, ON L8S 4L8, Canada. RP Nelson, JE (reprint author), CUNY Mt Sinai Sch Med, Box 1232,1 Gustave Levy Pl, New York, NY 10029 USA. EM judith.nelson@mountsinai.org RI Angus, Derek/E-9671-2012 FU NIA NIH HHS [K02 AG024476] NR 43 TC 119 Z9 121 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2006 VL 34 IS 10 BP 2547 EP 2553 DI 10.1097/01.CCM.0000239233.63425.1D PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 088EZ UT WOS:000240795700005 PM 16932230 ER PT J AU Verma, M Manne, U AF Verma, Mukesh Manne, Upender TI Genetic and epigenetic biomarkers in cancer diagnosis and identifying high risk populations SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE biomarker; epigenetics; risk assessment; screening ID CELL LUNG-CANCER; CIRCULATING TUMOR-CELLS; PROSTATE-CANCER; COLORECTAL-CANCER; PROMOTER METHYLATION; ANDROGEN RECEPTOR; HEPATOCELLULAR-CARCINOMA; PLASMA DNA; MITOCHONDRIAL-DNA; PANCREATIC-CANCER AB Biomarkers present the normal and/or disease state in humans. Genetic and epigenetic biomarkers assessed in easily accessible biological materials are useful in diagnosis, early onset or risk of developing cancer or to predict the treatment efficacy or clinical outcome of different human malignancies. Moreover, some of these markers are expressed during early stages of the tumor development and hence provide an opportunity to develop intervention and treatment strategies. Attempts are being made to validate cancer biomarkers in non-invasively collected samples. Multiplexing of clinically validated markers is still a challenge. Once validated, these markers can be utilized in clinical settings and to identify high risk populations. In this review, the current status of the clinical genetic and epigenetic biomarkers and their implication in cancer diagnosis and risk assessment are discussed. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res PRogram, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Verma, M (reprint author), NCI, Analyt Epidemiol Res Branch, Epidemiol & Genet Res PRogram, Div Canc Control & Populat Sci, Rm 5104,6130 Execut Blvd, Rockville, MD 20852 USA. EM vermam@mail.nih.gov RI Manne, Upender/D-5613-2009 NR 90 TC 15 Z9 16 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD OCT PY 2006 VL 60 IS 1 BP 9 EP 18 DI 10.1016/j.critrevonc.2006.04.002 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 094WW UT WOS:000241270900002 PM 16829121 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, Robert J. Pastan, Ira TI Immunotoxins in the treatment of hematologic malignancies SO CURRENT DRUG TARGETS LA English DT Review DE toxin; leukemia; lymphoma; Fv; Pseudomonas exotoxin; CD3; CD7; CD22; CD25; CD30; CD64; CD87; monoclonal antibody; leukemia; Hodgkin's disease; diphtheria toxin; interleukin 2; interleukin 3; granulocyte macrophage colony stimulating factor; fusion protein ID RICIN-A-CHAIN; HAIRY-CELL LEUKEMIA; NON-HODGKINS-LYMPHOMA; PHASE-I TRIAL; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; PSEUDOMONAS EXOTOXIN-A; COLONY-STIMULATING FACTOR; DIPHTHERIA-TOXIN RECEPTOR; TOXIN-INTERLEUKIN-3 FUSION PROTEIN AB Immunotoxins, composed of protein toxins connected to cell binding ligands including monoclonal antibodies and growth factors, have been developed for several decades to target hematologic malignancies. Protein toxins from either plants or bacteria are extremely potent based on their enzymatic inhibition of protein synthesis and induction of apoptosis. Plant toxins particularly ricin, are useful for chemically conjugating to monoclonal antibodies, and have shown clinical activity in several types of lymphoma and leukemia. Their dose is generally limited by vascular leak syndrome. Bacterial toxins have been used to produce single chain fusions with either growth factors or recombinant antibody fragments. These agents are smaller in size (55-65 kDa) and exit the bloodstream much more rapidly than the chemical conjugates, and generally do not cause severe vascular leak syndrome. The only approved drug containing a protein toxin is denileukin diftitox, a fusion of human interleukin 2 with truncated diphtheria toxin. Denileukin diftitox has shown efficacy in cutaneous T-cell lymphoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Recombinant immunotoxin BL22 is an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin; it induces complete remissions in a high percentage of patients with chemoresistant hairy cell leukemia. The anti-CD25 recombinant immunotoxin LMB-2 is active in several CD25+ hematologic malignancies. Several other recombinant immunotoxins are undergoing preclinical development for other target-antigens expressed on hematologic malignancies. C1 Natl Canc Inst, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), Natl Canc Inst, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov NR 235 TC 47 Z9 55 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD OCT PY 2006 VL 7 IS 10 BP 1301 EP 1311 DI 10.2174/138945006778559139 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 083MX UT WOS:000240461200010 PM 17073592 ER PT J AU Galperin, MY Ellison, MJ AF Galperin, Michael Y. Ellison, Michael J. TI Systems biology: sprint or marathon? Editorial overview SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Alberta, Dept Biochem, Inst Biomol Design, Edmonton, AB T6G 2H7, Canada. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov; mike.ellison@ualberta.ca RI Galperin, Michael/B-5859-2013; Infante, Diogenes/A-8444-2015 OI Galperin, Michael/0000-0002-2265-5572; Infante, Diogenes/0000-0002-8312-2198 NR 2 TC 1 Z9 1 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 2006 VL 17 IS 5 BP 437 EP 439 DI 10.1016/j.copbio.2006.08.008 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 099GE UT WOS:000241580500001 ER PT J AU Galperin, MY Kolker, E AF Galperin, Michael Y. Kolker, Eugene TI New metrics for comparative genomics SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID BURKHOLDERIA-XENOVORANS LB400; METABOLIC PATHWAYS; PROTEIN FAMILIES; PHYLOGENETIC NETWORK; HYPOTHETICAL GENES; SCALE ANALYSIS; EC NUMBERS; SEQUENCE; EVOLUTION; PROKARYOTES AB The availability of genome sequences from a variety of organisms presents an opportunity to apply this sequence information to solving the key problems of molecular biology. One of the principal roadblocks on this path is the lack of appropriate descriptors and metrics that could succinctly represent the new knowledge stemming from the genomic data. Several new metrics have recently been used in comparative genome analysis, yet challenges remain in finding an appropriate language for the emerging discipline of systems biology. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. BIATECH Inst, Bothell, WA 98011 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM ekolker@biatech.org RI Kolker, Eugene/C-6711-2008; Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS [Z99 LM999999] NR 61 TC 25 Z9 25 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 2006 VL 17 IS 5 BP 440 EP 447 DI 10.1016/j.copbio.2006.08.007 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 099GE UT WOS:000241580500002 PM 16978854 ER PT J AU Koonin, EV Wolf, YI AF Koonin, Eugene V. Wolf, Yuri I. TI Evolutionary systems biology: links between gene evolution and function SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; INTERACTION NETWORK; SIMPLE DEPENDENCE; EXPRESSION LEVEL; MOLECULAR-LEVEL; DISPENSABILITY; NUMBER; GENOMICS; DETERMINANTS; MODULARITY AB The recent accumulation of genome-wide data on various facets of gene expression, function and evolution stimulated the emergence of a new field, evolutionary systems biology. Many significant correlations were detected between variables that characterize the functioning of a gene, such as expression level, knockout effect, connectivity of genetic and protein-protein interaction networks, and variables that describe gene evolution, such as sequence evolution rate and propensity for gene loss. The first attempts on multidimensional analysis of genomic data yielded composite variables that describe the 'status' of a gene in the genomic community. However, it remains uncertain whether different functional variables affect gene evolution synergistically or there is a single, dominant factor. The number of translation events, linked to selection for translational robustness, was proposed as a candidate for such a major determinant of protein evolution. These developments show that, although the methodological basis of evolutionary systems biology is not yet fully solidified, this area of research is already starting to yield fundamental biological insights. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 43 TC 60 Z9 61 U1 1 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 2006 VL 17 IS 5 BP 481 EP 487 DI 10.1016/j.copbio.2006.08.003 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 099GE UT WOS:000241580500007 PM 16962765 ER PT J AU Larsen, M Artym, VV Green, JA Yamada, KM AF Larsen, Melinda Artym, Vira V. Green, J. Angelo Yamada, Kenneth M. TI The matrix reorganized: extracellular matrix remodeling and integrin signaling SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; COLLAGEN MATRIX; CELL-MIGRATION; FIBRONECTIN FIBRILLOGENESIS; BRANCHING MORPHOGENESIS; 3-DIMENSIONAL MATRICES; I COLLAGEN; FIBROBLASTS; POLYMERIZATION; METALLOPROTEINASE AB Via integrins, cells can sense dimensionality and other physical and biochemical properties of the extracellular matrix (ECM). Cells respond differently to two-dimensional substrates and three-dimensional environments, activating distinct signaling pathways for each. Direct integrin signaling and indirect integrin modulation of growth factor and other intracellular signaling pathways regulate ECM remodeling and control subsequent cell behavior and tissue organization. ECM remodeling is critical for many developmental processes, and remodeled ECM contributes to tumorigenesis. These recent advances in the field provide new insights and raise new questions about the mechanisms of ECM synthesis and proteolytic degradation, as well as the roles of integrins and tension in ECM remodeling. C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. RP Yamada, KM (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kyamada@mail.nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 49 TC 282 Z9 293 U1 4 U2 31 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 OCT PY 2006 VL 18 IS 5 BP 463 EP 471 DI 10.1016/j.ceb.2006.08.009 PG 9 WC Cell Biology SC Cell Biology GA 090HY UT WOS:000240943000002 PM 16919434 ER EF